Solifenacin Pharmacology

Solifenacin is a bladder antimuscarinic medication most commonly used for overactive bladder (OAB) with symptoms of urinary frequency, urgency, and urge incontinence. Like other agents in its class, understanding the pharmacology can help anticipate potential side effects, drug interactions, and downstream prescribing problems.

Mechanism of Action

Solifenacin selectively blocks muscarinic M3 receptors in the bladder detrusor muscle. Inhibiting these receptors reduces involuntary bladder contractions, increases bladder capacity, and delays the urge to void. While M3 selectivity may theoretically reduce side effects compared to nonselective antimuscarinics, in clinical practice, many anticholinergic effects still occur.

Adverse Effects

Because muscarinic receptors are present throughout the body, solifenacin can lead to a range of anticholinergic adverse effects:

  • Dry mouth – among the most common, can be significant enough to cause dental issues with long-term use.
  • Constipation – especially problematic in older adults; severe cases may require hospitalization.
  • Blurred vision – due to impaired accommodation.
  • Cognitive impairment – increased risk in older adults, particularly with cumulative anticholinergic burden.
  • Urinary retention – paradoxical worsening in patients with bladder outlet obstruction.

Drug Interactions

  • CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir) can increase solifenacin plasma concentrations, raising the risk of side effects.
  • Other anticholinergics (e.g., diphenhydramine, tricyclic antidepressants, other bladder antimuscarinics) can result in additive toxicity and higher anticholinergic burden.
  • QT-prolonging drugs (e.g., amiodarone, certain fluoroquinolones) may have additive cardiac risk since solifenacin has been associated with QT prolongation in rare cases.

Prescribing Cascade Examples

  1. Constipation → Laxative initiation – A patient starts solifenacin for OAB and develops severe constipation, leading to chronic use of stimulant laxatives like senna or bisacodyl.
  2. Dry mouth → Mouth rinse prescription – Dry mouth is treated with saliva substitutes or prescription rinses, instead of reassessing the anticholinergic therapy.
  3. Cognitive decline → Donepezil initiation – In older adults, cognitive impairment may be mistaken for dementia progression, leading to cholinesterase inhibitor prescribing—directly counteracting the anticholinergic effects of solifenacin.

Solifenacin can be an effective treatment for OAB, but the risk of adverse effects and prescribing cascades—especially in older adults—cannot be ignored. Healthcare professionals should regularly review the indication, monitor for anticholinergic burden, and look for opportunities to deprescribe when appropriate.

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Itraconazole Pharmacology

In this episode, we break down itraconazole—a potent antifungal with a lot of baggage. If you’re a pharmacist, clinician, or student who needs to understand how this drug works and why it can be tricky to use, this episode is for you.

We start with the basics. Itraconazole blocks 14α-demethylase, an enzyme fungi need to make their cell membranes. That disruption kills or slows the fungus. It works against tough bugs like Aspergillus, Histoplasma, and Blastomyces, plus common skin infections.

Side effects? Nausea, liver enzyme elevations, and more seriously, heart failure. Yes, itraconazole has a black box warning for worsening or causing congestive heart failure. If your patient has heart issues, think twice.

Drug interactions are everywhere. Itraconazole is a strong CYP3A4 inhibitor. It can raise levels of drugs like statins, benzos, calcium channel blockers, and immunosuppressants—sometimes to dangerous levels. Don’t co-prescribe without checking.

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Levomilnacipran Pharmacology

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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Asenapine Pharmacology

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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Ketoconazole Pharmacology

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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Fluphenazine Pharmacology

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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Quinapril Pharmacology

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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Nifedipine Pharmacology

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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Clotrimazole Pharmacology

On this podcast episode, I discuss Clotrimazole pharmacology, adverse effects, indications, administration, and much more.

Clotrimazole is an imidazole antifungal that exerts its pharmacological effect by inhibiting the synthesis of ergosterol, an essential component of fungal cell membranes. This inhibition compromises membrane integrity, leading to leakage of cellular contents and ultimately fungal cell death.

Clotrimazole is primarily used topically due to poor systemic absorption when administered via the skin or mucous membranes, which limits systemic side effects.

When clotrimazole is used intravaginally or orally in lozenge form, localized concentrations are sufficient to treat mucocutaneous infections without significant systemic exposure.

Pay attention when clotrimazole is used frequently to treat Candida infections as corticosteroids, immunosuppression, and antibiotics may increase the risk of this type of infection.

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Irbesartan Pharmacology

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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