Tag: drug interactions

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July 31, 2025July 26, 2025

Levomilnacipran Pharmacology

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In this episode of our pharmacology podcast, we take a deep dive into the pharmacology of levomilnacipran (Fetzima), a unique serotonin-norepinephrine reuptake inhibitor (SNRI) approved for the treatment of major depressive disorder (MDD) in adults. Designed for pharmacy students, clinicians, and anyone interested in psychopharmacology, this episode breaks down what makes levomilnacipran different from other antidepressants and how to use it effectively in clinical practice.

We explore levomilnacipran’s mechanism of action, which features a greater affinity for norepinephrine reuptake inhibition compared to serotonin—an uncommon trait among SNRIs. This pharmacologic profile gives it a distinctive effect on energy, motivation, and physical symptoms of depression. Listeners will also learn about its pharmacokinetics, including once-daily dosing, renal elimination, and metabolism via the CYP3A4 pathway—making drug interactions an important consideration.

The episode also covers levomilnacipran side effects, including common adverse reactions like nausea, dry mouth, constipation, and increased heart rate or blood pressure. We’ll also highlight rare but serious risks like serotonin syndrome and urinary hesitation.

Because levomilnacipran drug interactions can impact safety and efficacy, we review important combinations to avoid, such as CYP3A4 inhibitors (e.g., ketoconazole), serotonergic drugs, and blood pressure-altering agents. For pharmacists and prescribers, this is a key segment to help guide safer medication use and monitoring.

Finally, we wrap up with clinical pearls for starting, titrating, and monitoring levomilnacipran therapy—including renal dose adjustments and differences with duloxetine.

Whether you’re studying for boards or optimizing your patient’s antidepressant regimen, this episode delivers a concise, evidence-based overview of levomilnacipran pharmacology in a digestible, podcast-friendly format.

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July 24, 2025July 13, 2025

Asenapine Pharmacology

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Asenapine is an atypical antipsychotic that acts as an antagonist at multiple receptors, including dopamine D2 and serotonin 5-HT2A, contributing to its antipsychotic and mood-stabilizing effects.

Adverse effects of asenapine include somnolence, dizziness, and extrapyramidal symptoms.

Because asenapine is significantly metabolized by CYP1A2, inhibitors or inducers of these enzymes can affect its plasma concentrations.

Co-administration with other CNS depressants may increase the risk of sedation and impaired cognitive or motor function.

Asenapine can prolong the QT interval, so caution is advised when used with other medications that affect cardiac conduction.

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July 10, 2025June 28, 2025

Ketoconazole Pharmacology

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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.

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July 3, 2025June 28, 2025

NSAID Drug Interactions

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NSAIDs can reduce the effectiveness of antihypertensive medications such as ACE inhibitors, ARBs, beta-blockers, and diuretics by promoting sodium and water retention and decreasing renal blood flow.

Combining NSAIDs with anticoagulants or antiplatelet agents like warfarin or aspirin significantly increases the risk of gastrointestinal bleeding, due to additive effects on platelet inhibition and mucosal irritation.

NSAIDs can elevate lithium levels and increase the risk of toxicity, as they reduce renal clearance of lithium by decreasing renal perfusion.

Co-administration of NSAIDs with methotrexate can impair methotrexate elimination, leading to elevated levels and potential toxicity, especially at high methotrexate doses.

When NSAIDs are used with corticosteroids, the risk of gastrointestinal ulcers and bleeding is greatly amplified due to synergistic impairment of gastric mucosal protection.

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June 19, 2025June 1, 2025

Fluphenazine Pharmacology

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Fluphenazine is a high-potency typical antipsychotic that primarily acts as a dopamine D2 receptor antagonist in the mesolimbic pathway, reducing positive symptoms of schizophrenia.

Extrapyramidal symptoms (EPS), such as dystonia, akathisia, and parkinsonism, are common due to potent D2 blockade in the nigrostriatal pathway.

Neuroleptic malignant syndrome (NMS), though rare, is a life-threatening adverse effect characterized by rigidity, hyperthermia, altered mental status, and autonomic instability.

CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) can increase fluphenazine plasma concentrations, potentially raising the risk of toxicity and side effects.

Concomitant use of fluphenazine with CNS depressants (e.g., alcohol, benzodiazepines) can enhance sedation and respiratory depression.

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June 12, 2025May 31, 2025

Quinapril Pharmacology

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On this podcast episode, I discuss quinapril pharmacology, adverse effects, drug interactions, pharmacokinetics, and much more.

Quinapril is a prodrug that is converted in the liver to its active metabolite, quinaprilat, which inhibits ACE, leading to decreased formation of angiotensin II and reduced aldosterone secretion.

Hyperkalemia can occur with quinapril use due to decreased aldosterone, leading to potassium retention—especially in patients with renal impairment.

Concomitant use of potassium-sparing diuretics or potassium supplements with quinapril increases the risk of hyperkalemia.

NSAIDs may reduce the antihypertensive effect of quinapril and increase the risk of nephrotoxicity, especially in patients with preexisting renal dysfunction.

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June 5, 2025May 29, 2025

Nifedipine Pharmacology

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Nifedipine is a dihydropyridine calcium channel blocker that selectively inhibits L-type calcium channels in vascular smooth muscle, leading to vasodilation and reduced peripheral vascular resistance.

The extended-release formulation of nifedipine provides more stable plasma concentrations and is preferred for chronic management of hypertension and angina.

Common adverse effects include headache, flushing, peripheral edema, and dizziness, all related to its vasodilatory action.

Nifedipine undergoes extensive first-pass metabolism in the liver, primarily via CYP3A4 enzymes, which significantly influences its bioavailability and potential drug interactions.

CYP3A4 inhibitors (e.g., ketoconazole, erythromycin, grapefruit juice) can increase plasma levels of nifedipine, raising the risk of hypotension and adverse effects.

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May 22, 2025May 14, 2025

Irbesartan Pharmacology

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Irbesartan is an angiotensin II receptor blocker (ARB) used primarily for the management of hypertension and diabetic nephropathy in type 2 diabetes.

It selectively inhibits the binding of angiotensin II to the AT1 receptor found in vascular smooth muscle and the adrenal gland. This blockade results in vasodilation, reduced aldosterone secretion, decreased sodium and water retention, and ultimately lower blood pressure.

Irbesartan is administered orally, with a typical starting dose of 150 mg once daily, which may be increased to 300 mg depending on the patient’s clinical response and tolerability.

Adverse effects of irbesartan are generally mild but can include hyperkalemia and dizziness. Hypotension may occur, especially in volume-depleted individuals or those on diuretics.

Routine monitoring of renal function and serum potassium is recommended, especially in patients with underlying kidney disease or those taking potassium-sparing agents or supplements.

Irbesartan is contraindicated in pregnancy due to the risk of fetal toxicity and should be discontinued as soon as pregnancy is detected.

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