과나드렐설페이트(200MG)

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ No evidence of carcinogenic potential appeared in a 2 yr mouse study of guanadrel sulfate. In a 2 yr rat study, an increased number of benign testicular interstitial cell tumors was observed at dosages of 100 mg/kg/day and 400 mg/kg/day.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ A reproduction study was performed in male and female rats at dosages of 0, 10, 30, 100 mg/kg/day. Suppresed libido and reduced fertility were noted at 100 mg/kg/day and libido was suppressed to a lesser extent at 30 mg/kg/day.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Teratology studies performed in rats and rabbits at doses up to 12 times the maximum recommended human dose (in a 50 kg subject) revealed no significant harm to the fetus due to guanadrel sulfate.

/GENOTOXICITY/ Salmonella testing (Ames test) showed no evidence of mutagenic activity.

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.

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.

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.