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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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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Lotrisone is a topical cream that contains a combination of clotrimazole, an antifungal, and betamethasone dipropionate, a corticosteroid.

It is used to treat fungal skin infections such as athlete’s foot, jock itch, and ringworm that also involve inflammation or itching.

Clotrimazole works by disrupting the fungal cell membrane, while betamethasone reduces redness, swelling, and itching.

Lotrisone should not be used on the face, groin, or underarms for extended periods due to the risk of skin thinning and other steroid-related side effects.

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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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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 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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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 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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On this episode, I discuss benzonatate pharmacology, adverse reactions, and much more.

Tessalon Pearls (benzonatate) are a non-narcotic antitussive commonly prescribed to relieve dry, non-productive coughs.

Benzonatate acts by numbing stretch receptors in the respiratory tract, lungs, and pleura, which helps suppress the cough reflex at its source. Unlike opioid-based cough suppressants, it doesn’t work in the brain’s cough center.

The usual adult dose is 100 to 200 mg taken orally three times a day as needed, with a maximum daily dose of 600 mg.

One of the most critical points is that the capsules must be swallowed whole. Chewing, sucking, or crushing them can cause numbness in the mouth and throat, leading to a risk of choking or aspiration.

There are no major drug interactions associated with benzonatate.

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On this episode of the Real Life Pharmacology podcast, I discuss Miralax (polyethylene glycol) pharmacology, adverse effects, and much more.

MiraLAX is an osmotic laxative commonly used to treat occasional constipation by retaining water in the stool to increase stool frequency and soften consistency.

The standard adult dose of MiraLAX is 17 grams (approximately one heaping tablespoon) dissolved in 4 to 8 ounces of liquid once daily.

Electrolyte imbalances are rare but possible with prolonged or excessive use of Miralax, particularly in elderly or renal-impaired patients.

Advise patients to maintain adequate hydration while using MiraLAX to support its mechanism and reduce side effects.

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