In this episode, we provide a concise overview of the diagnosis and treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI) with a focus on the new HRS-1 definition (now called HRS-AKI), new data with terlipressin, and the AASLD 2021 guidelines.

Key Concepts

1. At a basic level, HRS-AKI is caused by portal hypertension leading to systemic vasodilation and a prerenal state.  Our treatment focuses on increasing vascular volume (usually with albumin) and vasoconstriction to increase renal perfusion.
2. The newest HRS-AKI definition borrows most of the AKI definitions from the KDIGO criteria for AKI.  HRS-AKI requires cirrhosis, ascites, AKI, and an exclusion of other etiologies of AKI.
3. In AKI and HRS-AKI, concentrated (25%) albumin is given. A dose of 1 gm/kg/day (max 100 gm) for two days is used for AKI.  For HRS-AKI, a dose of 20-50 grams/day is recommended.
4. The preferred vasoconstrictor in HRS-AKI is terlipressin; however, it is not available in the US. Norepinephrine (if in the ICU) is second-line.  If not in the ICU, midodrine and octreotide are recommended.  Therapy is continued until renal function recovers, if there is no improvement at 4 days, or if a full 14 days of therapy has been given.

References

1. Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74(2):1014-1048. doi:10.1002/hep.31884
2. European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406-460. doi:10.1016/j.jhep.2018.03.024

In this episode, we review the pharmacology, indications, adverse effects, and unique drug characteristics of the most common SSRIs on the market.

Key Concepts

1. SSRIs (selective serotonin reuptake inhibitors) are the drug of choice for depression, anxiety, and a variety of other psychiatric indications.
2. Fluoxetine (Prozac) and paroxetine (Paxil) inhibit CYP2D6, a metabolic pathway for several opioid analgesics, tamoxifen, and many other antidepressants.
3. Adverse effects of SSRIs start immediately but the beneficial psychiatric effects take up to 1 to 2 months to occur. Patient counseling about the timing of adverse effects and efficacy are important!
4. SSRIs should not be abruptly discontinued in patients taking the medication chronically. Withdrawal symptoms can include flu-like symptoms, changes in mood or sleep, and (rarely) even electric-like shocks. To discontinue, the SSRI dose should be tapered down over the period of several weeks.

In this episode, we discuss the recent accelerated approval of the new monoclonal antibody-based treatment agent, aducanumab (Aduhelm), by the FDA. We dive into the drug approval process, the efficacy and safety data, and the behind-the-scenes story of the FDA approval. Furthermore, we will present the controversy behind the approval and what it means for stakeholders.

Key Concepts

1. Aducanumab (Aduhelm) is a monoclonal antibody proven to reduce beta amyloid plaques in patients with Alzheimer’s disease.
2. Despite reducing plaques, aducanumab did NOT result in meaningful cognitive improvements in patients receiving the drugs versus placebo; additionally, the drug was associated with a potentially concerning adverse effect called ARIA-E (amyloid related imaging abnormalities-edema).
3. Despite an advisory panel unanimously recommending AGAINST approval and a lack of clinical outcome improvement, the FDA did go on to approve the drug in patients with Alzheimer’s disease using an accelerated approval process.
4. In the episode, we discuss the substantial ramifications of the FDA’s approval primarily in hurting its credibility in validating the safety and efficacy of other medications on the US market.

In this episode, we discuss the fascinating science of pharmaceutics with Dr. Kristen Ahlschwede and Dr. Rahul Deshmukh. We explore how dosage forms and excipients play an important role in how a drug product behaves in the human body with a particular focus on fentanyl patches, osmotic tablets (with laser-drilled holes), Depakote Sprinkles, and IV amiodarone.

Key Concepts

1. Fentanyl patches were reformulated from a drug-in-a-reservoir system to an adhesive matrix system to prevent abuse and misuse. The new formulation prevents fentanyl from "leaking" out when cut.
2. Osmotic tablet systems, such as Procardia XL, Glucotrol XL, and Concerta, use an "active" layer (containing drug) adjacent to a "push" layer that is osmotically active. When the push layer is exposed to water in the GI tract, it swells and pushes the active layer through a small laser-drilled precision hole.
3. "Sprinkle" dosage forms typically involve small pellets inside a capsule, such as Depakote Sprinkles. The capsule itself does not delay or extend release; instead, the pellets themselves are involved in prolonging the absorption profile of the drug.
4. Amiodarone IV is commercially available in two formulations -- the conventional formulation (Cordarone) contains benzyl alcohol and tween 80 to solubilize the drug but these excipients are associated with hypotension. A newer formulation (Nexterone) uses cyclodextrin as a solubilizing agent and is not associated with hypotension (although has a risk of nephrotoxicity, especially at higher cumulative doses).

In this episode, we reveal what goes on behind the scenes for drug pricing and pharmacy reimbursement with Dr. Benjamin Jolley. Our discussion covers important concepts like PBMs, DIR fees, MAC pricing, and even possible upcoming changes at the federal government.

Key Concepts

1. Prescription drug reimbursement is a major factor in the decline of independent pharmacies nationwide. Complex reimbursement models, fees, and drug pricing structures are frequently not well understood by both patients and many healthcare providers.
2. A pharmacy benefits manager (PBM) is a company hired by an insurance company to handle prescription drug coverage and reimbursement. Three PBMs control more than three-quarters of the entire US market and can often dictate the terms of a drug reimbursement contract with pharmacies.
3. PBMs determine how much they will pay for the cost of a medication using either a benchmark (such as the average wholesale price minus some percentage) or a list of the maximum allowable cost (MAC) maintained by the PBM. Pharmacies are required to accept the PBM’s reimbursement amount regardless of the cost the pharmacy paid to acquire the drug from a wholesaler.
4. DIR fees, clawbacks, and PBM rebate or discount agreements with manufacturers have resulted in lower reimbursements to pharmacies, higher drug prices for patients, and increased profits for PBMs.

In this episode, we discuss the recently published major updates in the 9th edition of the anticoagulation guidelines from CHEST. These new recommendations range from initiation of therapy, secondary prevention, and management of post-thrombotic syndrome.

Key Concepts

1. Among patients with cancer-associated VTE, DOACs are preferred over low molecular weight heparins (LMWH) EXCEPT in patients with GI cancers. The preferred anticoagulant in those with GI cancers is either LMWH or apixaban.
2. Among patients with antiphospholipid antibody syndrome, warfarin (INR goal 2-3) is preferred over DOAC therapy.
3. In the extended phase of treatment (secondary prevention after 3 months of treatment), lower anticoagulant doses should be used (such as apixaban 2.5 mg BID or rivaroxaban 10 mg daily).
4. In patients with a DVT, IVC filters should only be used when anticoagulation therapy is contraindicated. IVC filters reduce the risk of PE but do not alter the risk of DVT extension or future DVTs.
5. Compression stockings are not recommended for prevention of post-thrombotic syndrome nor for recurrent DVT prevention.

In this episode, we debunk four medication myths that have persisted for decades: metronidazole and alcohol; statins and hepatotoxicity; cidal vs. static antibiotics; and "sulfa" allergies.

Key concepts

1. Metronidazole does not interact with alcohol (ethanol) and does not cause a disulfiram-like reaction.
2. Statins can cause transient increases in liver function tests; however, these increases are not associated with hepatotoxicity. Routine LFT monitoring is not recommended unless clinically indicated signs or symptoms of liver injury exist.
3. The distinction of bactericidal versus bacteriostatic antibiotics is irrelevant. No evidence exists showing that having a bactericidal drug has superior efficacy to a bacteriostatic drug.
4. A “sulfa” allergy nearly always means an allergy to Bactrim (sulfamethoxazole-trimethoprim). There are many non-antibiotic sulfonamide-containing medications that do not need to be avoided in patients with a sulfa allergy; however, patients with an allergy to any medication have an increased risk of an allergic reaction to other medication classes.

In this episode, we provide a concise review of the diagnostic criteria and general treatment approach to patients with hypertensive emergencies.

Key Concepts

1. Hypertensive “urgency” is a misnomer - patients do not require immediate therapy and definitely should not receive IV therapy.
2. In most cases, the goal blood pressure in hypertensive emergencies is to decrease by no more than 25% in the first hour, achieve a BP of 160/100 in hours 2-6, then over the next 24-48 hours lower to a more normal blood pressure goal.
3. Labetalol is the preferred IV push antihypertensive UNLESS patients have acute heart failure, bradycardia, or possibly in patients with asthma/COPD.
4. Nicardipine is one of the most commonly used IV infusions for hypertensive emergencies. Most other continuous infusions are reserved for special types of hypertensive emergencies (e.g. nitroglycerin for pulmonary edema or acute MI, esmolol for aortic dissection).

In this episode, we will explore depths of COVID 19 vaccine hesitancy - what it is, how to identify and address it, and some helpful resources.

Key Concepts

1. When a patient seems hesitant to consider the COVID-19 vaccine, explore their hesitations further with a simple “why” or “tell more more” question.
2. Understand the root of hesitancy and provide personalized responses using motivational interviewing. Key concepts of motivational interviewing include asking open-ending questions, asking the patient to share their concerns, reflective listening, acknowledging without judgement, and asking for permission to share information.
3. The goal of a vaccine hesitancy conversation is not necessarily to have the patient receive the vaccine today; the goal is to move the patient one step closer to validated facts (combating misinformation) and consideration of receiving the vaccine.

In this episode, we will explore the history of COVID vaccine development and have a heart-to-heart conversation with Dr. Archana Chatterjee regarding her role as a dean of the RFUMS Chicago Medical School, her career path, and her position and functions on the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC).