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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NSAID Drug Interactions
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.
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 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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