Guanadrel sulfate

524.6 g/mol

524.26283343 g/mol

DTXSID8045432

White to off-white crystalline powder|Crystals from methanol/ethanol

249 Ų

213.5-215 °C

In water, 76 mg/ml @ 25 °C

Guanadrel sulfate tablets should be stored in well-closed containers at a temperature less than 40 °C, preferably between 15-30 °C.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl guanadrel sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Tricyclic antidepressants, phenothiazines, and indirect-acting sympathomimetics (eg, ephedrine, phenylpropanolamine) may block the uptake of guanadrel into adrenergic neurons or reverse the hypotensive effect of guanadrel. Ephedrine has been shown to rapidly reverse the pharmacologic effects of guanadrel. Guanadrel may potentiate the pharmacologic activity of direct-acting sympathomimetic agents such as norepinephrine or phenylephrine.|Monoamine oxidase inhibitors reportedly antagonize the hypotensive effect of guanadrel; ... guanadrel is contraindicated in patients receiving MAO inhibitors and that these drugs should be discontinued for at least 1 week prior to administration of guanadrel.|Vasopressors should be administered with caution since guanadrel may enhance the pressor and arrhythmogenic responses to these drugs.|Caution should be exercised when tricyclic antidepressant therapy is discontinued in patients receiving guanadrel, particularly if discontinuance of the antidepressant is abrupt, since enhanced clinical effects (e.g., hypotension) of guanadrel may occur. Because many nonprescription cold, allergy, and asthma preparations contain sympathomimetic agents, patients receiving guanadrel should be warned not to use these preparations for self-medication unless first consulting with their physician or pharmacist.|For more Interactions (Complete) data for GUANADREL SULFATE (6 total), please visit the HSDB record page.

LD50 Rat oral 2220 mg/kg|LD50 Rat iv 26 mg/kg|LD50 Dog oral 225 mg/kg|LD50 Dog iv 45 mg/kg|For more Non-Human Toxicity Values (Complete) data for GUANADREL SULFATE (6 total), please visit the HSDB record page.

Antihypertensive Agents|Eleven patients with Graves' disease were treated with guanadrel sulfate and observed for changes in neuromuscular and cardiovascular manifestations. No notable changes in pulse rate or muscle strength were detected in either these patients during a 3-day pretreatment period or in 5 control patients with Graves' disease receiving placebo for 6 days. Thyroid hormone levels were not altered by 7 days of guanadrel sulfate therapy..., and no adverse side effects were encountered. Mean supine resting pulse fell from 102 +/- 6 (mean +/- SEM) to 90 +/- 3 beats/min (P<0.02). The patients' proximal and distal muscle strengths were initially decreased, when compared with healthy subjects, and improved substantially with guanadrel therapy. We conclude that guanadrel sulfate may be useful in the symptomatic management of patients with thyrotoxicosis.|Because of the availability of a number of drugs that lower blood pressure without producing orthostatic hypotension, guanadrel is not employed in the monotherapy of hypertension, and is used chiefly as an additional agent in patients who have not achieved a satisfactory antihypertensive effect on two or more other agents.

Patients and clinicians should be aware of the possibility of marked guanadrel induced orthostatic hypotension and its consequences of dizziness, weakness, and fainting. Clinicians should monitor both erect and supine blood pressures, as supine blood pressures alone may not reveal the possibility of orthostatic hypotension. Patients should be cautioned to avoid sudden or prolonged standing (especially in the morning) or exercise and should be advised of measures to take if dizziness or weakness occurs (eg, lying or sitting down). A hot environment, alcohol ingestion, or fever may aggravate postural hypotension. Because of the risk of orthostatic hypotension, the drug should be used cautiously in geriatric patients. Geriatric patients may be more sensitive to sympathetic inhibition than younger patients, because they frequently have impaired cardiovascular reflexes, making them more susceptible to hypotension.|Guanadrel should be used cautiously in patients with bronchial asthma, since asthma may be aggravated by catecholamine depletion in these patients and because sympathomimetic amines used in the treatment of asthma may interfere with the hypotensive effect of guanadrel. The drug also should be used with caution in patients with peptic ulcer disease, as this condition may be aggravated by a guanadrel induced relative increase in parasympathetic tone.|Guanadrel therapy should be discontinued 2-3 days prior to elective surgery to reduce the possibility of cardiovascular collapse and cardiac arrest during anesthesia. If emergency surgery is necessary, the anesthesiologist should be advised that the patient is receiving the drug and preanesthetic and anesthetic agents should be administered cautiously and in reduced dosage. Vasopressors should be administered with caution since guanadrel may enhance the pressor and arrhythmogenic responses to these drugs.|Guanadrel should be used with caution in patients who may be adversely affected by sodium and water retention; however, concomitant use of a diuretic will usually overcome this effect.|For more Drug Warnings (Complete) data for GUANADREL SULFATE (19 total), please visit the HSDB record page.

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)

Guanadrel sulfate is rapidly and almost completely absorbed following oral administration. Peak plasma concentrations usually are achieved 1.5-2 hr after oral administration. The hypotensive effect of guanadrel sulfate usually has an onset of 0.5-2 hrs, peaks at 4-6 hr, and persists for 4-14 hr.|Approximately 20% of guanadrel is bound to plasma proteins over a wide concentration range. The drug is widely distributed into most body tissues and fluids. Little, if any, of the drug crosses the blood-brain barrier or distributes into the eye. It is not known whether guanadrel is distributed into milk or crosses the placenta in humans. The drug has been shown to cross the placenta in small concentrations in mice|Guanadrel is cleared from the body by both renal and nonrenal disposition. Its elimination is impaired in patients with renal insufficiency; total-body clearance was reduced by 4- to 5-fold in a group of patients with a clearance of creatinine averaging 13 ml per minute.|Approximately 40-50% of the drug is metabolized in the liver ... . Guanadrel and its metabolites are excreted principally in urine. Approximately 85% of an oral dose of the drug is excreted in urine within 24 hrs; 40-50% of the dose is excreted in urine unchanged.

Approximately 40-50% of the drug is metabolized in the liver to 2,3-dihydroxypropylguanidine and several unidentified metabolites. The hypotensive activity of the metabolites is not known.

Plasma concentrations of guanadrel appear to decline in a biphasic manner. There is considerable interindividual variation in plasma half-life of the drug. In patients with normal renal function, guanadrel has a plasma half-life in the initial phase of about 2 hr (range: 1-4) and an elimination half-life of about 10-12 hr (range: 5-45).

Guanadrel is targeted uniquely to the peripheral adrenergic neuron, where it inhibits sympathetic function. The drug reaches its site of action by active transport into the neuron by the same transporter that is responsible for the reuptake of norephinephrine. In the neuron, guanadrel is concentrated within the neurosecretory vesicles, where it replaces norepinephrine. During chronic administration, guanadrel acts as a "substitute neurotransmitter," in that it is present in storage vesicles, it depletes the normal transmitter, and it can be released by stimuli that normally release norepinephrine. This replacement of norephinephrine with an inactive transmitter is probably the principal mechanism of its neuron-blocking action.|Guanadrel sulfate, like guanethidine, produces a selective block of efferent, peripheral sympathetic pathways. The drug depletes norepinephrine stores from adrenergic nerve endings and, unlike guanethidine, from the adrenal medulla; guanadrel also prevents the release of norepinephrine from adrenergic nerve endings in response to sympathetic nerve stimulation. Guanadrel reportedly depletes norepinephrine stores in the GI tract to a lesser extent than does guanethidine. Chronic administration of guanadrel results in an increased sensitivity of effector cells to catecholamines. Following oral administration of guanadrel, depletion of catecholamine stores produces a fall in blood pressure which usually, but not always, is accompanied by a 5 to 10 beat/min reduction in heart rate. Venous dilation and peripheral pooling of blood may cause a slight decrease or no change in cardiac output. Total peripheral resistance usually is decreased slightly.

The most important complication of overdose being profound hypotension (usually orthostatic). ...Hypotension should be treated by the use of Trendelenburg position, and iv fluids should be administered when necessary.|...The effect of activated charcoal in adsorbing guanadrel in the GI tract and decreasing the drug's absorption has not been determined. Management of guanadrel overdosage includes keeping the patient supine and other symptomatic treatment. If excessive hypotension persists despite symptomatic treatment, more intensive supportive care may be required. If vasopressors are necessary, phenylephrine may be used, but it should be administered cautiously and in small doses because patients may be hypersensitive to phenylephrine's pharmacologic effects.|Given that tolazoline treatment is variably successful and that most physicians are unfamiliar with this agent, it cannot be recommended in the primary management strategy... . It should be considered only after tactile stimulation, naloxone, atropine, iv fluids, and dopamine have failed.|If the patient presents early or after a massive overdose, paradoxical hypertension may occur. It is typically self-limited and is routinely followed by profound hypotension. If severe or prolonged then treatment with a short-acting antihypertensive such as sodium nitroprusside is appropriate.|Appropriate therapy begins with particular focus on the patient's respiratory and hemodynamic status. Administration of activated charcoal is the primary mode of gastrointestinal decontamination. Emesis... is contraindicated. Lavage has limited utility... . All patients with CNS depression should be routinely evaluated for hypoxia and hypoglycemia. Respiratory compromise, including apnea, often responds well to simple auditory or tactile stimulation. ...Endotracheal intubation may be required.

/HUMAN EXPOSURE STUDIES/ Overdosage of guanadrel produces symptoms that are mainly extensions of common adverse effects including postural hypotension with dizziness, blurred vision, and syncope when standing.

guanadrel

Oral Tablets 10 mg, Hylorel (scored), Medeva; 25 mg, Hylorel (scored), Medeva|(1,4-Dioxaspiro[4.5]dec-2-ylmethyl)-guanidine

Analyte: guanadrel sulfate; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: guanadrel sulfate; matrix: chemical purity; procedure: liquid chromatography with refractive index detection and comparison to standards|Analyte: guanadrel sulfate; matrix: pharmaceutical preparation (tablet); procedure: colorimetric reaction with 1-naphthol and 2,3-butanedione (chemical identification)|Analyte: guanadrel sulfate; matrix: pharmaceutical preparation (tablet); procedure: liquid chromatography with refractive index detection and comparison to standards (chemical purity)

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients