Generic Name

Yohimbine

Mechanism

• Selective antagonist of presynaptic α₂‑adrenergic receptors
• ↓ presynaptic inhibition → ↑ norepinephrine release → vasoconstriction, increased cardiac output
• Inhibits dopamine β‑hydroxylase → ↓ conversion of dopamine to norepinephrine, contributing to sympathomimetic activity
• Central sympathetic activation leading to increased catecholamine release in the CNS
• Stimulation of β‑adrenergic receptors in skeletal muscle → enhanced lipolysis (explains its use in weight‑loss protocols)

Pharmacokinetics

Indications

• Male erectile dysfunction – often reserved for patients refractory to PDE‑5 inhibitors or with concomitant low testosterone.
• Weight‑loss adjunct – short‑term therapy to augment lipolysis; not FDA‑approved for obesity.
• Reversible pulmonary hypertension – off‑label use for vasodilatory support in severe cases.
• Anxiety and depression – experimental use, not clinically endorsed.

Contraindications

• Uncontrolled hypertension or severe coronary artery disease – sympathetic surge may precipitate cardiac events.
• Arrhythmias (e.g., atrial fibrillation, ventricular ectopy).
• Severe hepatic impairment – reduced metabolism increases systemic exposure.
• Pregnancy and lactation – teratogenic potential; contraindicated.
• Concurrent use of MAO inhibitors or SSRIs – risk of serotonin syndrome due to catecholamine elevation.
• Psychoactive substance interactions – e.g., stimulants can amplify adverse cardiovascular effects.

> Warning: Yohimbine can provoke acute hypertension, tachycardia, anxiety, and, rarely, seizures. Use lowest effective dose for the shortest duration possible.

Dosing

• Form: Oral tablets (0.5–10 mg) or intravenous solution (10 mg/mL).
• Administration: Take with food to reduce GI upset.

Adverse Effects

> Patients should be educated to report abrupt onset of severe headaches, chest pain, or palpitations.

Monitoring

• Vital signs: Blood pressure and heart rate before first dose and 1 hour post‑dose.
• Laboratory: Liver function tests (ALT, AST) if used >4 weeks; electrolytes if renal impairment.
• Cardiac assessment: Baseline ECG for patients with cardiac comorbidities; repeat if symptomatic.
• Pregnancy tests for females of childbearing potential.

Clinical Pearls

• Start low, go slow: A 2–5 mg/day dose for erectile dysfunction is often sufficient; exceeding 10 mg/day markedly increases cardiovascular risk.
• Avoid with MAOIs and SSRIs: The catecholamine surge can precipitate serotonin syndrome; a 4–6 week washout period is recommended.
• Use caution in the elderly: Age‑related decline in renal/hepatic clearance elevates plasma levels; consider dose reduction to 5 mg/day.
• Drug‑drug interplay: Strong CYP3A4 inhibitors (e.g., ketoconazole) can raise yohimbine concentrations by up to 40 %; dose adjustment may be necessary.
• Weight‑loss adjunct: Despite lipolytic activity, long‑term safety remains uncertain; limit use to short courses and avoid in patients with metabolic syndrome unless monitored closely.
• Pregnancy contraindication: Animal studies show fetal growth restriction; abstain altogether for women planning conception.

Key Takeaway: Yohimbine’s potent sympathomimetic effects render it valuable for specific indications, but its narrow therapeutic window demands vigilant dosing, careful patient selection, and proactive monitoring to mitigate serious cardiovascular complications.