Guanethidine depression with

In patients with coronary insufficiency, a -blocker can be given in conjunction with diazoxide to decrease the cardiac work associated with reflex increases in sympathetic stimulation of the heart. However, 3-blockers potentiate the hypotensive effect of diazoxide, and therefore, the dose of the vasodilator should be lowered. The dose of diazoxide should also be lowered if the patient has recently been treated with guanethidine or another drug that depresses the action of the sympathetic nervous system. Such drugs permit a greater hypotensive effect because they reduce the increase in cardiac output that normally partially counteracts the fall in pressure. 

ADRENERGIC NEURONE BLOCKERS-GUANETHIDINE CENTRALLY ACTING ANTIHYPERTENSIVES-METHYLDOPA MAOIs Risk of adrenergic syndrome (see above). Reports of an enhanced hypotensive effect and hallucinations with methyldopa, which may cause depression Due to inhibition of MAOI, which breaks down sympathomimetics Avoid concurrent use. Onset may be 6-24 hours after ingestion... 

Indications Psychosis, manic-depressive disorders Category Antipsychotic, phenothiazine Muscarinic antagonist Half-life initial 2 hours terminal 30 hours Clinically important, potentially hazardous interactions with alcohol, antihistamines, arsenic, chlorpheniramine, dofetilide, epinephrine, evening primrose, guanethidine, mivacurium, quinolones, sparfloxacin... 

Clinically important, potentially hazardous interactions with alcohol, amprenavir, arbutamine, cholestyramine, clonidine, CNS depressants, epinephrine, formoterol, guanethidine, isocarboxazid, linezolid, MAO inhibitors, phenelzine, QT interval prolonging agents, quinolones, selegiline, sparfloxacin, sympathomimetics, tranylcypromine... 

Tricyclic drug interactions (Table 30-3) include additive depression of the CNS with other central depressants, including ethanol, barbiturates, benzodiazepines, and opioids. Tricyclics may also cause reversal of the antih)pertensive action of guanethidine by blocking its transport into sympathetic nerve endings. Less commonly, tricyclics may interfere with the antihypertensive actions of methylnorepinephrine (the active metabolite of methyl-dopa) and clonidine. 

Guanethidine (e.g., Esimel) Sequestered into adrenergic nerve endings. Initially releases norepinephrine (increase BP and HR). Then depletes norepinephrine from terminal and interferes with release. Reflex tachycardia is then impossible because of depletion of norepinephrine. Severe hypertension when other agents fail. Rarely used. Initial increase in neart rate and blood pressure (due to release of norepinephrine). Resting and orthostatic hypotension. Bradycardia, decreased cardiac output, dyspnea in COPD patients, severe nasal congestion. No depression (poor CNS penetration)... 

After a study of the cardiac depressant action of KL-255, it was suggested that myocardial depression may be a result of 3-blockade of the basal tone established by endogenously released catecholamines. Catecholamine depletion by guanethidine resulted in a loss of the depression of contractile force normally observed with KL-255. The depressant effects did not appear to be dose-related to local anesthetic action. 

---