Alprazolam is a short-acting benzodiazepine that enhances the inhibitory effects of gamma-aminobutyric acid (GABA) at the GABA-A receptor. Clinically, this results in anxiolytic, sedative, muscle-relaxant, and anticonvulsant effects.

After oral administration, alprazolam is rapidly absorbed, with onset of action typically within 30–60 minutes. It undergoes extensive hepatic metabolism primarily via CYP3A4 to inactive metabolites, and has an elimination half-life of approximately 11 hours, which may be prolonged in elderly patients or those with hepatic impairment.

Common adverse effects include sedation, dizziness, impaired coordination, and cognitive slowing. More serious risks include respiratory depression, especially when combined with opioids, alcohol, or other CNS depressants.

Clinically, alprazolam should be used at the lowest effective dose for the shortest possible duration. Abrupt discontinuation should be avoided; gradual tapering is essential to reduce withdrawal risk. It is a controlled substance that carries the risk of addiction and dependence.

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Pimavanserin is an atypical antipsychotic approved for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. Unlike traditional antipsychotics, it does not block dopamine receptors, making it a unique option for patients with Parkinson’s disease who are highly sensitive to dopamine antagonism.

Pimavanserin works primarily as a selective serotonin 5-HT2A inverse agonist and antagonist, with minor activity at 5-HT2C receptors. This dopamine-sparing effect is the key reason it does not worsen motor symptoms in Parkinson’s disease.

The most commonly reported side effects include peripheral edema, nausea, confusion, and hallucinations. QT interval prolongation is a clinically important concern, especially in patients with existing cardiac risk factors. Somnolence may occur but is generally less prominent compared with dopamine-blocking antipsychotics.

Pimavanserin carries a boxed warning for increased mortality in elderly patients with dementia-related psychosis, consistent with other antipsychotics. It should not be used in patients with known QT prolongation, a history of ventricular arrhythmias, or in combination with other QT-prolonging agents when possible.

Strong CYP3A4 inhibitors, such as ketoconazole or clarithromycin, can significantly increase pimavanserin concentrations and require dose reduction. Strong CYP3A4 inducers, such as rifampin or carbamazepine, may reduce efficacy and should generally be avoided. Additive QT prolongation may occur when combined with other QT-prolonging medications, including certain antiarrhythmics, fluoroquinolones, and macrolide antibiotics.

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Aldosterone antagonists, such as spironolactone and eplerenone, are potassium-sparing diuretics that block aldosterone at the mineralocorticoid receptor in the distal nephron. By reducing sodium and water reabsorption while conserving potassium, they play a key role in heart failure, resistant hypertension, and primary hyperaldosteronism. Clinically, they improve mortality in heart failure with reduced ejection fraction, making them much more than just “add-on” diuretics.

From a safety standpoint, the biggest concerns with aldosterone antagonists are hyperkalemia and renal function decline. These risks increase in patients with chronic kidney disease or when combined with ACE inhibitors, ARBs, or potassium supplements. Spironolactone can also cause endocrine-related adverse effects such as gynecomastia and menstrual irregularities, which is why eplerenone may be preferred in some patients.

Direct-acting vasodilators, most notably hydralazine and minoxidil, lower blood pressure by relaxing arteriolar smooth muscle and reducing systemic vascular resistance. Hydralazine is commonly used in heart failure in combination with nitrates, particularly in select patient populations, while minoxidil is reserved for severe, refractory hypertension due to its potency.

Despite their effectiveness, direct-acting vasodilators come with important clinical trade-offs. Reflex tachycardia and fluid retention are common, so they are typically prescribed alongside a beta blocker and a diuretic. Hydralazine is associated with drug-induced lupus, while minoxidil can cause significant edema and hypertrichosis, making careful patient selection and monitoring essential.

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