Podcasts about p450

Broadcast from KSQD, Santa Cruz on 7-09-2026: Researchers refined a technique to reverse skin cell aging by about 30 years while preserving cellular identity. Exposing adult fibroblasts to Yamanaka factors—stopping before full reversion to pluripotent stem cells,reset the epigenetic clock and gene expression patterns to resemble much younger cells. The rejuvenated fibroblasts produced significantly more collagen, migrated faster to close artificial wounds, and showed reversal of gene expression patterns associated with Alzheimer's and cataracts. Since long-term epidemiologic data doesn't yet exist, Dr. Dawn follows up on last week's vaping question by exploring cancer mechanisms. Vaping aerosols impair DNA repair fidelity while triggering IL-6, IL-8, and TNF-alpha secretion. Nicotine-derived nitrosamines, reactive carbonyls (formaldehyde, acetaldehyde, acrolein) are generated when propylene glycol and vegetable glycerin are heated. Upregulated cytochrome P450 enzymes convert precarcinogens like benzopyrene into carcinogens. Mice exposed for 54 weeks developed lung adenocarcinomas in 22% and precancerous bladder hyperplasia in 57%, with markers matching those show predict lung cancer years before diagnosis. The Mexican Biobank—which includes over 40,000 samples from all 31 Mexican states revealed dramatic regional variation in drug-metabolism genes driven by Indigenous ancestry. In Chiapas, nearly 40% of the population carries two copies of a CYP2D6 variant reducing fentanyl metabolism, versus just 10% in Sinaloa. The SLCO1B1 variant hindering statin metabolism is found in over 15% of Yucatán residents., where 8 million Mexicans take statins. Dr. Dawn discusses both the promise and potential dark side of population genetic testing, including UK plans to genotype all children at birth for inborn errors of metabolism. Dr. Dawn briefly revisits the recent Indian study showing conch-shell blowing reduces sleep apnea by 34%, comparing it to earlier didgeridoo research, both of which strengthen airway muscles through forced-blowing exercises. A caller from Capitola recovering from non-Hodgkin's lymphoma near the L5 nerve asks about Japanese Kampo medicine formulas (Goshajinkigan, Yokukansan) for post-treatment nerve pain. Dr. Dawn suggests the pain likely originates from scar tissue tethering the nerve, and recommends consulting the Oriental Medicine Doctor program at Five Branches in Santa Cruz where faculty can advise on herbal formulas that trace back thousands of years through cultural exchange between China and Japan. Dr. Dawn explains Lp(a):lipoprotein(a), a small protein string attached to LDL particles that promotes clumping and clotting, is a genetically-determined coronary artery disease and stroke risk factor invisible to standard lipid panels. Levels of 250 particles double coronary risk and 350 particles triple it. Less than 75 is normal. Two new pharmaceutical strategies are in development to reduce Lp(a) : antisense oligonucleotides (single-stranded RNA that recruits RNase H to cleave target mRNA) and small interfering RNA (double-stranded RNA that triggers destruction of matching mRNA). Pelacarsen, a monthly injection in Phase 3 trials, reduces Lp(a) by 80%. These gene-silencing platforms open therapeutic possibilities for previously undruggable orphan diseases. Vitamin K2 is produced in the gut microbiome. MK-4 is most common in humans. Dr. Dawn recommends MK7 for stabilizing coronary calcium plaques and directing calcium into bone. A study of hepatitis B and C patients found MK4 to be protective in hepatocellular carcinoma. HCC developed in 2 of 21 MK-4-treated patients versus 9 of 19 controls, with a risk ratio of 0.2. MK-4 activates protein kinase A in vitro, inhibits HCC invasiveness, and restores apoptosis signaling that cancer cells normally block. Dr. Dawn recommends a couple milligrams of MK-4 daily for anyone with cirrhosis or prior hepatitis B or C infection.

What happens when medical cannabis is legal—but medical patients are still left without meaningful guidance?Part 2 of Kirk's conversation with Ted Smith of the Victoria Cannabis Buyers Club explores the widening gap between legalization, Health Canada's medical cannabis framework, and the real-world needs of patients. It seems many Canadians using cannabis for medical reasons are now being pushed toward recreational stores, where staff are not equipped to discuss drug interactions, dosing, high-potency extracts, suppositories, cancer care, or complex chronic conditions.Kirk, Trevor, and Ted dig into why compassion clubs still matter after legalization, how cannabis coaches, and community-based educators are filling gaps left by doctors, nurses, pharmacists, and regulators, and why “legal cannabis” is not the same as “medical cannabis.” The conversation also touches on RSO, cytochrome P450 drug interactions, CBD and prescription medications, harm reduction, stigma, raids on the Victoria Cannabis Buyers Club, and Ted's long-term vision for integrated cannabis-focused palliative care.Listen now to understand why medical cannabis advocacy did not end with legalization—and why patients, healthcare professionals, and policymakers still need to pay attention.The Victoria Cannabis Buyers Club - websiteTed Smith - LinkedInAdditional Music:Desiree Dorion desireedorion.comMarc Clement - FacebookTranscripts, papers and so much more at: reefermed.ca

Drug interactions do not have to feel confusing. Once the cytochrome P450 system clicks, it becomes much easier to reason through medication metabolism and pharmacology questions that nurse practitioners need to know.    In this episode, Alex and I explain the cytochrome P450 system and why it matters for drug metabolism, medication interactions, and clinical decision-making. You will walk away with a clearer framework for understanding pharmacology concepts that nurse practitioners need to know for both exams and real-world prescribing decisions.               Get full show notes, transcript, and more information here: https://blog.npreviews.com/cytochrome-p450-system       Follow us on Instagram: instagram.com/smnpreviewsofficial        

¿Qué sabemos realmente, a nivel molecular, sobre el efecto del aceite de oliva en la salud cardiovascular?Jesús de la Osada lleva más de treinta años investigando las bases moleculares de la aterosclerosis y el papel de los componentes de la dieta mediterránea en la salud cardiovascular. En este episodio repasa cómo se construye conocimiento riguroso en un área donde la divulgación de baja calidad abunda, y qué significa eso en términos de lo que podemos afirmar con fundamento sobre el aceite de oliva virgen extra.La investigación del grupo arrancó cuando los estudios disponibles medían únicamente colesterol total, un marcador tan poco específico que el aceite de oliva resultó neutro y quedó décadas fuera del foco. Con la llegada de modelos animales que reproducen aterosclerosis en semanas y el avance de la química analítica, el panorama cambió. El aceite de oliva virgen extra contiene cerca de 400 compuestos identificados. El candidato inicial, el ácido oleico por ser el componente mayoritario, fue descartado experimentalmente. El compuesto que concentra hoy el trabajo del grupo es el escualeno: el más abundante, el más estable durante el almacenamiento y el que se absorbe y acumula en órganos. Es además un intermediario universal en la biosíntesis de esteroles, lo que explica su presencia en organismos tan distintos como el olivo o el tiburón, y su coincidencia en las dos poblaciones con menor mortalidad cardiovascular históricamente documentada: la mediterránea y la japonesa.Estudiarlo de forma aislada presenta un problema importante: fuera de su matriz natural, el escualeno se oxida con facilidad. La solución que el grupo ha desarrollado en colaboración con el Instituto de Nanomateriales de Aragón es la encapsulación en nanopartículas que aíslan el compuesto y replican la protección que ejerce el propio aceite. En paralelo, trabajan con un aceite de oliva virgen enriquecido en escualeno y un compuesto fenólico, desarrollado junto a una empresa chipriota, cuyos resultados preliminares son prometedores.Dedicamos parte de la conversación a la diferencia entre evidencia in vitro y evidencia clínica, y por qué esa distinción es relevante para evaluar las afirmaciones que rodean a suplementos y nutracéuticos. El marco regulatorio para uso alimentario no exige demostrar eficacia, solo ausencia de toxicidad. Eso permite construir argumentos sobre mecanismos reales sin evidencia de que funcionen en humanos a las dosis habituales. No es necesariamente fraudulento, pero el salto entre ambas cosas rara vez se explicita.Hablamos también del estado actual del diagnóstico cardiovascular. Más allá del colesterol total y la distinción LDL/HDL, hay marcadores con mayor valor predictivo que no se usan de rutina: la Lp(a), el tamaño de las partículas de LDL, o la cuantificación de ApoB-100, que refleja el número de partículas en circulación independientemente del colesterol que transportan. La razón por la que estos marcadores no se incorporan de forma sistemática no es científica sino económica. Lo mismo ocurre con la farmacogenómica aplicada a estatinas: sabemos que los citocromos P450 implicados en su metabolismo tienen variantes con distinta actividad, pero la caracterización de cada paciente antes de prescribir sigue siendo la excepción, no la norma.Página Web del grupo: https://osada.unizar.esNuevos aceites: https://onlinelibrary.wiley.com/doi/10.1002/mnfr.70223Escualeno: https://onlinelibrary.wiley.com/doi/abs/10.1002/mnfr.201800136Aceite de oliva virgen: https://onlinelibrary.wiley.com/doi/10.1002/mnfr.201100668Nuevos modelos para estudio de aterosclerosis: https://www.imrpress.com/journal/FBL/11/1/10.2741/1852Si el episodio te ha resultado interesante, puedes apoyarlo dándole a like, suscribiéndote o compartiéndolo en tu plataforma habitual (Spotify, Apple Podcasts, iVoox, YouTube, etc.). Es un gesto que te cuesta muy poco y que ayuda muchísimo a que este podcast siga creciendo y llegue a más personas.

In this final episode of the Progesterone Promise series, Dr. Brendan McCarthy, Chief Medical Officer of Protea Medical Center, breaks down one of the most misunderstood hormones in women's health: progesterone. Progesterone is not “good” or “bad.” It's contextual. In today's world of quick sound bites and social media medicine, hormones are often reduced to oversimplified claims like “progesterone fixes anxiety” or “progesterone causes breast cancer.” The truth? It depends on your body, your stress levels, your liver health, your inflammation, your delivery method, and whether you're using bioidentical progesterone or synthetic progestins.   Citations: 1. Oral Progesterone → First-Pass Metabolism & Allopregnanolone Claim: Oral micronized progesterone undergoes significant hepatic first-pass metabolism, increasing neuroactive metabolites (especially allopregnanolone), which positively modulate GABA-A receptors and produce sedative/anxiolytic effects. Core Evidence: Simon et al., 1993; de Lignières et al., 1995; Freeman et al., 1990 — Oral progesterone produces measurable neuroactive metabolites. Paul & Purdy, 1992; Rupprecht et al., 2001 — Allopregnanolone enhances GABA-A receptor activity. Supports: Sedation variability by route • Neurosteroid generation • GABA-A modulation 2. Sulfation vs 5α-Reduction → Opposing Neurologic Effects Claim: Progesterone metabolites can produce calming (5α-reduced) or excitatory (sulfated) neurologic effects depending on enzyme routing. Core Evidence: Majewska et al., 1990 — Pregnenolone sulfate negatively modulates GABA-A. Wu et al., 1991 — Sulfated neurosteroids enhance NMDA signaling. Schumacher et al., 2007; Reddy, 2010 — Pathway reviews of sulfation vs 5α-reduction. Supports: Reverse responding hypothesis • Divergent neurologic experiences • Enzyme-dependent effects 3. Stress & Enzyme Modulation Claim: Chronic stress alters HPA axis tone and hepatic enzyme expression, influencing steroid metabolism balance. Core Evidence: McEwen, 1998 — Allostatic load model. Charmandari et al., 2005 — Cortisol's systemic regulatory effects. Zanger & Schwab, 2013; Gibson & Skett, 2001 — Stress alters cytochrome P450 expression. Supports: Stress-biased metabolism • Context-dependent hormone response 4. Breast Tissue Signaling & Context Claim: Progesterone influences mammary differentiation and interacts with estrogen signaling in context-dependent ways. Core Evidence: Brisken & O'Malley, 2010 — Progesterone receptor biology in breast tissue. Beleut et al., 2010 — RANKL mediates progesterone-driven proliferation. Hofseth et al., 1999 — PR-ER signaling interaction. Stanczyk & Bhavnani, 2014 — Natural vs synthetic differences in breast effects. Supports: Lobuloalveolar differentiation • RANKL pathway • Context-dependent proliferation 5. Synthetic Progestins vs Bioidentical Progesterone Claim: Synthetic progestins differ structurally and bind off-target receptors, producing distinct tissue effects. Core Evidence: Stanczyk et al., 2013 — Receptor binding differences. Sitruk-Ware, 2004 — Biologic comparisons. Chlebowski et al., 2003 (WHI) — Breast cancer signal with CEE + MPA. Supports: Structural divergence • Receptor-level differences • WHI clarification 6. Route of Delivery Differences Claim: Oral, vaginal, transdermal, and sublingual progesterone produce distinct pharmacokinetic profiles and tissue targeting. Core Evidence: Simon, 1995 — Oral vs vaginal PK comparison. Cicinelli et al., 2000 — “First uterine pass effect.” Wren et al., 2003 — Route-dependent systemic levels. Supports: Uterine targeting • Neurosteroid variability • Sedation differences 7. Progesterone, PMS & Migraine Claim: Neurosteroid fluctuations influence GABAergic tone and may contribute to PMS and migraine susceptibility. Core Evidence: Backstrom et al., 2011 — Allopregnanolone fluctuations in PMS. Reddy & Rogawski, 2002 — Neurosteroids and seizure threshold. Martin & Behbehani, 2001 — Hormonal fluctuations and migraine. Supports: Luteal neurosteroid shifts • GABA instability • Migraine association   Dr. Brendan McCarthy is the founder and Chief Medical Officer of Protea Medical Center in Arizona. With over two decades of experience, he's helped thousands of patients navigate hormonal imbalances using bioidentical HRT, nutrition, and root-cause medicine. He's also taught and mentored other physicians on integrative approaches to hormone therapy, weight loss, fertility, and more. If you're ready to take your health seriously, this podcast is a great place to start.  

Midodrine is an oral alpha-1 agonist most commonly used for the treatment of symptomatic orthostatic hypotension. Its mechanism of action is through peripheral vasoconstriction, which helps increase blood pressure. Because of its short duration of action, it is typically dosed three times daily, with the last dose recommended in the late afternoon to reduce the risk of hypertension at night. Clinically, midodrine is often considered when non-pharmacologic strategies for orthostatic hypotension (such as increased salt/fluid intake, compression stockings, or physical counter-maneuvers) are not enough. Pharmacists should also be aware of prescribing cascades—such as urinary retention leading to tamsulosin initiation—that can arise when midodrine is used. Midodrine is generally not metabolized through cytochrome P450 pathways, so significant drug–drug interactions are less common. However, caution should be exercised with other agents that can raise blood pressure (like decongestants) or slow the heart rate (such as beta-blockers). Monitoring parameters include blood pressure, pulse, symptoms of urinary retention, and the patient's overall response to therapy.

In dieser Episode von „Der Schmerzcode“-Podcasts tauchen wir tief in die Welt der Opiate und Opioide ein. Gemeinsam mit Professor Lipp klären wir die Unterschiede zwischen beiden Begriffen und deren Rolle in der Schmerzbehandlung. Wir diskutieren die Funktionsweise der verschiedenen Rezeptoren im zentralen Nervensystem und beleuchten die praktischen Anwendungen von Morphin, Hydromorphon, Buprenorphin und Fentanyl in der Therapie. Professor Lipp gibt wertvolle Hinweise zur Dosierungsanpassung und beleuchtet Herausforderungen, die sich aus genetischen Unterschieden ergeben können. Zudem werfen wir einen kritischen Blick auf die Opiatkrise in den USA und die Lehren, die daraus für Deutschland gezogen werden sollten. Die Episode schließt mit einer Diskussion über opioidfreie Anästhesie und der Notwendigkeit von Fortbildung im Bereich Schmerztherapie.

Ketoconazole is an imidazole antifungal that works by inhibiting fungal cytochrome P450 14α-demethylase, an enzyme essential for ergosterol synthesis, which disrupts fungal cell membrane integrity. Common adverse effects of ketoconazole include nausea, vomiting, abdominal pain, and elevated liver enzymes, with hepatotoxicity being a notable concern. Ketoconazole carries a boxed warning for severe hepatotoxicity, including cases of liver failure and death, and should not be used as a first-line treatment for fungal infections when other safer antifungals are available. Another boxed warning highlights ketoconazole's potential to prolong the QT interval, increasing the risk for life-threatening ventricular arrhythmias such as torsades de pointes. Ketoconazole is a strong inhibitor of CYP3A4 and can cause significant drug interactions by increasing serum concentrations of medications metabolized by this pathway, including statins, certain benzodiazepines, and some antiarrhythmic.

Ever thought about why medications work differently for different people? In this episode of Absolute Gene-ius, we explore the exciting field of pharmacogenomics with Wendy Wang, pharmacogenetic laboratory supervisor at Children's Mercy Hospital in Kansas City. Wendy shares how genetics can influence drug metabolism, offering a glimpse into how precision medicine can revolutionize healthcare by tailoring treatments based on an individual's unique genetic makeup.At the heart of Wendy's research is CYP2D6, a cytochrome P450 enzyme responsible for metabolizing around 20% of all prescribed medications. She explains how her lab uses digital PCR to analyze copy number variations (CNV), offering a reliable and precise method to predict drug metabolism. Wendy dives into the complexities of structural variants, the role of digital PCR in enhancing assay efficiency, and why pharmacogenomics is a critical piece of the precision medicine puzzle. Her use of delightful metaphors—like comparing genetic testing to ladling soup—makes complex science both relatable and engaging.In the Career Corner, Wendy opens up about her winding path to molecular biology, which included studying classical antiquity and nearly pursuing a career in history. She emphasizes the importance of resilience in research, embracing failure as a learning opportunity, and encourages budding scientists to reach out to mentors and explore diverse interests. Plus, hear about her most embarrassing lab mishap (hint: it involves a fire alarm) and the proud moment of publishing her first, first-author paper.Visit the Absolute Gene-ius page to learn more about the guests, the hosts, and the Applied Biosystems QuantStudio Absolute Q Digital PCR System. 

L'intelligence artificielle capte toutes les attentions, mais dans l'ombre, une autre révolution technologique se prépare. L'informatique quantique, encore méconnue du grand public, pourrait bien être le véritable tremplin du progrès pour les décennies à venir. Et ce n'est pas Google qui dira le contraire. En ce 14 avril, Journée mondiale de l'informatique quantique, la firme de Mountain View a partagé sa vision du futur : dans 10 à 15 ans, nos ordinateurs pourraient résoudre des problèmes aujourd'hui insolubles, propulsant l'humanité vers une nouvelle ère technologique. Trois domaines majeurs sont concernés par cette promesse.D'abord, l'énergie. Grâce à la puissance de calcul phénoménale des ordinateurs quantiques, la maîtrise de la fusion nucléaire pourrait devenir réalité. Une énergie quasi illimitée, produisant plus qu'elle ne consomme. Pour Google, les algorithmes quantiques permettront de simuler plus efficacement les réactions de fusion soutenues, jusque-là hors de portée des machines classiques. Deuxième promesse : les batteries. Le quantique pourrait aider les ingénieurs à concevoir de nouveaux matériaux, optimisant autonomie et performance, un enjeu crucial dans notre transition énergétique.Enfin, la santé. En collaboration avec le laboratoire Boehringer Ingelheim, Google a déjà montré des résultats prometteurs : les simulations quantiques des cytochromes P450, enzymes clés dans la transformation des médicaments par le corps, s'avèrent plus précises. À terme, cela pourrait accélérer le développement de traitements plus efficaces. Amazon, Microsoft, Google : les géants américains sont dans la course. Reste à savoir si l'Europe saura se positionner dans cette révolution silencieuse… mais potentiellement plus bouleversante que celle de l'intelligence artificielle. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

Contributor: Jorge Chalit-Hernandez, OMS3 Educational Pearls: CYP enzymes are responsible for the metabolism of many medications, drugs, and other substances CYP3A4 is responsible for the majority Other common ones include CYP2D6 (antidepressants), CYP2E1 (alcohol), and CYP1A2 (cigarettes) CYP inducers lead to reduced concentrations of a particular medication CYP inhibitors effectively increase concentrations of certain medications in the body Examples of CYP inducers Phenobarbital Rifampin  Cigarettes St. John's Wort Examples of CYP inhibitors -azole antifungals like itraconazole and ketoconazole Bactrim (trimethoprim-sulfamethoxazole) Ritonavir (found in Paxlovid) Grapefruit juice Clinical relevance Drug-drug interactions happen frequently and often go unrecognized or underrecognized in patients with significant polypharmacy A study conducted on patients receiving Bactrim and other antibiotics found increased rates of anticoagulation in patients receiving Bactrim Currently, Paxlovid is prescribed to patients with COVID-19, many of whom have multiple comorbidities and are on multiple medications Paxlovid contains ritonavir, a powerful CYP inhibitor that can increase concentrations of many other medications A complete list of clinically relevant CYP inhibitors can be found on the FDA website: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers  References Glasheen JJ, Fugit RV, Prochazka AV. The risk of overanticoagulation with antibiotic use in outpatients on stable warfarin regimens. J Gen Intern Med. 2005;20(7):653-656. doi:10.1111/j.1525-1497.2005.0136.x Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician. 2007;76(3):391-396. PAXLOVID™. Drug interactions. PAXLOVIDHCP. Accessed March 16, 2025. https://www.paxlovidhcp.com/drug-interactions Summarized & Edited by Jorge Chalit, OMS3 Donate: https://emergencymedicalminute.org/donate/  

In this episode, we delve into the art of detoxification, focusing on two key areas: sleep and liver health. We'll also introduce Liver Boost, a supplement designed to support your liver's detoxification processes. Join us as we unravel the secrets of effective detox and discover how Liver Boost can enhance your journey to wellness.   Show Notes: Improving Sleep for Effective Detox: Understanding the metabolic dysregulation caused by sleep issues[^1^]. The antioxidant role of melatonin in detoxification[^3^]. Genetic factors influencing sleep and the role of melatonin supplementation[^2^]. Studies: PMC on Sleep and Metabolism: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929498/ PMC on Genetic Influences on Sleep: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8974368/ PubMed on Melatonin: @8/ Supporting Liver Detoxification (Phase I & II): The role of xenobiotic biotransforming enzymes in liver detox[^1^]. Phase I detoxification involving the cytochrome P450 enzymes[^1^]. Personalized dietary considerations for optimizing liver detoxification[^1^]. Crucial foods for Phase II detoxification[^1^]. Study: PubMed on Liver Detoxification: https://pubmed.ncbi.nlm.nih.gov/1749210/ Foods to Support Detox Organs: Nrf2/GST/Sulfurnarse supportive foods like curcumin, green tea, and garlic. Cruciferous vegetables, citrus fruits, and specific beverages beneficial for liver health[^1^].   Study: PMC on Foods and Liver Detox: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488002/ Acute Exposure Detox with NAC (Liver Boost): The importance of N-acetyl cysteine (NAC) in increasing GST for liver detox[^1^][^2^]. Dietary sources to support methylation and Nrf2 activation[^2^].   Studies: PMC on NAC and Liver Health: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488002/ PMC on GSH and Metabolism: @icles/PMC3464379/ MTHFR Issues Hindering Detox: The impact of MTHFR polymorphisms on detoxification processes[^1^][^2^]. Importance of nutrient cofactors and methyl donors in managing MTHFR issues[^1^]. Studies: PMC on MTHFR and Detox: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488002/ PMC on MTHFR Polymorphisms: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703276/   Remember that effective detoxification is crucial for overall health. To support your liver's natural detoxification processes, consider adding Liver Boost to your regimen. Formulated to enhance Phase I and II liver detoxification, Liver Boost can be your ally in achieving optimal health and vitality. Click https://www.mswnutrition.com/products/liver-love/?ref=nursedoza  to embark on a journey towards a cleaner, more energized you.

The United States spends almost twice as much on healthcare compared to other developed nations. And in spite of all of the technologies, specialists, and medications we have available, The United States ranks dead last in terms of health outcomes. It's clear that something isn't working. The problem is, we don't have a healthcare system; we have a sickcare system that profits off of the farming of sick people. The pharmaceutical companies and the insurance companies only exist to make money. The United States healthcare system doesn't have an interest in helping our citizens find the root cause of their ailments. On this episode of The Model Health Show, our guest is Brigham Buhler, the founder and CEO of Ways2Well. He's here to share insider secrets from his previous career as a pharmaceutical representative. You're going to learn interesting facts about how insurance companies profit, the truth about Big Pharma, and how the American people can take control of their health.    In this episode you'll discover:  The amount of money the United States spends on healthcare.  How corporate America got its grips on our healthcare system.   Why the competitive field of medical sales leads to worse patient care.  How health education quickly becomes obsolete.   The first drug Big Pharma taught doctors to prescribe to a wide audience.  How many American people die every year from chronic illnesses.   The sad truth about how the opioid crisis and the valium crisis were created.   How the incentive system hurts people.   What a cytochrome P450 test is & how it could be used to change prescription practices.  The dirty secret the insurance companies use to exacerbate illnesses.   How insurance companies make money on your prescriptions.   What a pharmacy benefit manager is.   Why insulin prices have reached an all-time high.   The shocking truth about the gag clause at your pharmacy.  How insurance companies impact the way doctors provide care.   The #1 reason for bankruptcy in America.   Why metabolic health is an important lever we can pull.  What Ways2Well does.     Items mentioned in this episode include:  Foursigmatic.com/model - Get an exclusive discount on your daily health elixirs!  Onnit.com/model - Save an exclusive 10% on performance supplements & tools!  Comprehensive Bloodwork Panel  - Get 10% off Ways2Well your bloodwork panel!  Connect with Brigham Buhler Website / Instagram     Be sure you are subscribed to this podcast to automatically receive your episodes:   Apple Podcasts  Spotify  Soundcloud  Pandora  YouTube     This episode of The Model Health Show is brought to you by Foursigmatic and Onnit. Visit foursigmatic.com/model to get an exclusive 10% discount on mushroom and adaptogen-packed blends to improve your life. Visit Onnit.com/model for an exclusive 10% discount on human performance supplements and fitness equipment.  

Explore effective strategies for enhancing recovery post-surgery through dietary adjustments and targeted supplements.   5 KEY TAKEAWAYS   1.Pre and Post-Surgery Nutrition: Changing your diet before and after surgery can significantly impact your recovery speed and quality. 2.Importance of Liver Health: Supporting your liver is crucial as it processes medications and helps in detoxifying your body post-surgery. 3.Benefits of Supplements: Specific supplements like Vitamin C, L-Arginine, and L-Glutamine can enhance wound healing and reduce recovery time. 4.Red Light Therapy: Utilizing red light therapy can aid in healing and potentially reduce scarring post-surgery. 5.Soft Tissue Therapy: Engaging in soft tissue therapy can help manage and minimize post-surgical scarring and improve flexibility.   FEATURED PRODUCT Liver Boost and Berberine by MSW Nutrition are designed to support metabolic health, crucial for anyone recovering from surgery. These supplements aid in liver function, helping to process medications and reduce inflammation, which is essential for a smooth recovery. visit www.mswnutrition.com to learn more   TIMESTAMPS 00:00 START: Introduction to surgery recovery and the importance of preparation. •01:00: Discussing the critical role of diet in surgery recovery. •02:00: The benefits of adjusting your diet pre-surgery. •03:00: How liver health impacts recovery and the importance of supporting the liver with Liver Boost. •05:00: The effectiveness of red light therapy in post-surgery care. •06:00: Exploring soft tissue therapy as a method to enhance recovery post-surgery. •07:00: The role of dietary changes in reducing post-operative complications. •08:00: Strategies for managing pain and inflammation with natural supplements. •09:00: How to integrate physical therapy early to speed up recovery. •13:00: Importance of following medical advice and the role of regular follow-ups. •17:00: The benefits of holistic approaches like meditation and yoga in recovery. •18:00: Preparing for surgery: what to do in the days leading up to it. •19:00: Closing advice on maintaining health post-recovery. •20:00: Recap of key points and final thoughts on effective recovery strategies. RESOURCES   1.“What to Eat During Your Recovery After Surgery” - Discusses nutritional strategies for postoperative healing 2.“Pharmacogenetics - Genes affecting cytochrome P450 enzymes” - Details how genetic factors influence drug metabolism 3.“The Importance of Antioxidants in Healing” - Explains the role of antioxidants like NAC and Curcumin in recovery 4.“Glutamine and Wound Healing” - Outlines how glutamine supports nitrogen balance and reduces hospital stays 5.“Vitamin C and Wound Healing” - Discusses the benefits of Vitamin C, especially in combination with other supplements for pressure ulcer patients 6.“Red Light Therapy and Its Benefits in Postoperative Care” - Details how low-level laser therapy aids in reducing scarring and enhancing healing 7.“Soft Tissue Management Post-Surgery” - Highlights the benefits of soft tissue therapy in post-surgical recovery   CONNECT WITH NURSE DOZA   •JOIN MY SCHOOL for $5: Sign Up Here •YouTube: https://www.youtube.com/channel/UCwcKyagDi468WscAOWM5VHA •Instagram: https://www.instagram.com/nursedoza/ •Website: http://www.nursedoza.com/ •LinkedIn: https://www.linkedin.com/in/jonathan-mendoza-dc-aprn-np-c-0609a038/ •TikTok: https://www.tiktok.com/@nursedoza •Twitter: https://twitter.com/nursedoza

Dr. Vrzal, a chiropractor and author of "The Headache Advantage" helps us understand helping the body from a whole person perspective and using symptoms to get to the actual cause of the problem.RESOURCES:https://headacheadvantage.com/https://www.drvrzal.com/https://www.youtube.com/@DrVrzalhttps://www.youtube.com/watch?v=YU7UrlpIEKUTIMESTAMPS:00:00 Intro Snip01:46 Why did Dr. Haley become a chiropractor?02:35 Why did Dr. Vrzal become a chiropractor?05:09 Dr. Haley tells of his first headache patient06:42 How is a headache an advantage?09:00 How is applied kinesiology used to help correct the problem10:00 What are common problems in people's diets?11:10 What is the difference between eastern and western medicine?14:15 Describe a first visit with Dr. Vrzal16:16 What is the Dr. Vrzal technique?18:00 What is Neuroemotional Technique?23:12 What does low back pain have to do with bowel function?25:30 What is yeast over-growth, leaky gut and how does that affect the gut brain connection?27:55 What are the various communication methods in the body?29:40 How does the diet log work?31:24 How you can use the blood type to figure things out32:23 What is the one best diet for everyone?34:50 Will the vegetarian diet work for you?35:35 will Paleo diet work for you?37:30 Does soda make you fat or is it the bubbles?38:18 What causes tinnitis?39:45 What causes Alzheimer's Disease?40:50 Are there safe sugar substitutes?42:10 How to kill lyme42:35 P450 the first phase of liver detoxification

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In the last episode, we discussed the fact that toxins come from food, air, water, personal care products, and pretty much everything we encounter. Detoxification is an ongoing process that is always at work in your body. Here are the basics about how detoxification happens, what resources your body needs, and why it sometimes feels yucky. Detoxification happens in three phases. Phase one involves chemical reactions, mostly in the cytochrome P450 system. Phase two comprises conjugation reactions so that substances can be transported out of the tissues, and phase three is the active transport of these toxins out of your tissues and into waste material. 00:00 - intro 00:29 - Why Detox is easy to get wrong 01:19 - Three phases of detoxification 01:40 - Detoxification Phase one and cytochrome P450 system 02:31 - Genetic Rockstars quick walk-through 04:36 - Detoxification Phase two, conjugation reactions, and gene SNPS 05:15 - Phase three reactions and toxin transport 05:43 - You have to eliminate to detox 06:26 - Water and detox 06:50 - Limit toxin exposure 08:05 - Detox uses energy and nutrients 09:01 - Practitioner support and detox kits GENETIC ROCKSTARS (an MTHFR community): community.tohealthwiththat.com FREE COURSE: MTHFR Basics: https://courses.tohealthwiththat.com/p/mthfr-basics WORK WITH DR. AMY ONE-ON-ONE: Set up a free meet and greet appointment to see if we're a good fit to work together, or if group coaching, community, or something else might be a better option: https://calendly.com/amy-tohealthwiththat/15min GROUP COACHING: https://www.tohealthwiththat.com/group-coaching/ WEBSITE: https://tohealthwiththat.com/ AFFILIATE LINKS: I appreciate you using these links to purchase products you would buy anyway, because they allow me to keep putting information out there. Thank you! SEEKING HEALTH (metylation and histamine support supplements - these ship internationally): https://bit.ly/3afXYH4 STRATEGENE REPORT (detailed genetics using 23andme or ancestry raw data): https://bit.ly/3retbm5 FULLSCRIPT (professional grade supplements): https://us.fullscript.com/welcome/thwt QUEEN OF THE THRONE (castor oil and castor oil packs):  https://shop.queenofthethrones.com/amy-tohealthwiththat use code AMY_TOHEALTHWITHTHAT10 for 10% off of any order of $59 or more --- Send in a voice message: https://podcasters.spotify.com/pod/show/tohealthwiththat/message

Hasta aquí el programa de hoy del podcast de seguridad vial y educación vial. ¿Quieres escuchar episodios anteriores del podcast de educación vial y seguridad vial? • P6 Coronavirus y Seguridad Vial https://go.ivoox.com/rf/49513283 • P169 Seguridad vial en Onda Cero https://go.ivoox.com/rf/74292123 • P125 ¿Isofix en un SsangYong Rodius? Y mucha más seguridad vial https://go.ivoox.com/rf/71289331 • P196 Seguridad vial para bebés prematuros y CIPSEVI https://go.ivoox.com/rf/78652365 • P168 Sin ruedas no hay seguridad vial https://go.ivoox.com/rf/74292023 • P182 La educación vial en El Enfoque, Onda Madrid https://go.ivoox.com/rf/76018355 • P7 Mascarillas y guantes son al coronavirus lo que el cinturón de seguridad y los SRI a la violencia vial https://go.ivoox.com/rf/50038459 • P197 Estudio sobre la inseguridad vial en el contenido de las series en Capital Radio https://go.ivoox.com/rf/78897119 “El verdadero viaje es el que termina como comenzó, con felicidad e inocencia” Feliz viaje hasta el próximo programa. _______________________________________

In this episode, we delve into the art of detoxification, focusing on two key areas: sleep and liver health. We'll also introduce Liver Boost, a supplement designed to support your liver's detoxification processes. Join us as we unravel the secrets of effective detox and discover how Liver Boost can enhance your journey to wellness.   Show Notes: Improving Sleep for Effective Detox: Understanding the metabolic dysregulation caused by sleep issues[^1^]. The antioxidant role of melatonin in detoxification[^3^]. Genetic factors influencing sleep and the role of melatonin supplementation[^2^]. Studies: PMC on Sleep and Metabolism: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929498/ PMC on Genetic Influences on Sleep: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8974368/ PubMed on Melatonin: @8/ Supporting Liver Detoxification (Phase I & II): The role of xenobiotic biotransforming enzymes in liver detox[^1^]. Phase I detoxification involving the cytochrome P450 enzymes[^1^]. Personalized dietary considerations for optimizing liver detoxification[^1^]. Crucial foods for Phase II detoxification[^1^]. Study: PubMed on Liver Detoxification: https://pubmed.ncbi.nlm.nih.gov/1749210/ Foods to Support Detox Organs: Nrf2/GST/Sulfurnarse supportive foods like curcumin, green tea, and garlic. Cruciferous vegetables, citrus fruits, and specific beverages beneficial for liver health[^1^].   Study: PMC on Foods and Liver Detox: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488002/ Acute Exposure Detox with NAC (Liver Boost): The importance of N-acetyl cysteine (NAC) in increasing GST for liver detox[^1^][^2^]. Dietary sources to support methylation and Nrf2 activation[^2^].   Studies: PMC on NAC and Liver Health: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488002/ PMC on GSH and Metabolism: @icles/PMC3464379/ MTHFR Issues Hindering Detox: The impact of MTHFR polymorphisms on detoxification processes[^1^][^2^]. Importance of nutrient cofactors and methyl donors in managing MTHFR issues[^1^]. Studies: PMC on MTHFR and Detox: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488002/ PMC on MTHFR Polymorphisms: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703276/       Remember that effective detoxification is crucial for overall health. To support your liver's natural detoxification processes, consider adding Liver Boost to your regimen. Formulated to enhance Phase I and II liver detoxification, Liver Boost can be your ally in achieving optimal health and vitality. Click https://www.mswnutrition.com/products/liver-love/?ref=nursedoza  to embark on a journey towards a cleaner, more energized you.

We are diving into a pretty amazing bioregulator peptide called Svetinorm. Extracted from liver cells, this bioregulator peptide has been shown to help restore function to hepatocytes, improve conditions of hepatitis, decrease symptoms such as fatigue and indigestion, and more. All-in-all, the liver is critical for detoxification, processing excess hormones, producing bile, and more, so ensuring that the hepatocytes are functioning correctly is paramount! Stay tuned - this peptide is a game-changer... Topics: 1. Introduction to Liver Detoxification and Svetinorm - Overview of liver detoxification processes. - Introduction of Svetinorm as a bioregulatory peptide derived from cattle liver cells. 2. Liver Function and Structure - Exploration of the vital role of the liver in detoxification, metabolism, and overall health. - Description of the anatomical structure of the liver. - Introduction of hepatocytes as the primary functional cells responsible for various liver functions. 3. Blood Flow and Hepatic Lobules - Details about the intricate blood flow within the liver. - Discussion of hepatic lobules as the fundamental structural units of the liver. - Highlighting the hexagonal shape of hepatic lobules and their central hepatic vein. - Explanation of the role of sinusoidal endothelial cells in facilitating molecule exchange between blood and hepatocytes. - Description of how these cells line the walls of sinusoids within hepatic lobules. 4. Hepatocyte Detoxification Process - Toxins entering the bloodstream and reaching hepatocytes. - Explanation of Phase I metabolism, involving cytochrome P450 enzymes modifying toxins. - Introduction of Phase II metabolism or conjugation, where toxins become more water-soluble. - Examples of common conjugation agents such as glucuronic acid, sulfate groups, glutathione, amino acids, acetyl groups, methyl groups, and others. 5. Toxin Elimination Pathways - Explanation of the routes for water-soluble conjugates to exit the liver. - Details about options for conjugates to reenter the bloodstream or enter the bile. - Mention of how toxins may be further processed and eliminated through urine, feces, or bile. 6. Impaired Hepatocytes and Associated Symptoms - Discussion of the consequences of impaired detoxification pathways and dysfunctional hepatocytes. - Enumeration of common symptoms that may arise from liver dysfunction, such as fatigue, skin issues, digestive problems, bloating, fluid retention, inflammation, and hormone imbalances. 7. Svetinorm - Clinical studies - Proposed mechanisms: bioregulatory peptides 8. Administration - Details about recommended Svetinorm dosage and administration methods. - Highlights of clinical studies, primarily focused on chronic hepatitis patients. - Notation of the positive outcomes observed in these studies, such as improved energy and decreased dyspepsia. - Always work with a licensed medical professional. 9. Personal Experience with Svetinorm - Sharing personal perspectives and experiences with Svetinorm for detoxification and liver support during CIRS Thanks so much for tuning in! Order Chloe's Book "⁠⁠⁠⁠⁠⁠⁠75 Gut-Healing Strategies & Biohacks⁠⁠⁠⁠⁠⁠⁠" TODAY! If you liked this episode, please leave a rating and review or share it to your stories over on Instagram. If you tag @synthesisofwellness, Chloe would love to personally thank you for listening! Follow Chloe on Instagram ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Follow Chloe on TikTok @chloe_c_porter Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠synthesisofwellness.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to purchase products, subscribe to our mailing list, and more! Or visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠linktr.ee/synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to see all of Chloe's links, schedule a BioPhotonic Scanner consult with Chloe, or support the show! Thanks again for tuning in! --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support

In this episode we combine many of the pharmacy school raps that have complemented to understanding and learning concepts in Pharmacy School. -- Note: Purpose of these episodes-  not at all, for advice or medical suggestions. These are aimed to provide support for peer pharmacists in training in educational and intellectual stimulating ways. Again, these are not at all for medical advice, or for medical suggestions. Please see your local state and board certified physician, PA or NP, and pharmacist for medical advice and suggestions. --

Treba lieky zapíjať grapefruitovou šťavou? Je ľudská pamäť najspoľahlivejší harddisk na svete? Nahradíme betón kávovým gruntom? Aj na tieto otázky odpovieme v dnešnom Pseudocaste. Pseudocast 625 na YouTube Zdroje Drug Interactions with Grapefruit Juice Drug Interactions Reported with Grapefruit Juice Cytochróm P450 - izoenzým CYP3A4 Interaction of citrus juices with felodipine and nifedipine Effect of grapefruit juice volume on the reduction of fexofenadine bioavailability: possible role of organic anion transporting polypeptides Grapefruit False Memories for Ending of Events Video Experiment Scary Car Commercial - jumpscare! Scientists Discover Amazing Practical Use For Leftover Coffee Grounds Coffee offers performance boost for concrete Image by Bob from Pixabay

Thank you for listening to this episode of "Health and Fitness" from the Nezpod Studios! Enjoy your night or the start of your day, spiced by our top-notch health and fitness/wellness updates coined from the best sources around the globe: made only for your utmost enjoyment and enlightenment… Click on subscribe to get more spicy episodes for free! See you again soon on the next episode of Health and fitness updates! Learn more about your ad choices. Visit megaphone.fm/adchoices

Thank you for listening to this episode of "Health and Fitness" from the Nezpod Studios! Enjoy your night or the start of your day, spiced by our top-notch health and fitness/wellness updates coined from the best sources around the globe: made only for your utmost enjoyment and enlightenment… Click on subscribe to get more spicy episodes for free! See you again soon on the next episode of Health and fitness updates! Learn more about your ad choices. Visit megaphone.fm/adchoices

Thank you for listening to this episode of "Health and Fitness" from the Nezpod Studios! Enjoy your night or the start of your day, spiced by our top-notch health and fitness/wellness updates coined from the best sources around the globe: made only for your utmost enjoyment and enlightenment… Click on subscribe to get more spicy episodes for free! See you again soon on the next episode of Health and fitness updates! Learn more about your ad choices. Visit megaphone.fm/adchoices

Dear Wild One, if you have one or more fibroids, and you want to know all of the potential #naturalremedies to treat them non-surgically, this episode is for you!   You'll learn: ☑️ Based on our understanding of what causes fibroids, what foods can we use to treat them naturally?  ☑️ Is it even possible to shrink / reduce the size of fibroids using nutrition and strategic foods? ☑️ What is the best food plan to reduce the size of fibroids naturally?   Check out the Fibroids playlist in case you missed last week's episode introducing this very hot topic.   LIKE, SHARE and SUBSCRIBE as I post a new video weekly on a hot topic on the root cause solutions for women's health concerns!   

References JLR 2014 55(6) Pages 1165-1172. JLR 2018 59(6): 1058–1070. --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message

Asetaminofen ismiyle de bilinen parasetamol, tüm dünyada yaygın kullanılan ve kolay erişilebilen bir analjezik ve antipiretiktir. Terapötik dozlarda güvenli kabul edilse de akut ya da kronik aşırı alımda toksik etkileri olabilir. Karaciğer yetmezliğinin en sık nedenlerinden biri olan parasetamol zehirlenmesi ve yönetimi üzerine hatırlatmalar yapmak istedim.​1​ ​2​ ​3​ İyi okumalar! Farmakokinetik ve Toksisite Mekanizması Parasetamol oral alımdan sonra duedonumdan tamamen emilir ve terapötik alımlarda serum konsantrasyonu yarım saat ila iki saat arasında pik yapar. Aşırı alımlarda serum konsantrasyonu dört saatte pik yapar, toksisitesinde 4. saat düzeyi bu nedenle değerlidir. Eğer gastrik boşalmayı uzatan ilaçlarla (opiatlar, antikolinerjik ajanlar vb.) birlikte alınmışsa ya da uzun salımlı preparatların alımı söz konusuysa pik süresi dört saatin üzerine uzayabilir. Özellikle parasetamol içeren kombine preparat alımı söz konusuysa bu nokta göz önünde bulundurulmalıdır. Parasetamolün toksik dozu genellikle erişkinlerde tek seferde ya da 24 saatte 10 gr ve üzeri, çocuklarda 150 mg/kg ve üzeri olarak kabul edilir.​4​ Ardışık 2 gün veya daha fazla 6 gr ve üzeri alım (çocuklarda 100 mg/kg üzeri alım) da akut toksisiteye neden olur. Altta yatan karaciğer hastalığı olan veya düzenli olarak alkol tüketen hastalarda uzun süre parasetamol kullanımı sonucu terapötik bir doz alımında da ortaya çıkabilir. Terapötik dozlarda parasetamol metabolizmasının %20-40'ı karaciğerde sülfasyon yoluyla, %40-67'si karaciğerde glukuronidasyon yoluyla olurken %5'ten azı böbrekten direkt elimine edilir. Düşük bir oranda sitokrom P450 sistemi ile N-asetil-p-benzokinonimin (NAPQI) reaktif metabolitine dönüşür. Normalde NAPQI, endojen bir antioksidan olan glutatyon tarafından detoksifiye edilir, ancak parasetamol doz aşımında, glutatyon depoları tükenir ve NAPQI hücresel proteinlere (özellikle mitokondriyal proteinlere) bağlanır. Artan mitokondriyal strese bağlı olarak intrasellüler sinyal artışı ve oksidatif hasar oluşur, ardından karaciğer hasarı ve nekroz gelişir.​5​ Toksisiteyi Etkileyen Faktörler Aşırı alım Alım ile N - asetilsistein (NAC) tedavisi arasındaki gecikme Aşırı sitokrom P450 aktivitesi Glukuronidasyon veya sülfasyon kapasitesinin azalması Glutatyon depolarının tükenmesi Toksisiteyi arttıran durumlardan biri kronik alkol alımıdır. Kronik alkol alımı, CYP2E1 sentezini ve aktivitesini iki kat arttırarak glutatyon depolarını tüketir. CYP2E1 enzimini indükleyen ilaçların veya bitkisel ürünlerin kullanımı da benzer sonuçlara neden olur, bazı antikonvülzanlar (karbamazepin, fenobarbital ve fenitoin) izoniazid ve rifampin bu gruptadır. Trimetoprim-sülfametoksazol, opioidler ve zidovudin gibi ilaçlar ise glukuronidasyon yolları için parasetamolle rekabet ederek hepatotoksisiteyi arttırır. Klinik Özellikler Parasetamol zehirlenmesinin klinik bulguları tipik olarak dört aşamada ortaya çıkar. İlk evre bulantı, kusma, karın ağrısı ve halsizlik gibi spesifik olmayan semptomlarla karakterizedir ve ilk 24 saatte görülür. Ciddi toksisitesi olmayan hastalarda bu evrede karaciğer fonksiyon testleri normal izlenebilir. İkinci evre alımdan 24-72 saat sonra ortaya çıkar ve hepatotoksisite ile karakterizedir. Hepatik aminotransferazlarda yükselme başlar ve hastalarda hepatomegali ile birlikte sağ üst kadran ağrısı gelişir. Üçüncü evre, alımdan 3-4 gün sonra ortaya çıkar ve bu evrede karaciğer fonksiyon testi anormallikleri en üst noktadadır. Sarılık, konfüzyon (hepatik ensefalopati), hiperamonyemi ve koagülopatiye bağlı kanama diyatezi ile birlikte karaciğer yetmezliğine bağlı sistemik semptomlar görülmeye başlar. Şiddetli hepatotoksisiteyi gösteren laboratuvar bulguları 10.000 IU/L üzeri plazma ALT ve AST seviyeleri, PT/INR'nin uzaması, hipoglisemi, laktik asidoz ve 4.0 mg/dL üzerinde total bilirubin düzeyidir. Toksisite şiddeti arttıkça akut böbrek yetmezliği tablosu da ortaya çıkar.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.05.522933v1?rss=1 Authors: Sarparast, M., Pourmand, E., Hinman, J., Vonarx, D., Reason, T., Zhang, F., Paithankar, S., Chen, B., Borhan, B., Watts, J. L., Alan, J., Lee, K. S. S. Abstract: Even after decades of research, the mechanism of neurodegeneration remains understudied, hindering the discovery of effective treatments for neurodegenerative diseases. Recent reports suggest that ferroptosis could be a novel therapeutic target for neurodegenerative diseases. While polyunsaturated fatty acid (PUFA) plays an important role in neurodegeneration and ferroptosis, how PUFAs may trigger these processes remains largely unknown. PUFA metabolites from cytochrome P450 and epoxide hydrolase metabolic pathways may modulate neurodegeneration. Here, we test the hypothesis that specific PUFAs regulate neurodegeneration through the action of their downstream metabolites by affecting ferroptosis. We find that the PUFA, dihomo gamma linolenic acid (DGLA), specifically induces ferroptosis-mediated neurodegeneration in dopaminergic neurons. Using synthetic chemical probes, targeted metabolomics, and genetic mutants, we show that DGLA triggers neurodegeneration upon conversion to dihydroxyeicosadienoic acid through the action of CYP-EH, representing a new class of lipid metabolite that induces neurodegeneration via ferroptosis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Dr. Judith Paice and Dr. Eduardo Bruera discuss the latest evidence-based recommendations from ASCO on the use of opioids in managing cancer-related pain. They review the safe and effective use of opioids, including when clinicians should offer opioids, which opioids should be offered, how opioids should be initiated and titrated, management of opioid-related adverse events, modifying opioid use for patients with specific comorbidities, management of breakthrough pain, and how opioids should be switched. Additionally, they address barriers to care, considerations of health disparities, cost, and patient-clinician communication in achieving optimal pain management. Read the full guideline, “Use of Opioids for Adults with Pain from Cancer or Cancer Treatment: ASCO Guideline” at www.asco.org/supportive-care-guidelines. TRANSCRIPT Brittany Harvey: Hello, and welcome to the ASCO Guidelines Podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today, I'm interviewing Dr. Judith Paice from Northwestern University Feinberg School of Medicine in Chicago, Illinois and Dr. Eduardo Bruera from the University of Texas MD Anderson Cancer Center in Houston, Texas, co-chairs on “Use of Opioids for Adults with Pain from Cancer or Cancer Treatment: ASCO Guideline.” Thank you for being here, Dr. Paice and Dr. Bruera. Dr. Judith Paice: Thank you. Dr. Eduardo Bruera: Thank you for having us. Brittany Harvey:  First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Paice, do you have any relevant disclosures that are directly related to this guideline topic? Dr. Judith Paice: I have no relevant disclosures. Brittany Harvey:  Thank you. And then Dr. Bruera, do you have any relevant disclosures that are directly related to this guideline topic? Dr. Eduardo Bruera: Regrettably, I don't. Brittany Harvey: Great. Then getting into the content of this guideline, to start us off, Dr. Paice, can you provide an overview of the purpose and the scope of this guideline? Dr. Judith Paice: The use of opioids has become so complicated, so controversial, and just so associated with so much stigma that we wanted to provide oncology clinicians some guidance about safe and effective use of opioids. We wanted to help people be aware of the current literature, and so we conducted a systematic review and identified randomized controlled clinical trials and other systematic reviews. And we found that there were 31 systematic reviews in 16 RCTs. We carefully reviewed all of these literature and all of these studies, and our expert panel met via the web and via numerous conference calls and emails, and we came to consensus regarding these recommendations related to the use of opioids for people with cancer. Brittany Harvey: Great. Sounds like there was a lot of effort that went into developing this and to tackle an important topic. So, then Dr. Bruera, I'd like to review the key recommendations of this guideline for our listeners. This guideline addresses seven different clinical questions. So, let's review these questions starting with; in what circumstances should opioids be offered? Dr. Eduardo Bruera: That's a very important point because the reality is that although opioids have been around for more than 300 years in different modalities, they continue to be the mainstay of care of patients with severe pain. So, it's very important to try to figure out in the clinical practice why the patient has a pain syndrome. But in the great majority of patients who have pain that is due to the presence of the primary cancer or metastatic disease. And also, in the vast majority of patients who develop severe complications from treatment such as mucositis from radiation and chemotherapy, an opioid will be needed. And the oncologist and the oncology clinician is in perfect conditions to safely prescribe that opioid so the patient can achieve fast relief of their pain. Brittany Harvey: Great. Thank you for that explanation. So, then the next clinical question that the panel addressed, Dr. Paice, which opioids does the panel recommend clinicians should offer? Dr. Judith Paice:  Yeah, thank you. This is a really important question, one that gets asked all of the time, and yet, the data are insufficient to really suggest that there is one preferred opioid over another. So, a patient with moderate to severe cancer-related pain is a candidate for any of the approved medications either approved by the FDA or because our audience also includes international experts, other regulatory agencies for pain treatment. We did call out a couple agents for which there is some concern or for issues where they are less than desirable in some settings. So, one of those drugs is tramadol. And our rationale for identifying tramadol as a potential agent of concern is that it's a prodrug. It has a threshold, a ceiling unlike most of the other opioids, and that threshold is pretty low for neurotoxicity, which is of particular concern in the person with cancer. And it also, has a significant amount of drug-drug interactions. So, we were concerned about tramadol, even though it is an agent that many, many people are using, in part, because it is a lower schedule on the controlled substance scheduling system, and there's a perception that it is less potent, and it is less potent. The other drug that we call out is codeine. And our rationale for identifying it as an agent that may be of difficulty in certain populations of patients, is that it is also a prodrug and it is metabolized through the cytochrome P450 system, particularly through the isoenzyme CYP2D6. And that's what allows codeine to be metabolized to morphine, which allows it to be analgesic. The challenge is there are some individuals who are poor metabolizers, and so they will not receive an analgesic effect. And then there are others who are ultra-rapid metabolizers, and they may actually experience a greater prevalence of adverse effects. So, for those reasons, we call out tramadol and codeine. Now, we don't call out methadone as an agent that we're concerned about in terms of not being desirable. It is an agent that has a role in cancer pain management. However, we do caution clinicians that it is a complex drug to use. And so, as result, people should obtain some guidance either from their palliative care program, their supportive care program, pain experts, or pharmacists, whomever can assist them in the dosing associated with this really important, but somewhat complicated drug to use. Brittany Harvey: Understood. And I appreciate you reviewing where there's a lack of evidence and where there is evidence in identifying those potential agents of concern or where clinicians need to seek other expertise in this area. So, then following those recommendations, after identifying patients who should be offered opioids, Dr. Bruera, how should opioids be initiated and titrated? Dr. Eduardo Bruera: One possible way to do this is to give the patient an immediate release opioid. That could be a combination of hydrocodone with acetaminophen, a combination of other opioids or a straight strong opioid in a low concentration. And ideally, we suggest that you use it as needed for the first few days and see if the patient needs to take it frequently. And there is a magic number around 30 milligrams of morphine equivalent per day. Once the patient needs to take that opioid on a more frequent basis and gets through that threshold of needing about five, six tablets a day of immediate release opioid, then it might be necessary to start a regular opioid that is to stay on top of the pain. And the way we do that are two ways; if the patient can afford it and insurance covers it, an extended release opioid is a wonderful option, because then, the patient can take the opioid a couple of times a day or put a patch for three days and they're going to be comfortable. But if that is not an option, taking the immediate release opioid around the clock, not anymore as needed. But now, around the clock, will maintain that blood level and allow the patient to have less episodes of breakthrough pain. An important thing to remember is that whether we decide to go with the extended release opioid or immediate release, it's nice to tell the patient that there might be moments in which the pain might break through. And so, giving that extra prescription and advice might help if there are moments in which the patient might break through. Brittany Harvey: Understood. And then the next clinical question that the guideline panel addressed, Dr. Paice, how should opioid-related adverse events be prevented or managed? Dr. Judith Paice: So, Brittany, I'm glad you asked me that question because I am called the pain and the poop nurse in the clinic, and it is so important whenever we can to prevent the adverse effects of opioids, and constipation is one where we can implement some preventive measures, and then treat unfortunately if your measures have not been totally effective. But we wanted to address the gamut of potential adverse effects. So, we included not only constipation, but delirium, endocrinopathies, sedation, nausea, vomiting, itching, and urinary retention. And we've included a table with very specific suggestions about how to prevent in some cases, and how to manage these adverse effects. Again, we wanted to make this document of the most use for all oncology clinicians who might be prescribing opioids for people with cancer. Brittany Harvey: Absolutely. And that's key to maintaining quality of life for patients. So, then Dr. Bruera, what does the panel recommend regarding modifying opioid use in patients with either renal or hepatic impairment? Dr. Eduardo Bruera: That's a great question, Brittany, and I think we have some evidence that some opioids are particularly desirable when the patient has renal dysfunction. One of the ones that comes to mind is methadone because it has almost no major renal elimination, and therefore, that might be a wonderful option. One of the challenges is that changing from one opioid to another sometimes is a little bit more complex than maintaining the opioid that is being used. And so, in absence of a major and fast deterioration, one option is to carefully titrate the dose of the opioid we're using to reduce the risk of accumulation in a given patient. There are some opioids that have traditionally been associated with a little bit more accumulation in cases of renal failure and traditionally, morphine is included, but there are other opioid agonists that also produce metabolites that are massively eliminated by urine that might be a little bit less desirable in patients with renal failure. With regards to liver failure, it's very hard to find a complete consensus about the opioids that are less desirable or potentially more desirable. And we could say that careful titration is important. But the one that was so good for renal failure might be the one you might not want to use for liver failure, and that would be methadone, because a vast majority of its metabolism happens in liver. So, I think cautious individualized titration might be a nice recommendation to our patients. And perhaps, the most important thing is that there might be a little bit of renal failure or liver failure, but it's very, very important that we maintain the opioid therapy, that we don't give up on the opioids. Brittany Harvey: Yes, those are important clinical considerations for individualized patient care. So, then Dr. Paice, Dr. Bruera touched on this a little bit earlier, but what are the recommendations regarding management of breakthrough pain? Dr. Judith Paice: So, breakthrough pain is very common in the person with cancer. We see this when the individual has bony metastases and they place pressure on that limb or joint. And the patient who's normally well-controlled with either a regularly scheduled immediate release agent or a long-acting agent, now experiences what we call breakthrough. And that's probably the most common type of breakthrough pain. There are also other breakthrough pains where the short-acting agent that's given regularly doesn't provide the relief that lasts four hours or six hours. Or similarly, if a long-acting agent is given every 12 hours, we may see that the pain breaks through prior to the next dose. But for that patient who requires breakthrough medication, unfortunately, the literature does not reveal that one agent is superior to another. So, any immediate release opioid that's appropriate for that patient can be used for breakthrough-related pain. Now, a common clinical conundrum is - which dose? What's the correct dose for the breakthrough medication? And again, the literature has a wide range of appropriate doses, and our committee established a range of 5 to 20% of the daily regular oral morphine equivalent daily dose. And our rationale for that was that you really cannot come up with one figure. Every patient is different. So, on average it's somewhere around 10%, but the range is five to 20% of the daily regular morphine equivalency. And so, what you need to do as you're examining the patient and exploring their needs is to look at the patient's frailty, the patient's pain, of course, their function when these breakthrough episodes occur. What about the comorbid kinds of organ dysfunction that Eduardo just spoke about? So, all of those other factors need to be considered when selecting the appropriate opioid for the breakthrough as well as the appropriate starting dose. Brittany Harvey: Definitely, it's important to consider all of those factors that you just mentioned. So, then the last clinical question that the panel addressed, Dr. Bruera, when and how should opioids be switched or rotated? Dr. Eduardo Bruera: Thank you, Brittany. This is a hugely important issue because for many, many years, we believe that since opioids stimulated an opioid Mu receptor, and they all had a similar effect, there will be limited rationale for changing. The answer to increasing pain was what we call opioid dose escalation. Just give more of the same. And we realized that that had serious limitations. And one of them is the development of side effects. And a lot of those side effects are neurotoxic side effects. Patients get unduly sedated, get hyperalgesia, paradoxical increase in pain due to active metabolites and changes in their receptors, and they also get sometimes myoclonus, hallucinations, confusion. And so, there are moments in which the side effects require us to say, okay, this opioid has done a good job for a while, but now, we have to change. And so, changing can be done due to side effects. But also, sometimes, since we're all different and there's a lot of interpersonal variation in response — as some patients may just not be controlled, their pain syndrome might not be controlled well-enough with one type of opioid because we know there are multiple sub-Mu receptors, and they might really benefit from another. So, the two main reasons are the development of toxicity to the opioid that so far was working reasonably well. And the second is failure, inability to control the pain, and in that case, going cautiously respecting the fact that there is limited cross-tolerance so that the dose of one opioid is not always exactly equivalent to the dose of the other opioid that you find in the actual tables that are published around is necessary to understand that that's a general guideline. But the most important thing is to go progressively and monitor your patient frequently when you change from one opioid agonist to another opioid agonist. There is limited understanding in the literature about the exact equianalgesic dosing. And because of that, a new guideline is being produced that addresses opioid rotation and deals exactly with trying to find out consensus from all the different existing tables on how to change what is the dose that is most likely to be appropriate when you move from one opioid, for example, morphine to hydromorphone or to fentanyl, or to oxycodone or vice versa. We dealt with great trepidation to give all our oncology clinicians some kind of a fixed table, but the evidence is unfortunately not there at this point. It is sad because these medications are not that new, but the evidence unfortunately, is not there. And that's why I think what we can tell you is go through your guidelines, use in a very careful monitoring of your patient to see if the dose you're giving is clearly not enough or it's a little bit too much. And you will learn that very rapidly — in a couple of days, you'll learn if you're doing okay or if you're doing too much or not enough. And stay tuned because hopefully, very soon, ASCO, together with MASCC and a couple of other organizations will provide you with a little bit more evidence around this. Brittany Harvey: Definitely, we'll look forward to that future guideline on opioid conversion tables as it is a confusing and complicated area, but it sounds like a lot of these recommendations are about providing individualized care for your patients. So, I want to thank you both for reviewing all of those recommendations that the panel came up with. So, then Dr. Paice, what does this guideline mean for both clinicians and for patients with pain from cancer or their cancer treatment? Dr. Judith Paice: Well, speaking on behalf of the panel, our wish is that this will improve the management of cancer-related pain, that people will feel more comfortable in safe and effective use of these agents, and they'll be used more effectively. There are other barriers that we've addressed, in addition to all of these recommendations. We talk about the care of people who have multiple chronic conditions. We address the disparities that we see in cancer pain management, and we talk about cost as another consideration, as one is developing a treatment plan for patients. We also address the patient-clinician communication that is so essential. This is definitely a team effort, and we guide our clinicians and offer for patients the need to have clear communication, open dialogue throughout the development of a treatment plan, and then throughout the course of treatment while we reassess whether the plan has been effective. Brittany Harvey: Absolutely. And it's really key what you just said about the safe and effective use of opioids for patients. So, then finally, Dr. Bruera, you've both mentioned this throughout our conversation today, where the literature is either inconclusive or evidence is insufficient. So, what are the outstanding questions about the use of opioids for pain from cancer or cancer therapies? Dr. Eduardo Bruera: I think there are questions that relate to the relative lack of specificity of the opioids for the different receptor pathways, and there are very likely considerable differences because they're chemically quite different, but they're considerable differences. But we have not done an awful lot of the head on comparisons that would be so wonderful to do. And I think we need more studies comparing the different existing medications, and more importantly, we need a lot of translational work to get to specific areas. Wouldn't it be fantastic if we were able to stimulate the Mu receptor all along the nociceptive pathway to reduce nociceptive input, but avoid completely the limbic system and avoid those Mu receptors in the area where reward is going to happen, an anti-reward and the possibility of developing non-medical use and eventually, opioid use disorder. That would be, to me, the corollary, the ability to dissociate those receptors along the nociceptive pathway from those receptors in the areas where we would like our opioids to not go, but we cannot avoid it because they're a bit dummy drugs. And so, hopefully, getting smarter opioids would be wonderful. Brittany Harvey: Absolutely. Well, I want to thank you both so much for your work developing this guideline, addressing these important questions for optimal pain management in patients with cancer. And thank you for your time today, Dr. Paice and Dr. Bruera. Dr.  Judith Paice: Thank you. Dr. Eduardo Bruera:Thank you so much. Brittany Harvey:And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/supportive-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. Voiceover: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy, should not be construed as an ASCO endorsement.  

Pomegranate Health is seeking fresh ears on the Podcast Editorial Group.Responsibilities of group members are to> discuss new podcast topics> suggest themes to explore and people to interview> listen to audio drafts and provide feedback before publicationGroup communication is done informally by email and there's a time commitment of approximately 90 minutes per month. Please download an application form and return it before February 2023 to podcast@racp.edu.au. ******About two thirds of Australians use complementary and alternative medicines but only around half of these people will mention it to their doctor. Patients in palliative care settings may be more inclined than most to try therapies from outside the box. But they are also more vulnerable to side effects and interactions given that their drug metabolism and clearance mechanisms are often impaired. In this podcast you'll hear the authors of a Clinical Perspectives article titled "Complementary and alternative therapies in the palliative setting." It's published in the in the October issue of the Internal Medicine Journal which can be accessed by all RACP members at the login page racp.edu.au/fellows/resources/journals.Professor Jennifer Martin and Joanne Patel describe how cannabinoid products, especially, have become more readily accessible to patients in recent years and often considered a panacea for many different symptoms. But given the wide variety of products each with a different concentration of active ingredients, drug effects are not always as a patient or doctor might expect. These compounds also have suppressive effects on P450 and other clearance enzymes which can alter the outcomes of other prescribed drugs.  But practitioners also need to consider their relationship with a patient when giving advice on the use of complementary medicines.     GuestsDr Jonathan Brett FRACP FAChAM (St Vincent's Hospital, Sydney)Professor Jennifer Martin FRACP (University of Newcastle, John Hunter Hospital)Dr Joanne Patel FRACP FAChPM (University of Newcastle, John Hunter Hospital)ProductionWritten and produced by Mic Cavazzini DPhil. Music licenced from Epidemic Sound includes ‘Crossing Borders' by Mindserver Unlimited. Image by DrAfter123 licenced from Getty Images.Please visit the Pomegranate Health web page for a transcript and supporting references. To claim learning credits login to MyCPD at this link, review/amend the prefilled activity details and click save. Subscribe to new episode email alerts or search for ‘Pomegranate Health' in Apple Podcasts, Spotify, Castbox, or any podcasting app.

Deportres en Comunicante Mx 28 de Septiembre del 2022 En el Deportres de hoy: La selección mexicana de futbol, la tenía ganada, y Colombia le dio la vuelta para sacarle el partido e intensificar la ola de comentarios adversos contra el Tri del Tata Martino, y todos los resultados de la fecha FIFA, mientras que en las grandes ligas, los Padres vencieron a los Dodgers en un partido lleno de emociones, como siempre, dinámicas NBA, lo mejor de la NFL, tu participación y ¡mucho mas! Visitanos en www.deportres.com --- Support this podcast: https://anchor.fm/deportres/support

Deportres en Comunicante Mx 28 de Septiembre del 2022 En el Deportres de hoy: La selección mexicana de futbol, la tenía ganada, y Colombia le dio la vuelta para sacarle el partido e intensificar la ola de comentarios adversos contra el Tri del Tata Martino, y todos los resultados de la fecha FIFA, mientras que en las grandes ligas, los Padres vencieron a los Dodgers en un partido lleno de emociones, como siempre, dinámicas NBA, lo mejor de la NFL, tu participación y ¡mucho mas! --- Support this podcast: https://anchor.fm/deportres/support

Seguimos con las interacciones fármaco-alimento: - Cefuroxima axetilo (Zinnat)Los alimentos favorecen la absorción de la cefuroxima axetilo. Se desconoce a través de qué mecanismo.Para aumentar la biodisponibilidad del antibiótico se recomienda administrarlo juntamente con alimentos. - EtanolLa ingesta continuada o puntual de alcohol, habitual durante las comidas de la cultura occidental, puede provocar también la inhibición o la inducción de ciertos fármacos, especialmente de la mayoría de los que actúan sobre el sistema nervioso central. De hecho, el alcohol interacciona con casi el 50% de los medicamentos más dispensados en la oficina de farmacia (psicofármacos, analgésicos, anticoagulantes, antihipertensivos, antihistamínicos). Muchos de estos fármacos son EFP (p. ej., los antigripales).Es importante desaconsejar la administración conjunta de alcohol mientras dure el tratamiento, así como tener un mayor cuidado en el manejo de maquinaria o vehículos. - Fenilpropanolamina (presente en algunos preparados antigripales)El efecto hipertensor de la fenilpropanolamina puede resultar potenciado por el efecto de la cafeína. La fenilpropanolamina puede también aumentar significativamente las concentraciones plasmáticas de la cafeína. Existe el peligro de crisis hipertensivas y hemorragias intracraneales.Deben evitar el uso de este fármaco los pacientes vulnerables, como los hipertensos (atención a los antigripales EFP como Aspirina Complex y Vincigrip) y evitar la cafeína. - Furosemida (Seguril, Salidur)No se conoce el mecanismo de acción, pero la administración de furosemida conjuntamente con alimentos disminuye su biodisponibilidad.En caso de inicio del tratamiento, hay que recomendar la toma de furosemida en ayunas. Si no es así, no modificar la pauta de administración. - IMAO (Inhibidor de la monoaminoxidasa o un tipo de antidepresivos)Cuando hay interacción de cierto grupo de alimentos con los inhibidores de la monoaminooxidasa (IMAO) se trata de una interacción farmacodinámica.Los fármacos IMAO son un grupo de sustancias que tienen en común su capacidad de bloquear la desaminación oxidativa de aminas endógenas como la noradrenalina y la adrenalina y también la serotonina y la dopamina. También inhiben la metabolización de la tiramina, histamina, betafeniletilamina y triptamina tanto de origen endógeno como ingeridas a través de la alimentación. Podría ocasionarse una crisis hipertensiva a causa de la interacción entre aminas biógenas contenidas en ciertos alimentos (tabla 1) en el caso de una administración conjunta con alguno de estos fármacos.Como consecuencia de la interacción pueden aparecer crisis hipertensivas que pueden ser graves e incluso provocar la muerte por hemorragias intracraneales. Otros posibles síntomas son midriasis, dolor de cabeza, diaforesis, palpitaciones, y nauseas.La medida más adecuada es restringir la ingesta de ciertos alimentos que pueden aportar una concentración variable de estas aminas. - Quinolonas más derivados lácteosCiprofloxacina (Baycip) y norfloxacina (Noroxin) forman quelatos con el calcio si se administran conjuntamente con lácteos. Se interfiere en su absorción y la biodisponibilidad será también mucho menor.Se recomienda no administrar estas quinolonas con derivados lácteos ni ingerir lácteos hasta 2 horas después de la administración del medicamento. Con ello se respetará la eficacia antibacteriana de los fármacos. - TetraciclinasLa administración conjunta de tetraciclinas (Bristaciclina dental) con leche o derivados lácteos es una interacción ampliamente conocida. A causa de la formación de quelatos con el calcio la absorción del fármaco es mucho menor con estos alimentos. Dicha interacción se produce también con otros alimentos que contengan calcio. La doxiciclina (Vibracina) y la minociclina (Minocin), mucho más actuales, interaccionan mucho menos con estos alimentos (se reduce su biodisponibidad en tan sólo un 25-30%).Se deben evitar los lácteos al administrar tetraciclinas. Las tetraciclinas de acción prolonagada (minociclina y doxiciclina) son, además, de elección por ser tratamientos largos. Es preferible la administración del fármaco en ayunas, ya que la quelación puede ser también con otros cationes divalentes distintos del calcio y que se hallen presentes en la comida.- Zumo de pomelo más fármacosLa administración conjunta de ciertos fármacos con zumo de pomelo provoca un incremento significativo en la concentración plasmática de muchos de ellos. Ello es debido a la supresión de la enzima CYP3A4 del citocromo P450 en la pared del intestino delgado, lo que provoca una disminución del metabolismo de primer paso. Ello implica un aumento en la biodisponibilidad y concentraciones plasmáticas más elevadas de los sustratos de esta enzima. En algunos fármacos se pueden encontrar incrementos en el área bajo la curva y la concentración máxima de más del 70%. Hay que añadir a esto que la administración a largo plazo del zumo de pomelo no disminuye la magnitud de la interacción ni se desarrolla tolerancia.Los componentes que tienen una mayor probabilidad de ser los responsables de la interacción son los flavonoides y los derivados cumarínicos.Son muchos los fármacos que interaccionan con el zumo de pomelo y pertenecen a distintas estructuras farmacológicas.Los primeros fármacos que se estudiaron fueron antagonistas de los canales del calcio como felodipina (Perfudal), nifedipina, nitrendipina (Tensogradal), nisoldipina (Syscor) y amlodipina (Norvas); también en otros como diltiazem (Masdil) y verapamilo (Manidon).En algunos casos, al aumentar la concentración del principio activo en sangre se puede aumentar la frecuencia de ciertos efectos secundarios que son dosisdependientes como, por ejemplo, un antiarrítmico como la amiodarona (Trangorex).El incremento de las concentraciones plasmáticas tras la administración conjunta de un fármaco con zumo de pomelo puede ser una ventaja o un inconveniente. Sería una ventaja en fármacos en los que es difícil alcanzar la biodisponibilidad deseada, que son caros y que la pauta posológica requiere mucha frecuencia. Pero, por otro lado, no todos los pacientes reaccionan igual (amplia variabilidad interindividual). La administración conjunta con zumo de pomelo demandaría una complicada monitorización del fármaco o efectos adversos importantes en alguno de los fármacos. Por ello, se recomienda evitar tanto el pomelo como su zumo si se está llevando a cabo un tratamiento con algún fármaco de los antes mencionados. Con otros principios activos que sean extensamente metabolizados hay que evitar esta fruta, a menos que se haya demostrado para los fármacos una ausencia total de interacciones con el pomelo.*

Your liver is seriously pretty amazing. I'm a 'mechanisms' kind of guy, and the liver is the king of mechanisms, including:- The liver is crucial for metabolism, regulating blood sugar, lipid, and protein metabolism.- The liver participates in immune surveillance and pathogen clearance, and is intimately connected with the gut. - The liver performs "hepatic biotransformation", or transforming toxins into things that can be excreted, aka DETOXIFICATION. The liver can be damaged by many things including lifestyle, alcohol, viruses, parasites, and especially toxins. As liver damage progresses, the liver becomes more congested, toxins begin to accumulate, and metabolic dysfunction can follow. Liver damage is generally a spectrum of worsening fibrosis, and often starts with "fatty liver" and then progresses toward cirrhosis, which is liver scarring. Liver damage can be detected by several labs, and I discuss these labs in detail. In the liver there are many functions, but this podcast focuses mostly on hepatic biotransformation, or detoxification. This includes Phase 1 and Phase 2 of liver detox, cytochrome P450, and includes processes like methylation, sulfation, conjugation, and more. These processes require many cofactors such as B vitamins and amino acids, and I discuss these all in detail. There are also many genetic mutations that can affect liver and detoxification, so I discuss these as well, along with the common and popular liver supplements and what their mechanisms are. All together this is a comprehensive overview of everything I know about the liver and how I use that information clinically in helping sick people get well!Youtube video about Liver, Carnitine, and Depression....

See all the Healthcasts at https://www.biobalancehealth.com/healthcast-blog/ Women always ask about my goal for their blood level of free Testosterone after insertion of testosterone pellets.  That is a good question, and it is not easily answered. When I was trained by Dr Gino Tutera in 2002, and he taught me that the optimal range for Free T in women who take T pellets to be over 15 pg/ml.  He taught me that each woman is an individual and the blood level that they need is specific to their metabolism and genetics.   To determine the perfect level of T free for an individual we should follow the resolution of her symptoms after her T pellets are inserted. Today we will talk about the research done by Dr Rebecca Glaser, published in Maturitis 74(2013) that confirms my practice of adjusting the dose of pellets based primarily on the resolution of Low T symptoms.  Prescribing pellet Testosterone for woman is not easy and her doctor must find her own ideal blood level. Testosterone replacement for women has been ignored as an essential hormone replacement for women, and until recently was not considered a major sex hormone in women. Premenopausal women have 15-20 times more testosterone than estradiol circulating in their blood streams. This makes testosterone the most prevalent sex hormone in premenopausal women, yet it is still mislabeled as a strictly male hormone!  After late 30s to mid 40s women develop a deficiency in testosterone and develop a host of symptoms that doctors have sadly called the symptoms of “aging”, when the symptoms are directly related to the lack of free T in a woman's circulation. Both pre- and post-menopausal women over 36 may experience the following symptoms of testosterone deficiency: Sexual dysfunction-lack of libido and loss of orgasmic function Anxiety, irritability, depression Physical fatigue Lack of the feeling of well-being Poor cognition Memory loss Insomnia Hot flashes New autoimmune diseases Arthritis Weight gain Muscle loss and physical weakness Pain Vaginal Dryness Irritable Bladder Migraine headaches Osteoporosis One of the reasons that the majority of doctors don't use T pellets is because it takes intense individual training after residency and time and attention to each patient, her symptoms, and time for multiple adjustments of dose before the maintenance dose is determined.  This is something a doctor or nurse must do all the time to be good at it and the doctor must have a complete grasp of endocrinology, nutrition, and gynecology to become good at this type of T hormone treatment. Once the pellet dose is determined it is the most convenient dosing schedule (once q 4 months, only 3 doctor visits a year) with 100% compliance because the T Pellet dose is given in the office, very rare complications, and an amazingly complete resolution of symptoms, which has not been seen in any other T preparations, bio-identical or not, given with a different delivery system. With the right doctor or Nurse Practitioner, a knowledge of pharmacology, endocrinology, gynecology and nutrition, this form of T delivery to women brings them back to a more youthful body and mind as well as prevents diseases of old age such as Osteoporosis, Heart disease, Sexual Dysfunction, mood disorders and autoimmune diseases to name a few. In the research paper by Dr Rebecca Glaser: Testosterone implants in women: Maturitis 2013 Dr Glaser explains that there are many problems secondary to following blood levels to determine dosage, and explains why following symptom resolution is the preferred way to provide this type of Testosterone replacement:   Specifically, Blood tests of free T are rarely repeatable and often wrong—it is not a good, repeatable blood test. The only thing less reliable is saliva testing which I don't recommend. No single blood test represents the true daily blood level of free T in pellet patients. How fast your body uses the available T up, varies by number of hours or sleep, stress level, estradiol and estrone levels and amount of exercise engaged in per day. Fat metabolic activity: T pellets are inserted into fat in the hip and as we are now discovering, the ability of fat to dissolve a steroid hormone placed in fat is individual and determines how quickly the pellet is dissolved and needs to be re-dosed. There is no test for this, so trial and error is needed using different dosage to determine ongoing maintenance dose. ARs (Androgen receptors) are distributed throughout the body and the number of Ars plus the “stickiness” of the receptors for free-Testosterone in the blood, is determined both by genetic makeup and age. ARs of people with dominant genetics from the northern latitudes, are relatively resistant to binding, and these receptors must have a higher blood level to respond at an optimal level.  Women who have their dominant genetics closer to the equator, require less free T to achieve optimal symptom relief.  The genes are not specifically discovered as of yet, it is impossible to test a patient to see if they have strong or weak receptors. This discovery is found through trial and error.  Age also causes a loss of the # of receptor sites, therefore more T mgs are needed in the pellets. Estrogen interferes with the free T level from a particular dose: Binding to SHBG decreases the active form of T (T free) per dose of T pellet. The amount of estradiol and estrone a woman has been given or makes, decreases the amount of active T free.  The lower the Estrogen levels, the lower the SHBG and the more T free is available. Cortisol Binding Globulin goes up when Cortisol increases secondary to life stress, surgeries and illness. This binding globulin inactivates the testosterone and decreases the percentage of active T. Speed of a woman's Liver metabolism is increased by multiple drugs that go through the P450 system, alcohol intake, fatty food intake, and amount of environmental chemicals that act like estrogens. One patient's liver metabolism of T through the P450 system is individual and is not the same for another woman of the same age, weight, etc.  The speed of breakdown of T determines how fast the T pellet is used up. There are several other dosing issues that are addressed after the first pellet insertion in preparation for the second insertion. Most important is whether their symptoms are completely gone.  If they are, we leave the dose the same, if not they usually need more T dose, or they are converting T into E1 and E2 which binds the T free and lowers the effect.  For this we exchange one of the T100 mg pellets with one TA 90/10 pellets, which blocks the conversion, and releases the T free and stops increasing the E1 and E2. There is a small percentage of women of women who do not tolerate TA pellets.  They feel like they have no sex drive and don't feel their T free as they should….it is an opposite reaction, because in everyone else the T free is higher, they feel more sex drive and lose belly fat.  If the “opposite” patients still need to lose belly fat and lower their T-free, DIM, zinc, and Calcium D glucarate can be used to lower the Estrogen in the circulation. I agree with Dr Rebecca Glaser MD, who states that dosage should be guided by safety, tolerability and clinical response, rather than a random T or T free levels, yet I always draw blood levels to find out if a woman's ideal blood level specific to her has been reached, and if it is repeatable.

Polycystic ovary syndrome (PCOS) is a common condition impacting roughly one in four women of reproductive age. , In this show we discuss natural ways to reverse the underlying factors driving PCOS.  Save 15% OFF on Berberine HCl and Myo-Inositol containing Sleep Formulations from MYOXCIENCE Save with code podcast at checkout  Links to Studies, Images and the Video Version: https://bit.ly/3nMt9QJ Time Stamps 00:04 PCOS (polycystic ovarian syndrome) is about 1 in 5 of women of childbearing age. 00:26 The root cause of PCOS is poor metabolic health. 01:54 Ovaries hyper secrete androgens that are linked with challenges within the ovaries and the formation of water-forming cysts. 02:39 Hormonal birth control is frequently prescribed to increase sex hormone binding globulin and neutralize the elevated androgens. 04:04 Some cytochrome P450 enzymes are involved in the formation of steroid-like hormones, like testosterone. 05:04 Insulin and IGF-1 increase the activity of a cytochrome P450 enzyme called CYP17A1, which then increases testosterone, dihydrotestosterone, and DHEA within the ovaries. 06:36 Excessive levels of androgens cause hair loss, infertility, lack of ovulation, and cause the formation of water forming cysts within the ovaries. 08:24 Autoimmunity often co-occurs with PCOS. 08:44 Deliberate cold exposure helps metabolic health by stimulating brown and beige fat cells. 09:54 Metabolic health increases the activity of enzymes that create hormones. It does the inverse in men and women. 10:04 Men's poor metabolic health drives the formation of extra estrogen. 10:14 Women's poor metabolic health drives the formation of extra testosterone. 12:44 97% of obese women have PCOS. 65% of non-obese women have PCOS. 13:14 Fat cells secrete hormones, called adipocytokines. One of these is leptin. 13:54 Leptin decreases activity of T-regulatory cells that help to prevent autoimmunity. 16:04 Belly fat cells convert androgens into estrogens. This is impacted by insulin. 18:14 Nutrition and exercise are fundamental ways to address poor metabolic health. 18:24 A ketogenic or low carb diet is helpful because it manages blood sugar and insulin, and ketones have immune signaling properties. 19:24 Intermittent fasting can support glycemic variability and improve insulin sensitivity. 19:46 Time restricted feeding with a 16 or 18 hour fast is also helpful for longevity, burning fat, and supporting metabolic health. 20:14 Poor sleep exacerbates insulin resistance. Tape your mouth shut when you sleep. 21:24 Resistance training decreases androgens in women with PCOS. All exercise supports underlying metabolic dysfunction. 22:24 Magnesium is helpful for supporting insulin sensitivity. 23:15 Myo-inositol and inositol makes ovaries more sensitive to insulin, preventing the increase in androgens. 24:04 Vitamin D is involved in blood sugar regulation, immune health, and sleep quality. 24:19 Gut health is important to metabolic health. Eat real food and ferments. 24:54 Berberine hydrochloride, 500 mg 1 to 3 times per day, is a natural Metformin. Studies Mentioned Witchel, S. F., & Plant, T. M. (2020). Intertwined reproductive endocrinology: Puberty and polycystic ovary syndrome. Current Opinion in Endocrine and Metabolic Research, 14, 127–136. http://doi.org/10.1016/j.coemr.2020.07.004 Stefanaki, C., Bacopoulou, F., Kandaraki, E., Boschiero, D., & Diamandi-Kandarakis, E. (2019). Lean Women on Metformin and Oral Contraceptives for Polycystic Ovary Syndrome Demonstrate a Dehydrated Osteosarcopenic Phenotype: A Pilot Study. Nutrients, 11(9), 2055. http://doi.org/10.3390/nu11092055 Moghetti, P., & Tosi, F. (2020). Insulin resistance and PCOS: chicken or egg? Journal of Endocrinological Investigation, 44(2), 233–244. http://doi.org/10.1007/s40618-020-01351-0 Scarfò, G., Daniele, S., Fusi, J., Gesi, M., Martini, C., Franzoni, F., et al. (2022). Metabolic and Molecular Mechanisms of Diet and Physical Exercise in the Management of Polycystic Ovarian Syndrome. Biomedicines, 10(6), 1305. http://doi.org/10.3390/biomedicines10061305 Witchel, S. F., & Plant, T. M. (2020). Intertwined reproductive endocrinology: Puberty and polycystic ovary syndrome. Current Opinion in Endocrine and Metabolic Research, 14, 127–136. http://doi.org/10.1016/j.coemr.2020.07.004 Optimal management of polycystic ovary syndrome in adolescence. (2015). Optimal management of polycystic ovary syndrome in adolescence, 1–8. http://doi.org/10.1136/archdischild-2014-306471&domain=pdf&date_stamp=2015-06-22

Detox Pathways and Protocols (Youtube)Free 15-min phone consult!Website and Supplement Store So - yup, toxins are a big problem. We are exposed to tons of them, and if our bodies aren't detoxifying properly, they can accumulate or cause damage to our cells, organs, and systems and wreak havoc on our lives. So how do you make sure you aren't overflowing your bucket? Here are 10 Important Concepts:Bucket Theory explains everything - keep this in mind if things are NOT getting better. SOMETHING is still filling the bucket from somewhere if you are actively trying to detoxify and leading a non-toxic life and you aren't improving. You have to empty the bucket faster than you are filling - you either aren't emptying it well, or you are still exposed somewhere.Breathing - There are only a few "exits" for things to get out of the body, breath is one of them. Think about a roadside alcohol test - you breathe out toxins to get rid of them.Peeing - this one is more obvious that you are "getting rid of waste", but the kidneys filter toxins and toxic metabolites, and you pee them out, so that system has to be working well too. Pooping - This one is the most obvious - - waste is bad so you want to get it out of you!! Your poop is how you get rid of MANY MANY toxins, and if your gut is not moving well, everything else backs up. Sweating - You are slightly limited on how much you can speed up your breathing, peeing, and pooping, but you can always open the other exit - sweat. Many toxins have been found excreted in the sweat - mycotoxins, BPA, parabens, metals, etc, so sweating is crucial for detoxification.Liver/Bile Flow - The liver filters toxins (through many processes - phase I and II, cytochrome P450 enzymes, glutathione, conjugation, glucuronidation, methylation, etc). These toxins are then put into bile, which is stored and released by the gallbladder. You have to have good liver function to filter the toxins, and then you have to have good gallbladder function and bile flow for the toxins to get into the gut, then you have to be pooping for them to get out.Lymph Drainage - The lymphatic system is one way that toxins and waste products are transported around the body to be excreted, and your lymphatic system has to be moving, it can't be stagnant. Cell Membranes - Toxins damage your cell membranes (including mitochondrial membrane), causing lipid peroxidation, stiffening, and poor membrane fluidity. Then toxins can also STORE in the cell membranes, so you need good healthy cell membrane support - this can be really important for detoxification.Mitochondria - THEY DO IT ALL!!!! Toxins store in the mitochondria, they damage the mitochondria, they affect fatty acid beta oxidation, Kreb's Cycle, Oxidative Phosphorylation, all the things - and mitochondria power detoxification in the liver, organs, cells, etc. It's all mitochondrial!Relevant Genes - There are a lot of relevant genes in detoxification, and it's super important. Many of them relate to "methylation", like MTHFR, COMT, PEMT, HNMT, but there are many others that regulate processes like glutathione recycling, cytochrome P450 activity, and many many more. 

How do you talk to patients about medicinal cannabis? Dr. Ashley Glode (University of Colorado) moderates a discussion on effectiveness and safety, misconceptions and more. Featuring Drs. Ilana Braun (Dana-Farber Cancer Institute), Daniel Bowles (University of Colorado), and Kent Hutchison (University of Colorado). Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 1/19/22   TRANSCRIPT ASHLEY GLODE: Hello, and welcome to ASCO Education's podcast on medical cannabis, also referred to as medical marijuana. My name is Ashley Glode, and I am an associate professor with the University of Colorado School of Pharmacy. It's my pleasure to introduce our three guest speakers Dr. Ilana Braun is chief of the division of adult psychosocial oncology at Dana-Farber Cancer Institute, and an assistant professor of psychiatry at Harvard Medical School. Dr. Daniel Bowles is an associate professor of Medical Oncology at the University of Colorado. We're also joined by Dr. Kent Hutchison, a professor of psychology and neuroscience at the University of Colorado Institute of Cognitive Science. Let's start with a simple but fundamental question. What is medical cannabis or medical marijuana? ILANA BRAUN: So Ashley, I think that's such a great first question. I think of medicinal cannabis as herbal nonpharmaceutical cannabis products that patients use for medicinal purposes. And typically they're recommended by a physician in compliance with state law. DANIEL BOWLES: Dr. Braun makes a really good point. And I think it's important to know when patients are referring to medical cannabis, there's a wide variety of different things they could be referring to. Sometimes they would be referring to smoked herbal products, but there are also edibles, tinctures, ointments, creams, all sorts of herbal-based products that people use and call medical cannabis. And then there are also the components that make up medical cannabis-- largely, the cannabinoids. And I think the big ones people think about are THC and CBD. And sometimes those are used in their own special way. So I think that it's important for us as providers to be able to ask our patients, what is it that you mean when you say, I'm using medical cannabis? ILANA BRAUN: I think that's such a great point. And I will add I think it's also important to remember that when you offer a medicinal cannabis card to a patient, you're giving them license in most states to access any number of products. It's not an insurmountable challenge, but it's a whole new world for traditional prescribers who are used to writing a prescription and defining what is the active ingredient, how often a patient will take the medicine, by what means. DANIEL BOWLES: I think the other thing we need to be very aware of, as hopefully people are listening to this across the country and elsewhere, is the laws vary wildly from jurisdiction to jurisdiction about what consists of medical cannabis, who is allowed to use it, and in what quantities. So I think it's really important that as we learn about these and we think about these, we think about how they apply to any of our specific situations in which we live in practice. KENT HUTCHISON: So it's interesting-- just follow up on what Dr. Braun and Dr. Bowles, what they're saying, those two words-- right-- medical and cannabis. I think the medical part is somewhat easier because it can refer to the reason the person is using. Are they using for medical reasons are they using for recreational reasons, even though that's a blur? But the cannabis part I think is what's really complicated. And this is what Dan was getting at. All the different products, all the different cannabinoids, I mean all the different bioactive terpenes and everything else in the material, all different forms of administration. That is where it gets super complicated to really define what that is. And then of course, there's so little research we don't really know what all those constituents do. ASHLEY GLODE: Now that we kind of have a little bit of familiarity with medical cannabis, can you comment on adult use cannabis and what that might mean for a patient? ILANA BRAUN: Ashley, I think it's a really good question. And in some of the early research I did to try to understand where medicinal ended and adult use began, or adult use ended and medicinal began, I began to discover a theme that emerged, which is they sort of blend into each other often. In other words, some of the oncologists that I spoke to believed that it was not such a bad thing for a patient with serious illness, and pain, and many other symptoms to have a sense of high or well-being. And conversely, when I spoke to patients using cannabis, sometimes a cancer patient used medicinal cannabis for enjoyment, and sometimes they used it for symptom management, and sometimes they used it for both. And so I think it is somewhat of a slippery slope between the two. Would you agree? DANIEL BOWLES: I think there are definitely blurred lines between the two. I think that the advantages of what most states would recognize as medicinal cannabis is usually they're less expensive, patients can use them in larger quantities. There are certain advantages. But there's also paperwork that goes along with medicinal cannabis that some patients don't feel comfortable with. Or particularly I think when you have a patient who's interested in trying cannabis or a cannabinoid for the first time, they might not want to go through all the extra steps required getting that medical marijuana card, whereas adult use, I think people feel more comfortable, at least in my state, sometimes walking into a dispensary to discuss the options with people who work at the dispensary and then get it from more of an adult use or recreational cannabis initially. And then if that's something that they find helpful for their symptom management, to then take those extra steps and try to get a medicinal card. ILANA BRAUN: I agree with Dr. Bowles that the target symptoms or the target effect is often similar and access can differ. KENT HUTCHISON: Yeah. Just to chime in, I agree. I agree also. It's definitely-- the lines get blurred. The recreational user might also appreciate-- for example, college students, I hear them say a lot of times that they appreciate some of the anxiety-reducing aspects-- right-- even though they're not necessarily a person who has an anxiety disorder. And then of course, patients appreciate a slight increase in euphoria or positive affect, and what does that mean? Is I mean they're also using for recreational reasons? Or is that completely, I guess, legitimate? On the other hand, there are sometimes I feel like when-- especially on the recreational side-- when people are using for the more psychological effects, the sort of psychotropic effects, I know sometimes the medical patients refer to that as being a little bit loopy as a side effect. So I feel like there's definitely some blurred lines. And maybe there are some places where we can think about in perhaps in a less blurred kind of way. ASHLEY GLODE: How often do you guys have a patient ask you about medical cannabis? And what are the most common questions they might have for you? ILANA BRAUN: In my psycho-oncology practice, patients frequently tell me they're using cannabis, often with good effect and minimal side effects for polysymptom management-- for instance to address nausea, or pain, or poor appetite, or sleep, or mood, or quality of life. But they don't ask me a lot of questions. For instance, one of my longest-standing patients. A man with metastatic cancer and gastroparesis. Vaporizes cannabis before meals to keep his weight up. And many of my patients also use cannabis as cancer-directed therapy. And for these patients, side effects can sometimes be more pronounced. For instance, I have a lovely patient with metastatic cancer who follows a Rick Simpson protocol. So what is that? That's an online recipe marketed with an antineoplastic claim. And so this patient targets hundreds milligrams of cannabinoids daily. And with such high cannabinoid doses, she sometimes feels spicy, or out of it, as she describes it. And then I had another patient who targeted high daily doses and developed a debilitating nausea and vomiting that was initially diagnosed as chemotherapy-induced nausea vomiting because it was so hard to tease out in the setting of so many medicinal agents, what was what. But the symptoms resolved completely within weeks of the cannabinoids being halted. And so as I mentioned, what's notable about all three of these patients, and many of the others I see, is that they are quite open with their oncology teams and me about their medicinal cannabis use. But they don't seem to rely me or other members of their oncology team for their therapeutic advice . We insert ourselves when we see potential harm, but much of the decision-making seems to be made-- I don't know in the naturopath's office, at the dispensary counter, or by trial and error. And this anecdotal experience in my practice is borne out in my research findings as well. Patients are just not getting the bulk of their cannabis therapeutics information from their medical teams. DANIEL BOWLES: In my clinical practice, I am asked about cannabis or cannabinoids a fair, amount often in the context that Dr. Braun is describing, where a patient is coming in and they're already using a cannabinoid or they are planning on doing it and they just want my opinion. And I think unlike talking about more conventional cancer-directed therapies where they really rely, I think, on their medical team for information and guidance, we are often more a supplement I think in terms of information. In terms of the patients who come to ask me about cannabis or let me know that they're using cannabis, it's a very wide selection of people. I see young people, old people talking about it, men, women, a variety of different malignancies. So there really is a lot of usage or are thought about usage of cannabis or cannabinoids amongst our cancer patients. I think if you look at the studies, they'll tell us that depending on where we're working, anywhere between 20% to 60% of patients have used cannabis in the last year to help manage some sort of cancer-related symptoms. And I think the other thing that is notable is you'll find people asking about cannabis or cannabinoids who I think we might not have otherwise expected. So for instance, Just this past week, I had a patient with anaplastic thyroid cancer in his 70s, and his daughter was wondering whether he could try CBD to help with his sleep and anxiety. She wanted to make sure that it wasn't going to interact with this cancer therapies. And I appreciated her bringing it up, and we could have a frank discussion about the pluses and minuses of it, just like we might any other therapeutic intervention. So I think that particularly as the laws have changed across the country, more and more people are willing to tell us that they're trying cannabinoids and cannabis than maybe would have even 10 or 15 years ago. KENT HUTCHISON: I think in an ideal world, patients would be talking a lot more with their physicians about this topic. And I think unfortunately that a lot of people do get their information from dispensaries. From the media, from social media, from their kids, and from whoever. And I think that's something that I hope will change in the future. DANIEL BOWLES: In terms of questions that I'm often asked, I'll be asked if it's going to interact with their cancer treatments, in terms of making their medications more or less effective. I do get questions about how I think their cannabis use might affect some of their symptoms. I get questions about other drug-drug interactions-- let's say, interactions with opiates, or benzodiazepines, or some of these other medications that a lot of our patients are on. ASHLEY GLODE: In a recent survey 80% of medical oncologists who discussed medical cannabis with their patients, 50% recommended it in the past year, but only 30% felt knowledgeable enough to make recommendations. What do you guys think needs to be done to address this knowledge gap? And what resources do clinicians have to get and stay informed? DANIEL BOWLES: So I'm a big fan of the NCI's PDQ as a great resource. It has a fairly objective information about cannabis and cancer specifically. So I think that's a nice reference for people who are interested in getting an initial overview on the topic. I think there are also a number of different educational programs. I know the University of Colorado, for instance, has a Cannabis Science Master's and also a certificate program. So there are courses available for people who want to educate themselves more on this topic. ILANA BRAUN: Yeah. I guess when I think about what needs to be done, I think that cannabis needs to become a routine part of medical training curricula and CME programs. I think that a federal funding for high-quality clinical trials and a loosening of federal restrictions on accessing study drug were to occur, that would be really a big boon for the medical community. And my colleagues on this podcast I know are doing some very creative pragmatic clinical trials naturalistic studying what is happening in the field. And I am doing clinical trials using an FDA-approved version of cannabinoids. But it's still very hard to study whole-plant cannabis in a form that is sort of a standardized trial drug in a cancer patient. And then when I think about where I would begin to read, I don't think there is a single source, unfortunately. But a great place to start reading is actually a project that Dr. Hutchinson was a part of, which was an expert panel that was assembled by the National Institute of Science Engineering and Medicine in 2017. And they produced a monograph on the health effects of cannabis and cannabinoids. And it's several hundred pages long, including sections devoted just to oncology. So in other words, there is scientific evidence to evaluate, and it's sizable. DANIEL BOWLES: The Austrian Center for Cannabinoid Clinical and Research Excellence also is a helpful resource. One of the nice things about that is they actually give some dosing suggestions or ideas for people who really don't quite know where to start. Right now, there aren't a lot of people in that position to say, here's how it should be done. Here's how it gets dosed. Here are the data to support those decisions. And so the folks in the next level of training don't learn it in the same way that we have learned how to prescribe other medications. And they can't then lay it down. So because the data are scant, in some respects, and particularly for herbal products that So. Many of our patients are using, I think it falls outside the medical model that we've all become so used to using to learn how to take care of patients. And I think that's one reason that so many oncology providers feel interested in learning more about this topic, but don't feel comfortable giving patients guidance on how to use them. KENT HUTCHISON: So both Dr. Braun and Dr. Bowles identified some of the key resources out there. And certainly the training issues that Dr. Bowles just talked about are important. And I do want to emphasize the one thing that Dr. Braun mentioned, which is basically that we do-- we lack research and we lack data on some key important issues, like dosing, for example. What dose is effective? So cannabidiol has been out there for a long time, but what dose is effective for what? We don't know, right? So we definitely lack research. And there are definitely obstacles to doing that research. ASHLEY GLODE: So you guys brought up some good points about there being a lack of data, but also there is some evidence. So what is the current research and evidence on the efficacy of medical cannabis for management of cancer symptoms and cancer pain, specifically? DANIEL BOWLES: So there was a really nice review article that just came out in the BMJ looking at cannabis and cannabinoids, not specific to cancer pain, but including cancer pain. And what they found-- they looked at different preparations from herbal products-- smoked herbal products, oral agents-- cannabinoids, more specifically. They found there is a modest, but a real improvement in pain in patients or research subjects treated with cannabinoids versus those usually typically treated with placebo. In particular, the data are supported in neuropathic pain, I'd say more so than the other pains. I think the data are less compelling with regards to many of the other symptoms that people often use cannabinoids for, such as sleep, anxiety, appetite, things along those lines. ILANA BRAUN: So I'll tell you a little bit about how I think about the evidence base in oncology for cannabis use. So I'll preface this with two points. The first is that, as I mentioned, cannabis products tend not to be one active ingredient, but hundreds of active ingredients-- cannabinoids, phenols, terpenes, they all have bioactivity. And they don't work individually, they work through complicated synergistic and inhibitory interactions that have been termed entourage effects. So I don't think one can easily extrapolate from clinical trials of, say, purified THC, to understand whole-plant cannabis' activity in the body and how it might perform in humans. And then the other point I'll make is that when I think about the types of clinical evidence that we as clinicians hold dearest, it's clinical trials of our agent of interest in our population of interest. So cancer patients using whole-plant full-spectrum cannabis that they would access at a dispensary or grow in their own home. With this in mind, I believe the strongest evidence, randomized double-blind placebo controlled trials of whole-plant cannabis and oncology populations begins to support its utility for chemotherapy-induced nausea and vomiting. So there have been a few studies that have looked at this. But just in 2020, the most recent is a study by Grimison, et al. It was a multicenter randomized double-blind placebo controlled crossover trial comparing cannabis extract. And I think the extract they use was a 1 to 1 THC to CBD ratio versus a placebo in patients with refractory chemotherapy-induced nausea and vomiting. And what they found was that with active drug, there was a complete response in 25% of participants versus only 14% with the placebo. And although a third of participants experienced additional side effects with the active drug-- so remember, this was a crossover trial, so they saw both arms-- 80% preferred cannabis to the placebo medication. So that's clinical trials of cannabis and cancer. But if we expand the base of the pyramid of acceptable evidence to include high-quality clinical trials for health conditions other than cancer and extrapolate back, then I agree fully with Dr. Bowles that there's a growing body of evidence that cannabis may be beneficial in pain management. And there have been many clinical trials done in this arena, and they span myriad pain syndromes, including diabetic neuropathy, post-surgical pain, MS pain, sickle cell pain. And so it does seem like cannabis works for pain management in several other illness models, so we could extrapolate back and hope that it works in cancer pain. And then there is a small body of evidence with nabiximols, which is a pharmaceutical that has a 1 to 1 THC to CBD ratio. And it's a sublingual metered dose spray. And it has been trialed for opioid-resistant cancer pain. And this is not as a single agent, but as an adjuvant to opioids. In early trials, two times as many participants in the active arm as compared to the placebo arm demonstrated a 30% pain reduction. And for the pain specialists who are listening, they will know that is a substantial pain reduction. But then, additional studies fail to meet primary endpoints. I think there were three clinical trials that followed. Nabiximols was found to be safe and effective by some secondary measures, but the FDA opted not to approve nabiximols for cancer pain. So I think there's some suggestion of effect, but there's some smoke, but no fire-- no pun intended. DANIEL BOWLES: I think many of the studies that have been done looking at cannabis-- or cannabinoids-- have been compared to placebo or they've been crossover. And I would say fairly consistently, there is some improvement in pain scores with the cannabis products versus placebo kind of across a wide variety of disease spectrums with regards to pain. I think one of the other questions that a lot of people have asked is, can you decrease people's opiate usage using cannabis? As we know, there's a huge epidemic of opiate misuse in the United States of America right now. And I think many people are looking for ways to decrease opiate usage. There was a nice study done from Minnesota in conjunction with the Minnesota dispensaries-- or state marijuana program-- where some researchers randomized people to starting kind of herbal cannabis products early in their study or three months into their study. So it was kind of a built-in control. And they looked at opiate usage rates, pain scores, quality of life scores, et cetera. What they found is there, again, was some improvement in pain control overall in the cannabis users. However, it did not equate to a decrease in opiate usage. So I think that it's an open question that I think a lot of people want to know the answers to before they start recommending or incorporating cannabis or cannabinoids more widely into their practice. KENT HUTCHISON: It's certainly a complicated issue, in some ways, right? Because the research which is summarized very nicely by both Dr. Braun and Dr. Bowles, it is suggested, but not overwhelming, by any stretch, right? It's not clear-cut. And I think that one of the big issues here we talked about the very beginning is how complicated this cannabis thing is. and Dr. Braun alluded to this also, that there are obviously many different formulations, many potentially active constituents in cannabis. And so what has mostly been studied so far is either synthetic versions of THC or nabiximols, which is probably the closest thing to what some people are using. So I think the jury's still out, for sure. And I think hopefully at some point, what will happen is that some of the products that are actually being used by people-- because most people aren't using nabiximols, most people are not using THC only, hopefully there'll be some trials of the things that people are actually using out there in the real world that will tell us something more about whether it's effective or not. And maybe even more specifically, which constituents-- which parts, together are most effective with respect to pain. DANIEL BOWLES: I think one of the other topics that some of my colleagues have alluded to already is not just cannabis' role in symptom management. I think pain is often what people think of, and people are using it for chemo-induced nausea and vomiting, anxiety, sleep, appetite, but a fair number of patients are also using cannabis or cannabinoids with the hopes that it is going to treat their cancer like a chemotherapy or an immunotherapy may. And oftentimes, patients will point to preclinical studies looking at oftentimes very high doses of THC or CBD that might show tumor cell death or tumor reduction in test tubes. And I spent a fair amount of time-- and I know some of my colleagues spent a fair amount of time-- talking with patients about how it's a big step between cannabis or cannabinoids working to slow cancer growth in a test tube, to working in an animal system, to working in people. ASHLEY GLODE: So what are the most important considerations clinicians should keep in mind before recommending medical cannabis to patients with cancer? DANIEL BOWLES: We should be asking why they want to use cannabinoids. I think just like we might any other medication that people are thinking about trying-- or herbal product that people are thinking about trying-- I think we need to ask why they're interested in using these products. So is it for symptom management? Is it for some of the ancillary side effects of cannabinoids or cannabis? Why are they wanting to use it? And I think trying to incorporate that more than into the medical model, I ask my patients, hey, if you're using this particular product, do you feel like it's doing what you intended it for it to do? If it is and it's legal in your state, great. Do it as you feel fit. If it's not meeting your goals, if it's not helping with the pain, or if it's not helping with the anxiety, or it's not helping with the nausea and vomiting, maybe we should rethink whether we would use it. Just as if I was prescribing more conventional anti-nausea medication and you didn't think it was working, we wouldn't keep using it. So I think that's a really important thing to keep in mind. I think the other thing to know from a safety standpoint is, who else is in the household? We have a psychiatrist on the call with us today. I think there is an ample amount of data that cannabis is not safe for young people. It's not safe for growing brains. And I think we need to make sure, just as we would want people's opiates to be secured, that their cannabinoids and cannabis products are secured as well, from those who do not want to use them. ILANA BRAUN: And the thing I would keep in mind is that in most states, giving patients a medicinal cannabis card is allowing them to access any number of products with different ratios of active ingredients, delivery mechanisms, onset of action, potencies. And if you don't discuss all of these issues with your patients, these are things that they will decide at the dispensary counter, or by discussing with friends and family, or by trial and error. And I think it's really important that we clinicians guide this narrative. ASHLEY GLODE: So what kinds of patients are not good candidates for medical cannabis? DANIEL BOWLES: I would not recommend medical cannabis for people who can't meet some of the criteria we already discussed. So people who can't keep it safe in their households or have concerns about diversion in their own households. Those are people who I think would not be great candidates for medicinal cannabis or cannabinoids. ILANA BRAUN: As the psychiatrist on the call, I would add that I worry for people with a strong history of psychosis, or currently psychotic, or with a strong family history of psychosis. And perhaps those severely immunocompromised, since there is evidence of fungal and mold contamination in some cannabis products. DANIEL BOWLES: The other group of people I discussed this with are patients on immunotherapies. One of the ways that cannabis may be effective in some of the symptoms we discussed is it's an anti-inflammatory agent. One of the ways it could be detrimental for patients on immunotherapies is that it's an anti-inflammatory agent. There is one small study that suggested that patients might have worse responses to immunotherapy who are cannabis users versus those who are not. So that is a conversation I like to have, just so patients feel like they can be informed. I think lastly, cannabis even for people with medical cards, is not free. So there can be a financial burden for people who are using it. So that's something that I'll often bring up with people as well. KENT HUTCHISON: One thing I would add to this would be history of a substance use disorder might also be a consideration here as well. Mainly because you don't know what the person is going to get, and it could be something that lends itself to relapse or encourages a problem. So I would add that to list. ILANA BRAUN: And I would second what Dr. Bowles said about the financial challenges of using cannabis regularly medicinally. It's not something that's covered by insurance, either. So these are out-of-pocket expenses, and they can add up fast, particularly for patients in the oncology space using it for antineoplastic therapy. ASHLEY GLODE: So is there a concern about drug-drug interactions for patients currently undergoing active cancer treatment? DANIEL BOWLES: There are some data that there can be drug-drug interactions with cannabis and certain agents. In particular, cannabidiol, or CBD, is a CYP3A4 inhibitor. And there are a lot of drugs that are metabolized through that particular system. So I think that that's the clinical relevance of those interactions, I think, is sometimes unknown. But that is another topic that I do think we need to make sure we bring up with our patients. ASHLEY GLODE: Thank you. Yeah. So a lot of what we'll do is from a drug interaction perspective, use the FDA-approved products that we have available to run through a drug interaction checker, like Dr. Bowles mentioned. So we'll use dronabinol as the THC-based product and epidiolex as the CBD-based product. There's also some resources, such as natural Medicines Database. And some of the pharmacy programs that we use, you can actually put in marijuana or cannabis as a drug and run drug interaction checks. So there's multiple potential interactions, like he mentioned, through the immune system. But through the cytochrome P450 pathway, cannabis has been shown in some instances to be an inhibitor, sometimes an inducer of certain enzymes, as well as a substrate. So it's really important to work with your pharmacy colleagues to run through different potential interactions that may be present. ILANA BRAUN: I'll just add one thing, just in case that's helpful. I mentioned earlier in the episode that I had a patient who used cannabis as an antineoplastic drug, and targeted very high doses and developed a terrible nausea and vomiting. And when she stopped, so did the nausea and vomiting, even though her chemotherapeutic continued. And I, to this day, don't know if that was a cyclic nausea and vomiting syndrome, which has been known to plague some heavy cannabis users, or whether drug-drug interactions led to her high-dose cannabis triggering high blood concentrations of her cancer-directed therapy at the time. And so I think that drug-drug interactions do need to be carefully weighed. ASHLEY GLODE: So wrapping up, has the medical community stance on medical marijuana shifted in recent years with legalization in many states? ILANA BRAUN: I don't think we know the answer to this, about how sentiment has shifted because there aren't longitudinal studies that I know of examining this question. But we need some. And one could imagine that as medicinal cannabis becomes are commonplace, providers are increasingly confronted with questions about how to guide care and the desire for high-quality clinical trials and in-depth cannabis therapeutics trainings increases-- and as one piece of evidence for this, at the end of 2020 the National Cancer Institute held a first-in-kind four-day conference at the intersection of cannabis and cancer. And so I'm hopeful that grant opportunities will follow from that. DANIEL BOWLES: I think overall there has been more willingness to discuss cannabis in the context of patient care in the last decade. A couple of ways that I see this is I much more frequently see cannabis use described not necessarily in the drug history, or in the social history, but in the medical history, or in their medications, if they're using it for medical or therapeutic purposes. I think the other place that I've noticed cannabis usage become a bit more mainstream is in the clinical trial setting-- not in clinical trials of cannabis, but one of the things that many of us do is clinical trials of new drugs. And very frequently, 10 years ago we ran into trouble trying to get our patients who were using cannabis products for cancer symptom control onto these clinical trials because of potential drug-drug interactions, or just the fear of the unknown. And I feel like we run into that less commonly now. KENT HUTCHISON: I think it's also worth pointing out that there have been more and more podcasts like this one, right? So to the credit of this organization, I think we are seeing some change. I just wanted to highlight that. And I compliment everyone here for putting us together and putting it out there. ASHLEY GLODE: All right. Well, thank you. That is all we have for today. And thank you very much Drs. Braun, Bowles, and Hutchison for a delightful conversation. Thank you so much to all the listeners tuning into this episode of the ASCO Education Podcast. [MUSIC PLAYING]   SPEAKER: Thank you for listening to this week's episode to make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit elearning.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Episode 21 of Cracking Addiction explores methadone pharmacokinetics, breakdown and interactions within the body and interactions with other drugs. Methadone is a drug with a wide variability in its absorption with oral bio-availability ranges from 35% to 100%. This is a significant amount of variability and explains why the same dose of Methadone can impact different patients differently. Methadone is metabolised within the liver by the cytochrome P450 enzymes but mainly 3A4. There is a 17-fold inter-individual variation of methadone blood concentration for a given dosage and variations in metabolism account for a large part of this variation. Kinetic interactions influenced by the CYP 450 enzyme can affect plasma methadone levels. • Inducers of CYP450 can • Accelerate the metabolism of methadone • lower methadone plasma levels • Precipitate opioid withdrawal • Inhibitors of CYP450 can • Slow the metabolism of methadone • Increase plasma levels • Produce opioid toxicity (sedation, overdose) Methadone is excreted renally with approximately 10% of drug renally eliminated unchanged. Renal excretion of methadone urinary pH dependent with increased Methadone excretion noted at pH less than 6 and decreased Methadone excretion at higher pH levels. About Meducate ® Meducate provides online education for doctors, clinicians, health professionals and the public. See the website to browse the many different talks and courses availablehttps://www.meducate.com.au

In today's episode of the podcast, we will be doing a deep dive into duloxetine, a serotonin-norepinephrine reuptake inhibitor (SNRI). In part one of this two-part series, we will cover the history of SNRIs as well as mechanisms of action, cytochrome P450 issues, side effects, and contraindications to consider when prescribing duloxetine and this class of medications. Link to Blog. Link to Resource Library. 

View the show notes in Google Docs here: http://bit.ly/3bFS43j Gonorrhea Updates Gonorrhea Treatment and Care. Centers for Disease Control and Prevention Website. https://www.cdc.gov/std/gonorrhea/treatment.htm. Published December 14, 2020. Accessed January 11, 2021. CDC No Longer Recommends Oral Drug for Gonorrhea Treatment. Centers for Disease Control and Prevention. https://www.cdc.gov/nchhstp/newsroom/2012/gctx-guidelines-pressrelease.html. Published August 9, 2012. Accessed January 11, 2021. Recurrent UTI Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline (2019). American Urological Association. https://www.auanet.org/guidelines/recurrent-uti?fbclid=IwAR1TwSTQNHv8PDWLfW7WjsDan46D_9b6Qs1ptJxaXr6YFnDpBeptpW3BY. Published 2019. Accessed January 11, 2021. Combo Ibuprofen and Acetaminophen / Pain Advil® Dual Action. GSK Expert Portal. https://www.gskhealthpartner.com/en-us/pain-relief/brands/advil/products/dual-action/?utmsource=google&utmmedium=cpc&utmterm=ibuprofen+acetaminophen&utmcampaign=GS+-+Unbranded+Advil+DA+-+Alone+-+PH. Accessed January 11, 2021. FDA approves GSK's Advil Dual Action with Acetaminophen for over-the-counter use in the United States. GSK. https://www.gsk.com/en-gb/media/press-releases/fda-approves-gsk-s-advil-dual-action-with-acetaminophen-for-over-the-counter-use-in-the-united-states/. Published March 2, 2020. Accessed January 11, 2021. Tanner T, Aspley S, Munn A, Thomas T. The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol. BMC clinical pharmacology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906415/. Published July 5, 2010. Accessed January 11, 2021. Searle S, Muse D, Paluch E, et al. Efficacy and Safety of Single and Multiple Doses of a Fixed-dose Combination of Ibuprofen and Acetaminophen in the Treatment of Postsurgical Dental Pain: Results From 2 Phase 3, Randomized, Parallel-group, Double-blind, Placebo-controlled Studies. The Clinical journal of pain. https://pubmed.ncbi.nlm.nih.gov/32271183/. Published July 2020. Accessed January 11, 2021. 1000 mg versus 600/650 mg Acetaminophen for Pain or Fever: A Review of the Clinical Efficacy. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/books/NBK373467/. Published June 17, 2016. Accessed January 11, 2021. Motov S. Is There a Limit to the Analgesic Effect of Pain Medications? Medscape. https://www.medscape.com/viewarticle/574279. Published June 17, 2008. Accessed January 11, 2021. Motov, Sergey. Faculty Forum: A Practical Approach to Pain Management. YouTube. https://www.youtube.com/watch?v=lJSioPsGw3A. The Center for Medical Education. Published December 2, 2020. Accessed January 1, 2021. Wuhrman E, Cooney MF. Acute Pain: Assessment and Treatment. Medscape. https://www.medscape.com/viewarticle/735034_4. Published January 3, 2011. Accessed January 11, 2021. Social Pain Dewall CN, Macdonald G, Webster GD, et al. Acetaminophen reduces social pain: behavioral and neural evidence. Psychological science. https://pubmed.ncbi.nlm.nih.gov/20548058/. Published June 14, 2010. Accessed January 11, 2021. Mischkowski D, Crocker J, Way BM. From painkiller to empathy killer: acetaminophen (paracetamol) reduces empathy for pain. Social cognitive and affective neuroscience. https://pubmed.ncbi.nlm.nih.gov/27217114/. Published May 5, 2016. Accessed January 11, 2021. Other / Recurrent liner notes Center for Medical Education. https://courses.ccme.org/. Accessed January 11, 2021. Roberts M, Roberts JR. The Proceduralist. https://www.theproceduralist.org/. Accessed January 11, 2021. The Procedural Pause by James R. Roberts, MD, & Martha Roberts, ACNP, PNP. Emergency Medicine News. https://journals.lww.com/em-news/blog/theproceduralpause/pages/default.aspx. Accessed January 11, 2021. The Skeptics' Guide to Emergency Medicine. sgem.ccme.org. https://sgem.ccme.org/. Accessed January 11, 2021. Trivia Question: Send answers to 2viewcast@gmail.com Please note that you must answer the 2 part question to win a copy of the EMRA Pain Guide. “What controversial drug was given a black box warning for prolonged QT and torsades in 2012 and now has been declared by WHICH organization to be an effective and safe treatment use for nausea, vomiting, headache and agitation?” Practical Pain Management in Acute Care Setting Handout Sergey Motov, MD @painfreeED • Pain is one of the most common reasons for patients to visit the emergency department and other acute care settings. Due to the extensive number of visits related to pain, clinicians and midlevel providers should be aware of the various options, both pharmacological and nonpharmacological, available to treat patients with acute pain. • As the death toll from the opioid epidemic continues to grow, the use of opioids in the acute care setting as a first-line treatment for analgesia is becoming increasingly controversial and challenging. • There is a growing body of literature that is advocating for more judicious use of opioids and well as their prescribing and for broader use of non-pharmacological and non-opioid pain management strategies. • The channels/enzymes/receptors targeted analgesia (CERTA) concept is based on our improved understanding of the neurobiological aspect of pain with a shift from a symptom-based approach to pain to a mechanistic approach. This targeted analgesic approach allows for a broader utilization of synergistic combinations of nonopioid analgesia and more refined and judicious (rescue) use of opioids. These synergistic combinations result in greater analgesia, fewer side effects, lesser sedation, and shorter LOS. (Motov et al 2016) General Principles: Management of acute pain in the acute care setting should be patient-centered and pain syndrome-specific by using multimodal approach that include non-pharmacological modalities and pharmacological ones that include non-opioid and opioid analgesics. Assessment of acute pain should be based on a need for analgesics to improve functionality, rather than patients-reported pain scores. Brief pain inventory short form BPI-SF is better than NRS/VAS as it assesses quantitative and qualitative impact of pain (Im et al 2020). ED clinicians should engage patients in shared decision-making about overall treatment goals and expectations, the natural trajectory of the specific painful condition, and analgesic options including short-term and long-term benefits and risks of adverse effects. If acute pain lasting beyond the expected duration, complications of acute pain should be ruled out and transition to non-opioid therapy and non-pharmacological therapy should be attempted. Non-Pharmacologic Therapies • Acute care providers should consider applications of heat or cold as well as specific recommendations regarding activity and exercise. • Music therapy is a useful non-pharmacologic therapy for pain reduction in acute care setting (music-assisted relaxation, therapeutic listening/musical requests, musical diversion, song writing, and therapeutic singing (Mandel 2019). • The use of alternative and complementary therapies, such as acupuncture, guided imagery, cognitive-behavioral therapy, and hypnosis have not been systemically evaluated for use in the Acute care setting including ED. (Dillan 2005, Hoffman 2007) • In general, their application may be limited for a single visit, but continued investigation in their safety and efficacy is strongly encouraged. • Practitioners may also consider utilization of osteopathic manipulation techniques, such as high velocity, low amplitude techniques, muscle energy techniques, and soft tissue techniques for patients presenting to the acute care setting with pain syndromes of skeletal, arthroidal, or myofascial origins. (Eisenhart 2003) Opioids • Acute Care providers are uniquely positioned to combat the opioid epidemic by thoughtful prescribing of parenteral and oral opioids in inpatient setting and upon discharge, and through their engagement with opioid addicted patients in acute care setting. • Acute Care providers should make every effort to utilize non-pharmacological modalities and non-opioid analgesics to alleviate pain, and to use opioid analgesics only when the benefits of opioids are felt to outweigh the risks. (not routinely) • When opioids are used for acute pain, clinicians should combine them with non-pharmacologic and non-opioid pharmacologic therapy: Yoga, exercise, cognitive behavioral therapy, complementary/alternative medical therapies (acupuncture); NSAID's, Acetaminophen, Topical Analgesics, Nerve blocks, etc. • When considering opioids for acute pain, Acute Care providers should involve patients in shared decision-making about analgesic options and opioid alternatives, risks and benefits of opioid therapies, and rational expectations about the pain trajectory and management approach. • When considering opioids for acute pain, acute care providers should counsel patients regarding serious adverse effects such as sedation and respiratory depression, pruritus and constipation, and rapid development of tolerance and hyperalgesia. • When considering administration of opioids for acute pain, acute care providers should make every effort to accesses respective state's Prescription Drug Monitoring Program (PDMP). The data obtained from PDMP's to be used to identify excessive dosages and dangerous combinations, identify and counsel patients with opioid use disorder, offer referral for addiction treatment. • PDMPs can provide clinicians with comprehensive prescribing information to improve clinical decisions around opioids. However, PDMPs vary tremendously in their accessibility and usability in the ED, which limits their effectiveness at the point of care. Problems are complicated by varying state-to-state requirements for data availability and accessibility. Several potential solutions to improving the utility of PDMPs in EDs include integrating PDMPs with electronic health records, implementing unsolicited reporting and prescription context, improving PDMP accessibility, data analytics, and expanding the scope of PDMPs. (Eldert et al, 2018) • Parenteral opioids when used in titratable fashion are effective, safe, and easily reversible analgesics that quickly relieve pain. • Acute care clinicians should consider administering these analgesics for patients in acute pain where the likelihood of analgesic benefit is judged to exceed the likelihood of harm. • Parenteral opioids must be titrated regardless of their initial dosing regimens (weight-based or fixed) until pain is optimized to acceptable level (functionality status) or side effects become intolerable. • When parenteral opioids are used, patients should be engaged in shared-decision making regarding the route of administration, as repetitive attempts of IV cannulation and intramuscular injections are associated with pain. In addition, intramuscular injections are associated with unpredictable absorption rates, and complications such as muscle necrosis, soft tissue infection and the need for dose escalation. (Von Kemp 1989, Yamanaka 1985, Johnson 1976) • Morphine sulfate provides better balance of analgesic efficacy and safety among all parenteral opioids. a. Dosing regimens and routes: b. IV: 0.05-0.1mg/kg to start, titrate q 10-20 min c. IV: 4-6 mg fixed, titrate q 10-20 min d. SQ: 4-6 mg fixed, titrate q 20 min e. Nebulized: 0.2 mg/kg or 10-20 mg fixed, repeat q 15-20 min f. PCA: prone to dosing errors g. IM: should be avoided (pain, muscle fibrosis, necrosis, increase in dosing requirements) • Hydromorphone should be avoided as a first-line opioid due to significant euphoria and severe respiratory depression requiring naloxone reversal. Due to higher lipophilicity, Hydromorphone use is associated with higher rates of euphoria and subsequent development of addiction. Should hydromorphone be administered in higher than equi-analgesic morphine milligram equivalents, close cardiopulmonary monitoring is strongly recommended. Dosing h. IV: 0.2-0.5 mg initial, titrate q10-15 min i. IM: to be avoided (pain, muscle fibrosis, necrosis, increase in dosing requirements) j. PCA: prone to dosing errors (severe CNS and respiratory depression) k. Significantly worse AE profile in comparison to Morphine l. Equianalgesic IV conversion (1 mg HM=8mg of MS) m. Overprescribed in >50% of patients n. Inappropriately large dosing in EM literature: 2 mg IVP o. Abuse potential (severely euphoric due to lipophilicity) • Fentanyl is the most potent opioid, short-acting, requires frequent titration. Dosing: p. IV: 0.25-0.5 μg/kg (WB), titrate q10 min q. IV: 25-50 μg (fixed), titrate q10 min r. Nebulization: 2-4 μg/kg, titrate q20-30 min s. IN: 1-2 μg/kg, titrate q5-10min t. Transbuccal: 100-200μg disolvable tablets u. Transmucosal: 15-20 mcg/kg Lollypops • Opioids in Renal Insufficiency/Renal Failure Patients-requires balance of ORAE with pain control by starting with lower-than-recommended doses and slowly titrate up the dose while extending the dosing interval. (Dean 2004, Wright 2011) • Opioid-induced pruritus is centrally mediated process via μ-opioid receptors as naloxone, nalbuphine reverse it, and can be caused by opioids w/o histamine release (Fentanyl). Use ultra-low-dose naloxone of 0.25 -1 mcg/kg/hr with NNT of 3.5. (Kjellberg 2001) • When intravascular access is unobtainable, acute care clinicians should consider utilization of intranasal (fentanyl), nebulized (fentanyl and morphine), or transmucosal (rapidly dissolvable fentanyl tablets) routes of analgesic administration for patients with acute painful conditions. • Breath actuated nebulizer (BAN): enclosed canister, dual mode: continuous and on-demand, less occupational exposures. a. Fentanyl: 2-4 mcg//kg for children, 4 mcg/kg for adults: titration q 10 min up to three doses via breath-actuated nebulizer (BAN): systemic bioavailability of 50-60% of IV route. (Miner 2007, Furyk 2009, Farahmand 2014) b. Morphine: 10-20 mg g10 min up to 3 doses via breath-actuated nebulizer (BAN)-Systemic bioavailability (concentration) of 30-35% of IV Route. (Fulda 2005, Bounes 2009, Grissa 2015) c. Intranasal Fentanyl: IN via MAD at 1-2 mcg/kg titration q 5 min (use highly concentrated solution of 100mcg/ml for adults and 50 mcg/ml for children)- systemic bioavailability of 90% of IV dosing. (Karisen 2013, Borland 2007, Saunders 2010, Holdgate 2010) d. IN route: shorter time to analgesia, titratable, comparable pain relief to IV route, minimal amount of side effects, similar rates of rescue analgesia, great patients and staff satisfaction. Disadvantages: requires highly concentrated solutions that not readily available in the ED, contraindicated in facial/nasal trauma. Oral Opioids • Oral opioid administration is effective for most patients in the acute care setting, however, there is no appreciable analgesic difference between commonly used opioids (oxycodone, hydrocodone and morphine sulfate immediate release (MSIR). • When oral opioids are used for acute pain, the lowest effective dose and fewest number of tablets needed should be prescribed. In most cases, less than 3 days' worth are necessary, and rarely more than 5 days' worth are needed. • If painful condition outlasts three-day supply, re-evaluation in health-care facility is beneficial. Consider expediting follow-up care if the patient's condition is expected to require more than a three-day supply of opioid analgesics. • Only Immediate release (short-acting) formulary are to be prescribed in the acute care setting and at discharge. • Clinicians should not administer or prescribe long-acting, extended-release, or sustained-release opioid formulations, which include both oral and transdermal (fentanyl) medications in the acute care setting. These formulations are not indicated for acute pain and carry a high risk of overdose, particularly in opioid-naïve patients. • Acute care providers should counsel patients about safe medication storage and disposal, as well as the consequences of failure to do this; potential for abuse and misuse by others (teens and young adults), and potential for overdose and death (children and teens). • Oxycodone is no more effective than other opioids (hydrocodone, MSIR). Oxycodone has highest potential for abuse, misuse and diversion as well as increased risks of overdose, addiction and death. Oxycodone should be avoided as a first-line oral opioid for acute pain. ( Strayer 2016) • If still prescribed, lowest dose (5mg) in combination with acetaminophen (lowest dose of 325 mg) should be considered as it associated with less abuse and diversion (in theory). Potential for acetaminophen overdose exist though with combination. • Hydrocodone is three times more prescribed than oxycodone, but three times less used for non-medical purpose. Combo with APAP (Vicodin)-Use lowest effective dose for hydrocodone and APAP (5/325). (Quinn 1997, Adams 2006) • Immediate release morphine sulfate (MSIR) administration is associated with lesser degree of euphoria and consequently, less abuse potential (Wightman 2012). ED providers should consider prescribing Morphine Sulfate Immediate Release Tablets (MSIR) (Wong 2012, Campos 2014) for acute pain due to: o Similar analgesic efficacy to Oxycodone and Hydrocodone o Less euphoria (less abuse potential) o Less street value (less diversion) o More dysphoria in large doses o Less abuse liability and likeability • Tramadol should not be used in acute care setting and at discharge due to severe risks of adverse effects, drug-drug interactions, and overdose. There is very limited data supporting better analgesic efficacy of tramadol in comparison to placebo, or better analgesia than APAP or Ibuprofen. Tramadol dose not match analgesic efficacy of traditional opioids. (Juurlink 2018, Jasinski 1993, Babalonis 2013) • Side effects are: o Seizures o Hypoglycemia o Hyponatremia o Serotonin syndrome o Abuse and addiction • Codeine and Codeine/APAP is a weak analgesic that provides no better pain relief than placebo. Codeine must not be administered to children due to: o dangers of the polymorphisms of the cytochrome P450 iso-enzyme: o ultra-rapid metabolizers: respiratory depression and death o poor metabolizers: absent or insufficient pain relief • Transmucosal fentanyl (15 and 20 mcg/kg lollypops) has an onset of analgesia in 5 to 15 minutes with a peak effect seen in 15 to 30 minutes (Arthur 2012). • Transbuccal route can be used right at the triage to provide rapid analgesia and as a bridge to intravenous analgesia in acute care setting. (Ashburn 2011). A rapidly dissolving trans-buccal fentanyl (100mcg dose) provides fast pain relief onset (median 10 min), great analgesics efficacy, minimal need for rescue medication and lack of side effects in comparison to oxycodone/acetaminophen tablet (Shear 2010) • Morphine Milligram Equivalent (MME) is a numerical standard against which most opioids can be compared, yielding a comparison of each medication's potency. MME does not give any information of medications efficacy or how well medication works, but it is used to assess comparative potency of other analgesics. • By converting the dose of an opioid to a morphine equivalent dose, a clinician can determine whether a cumulative daily dose of opioids approaches an amount associated with increased risk of overdose and to identify patients who may benefit from closer monitoring, reduction or tapering of opioids, prescribing of naloxone, and other measures to reduce risk of overdose. • Opioid-induced hyperalgesia: o opioid-induced hyperalgesia (OIH) is a rare syndrome of increasing pain, often accompanied by neuroexcitatory effects, in the setting of increasing opioid therapy. o Morphine is by far the most common opiate implicated in OIH. Hydromorphone and oxycodone, members of the same class of opiate as morphine (phenanthrenes), can also cause OIH. Fentanyl, a synthetic opioid in the class of phenylpiperidine, is less likely to precipitate OIH. Existing data suggests that OIH is caused by multiple opioid-induced changes to the central nervous system including: -Activation of N-methyl-D-aspartate (NMDA) receptors -Inhibition of the glutamate transporter system -Increased levels of the pro-nociceptive peptides within the dorsal root ganglia -Activation of descending pain facilitation from the rostral ventromedial medulla -Neuroexcitatory effects provoked by metabolites of morphine and hydromorphone • OIH can be confused with tolerance as in both cases patients report increased pain on opioids. The two conditions can be differentiated based on the patient's response to opioids. In tolerance, the patient's pain will improve with dose escalation. In OIH, pain will worsen with opioid administration. This paradoxical effect is one of the hallmarks of the syndrome. Non-opioid analgesics • Acetaminophen is indicated for management of mild to moderate pain and as a single analgesic and has modest efficacy at most. Addition of Acetaminophen to Ibuprofen does not provide better analgesia for patients with acute low back pain. The greatest limitation to the use of intravenous (IV) versus oral acetaminophen is the nearly 100-fold cost differential, which is likely not justified by any marginal improvement in pain relief. Furthermore, IV APAP provide faster onset of analgesia only after an initial dose. (Yeh 2012, Serinken 2012) • NSAIDs should be administered at their lowest effective analgesic doses both in the ED and upon discharge and should be given for the shortest appropriate treatment course. Caution is strongly advised when NSAIDs are used in patients at risk for renal insufficiency, heart failure, and gastrointestinal hemorrhage, as well as in the elderly. Strong consideration should be given to topical NSAID's in managing as variety of acute and chronic painful Musculo-skeletal syndromes. The analgesic ceiling refers to the dose of a drug beyond which any further dose increase will not result in additional analgesic efficacy. Thus, the analgesics ceiling for ibuprofen is 400 mg per dose (1200 mg/24 h) and for ketorolac is 10 mg per dose (10 mg/24 h). These doses are less than those often prescribed for control of inflammation and fever. When it comes to equipotent doses of different NSAIDs, there is no difference in analgesic efficacy. • Ketamine, at sub-dissociative doses (also known as low-dose ketamine or analgesic dose ketamine) of 0.1 to 0.4 mg/kg, provided effective analgesia as a single agent or as an adjunct to opioids (reducing the need for opioids) in the treatment of acute traumatic and nontraumatic pain in the ED. This effective analgesia, however, must be balanced against high rates of minor adverse side effects (14%–80%), though typically short-lived and not requiring intervention. In addition to IV rout, ketamine can be administered via IN,SQ, and Nebulized route. • Local anesthetics are widely used in the ED for topical, local, regional, intra-articular, and systemic anesthesia and analgesia. Local anesthetics (esters and amides) possess analgesic and anti-hyperalgesic properties by non-competitively blocking neuronal sodium channels. o Topical analgesics containing lidocaine come in patches, ointments, and creams have been used to treat pain from acute sprains, strains, and contusions as well as variety of acute inflammatory and chronic neuropathic conditions, including postherpetic neuralgia (PHN), complex regional pain syndromes (CRPS) and painful diabetic neuropathy (PDN). o UGRA used for patients with lower extremity fractures or dislocations (eg, femoral nerve block, fascia iliaca compartment block) demonstrated significant pain control, decreased need for rescue analgesia, and first-attempt procedural success. In addition, UGRA demonstrated few procedural complications, minimal need for rescue analgesia, and great patient satisfaction. o Analgesic efficacy and safety of IV lidocaine has been evaluated in patients with renal colic and acute lower back pain. Although promising, this therapy will need to be studied in larger populations with underlying cardiac disease before it can be broadly used. o knvlsd • Antidopaminergic and Neuroleptics are frequently used in acute care settings for treatment of migraine headache, chronic abdominal pain, cannabis-induced hyperemesis. • Anti-convulsant (gabapentin and pregabalin) are not recommended for management of acute pain unless pain is of neuropathic origin. Side effects, particularly when combined with opioids (potentiation of euphoria and respiratory depression), titration to effect, and poor patients' compliance are limiting factors to their use. (Peckham 2018) References: Chang HY, Daubresse M, Kruszewski SP, et al. Prevalence and treatment of pain in EDs in the United States, 2000 to 2010. Am J Emerg Med 2014;32(5):421–31. Green SM. There is oligo-evidence for oligoanalgesia. Ann Emerg Med 2012;60: 212–4. Strayer RJ, Motov SM, Nelson LS. Something for pain: Responsible opioid use in emergency medicine. Am J Emerg Med. 2017 Feb;35(2):337-341. Smith RJ, Rhodes K, Paciotti B, Kelly S,et al. Patient Perspectives of Acute Pain Management in the Era of the Opioid Epidemic. Ann Emerg Med. 2015 Sep;66(3):246-252 Meisel ZF, Smith RJ. Engaging patients around the risks of opioid misuse in the emergency department. Pain Manag. 2015 Sep;5(5):323-6. Wightman R, Perrone J. (2017). Opioids. In Strayer R, Motov S, Nelson L (Eds.), Management of Pain and Procedural Sedation in Acute Care. http://painandpsa.org/opioids/ Motov S, Nelson L, Advanced Concepts and Controversies in Emergency Department Pain Management. Anesthesiol Clin. 2016 Jun;34(2):271-85. doi: 10.1016/j.anclin.2016.01.006. Ducharme J. Non-opioid pain medications to consider for emergency department patients. Available at: http://www.acepnow.com/article/non-opioid-painmedications- consider-emergency-department-patients/. 2015. Wightman R, Perrone J, Portelli I, et al. Likeability and Abuse Liability of Commonly Prescribed Opioids. J Med Toxicol. September 2012. doi: 10.1007/s12181-012-0263-x Zacny JP, Lichtor SA. Within-subject comparison of the psychopharmacological profiles of oral oxycodone and oral morphine in non-drug-abusing volunteers. Psychopharmacology (Berl) 2008 Jan;196(1):105–16. Hoppe JA, Nelson LS, Perrone J, Weiner SG, Prescribing Opioids Safely in the Emergency Department (POSED) Study Investigators. Opioid Prescribing in a Cross Section of US Emergency Departments. Ann Emerg Med. 2015;66(3):253–259. Baehren DF, Marco CA, Droz DE, et al. A statewide prescription monitoring program affects emergency department prescribing behaviors. Ann Emerg Med. 2010; 56(1):19–23 Weiner SG, Griggs CA, Mitchell PM, et al. Clinician impression versus prescription drug monitoring program criteria in the assessment of drug-seeking behavior in the emergency department. Ann Emerg Med 2013;62(4):281–9. Greenwood-Ericksen MB, Poon SJ, Nelson LS, Weiner SG, et al. Best Practices for Prescription Drug Monitoring Programs in the Emergency Department Setting: Results of an Expert Panel. Ann Emerg Med. 2016 Jun;67(6):755-764 Patanwala AE, Keim SM, Erstad BL. Intravenous opioids for severe acute pain in the emergency department. Ann Pharmacother 2010;44(11):1800–9. Bijur PE, Kenny MK, Gallagher EJ. Intravenous morphine at 0.1 mg/kg is not effective for controlling severe acute pain in the majority of patients. Ann Emerg Med 2005; 46:362–7. Birnbaum A, Esses D, Bijur PE, et al. Randomized double-blind placebo- controlled trial of two intravenous morphine dosages (0.10 mg/kg and 0.15 mg/kg) in emergency department patients with moderate to severe acute pain. Ann Emerg Med. 2007;49(4):445–53. Patanwala AE, Edwards CJ, Stolz L, et al. Should morphine dosing be weight based for analgesia in the emergency department? J Opioid Manag 2012; 8(1):51–5. Lvovschi V, Auburn F, Bonnet P, et al. Intravenous morphine titration to treat severe pain in the ED. Am J Emerg Med 2008;26:676–82. Chang AK, Bijur PE, Napolitano A, Lupow J, et al. Two milligrams i.v. hydromorphone is efficacious for treating pain but is associated with oxygen desaturation. J Opioid Manag. 2009 Mar-Apr;5(2):75-80. Sutter ME, Wintemute GJ, Clarke SO, et al. The changing use of intravenous opioids in an emergency department. West J Emerg Med 2015;16:1079-83. Miner JR, Kletti C, Herold M, et al. Randomized clinical trial of nebulized fentanyl citrate versus i.v. fentanyl citrate in children presenting to the emergency department with acute pain. Acad Emerg Med 2007;14:895–8. Furyk JS, Grabowski WJ, Black LH. Nebulized fentanyl versus intravenous morphine in children with suspected limb fractures in the emergency department: a randomized controlled trial. Emerg Med Australas 2009;21:203–9. Borland M, Jacobs I, King B, et al. A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in children in the emergency department. Ann Emerg Med 2007;49:335–40 Im DD, Jambaulikar GD, Kikut A, Gale J, Weiner SG. Brief Pain Inventory-Short Form: A New Method for Assessing Pain in the Emergency Department. Pain Med. 2020 Sep 11:ppnaa269. doi: 10.1093/pm/pnaa269. Epub ahead of print. PMID: 32918473. Mandel SE, Davis BA, Secic M. Patient Satisfaction and Benefits of Music Therapy Services to Manage Stress and Pain in the Hospital Emergency Department. J Music Ther. 2019 May 10;56(2):149-173. Piatka C, Beckett RD. Propofol for Treatment of Acute Migraine in the Emergency Department: A Systematic Review. Acad Emerg Med. 2020 Feb;27(2):148-160. Tzabazis A, Kori S, Mechanic J, Miller J, Pascual C, Manering N, Carson D, Klukinov M, Spierings E, Jacobs D, Cuellar J, Frey WH 2nd, Hanson L, Angst M, Yeomans DC. Oxytocin and Migraine Headache. Headache. 2017 May;57 Suppl 2:64-75. doi: 10.1111/head.13082. PMID: 28485846. Yeh YC, Reddy P. Clinical and economic evidence for intravenous acetaminophen. Pharmacotherapy 2012;32(6):559–79. Serinken M, Eken C, Turkcuer I, et al. Intravenous paracetamol versus morphine for renal colic in the emergency department: a randomised double-blinded controlled trial. Emerg Med J 2012;29(11):902–5. Wright JM, Price SD, Watson WA. NSAID use and efficacy in the emergency department: single doses of oral ibuprofen versus intramuscular ketorolac. Ann Pharmacother 1994;28(3):309–12. Turturro MA, Paris PM, Seaberg DC. Intramuscular ketorolac versus oral ibuprofen in acute musculoskeletal pain. Ann Emerg Med 1995;26(2):117–20. Catapano MS. The analgesic efficacy of ketorolac for acute pain [review]. J Emerg Med 1996;14(1):67–75 Dillard JN, Knapp S. Complementary and alternative pain therapy in the emergency department. Emerg Med Clin North Am 2005; 23:529–549. Hoffman BM, Papas RK, Chatkoff DK, Kerns RD. Meta-analysis of psychological interventions for chronic low back pain. Health Psychol 2007;26:1–9. Eisenhart AW, Gaeta TJ, Yens DP. Osteopathic manipulative treatment in the emergency department for patients with acute ankle injuries. J Am Osteopath Assoc 2003;103:417–421.

This episode covers P450 interactions!

FDA 批准颈动脉窦压力反射刺激疗法治疗心衰Lancet 血ACE2水平与心血管疾病及死亡的关系Science子刊 一种具有几何适应性的人工心脏瓣膜BAROSTIM NEO系统BAROSTIM NEO系统包括一个植入式脉冲发生器（IPG）、一个颈动脉窦含铅套件和一个程序。医生将BAROSTIM NEO脉冲发生器植入晚期心力衰竭患者的左或右锁骨下方，并在患者的左或右颈动脉窦处放置颈动脉窦导线，然后将脉冲发生器连接到颈动脉窦导线上。医生根据病人的个人需求制定脉冲发生器程序，然后向颈动脉的压力感受器传递电脉冲。压力反射激活（BAT）疗法的目的是激活颈动脉壁的压力感受器，刺激自主神经系统的传入和传出神经，大脑接收到神经信号作出相应反应：松弛血管、降低心率、并通过改善肾功能来减少液体储留。2019年8月，FDA批准BAROSTIM NEO系统用于药物治疗无效的、不符合心脏再同步化治疗适应症的、难治性心力衰竭患者。《BeAT-HF研究：这项研究证明了压力反射刺激疗法（BAT）对射血分数降低的心力衰竭患者的安全性和有效性》Journal of American College of Cardiology，2020年7月 (1) BeAT-HF研究是一项多中心、前瞻性、随机对照研究，纳入408名射血分数降低的心力衰竭（HFrEF）患者中，入组要求：纽约心功能分级II-III级、射血分数≤35%、药物治疗方案稳定≥4周、不符合心脏再同步化治疗的I类指征。这篇报告重点汇报了D队列中、NT-proBNP

Jon Bloom, MD, CEO & Co-Founder, Podimetrics Dr. Jon Bloom is a board-certified physician and entrepreneur with over 15 years of experience in technology development, patient monitoring, biomedical research, and health care delivery. He is the chief executive officer of Podimetrics, a virtual care management company dedicated to preventing diabetic amputations, one of the most debilitating and costly complications of diabetes. Dr. Bloom was inspired to create a solution to help prevent diabetic foot complications while practicing anesthesia. He frequently treated patients with diabetes who required foot amputations, and knew there had to be a less drastic way to manage common complications of that disease. Dr. Bloom co-founded Podimetrics in 2011 while a student at the MIT Sloan School of Management. Podimetrics combines an FDA-cleared SmartMat™ with wraparound care management to spot early warning signs weeks before they usually would present clinically. By combining cutting-edge technology with best-in-class care management, Podimetrics earns high engagement rates from patients and achieves unparalleled outcomes - keeping vulnerable patients healthy at home and saving limbs, lives, and money. Dr. Bloom served as a Clinical Assistant Professor and staff anesthesiologist at the University of Pittsburgh Medical Center. He also served as the Director of Global Medical Affairs for Covidien's Respiratory and Monitoring Solutions division in Boulder, Colorado. Dr. Bloom is a diplomate of the American Board of Anesthesiology, completing residency at the Massachusetts General Hospital. He has co-authored more than 20 peer-reviewed publications with a primary focus on health care economics and perioperative complications. Prior to his career in medicine Dr. Bloom studied cytochrome P450 drug metabolism at The Scripps Research Institute. 

Clinical Drug Interaction Studies — Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Final Guidance - Podcast Transcript

Guidance Recap Podcast | In Vitro Drug Interaction Studies — Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Final Guidance - Podcast Transcript

Celery Juice, How Detox Actually Works & Food as Medicine. Are you curious about the celery juice trend? Is it a super food or a super fad? In episode 14, I am joined by Ali Miller, RD, LD, CDE who is hitting us with the facts with her food-as-medicine approach that is grounded in nature and supported by scientific evidence. We talk through the misinformation, the redeeming qualities of celery and why you may want to reconsider downing gallons of celery juice each and every week. From debunking some of the massive claims to talking through why some folks may be having great results drinking daily celery juice, Ali shares more about how the body's natural detox pathways work. Learn how you are better off consuming foods rich in sulfur, glycine, glutathione, cysteine, and nutrients that drive phase 2 encapsulation with ample fiber in the diet (that's right celery juice contains none of these things) to support the excretion of toxins from your body to actually detox vs. prevent detox process for short-term outcomes. Finally, Ali shares more about her food-as-medicine approach when it comes to anxiety, depression and cognitive dysfunction. I hope you enjoy this episode and if you have anecdotal evidence or personal experiences with celery juice that you would like to share, please feel free to use the comments below, we'd love to hear from you.   Find Ali Miller RD: Her website AliMillerRD.com Instagram @AliMillerRd The Naturally Nourished Podcast   Mentioned in this Episode: Ali's IGTV episode about why she will never drink celery juice Celery Juice is NOT a Miracle Drink Rat study showing the effect of celery and parsley juices on pharmacodynamic activity of drugs involving cytochrome P450 in their metabolism 10 Day Real Food DetoxProgram The Anti-Anxiety Diet: A Whole Body Program to Stop Racing Thoughts, Banish Worry and Live Panic-Free Ali's rebuttal to Jillian Michael'srecent rants on the Keto Diet   Show Notes: http://tasty-yummies.com/beweenmeals14