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C. DRUGS THAT ACT ON THE SYMPATHETIC POSTGANGLIONIC NERVE TERMINAL 1. Reserpine. Reserpine depletes norepinephrine from adrenergic nerve endings. Because it has serious toxicity when used in large doses, it is now used only in small doses as a step 2 adjunct to agents in other antihypertensive groups, especially diuretics. It has been used parenterally for the treatment of hypertensive emergencies, but is now obsolete for that indication. Indications: * Hypertension * Also labeled for management of psychotic behavior in individuals who cannot tolerate phenothiazines. However, it is no longer used for the latter indication (butyrophenones, eg, haloperidol, are preferred; Chap- ter 18). Contraindications and Warnings: * Depression or a history of it are absolute contraindications. * Pheochromocytoma. * Peptic ulcer * Patients receiving MAO inhibitors * Asthma (Warning) * Increased risk of breast and other malignancies has not been supported by recent studies. Adverse Reactions and Overdosage Toxicity: * Nasal congestion (common symptom) * CNS: depression, despondency, somnolence and dizziness, occur in- frequently when the drug is used in small doses but more frequently if doses exceed 0.5mg/d. Gastrointestinal effects include acid hypersecre- tion, nausea, diarrhea, and ulcers. * Cardiovascular: bradycardia, hypotension, arrhythmias, and syncope. * Hematologic abnormalities (rare). Interactions: * Reduced response to indirectly acting sympathomimetics such as ephedrine and hydroxyamphetamine. * Increased response to directly acting sympathomimetic drugs. * MAO inhibitors plus reserpine may result in a severe hypertensive reaction. 2. Guanethidine. Guanethidine blocks release of transmitter from adrenergic nerve terminals and can cause almost complete sympathetic blockade. Indications: Chronic management of moderate and severe hypertension. Contraindications and Warnings: * Pheochromocytoma and use of MAO inhibitors are absolute contraindica- tions, since guanethidine can release large quantities of stored catecholamines. * Hypovolemic patients are prone to excessive hypotensive responses. * Asthmatic patients may have an exacerbation of their airway disease (Warning). Adverse Reactions and Overdose Toxicity: All the manifestations of marked blockade of sympathetic nervous system effects have been reported. * Cardiovascular: Postural and exercise-induced hypotension and syncope are most common. Bradyarrhythmias, AV block, and hypotension are the most important manifestations of overdosage. * Sexual function: Impaired ejaculation. * Symptoms of parasympathetic excess: nasal stuffiness, diarrhea, and aggravation of peptic ulcers in patients with peptic disease. Interactions: * Tricyclic antidepressants may rapidly reverse the hypotensive effects of guanethidine. * Sympathoplegic and diuretic drugs may potentiate the effects of this agent. * Actions of direct-acting sympathomimetics may be potentiated. * Actions of indirectly acting sympathomimetics may be inhibited. 3.Guanadrel. Guanadrel is a newer agent that strongly resembles guanethidine in both actions and toxicity.


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