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GUANETHIDINE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Guanethidine and guanadrel are antihypertensive agents which block release of norepinephrine from sympathetic nerve terminals.
    B) Guanadrel is a sympatholytic agent with similar pharmacologic properties as guanethidine. It is one-third as potent as guanethidine on a weight basis, has a shorter onset, longer duration of action, and may be less likely to produce orthostatic hypotension.

Specific Substances

    A) GUANETHIDINE
    1) 1-(2-(Perhydroazocin-1-yl)ethyl)guanidine monosulfate
    2) Guanethidini monosulfas
    3) Guanethidine monosulfate
    4) Guanethidine sulfate
    5) Guanetidine (Mexican)
    6) CAS 55-65-2 (guanethidine)
    7) CAS 645-43-2 (guanethidine monosulfate)
    GUANADREL SULFATE
    1) 1-(Cyclohexanespiro-2'-(1',3')dioxolan-4'-ylmethyl)guanidine sulfate
    2) (1,4-Dioxaspiro(4.5)dec-2-ylmethyl)guanidine sulfate (2:1)
    3) CL 1388R
    4) U 28288D
    5) CAS 22195-34-2 (guanadrel sulfate)
    6) CAS 40580-59-4 (guanadrel)

Available Forms Sources

    A) FORMS
    1) Guanethidine is available as Ismelin(R) tablets 10 mg and 25 mg.
    2) Guanadrel is available as Hylorel(R) in 10 and 25 mg tablets.
    B) USES
    1) Guanethidine is a potent antihypertensive agent for moderate to severe hypertension. Guanethidine is also used in the treatment of renal hypertension, including that secondary to pyelonephritis, renal amyloidosis, and renal artery stenosis (USPDI , 2001).
    2) Guanadrel is used to treat mild to severe hypertension (USPDI , 2001).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH POISONING/EXPOSURE
    1) Dizziness, blurred vision, bradycardia, nausea, vomiting, and diarrhea are commonly seen. Profound hypotension (especially orthostatic) and shock are the most severe signs of toxicity following overdosage.
    2) A transient episode of early hypertension may be noted prior to the onset of hypotension. Hypertensive crisis due to sensitization by guanethidine to some indirect acting sympathomimetics (metaraminol and ephedrine) may occur.
    0.2.4) HEENT
    A) WITH THERAPEUTIC USE
    1) Blurred vision is common.
    0.2.5) CARDIOVASCULAR
    A) WITH THERAPEUTIC USE
    1) Guanethidine can result in severe hypertensive reactions in patients with pheochromocytoma. A transient episode of early hypertension may be noted prior to the onset of hypotension.
    2) Hypertensive crisis may be noted in patients who ingest sympathomimetic drugs while taking guanethidine.
    B) WITH POISONING/EXPOSURE
    1) Profound hypotension (most notably orthostatic) and shock may occur following overdosage. Hypotensive episodes may result in signs and symptoms of cerebral and myocardial ischemia. Hypotension may persist up to a week following a large overdosage.
    0.2.6) RESPIRATORY
    A) WITH THERAPEUTIC USE
    1) Two cases of apnea and syncope following intravenous injection have been reported.
    0.2.7) NEUROLOGIC
    A) WITH POISONING/EXPOSURE
    1) Cerebral ischemia with dizziness and syncope related to the hypotension may occur.
    0.2.8) GASTROINTESTINAL
    A) WITH POISONING/EXPOSURE
    1) Nausea, vomiting, and diarrhea are common.
    0.2.20) REPRODUCTIVE
    A) Guanadrel is classified in pregnancy category B.

Laboratory Monitoring

    A) Plasma guanethidine levels are not clinically useful.
    B) No specific lab work (CBC, urinalysis, electrolytes) is needed unless otherwise indicated.
    C) Continuous cardiac monitoring is recommended.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    C) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
    D) Administer dopamine or norepinephrine with caution since the hypertensive effects of these agents may be greatly enhanced following guanethidine therapy.
    E) HYPERTENSIVE CRISIS - Symptomatic hypertension episodes should be treated with nitroprusside (initiate 1 mcg/kg/min IV infusion and adjust to control blood pressure; average dose 3 mcg/kg/min).
    1) CAUTION - The hypertensive episodes following guanethidine overdose are usually transient and are followed by a profound hypotensive episode.
    2) However, hypertension following concomitant ingestion of sympathomimetic agents may be prolonged and require nitroprusside therapy. Nitroprusside is recommended due to a short duration of action and easy titratability.
    F) MONITOR CENTRAL VENOUS or pulmonary wedge pressure in severely symptomatic patients.
    G) ATROPINE: ADULT DOSE: BRADYCARDIA: BOLUS: 0.5 mg IV may repeat every 3 to 5 min. Maximum: 3 mg. PEDIATRIC DOSE: 0.02 mg/kg IV/IO (0.04 to 0.06 mg/kg ET). Repeat once, if needed. Minimum dose: 0.1 mg. Maximum single dose: Child: 0.5 mg; Adolescent: 1 mg. Maximum total dose: Child: 1 mg; Adolescent: 2 mg.

Range Of Toxicity

    A) Insufficient data in the literature to accurately assess human toxicity. Severity of intoxication should be based on clinical findings.

Clinical Effects

Summary Of Exposure

    A) WITH POISONING/EXPOSURE
    1) Dizziness, blurred vision, bradycardia, nausea, vomiting, and diarrhea are commonly seen. Profound hypotension (especially orthostatic) and shock are the most severe signs of toxicity following overdosage.
    2) A transient episode of early hypertension may be noted prior to the onset of hypotension. Hypertensive crisis due to sensitization by guanethidine to some indirect acting sympathomimetics (metaraminol and ephedrine) may occur.

Heent

    3.4.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Blurred vision is common.
    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) SYSTEMIC USE - BLURRED VISION related to the hypotension has been reported in 17% of patients receiving an average dose of 70 mg/day (USPDI , 2001; Brest & Novack, 1962).
    2) OCULAR USE - The use of guanethidine/epinephrine eye drops was associated with the development of conjunctival cicatrization (Wright, 1987).

Cardiovascular

    3.5.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Guanethidine can result in severe hypertensive reactions in patients with pheochromocytoma. A transient episode of early hypertension may be noted prior to the onset of hypotension.
    2) Hypertensive crisis may be noted in patients who ingest sympathomimetic drugs while taking guanethidine.
    B) WITH POISONING/EXPOSURE
    1) Profound hypotension (most notably orthostatic) and shock may occur following overdosage. Hypotensive episodes may result in signs and symptoms of cerebral and myocardial ischemia. Hypotension may persist up to a week following a large overdosage.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Profound hypotension (most notably orthostatic) and shock may occur following overdosage with guanethidine or guanadrel (Prod Info Ismelin(R), guanethidine, 1996; Prod Info Hylorel(R), guanadrel, 1996). Hypotensive episodes may result in signs and symptoms of cerebral and myocardial ischemia (Goldberg & Raftery, 1976).
    1) DURATION - Hypotension persisted 2 days to a week following a large overdosage in two patients treated with intravenous guanethidine blocks, 130 mg in one case and 30 mg in the other case (Sharpe et al, 1987; Kalmanovitch & Hardwick, 1988).
    B) HYPERTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Guanethidine can result in severe hypertensive reactions in patients with pheochromocytoma.
    b) A transient episode of early hypertension may be noted prior to the onset of hypotension. In hypertensive and in patients previously treated with guanethidine, one would not expect this hypertensive period.
    c) Hypertensive crisis may be noted in patients who ingest sympathomimetic drugs while taking guanethidine.
    d) Hypertensive crisis may result in patients withdrawing suddenly from therapeutic doses of guanethidine (Goldfrank, 1994).
    C) BRADYCARDIA
    1) WITH POISONING/EXPOSURE
    a) Bradycardia may occur with guanethidine overdose (USPDI , 2001).

Respiratory

    3.6.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Two cases of apnea and syncope following intravenous injection have been reported.
    3.6.2) CLINICAL EFFECTS
    A) APNEA
    1) WITH THERAPEUTIC USE
    a) Two cases of apnea and syncope following intravenous injection have been reported (Martin & Abram, 1986; Woo & McQueen, 1987).

Neurologic

    3.7.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Cerebral ischemia with dizziness and syncope related to the hypotension may occur.
    3.7.2) CLINICAL EFFECTS
    A) TRANSIENT CEREBRAL ISCHEMIA
    1) WITH POISONING/EXPOSURE
    a) Profound hypotension leading to cerebral ischemia with dizziness and syncope may occur in acute overdoses (USPDI , 2001; Goldfrank, 1994).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Nausea, vomiting, and diarrhea are common.
    3.8.2) CLINICAL EFFECTS
    A) GASTROENTERITIS
    1) WITH POISONING/EXPOSURE
    a) Nausea, vomiting and diarrhea (sometimes explosive) may occur with guanethidine or guanadrel overdose (Prod Info Ismelin(R), guanethidine, 1996; Prod Info Hylorel(R), guanadrel, 1996).

Reproductive

    3.20.1) SUMMARY
    A) Guanadrel is classified in pregnancy category B.
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    GUANADRELB
    Reference: Briggs et al, 1998

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Plasma guanethidine levels are not clinically useful.
    B) No specific lab work (CBC, urinalysis, electrolytes) is needed unless otherwise indicated.
    C) Continuous cardiac monitoring is recommended.

Methods

    A) OTHER
    1) Plasma guanethidine levels are not clinically useful.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) GUANETHIDINE -
    1) Due to the prolonged duration of action, symptomatic patients should be admitted, with continuous cardiac monitoring. Normal homeostatic mechanisms gradually return over approximately 72 hours (Prod Info, 1991).
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Asymptomatic patients should be observed in a health care facility with cardiac monitoring for a minimum of 6 to 8 hours after ingestion of amounts greater than therapeutic doses. Peak effects after therapeutic doses occur within 8 hours for guanethidine and 4 to 6 hours for guanadrel (Prod Info Hylorel(R), guanadrel, 1990).

Monitoring

    A) Plasma guanethidine levels are not clinically useful.
    B) No specific lab work (CBC, urinalysis, electrolytes) is needed unless otherwise indicated.
    C) Continuous cardiac monitoring is recommended.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    B) MALIGNANT HYPERTENSION
    1) NITROPRUSSIDE: Symptomatic hypertension episodes should be treated with nitroprusside (initiate 1 microgram/kilogram/minute by intravenous infusion and adjust to control blood pressure; average dose 3 micrograms/kilogram/minute).
    2) CAUTION: The hypertensive episodes following guanethidine overdose are usually transient and are followed by a profound hypotensive episode.
    a) However, hypertension following concomitant ingestion of sympathomimetic agents may be prolonged and require nitroprusside therapy. Nitroprusside is recommended due to a short duration of action and easy titratability.
    3) MONITORING PARAMETERS
    a) Monitor central venous or pulmonary wedge pressure in severely symptomatic patients.
    C) BRADYCARDIA
    1) Sinus bradycardia may be treated with atropine.
    2) ATROPINE/DOSE
    a) ADULT BRADYCARDIA: BOLUS: Give 0.5 milligram IV, repeat every 3 to 5 minutes, if bradycardia persists. Maximum: 3 milligrams (0.04 milligram/kilogram) intravenously is a fully vagolytic dose in most adults. Doses less than 0.5 milligram may cause paradoxical bradycardia in adults (Neumar et al, 2010).
    b) PEDIATRIC DOSE: As premedication for emergency intubation in specific situations (eg, giving succinylchoine to facilitate intubation), give 0.02 milligram/kilogram intravenously or intraosseously (0.04 to 0.06 mg/kg via endotracheal tube followed by several positive pressure breaths) repeat once, if needed (de Caen et al, 2015; Kleinman et al, 2010). MAXIMUM SINGLE DOSE: Children: 0.5 milligram; adolescent: 1 mg.
    1) There is no minimum dose (de Caen et al, 2015).
    2) MAXIMUM TOTAL DOSE: Children: 1 milligram; adolescents: 2 milligrams (Kleinman et al, 2010).
    D) DIARRHEA
    1) Severe or persistent diarrhea should be treated with anticholinergic agents and maintenance of fluid and electrolyte balance (Prod Info, 1991).

Range Of Toxicity

Summary

    A) Insufficient data in the literature to accurately assess human toxicity. Severity of intoxication should be based on clinical findings.

Therapeutic Dose

    7.2.1) ADULT
    A) SPECIFIC SUBSTANCE
    1) GUANETHIDINE
    a) RECOMMENDED DOSE: Initial dose in ambulatory patients is 10 mg, increasing daily dose by 10 to 25 mg increments at 5 to 7 day intervals to desired therapeutic response. The average daily dose is between 25 to 50 mg (Prod Info Ismelin(R), 1998). Loading doses of 125 to 525 mg in 6 hour intervals over 1 to 3 days have been used (Shand et al, 1975).
    2) GUANADREL
    a) Initial dose is 10 mg/day, increased gradually up to a usual daily dose of 20 to 75 mg, and a maximum recommended daily dose of 400 mg (Finnerty & Brogden, 1985).
    7.2.2) PEDIATRIC
    A) RECOMMENDED DOSE: The safety and efficacy of guanethidine has not been established in pediatric patients (Prod Info Ismelin(R), 1998). The use of doses between 10 mg/day to 60 mg/day have been reported in children (McLain, 1976).

Minimum Lethal Exposure

    A) GENERAL
    1) At the time of this review, no deaths due to acute poisoning have been reported (Prod Info Ismelin(R), guanethidine, 1996).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) GENERAL
    a) Adrenergic blockade occurs with minimum guanethidine plasma concentrations of 8 nanograms/milliliter (Prod Info Ismelin(R), guanethidine, 1996).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (ORAL)MOUSE:
    1) 845 mg/kg (RTECS, 2001)
    B) LD50- (ORAL)RAT:
    1) 1262 mg/kg (Prod Info Ismelin(R), 1996)
    2) 1050 mg/kg (RTECS, 2001)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Guanethidine is a postganglionic adrenergic nerve depressant. It produces only a sympathetic, not a parasympathetic, blockade. Alpha and beta receptors are suppressed about equally.
    B) Guanethidine prevents the release of norepinephrine, despite membrane depolarization. Transient releases of norepinephrine will occur with initial dosing or early in overdose and produce transient sympathomimetic effects (Goldfrank, 1994).
    C) Rapid IV administration produces a triphasic response:
    1) An initial rapid fall in blood pressure associated with decreased peripheral vascular resistance and an increased cardiac output.
    2) Hypertension may follow that may last for several hours.
    3) A progressive fall in blood pressure is seen that may last for several days. Bradycardia, decreased pulse pressure, and decreased cardiac output are seen. Blood pressure is lowered more in the erect than supine position.
    D) Chronic administration of guanethidine produces a supersensitivity of effector cells to catecholamines.

Toxicologic Mechanism

    A) Animal studies have demonstrated that guanethidine is neurotoxic to the area postrema (AP) of the brain. This area of the brain is involved with cardiovascular regulation, taste-aversion learning and emesis. Surrounding areas of the brain do not appear to be affected. The serotonin (5-HT) and enkephalin cell body population of the AP is significantly reduced following guanethidine exposure (Newton et al, 1987).

Physicochemical

Physical Characteristics

    A) Guanethidine sulfate: white or off-white crystalline powder
    B) Guanadrel sulfate: white or off-white crystalline powder

Ph

    A) 4.7-5.7 (2% aqueous solution)

Molecular Weight

    A) varies

References

General Bibliography

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