Introduction
Wytensin (guanabenz acetate) is a centrally acting alpha-2 adrenergic agonist antihypertensive agent that was previously marketed for the management of hypertension. While no longer commercially available in many countries, it remains a historically significant medication in the evolution of antihypertensive therapy. Wytensin works by stimulating alpha-2 receptors in the brainstem, resulting in reduced sympathetic outflow and subsequent lowering of blood pressure.
Mechanism of Action
Guanabenz acetate acts as a selective agonist at alpha-2 adrenergic receptors in the brainstem, particularly in the rostral ventrolateral medulla. This stimulation results in:
- Inhibition of central sympathetic outflow
- Reduction in norepinephrine release from peripheral sympathetic nerve terminals
- Decreased peripheral vascular resistance
- Lowering of both systolic and diastolic blood pressure
The drug does not significantly affect cardiac output at therapeutic doses and maintains renal blood flow and glomerular filtration rate.
Indications
FDA-approved indications:- Management of hypertension (as monotherapy or in combination with other antihypertensive agents, particularly thiazide diuretics)
- Opioid withdrawal symptom management (due to central alpha-2 agonist effects)
- Migraine prophylaxis (limited evidence)
Dosage and Administration
Initial dosage: 4 mg twice daily (morning and bedtime) Maintenance dosage: 8-32 mg twice daily (dose titration should occur at 1-2 week intervals) Maximum dosage: 32 mg twice daily Special populations:- Renal impairment: Use with caution; consider reduced initial dosing
- Hepatic impairment: Use with caution; consider reduced initial dosing
- Elderly: Start with lower initial dose (2-4 mg twice daily)
- Pediatric: Safety and effectiveness not established
Pharmacokinetics
Absorption: Well absorbed from GI tract (~75% bioavailability) Distribution: Widely distributed throughout body tissues; crosses blood-brain barrier Protein binding: Approximately 90% Metabolism: Extensive hepatic metabolism via cytochrome P450 system Elimination: Half-life: 6-8 hours; primarily renal excretion (~40% as unchanged drug) Time to peak effect: 2-4 hours Duration of action: 8-12 hoursContraindications
- Hypersensitivity to guanabenz or any component of the formulation
- Concomitant use with monoamine oxidase inhibitors (MAOIs)
- Severe hepatic impairment
- History of syncopal episodes with alpha-2 agonists
Warnings and Precautions
Boxed Warning: None Important precautions:- Sedation: Significant CNS depressant effects; caution when operating machinery
- Rebound hypertension: May occur with abrupt discontinuation
- Orthostatic hypotension: Risk increased in volume-depleted patients
- Depression: May exacerbate pre-existing depressive disorders
- Withdrawal syndrome: Taper gradually when discontinuing therapy
- Hepatic function monitoring: Recommended during therapy
Drug Interactions
Major interactions:- MAO inhibitors: Risk of hypertensive crisis (contraindicated)
- Other CNS depressants (alcohol, benzodiazepines, opioids): Additive sedative effects
- Antihypertensive agents: Additive hypotensive effects
- Tricyclic antidepressants: May antagonize antihypertensive effects
- Beta-blockers: Potential for enhanced bradycardia
- Levodopa: Reduced antihypertensive effect
- NSAIDs: Possible reduction in antihypertensive efficacy
Adverse Effects
Common (>10%):- Dry mouth (48%)
- Drowsiness/sedation (33%)
- Dizziness (15%)
- Weakness (12%)
- Headache
- Sexual dysfunction
- Constipation
- Orthostatic hypotension
- Hepatotoxicity
- Depression
- Syncope
- Rash
- Elevated liver enzymes
Monitoring Parameters
Baseline:- Complete blood count
- Liver function tests
- Renal function tests
- Electrolytes
- Blood pressure (standing and supine)
- Heart rate
- Blood pressure at each visit (first 1-2 months of therapy)
- Liver function tests every 6-12 months
- Assessment for sedation and CNS effects
- Orthostatic blood pressure checks
- Patient weight
- Adherence assessment
Patient Education
- Take medication exactly as prescribed; do not discontinue abruptly
- Avoid alcohol and other CNS depressants
- Rise slowly from sitting or lying position to prevent dizziness
- Use caution when driving or operating machinery until effects are known
- Maintain regular dental hygiene to manage dry mouth
- Report excessive drowsiness, depression, or yellowing of skin/eyes
- Continue non-pharmacologic hypertension management (diet, exercise)
- Inform all healthcare providers about Wytensin use
- Keep medication out of reach of children
References
1. FDA prescribing information for Wytensin (guanabenz acetate) 2. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12th Edition 3. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) Report 4. Oates JA, et al. The efficacy and safety of guanabenz: a multicenter study. Journal of Cardiovascular Pharmacology. 1984 5. Houston MC. Treatment of hypertension with centrally acting agents. Journal of Clinical Hypertension. 1985 6. Medical Letter on Drugs and Therapeutics. 1983;25:11-12 7. American Society of Health-System Pharmacists. AHFS Drug Information