Yohimbine - Drug Monograph

Introduction

Yohimbine is an indole alkaloid derived from the bark of the Pausinystalia yohimbe tree, native to Central and Western Africa. It functions primarily as an α₂-adrenergic receptor antagonist and has been used both traditionally and in modern medicine for various purposes. While historically used as an aphrodisiac, it currently holds FDA approval for specific medical indications and is also widely available as a dietary supplement.

Mechanism of Action

Yohimbine acts as a competitive antagonist at presynaptic and postsynaptic α₂-adrenergic receptors. This blockade increases norepinephrine release by preventing the negative feedback mechanism typically mediated by these receptors. The resulting increase in sympathetic nervous system activity leads to:

• Vasodilation of penile arteries via unopposed α₁-adrenergic activity
• Increased central sympathetic outflow
• Elevated blood pressure and heart rate
• Potential lipolytic effects through stimulation of β-adrenergic receptors

Indications

• Treatment of erectile dysfunction (ED) of vasculogenic, diabetic, or psychogenic origin

• Orthostatic hypotension
• Sexual dysfunction associated with selective serotonin reuptake inhibitors
• Weight loss supplement (limited evidence)

Dosage and Administration

• Adults: 5.4 mg orally three times daily
• May be titrated to 10.8 mg three times daily based on tolerance and response
• Administer with meals to reduce adverse effects

• Renal impairment: Use with caution; no specific dosage recommendations
• Hepatic impairment: Contraindicated in severe liver disease
• Elderly: Start with lower doses due to increased sensitivity
• Pediatrics: Not recommended

Pharmacokinetics

Contraindications

• Hypersensitivity to yohimbine or related compounds
• Renal disease severe enough to require dialysis
• History of gastric or duodenal ulcers
• Psychiatric disorders including anxiety, panic disorders, and schizophrenia
• Severe cardiovascular disease including hypertension, angina, and recent MI
• Concurrent use with antidepressants (MAOIs, SSRIs, TCAs)
• Pregnancy and breastfeeding

Warnings and Precautions

• Cardiovascular effects: May cause hypertension, tachycardia, and palpitations
• Psychiatric effects: Can exacerbate anxiety, panic attacks, and mood disorders
• Central nervous system: May cause dizziness, nervousness, and tremors
• Renal impairment: Use with caution due to reduced clearance
• Hepatic impairment: Contraindicated in severe disease due to extensive metabolism
• Withdrawal: Abrupt discontinuation may cause rebound effects

Drug Interactions

• MAO inhibitors: Risk of hypertensive crisis
• Tricyclic antidepressants: Increased sympathetic effects
• SSRIs/SNRIs: Increased risk of serotonin syndrome
• Sympathomimetics: Additive cardiovascular effects
• Antihypertensives: May antagonize effects

• CYP2D6 inhibitors: May increase yohimbine concentrations
• CNS depressants: May be antagonized
• Other α-adrenergic blockers: Additive effects

Adverse Effects

• Anxiety, nervousness, dizziness
• Headache, flushing
• Nausea, gastrointestinal distress
• Increased blood pressure and heart rate
• Sweating, tremors

• Severe hypertension
• Tachyarrhythmias
• Panic attacks
• Seizures (rare)
• Renal failure (in susceptible individuals)

Monitoring Parameters

• Blood pressure and heart rate at baseline and regularly during therapy
• Renal function (BUN, creatinine) in at-risk patients
• Liver function tests with prolonged use
• Mental status assessment
• Therapeutic response for erectile dysfunction
• Adverse effect profile

Patient Education

• Take with food to minimize gastrointestinal upset
• Report any chest pain, palpitations, or severe headache immediately
• Avoid alcohol and caffeine during therapy
• Do not exceed prescribed dosage
• Inform all healthcare providers about yohimbine use
• Be aware of potential interactions with over-the-counter medications
• Notify provider if experiencing increased anxiety or mood changes
• Understand that results may vary and full effect may take several weeks

References

1. National Library of Medicine. Yohimbine Monograph. PubChem Compound Summary CID 8969 2. FDA prescribing information for yohimbine hydrochloride 3. Tam SW, Worcel M, Wyllie M. Yohimbine: a clinical review. Pharmacol Ther. 2001;91(3):215-243 4. Goldberg MR, Robertson D. Yohimbine: a pharmacological probe for study of the alpha 2-adrenergic receptor. Pharmacol Rev. 1983;35(3):143-180 5. Ernst E, Pittler MH. Yohimbine for erectile dysfunction: a systematic review and meta-analysis of randomized clinical trials. J Urol. 1998;159(2):433-436 6. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2023 7. Micromedex® Healthcare Series [database online]. Greenwood Village, CO: Thomson Micromedex; 2023