Guanethidine monosulfate
Guanethidine monosulfate (Ismelin Sulfate)
Guanethidine monosulfate
(gwon- ETH-ih-deen)
Pregnancy Category: C Ismelin Sulfate (Rx)

Classification: Antihypertensive, peripherally acting antiadrenergic

See Also: See also Antihypertensive Agents .

Action/Kinetics: Produces selective adrenergic blockade of efferent, peripheral sympathetic pathways by depleting norepinephrine reserve and inhibiting norepinephrine release. Induces a gradual, prolonged drop in both SBP and DBP, usually associated with bradycardia, decreased pulse pressure, a decrease in peripheral resistance, and small changes in CO. Is not a ganglionic blocking agent and does not produce central or parasympathetic blockade. With depleted catecholamines, guanethidine can directly depress the myocardium and can cause an increase in the sensitivity of tissues to catecholamines. Incompletely and variably absorbed from the GI tract (3%-30%) but is relatively constant for any given client. Peak effect: 6-8 hr. Duration: 24-48 hr. Maximum effect: 1-3 weeks. Duration: 7-10 days after discontinuation. t 1/2: 4-8 days. From 25% to 50% excreted through the kidneys unchanged. Slowly excreted due to extensive tissue binding.

Uses: Moderate to severe hypertension--used alone or in combination. NOTE: The use of a thiazide diuretic may increase the effectiveness of guanethidine and reduce the incidence of edema. Also used for renal hypertension, including that secondary to pyelonephritis, renal artery stenosis, and renal amyloidosis.

Contraindications: Mild, labile hypertension; pheochromocytoma, CHF not due to hypertension, use of MAO inhibitors, lactation.

Special Concerns: Administer with caution and at a reduced rate to clients with impaired renal function, coronary disease, CV disease especially when associated with encephalopathy, or severe cardiac failure or to those who have suffered a recent MI. Use with caution in hypertensive clients with renal disease and nitrogen retention or increasing BUN levels. Fever decreases dosage requirements. During prolonged therapy, cardiac, renal, and blood tests should be performed. Used with caution in peptic ulcer. Geriatric clients may be more sensitive to the hypotensive effects of guanethidine; also, it may be necessary to decrease the dose in these clients due to age-related decreases in renal function. Safety and efficacy have not been determined in children.

Side Effects: CNS: Dizziness, weakness, lassitude. Rarely, fatigue, psychic depression. CV: Syncope due to exertional or postural hypotension, bradycardia, fluid retention and edema with possible CHF. Less commonly, angina. Respiratory: Dyspnea, nasal congestion, asthma in susceptible individuals. GI: Persistent diarrhea (may be severe enough to cause discontinuation of use), increased frequency of bowel movements. N&V;, dry mouth, and parotid tenderness are less common. GU: Inhibition of ejaculation, nocturia, urinary incontinence, priapism, impotence. Hematologic: Anemia, thrombocytopenia, leukopenia (rare). Miscellaneous: Dermatitis, scalp hair loss, blurred vision, myalgia, muscle tremors, chest paresthesia, weight gain, ptosis of the lids.

Laboratory Test Alterations: BUN, AST, and ALT. PT, serum glucose, and urine catecholamines. Alteration of electrolyte balance.

Overdose Management: Symptoms: Bradycardia, postural hypotension, diarrhea (may be severe). Treatment: If the client was previously normotensive, keep in a supine position (symptoms usually subside within 72 hr). If the client was previously hypertensive (especially with impaired cardiac reserve or other CV problems or renal disease), intensive treatment may be needed. Vasopressors may be required. Treat severe diarrhea.

Drug Interactions: Alcohol, ethyl / Additive orthostatic hypotension Amphetamines / Effect of guanethidine by uptake of the drug to its site of action Anesthetics, general / Additive hypotension Antidepressants, tricyclic / Effect of guanethidine by uptake of the drug to its site of action Antidiabetic drugs / Additive effect in blood glucose Cocaine / Effect of guanethidine by uptake of the drug at its site of action Digitalis / Additive slowing of HR Ephedrine / Effect of guanethidine by uptake of the drug at its site of action Epinephrine / Epinephrine effects Haloperidol / Effect of guanethidine by uptake of the drug at its site of action Levarterenol / See Norepinephrine MAO inhibitors / Reverse effect of guanethidine Metaraminol / Metaraminol effects Methotrimeprazine / Additive hypotensive effect Methoxamine / Methoxamine effect Methylphenidate / Effect of guanethidine Minoxidil / Profound drop in BP Norepinephrine / Norepinephrine effect probably R/T sensitivity of norepinephrine receptor and drug uptake by the neuron Oral contraceptives / Effect of guanethidine by uptake of the drug to its site of action Phenothiazines / Guanethidine effect by uptake of the drug to its site of action Phenylephrine / Guanethidine response Phenylpropanolamine / Effect of guanethidine by uptake of the drug to its site of action Procainamide / Additive hypotensive effect Procarbazine / Additive hypotensive effect Propranolol / Additive hypotensive effect Pseudoephedrine / Effect of guanethidine by uptake of the drug at its site of action Quinidine / Additive hypotensive effect Reserpine / Excessive bradycardia, postural hypotension, and mental depression Sympathomimetics / Effect of guanethidine; also, guanethidine potentiates the effects of directly acting sympathomimetics Thiazide diuretics / Additive hypotensive effect Thioxanthenes / Effect of guanethidine by uptake of the drug at its site of action Tricyclic antidepressants / Inhibition of guanethidine effects Vasodilator drugs, peripheral / Additive hypotensive effect Vasopressor drugs / Vasopressor effects probably R/T sensitivity of norepinephrine receptor and uptake of vasopressor agent by the neuron

How Supplied: Tablet: 10 mg, 25 mg

Dosage
?Tablets Ambulatory clients.
Initial: 10-12.5 mg/day; increase in 10-12.5-mg increments q 5-7 days; maintenance: 25-50 mg/day.
Hospitalized clients.
Initial: 25-50 mg; increase by 25 or 50 mg/day or every other day; maintenance: approximately one-seventh of loading dose. Pediatric, initial: 0.2 mg/kg/day (6 mg/m ²) given in one dose; then, dose may be increased by 0.2 mg/kg/day q 7-10 days to maximum of 3 mg/kg/day.