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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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.

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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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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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Polyethylene Glycol (Miralax) Pharmacology

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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Minoxidil Pharmacology

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On this episode of the Real Life Pharmacology Podcast, we cover minoxidil pharmacology, adverse effects, drug interactions, and much more.

Minoxidil is a potent arterial vasodilator used in the treatment of hypertension and androgenetic alopecia.

The route of administration greatly impacts the drug’s safety profile. Oral minoxidil is typically reserved for refractory hypertension due to its strong systemic effects and associated risks.

Topical formulations (2% or 5%) are widely used for hair regrowth, offering local benefits with minimal systemic absorption.

Systemic minoxidil can result in fluid retention, tachycardia, and even pericardial effusion, often requiring co-administration with a diuretic and beta-blocker.

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Prednisone Pharmacology

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Prednisone is a commonly used medication for its antiinflammatory and immunosuppressive action. On this episode I discuss prednisone pharmacology, ADRs, and much more.

In the episode, I discuss how prednisone affects the HPA system in the body. Cortisol production can be greatly impacted by long term use of prednisone.

GI adverse effects can be problematic with oral prednisone which is why we often give this medication with food or milk.

Hyperglycemia is a complication from the use of prednisone. I’ve commonly seen blood sugar spike by 50-100+ mg/dL due to this medication.

Osteoporosis is a long term risk with the use of prednisone. Prednisone can also impact the benefits of vaccination. I discuss this in greater depth in the drug interactions portion of the podcast.

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Amphetamine/Dextroamphetamine (Adderall) Pharmacology Podcast

In this episode, I discuss amphetamine/dextroamphetamine pharmacology, adverse effects, drug interactions, and much more.

Stimulants like Adderall are well known to cause insomnia. This adverse effect can be affected by the timing of the dose.

Lack of growth and poor appetite are two important things to monitor in pediatric patients taking Adderall.

Changes in the pH of the stomach/gut can alter the absorption of Adderall. I discuss this in greater detail in this podcast episode.

Cardiovascular monitoring is essential with the use of stimulants like Adderall. Pulse and heart rate are two important vital signs to assess.

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