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RESERPINE & RAUWOLFIA ALKALOIDS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Reserpine and other Rauwolfia alkaloids are derived from the roots of various Rauwolfia species, primarily R. serpentina and R. vomitoria.

Specific Substances

    A) ALSEROXYLON
    1) CAS 8001-95-4
    DESERPIDINE
    1) Canescine
    2) 11-Desmethoxyreserpine
    3) Raunormine
    4) Recanescine
    5) 11-Demethoxyreserpine
    6) Ester alkaloid from R. canescens
    7) Molecular Formula: C32-H38-N2-O8
    8) CAS 131-01-1
    RAUBASINE
    1) Ajmalicine
    2) Alkaloid F
    3) delta-Yohimbine
    4) Methyl 16,17-didehydro-19alpha-methyl-18-oxayohimban-16-carboxylate
    5) Raubasina
    6) Molecular Formula: C21-H24-N2-O3
    7) CAS 483-04-5
    RAUWOLFIA SERPENTINA
    1) Chotachand
    2) Rauvolfia
    3) Rauwolfia
    4) Rauwolfiae Radix
    5) Rauwolfiawurzel
    6) CAS Registry: 8063-17-0 (rauwolfia)
    RESCINNAMINE
    1) Methyl 18-O-(3,4,5-trimethoxy cinnamoyl) reserpate
    2) Molecular Formula: C35-H42-N2-O9
    3) CAS 24815-24-5
    RESERPINE
    1) Reserpinum
    2) Molecular Formula: C33-H40-N2-O9
    3) CAS 50-55-5
    GENERAL TERMS
    1) AUSTRAPINE
    2) ALSERIN
    3) RAU-SED
    4) RAUWOLFIA ALKALOIDS
    5) RESERPEX
    6) RESERPOID
    7) SERFIN
    8) SEROLFIA
    9) SERPASIL
    10) 3,4,5-TRIMETHOXYBENZOYL METHYL RESERPATE

Available Forms Sources

    A) FORMS
    1) Reserpine is available in 0.1 mg and 0.25 mg tablets (Prod Info reserpine oral tablets, 2010).
    2) Deserpidine, rauwolfia serpentina, rescinnamine, alseroxylon, and raubasine are not available in the US.
    B) USES
    1) Reserpine is used to treat patients with hypertension and approved for symptomatic relief of agitated psychotic states (eg, schizophrenia) in patients unable to tolerate phenothiazines or those who also require concomitant antihypertensive treatment (Prod Info reserpine oral tablets, 2010).
    2) Rauwolfia alkaloids are used to treat hypertension (USPDI , 2002).
    3) Rescinnamine, an ester alkaloid isolated from the root of Rauwolfia serpentina or R. vomitoria, has properties similar to reserpine. It has been used to treat hypertension (S Sweetman , 2002).
    4) Reserpine and rescinnamine are the most active ester alkaloids (as hypotensive agents) of rauwolfia serpentina (S Sweetman , 2002).
    a) Rauwolfia serpentina has been used by mouth as the powdered whole root (S Sweetman , 2002).
    b) In India, a crude form of rauwolfia serpentina (e.g., Sarpagandha) has been used for centuries to treat insomnia and certain forms of mental illness (S Sweetman , 2002).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Rauwolfia alkaloids are used to treat hypertension. In addition, reserpine has been used to treat Raynaud's phenomenon, psychotic disorders, as radioprotective agent, and experimentally as a contraceptive. Rescinnamine, an ester alkaloid isolated from the root of Rauwolfia serpentina or R. vomitoria, has properties similar to reserpine. It has been used to treat hypertension. Reserpine and rescinnamine are the most active ester alkaloids (as hypotensive agents) of rauwolfia serpentine. Rauwolfia serpentina has been used by mouth as the powdered whole root. In India, a crude form of rauwolfia serpentina (eg, Sarpagandha) has been used for centuries to treat insomnia and certain forms of mental illness.
    B) PHARMACOLOGY: Reserpine and its congeners deplete catecholamines and serotonin peripherally and centrally from nerve terminal fibers. The resulting responses exhibit as CNS depression and peripheral sympatholysis.
    C) TOXICOLOGY: Overdose effects result from an exaggerated therapeutic response secondary to depletion of catecholamine and reflects parasympathetic effects. Peripheral responses are biphasic. Responses initially may result from catecholamine release, then depletion. Specific chemical compounds include alseroxylon, deserpidine, raubasine, rauwolfia serpentina, rescinnamine, and reserpine.
    D) EPIDEMIOLOGY: Reserpine and rauwolfia alkaloid exposures are extremely rare. No estimations on overdose exposures are available.
    E) WITH THERAPEUTIC USE
    1) Gastrointestinal events including nausea, vomiting and diarrhea have occurred. Dysrhythmias (in particular when used with digitalis or quinidine), bradycardia, and angina-like symptoms have been reported. Other events that have developed with therapeutic use of reserpine include: dyspnea, epistaxis, extrapyramidal tract symptoms, headache, dizziness, depression, drowsiness, and muscle aches. Drug withdrawal has been associated with the development of the delusional psychosis.
    F) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Typical overdose effects result from the reflex parasympathomimetic effect of reserpine. Symptoms are primarily related to CNS depression, coma, and ataxia; tachycardia, and initial hypertension, then hypotension. Peripheral responses are biphasic. Responses initially may result from catecholamine release, then depletion. Subsequent symptoms include hypothermia, pinpoint non-reactive pupils, facial flushing, nasal congestion, and excessive salivation. CNS depression can range from drowsiness, lethargy, mental depression to stupor and coma. Higher doses may produce cardiac dysrhythmias and an angina-like syndrome. Symptomatology is usually delayed for 3 to 7 hours and persists from 2 to 4 days. Gastrointestinal symptoms can include diarrhea and intense gastric acid secretion. Acute hematemesis and hemorrhagic gastritis have been described in patients receiving large parenteral and oral loading doses.
    2) SEVERE TOXICITY: Severe CNS toxicity can lead to stupor and coma. Higher doses may produce cardiac dysrhythmias and an angina-like syndrome. In severe overdose, hypotension, hypothermia, central respiratory depression and bradycardia can develop.
    0.2.3) VITAL SIGNS
    A) Although rarely reported, patients may initially demonstrate hypertension and tachycardia for up to one day (Loggie et al, 1967) followed by hypotension and bradycardia (McKown et al, 1963).
    0.2.20) REPRODUCTIVE
    A) Reserpine crosses the placenta, and is excreted in breast milk.
    0.2.21) CARCINOGENICITY
    A) A possible connection between reserpine and tumors of the breast in women remains controversial.

Laboratory Monitoring

    A) Monitor vital signs.
    B) Obtain an ECG and institute continuous cardiac monitoring in symptomatic patients.
    C) Routine laboratory studies are not indicated; obtain studies as necessary.
    D) Plasma levels are generally not useful following an exposure.
    E) Epinephrine and norepinephrine urine levels may be elevated 1 to 2 days after an acute ingestion. Because reserpine is irreversibly bound to receptor sites, its concentration in plasma may have little to do with its pharmacological activity. Epinephrine and norepinephrine urine levels may be elevated 1 to 2 days subsequent to acute ingestion.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. HYPOTENSION: Monitor vital signs. Infuse 10 to 20 mL/kg of isotonic fluid and keep the patient supine. Consider central venous pressure monitoring to guide further fluid therapy. HYPOTHERMIA: Use warming blankets to maintain or achieve normal body temperature.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Support respiratory and cardiovascular function. If hypotension persists, administer norepinephrine or phenylephrine. Consider end-tidal CO2 monitoring for respiratory depression as well as advanced airway support including intubation and ventilation for respiratory insufficiency or failure. Avoid utilizing digitalis derivatives in cardiac failure; evidence of enhanced cardiac dysrhythmia production has been recorded when reserpine has been used simultaneously with digitalis derivatives.
    C) DECONTAMINATION
    1) PREHOSPITAL: Gastrointestinal decontamination is not indicated due to the potential risk of CNS depression or cardiovascular effects. Do NOT induce emesis.
    2) HOSPITAL: Gastrointestinal decontamination is typically not warranted. Given the risk for CNS and respiratory depression, carefully monitor the patient's airway or secure the airway prior to administering activated charcoal.
    D) AIRWAY MANAGEMENT
    1) Monitor for respiratory depression with end-tidal CO2. Consider advanced airway support including intubation and ventilation in severe CNS depression or respiratory failure.
    E) ANTIDOTE
    1) No specific antidote.
    F) ENHANCED ELIMINATION
    1) Enhanced elimination procedures are not indicated.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: Anyone with an intentional ingestion, symptoms other than mild vomiting or children who have ingested more than a "taste" amount of reserpine or rauwolfia alkaloids should be evaluated in a healthcare facility.
    2) OBSERVATION CRITERIA: Patients who are asymptomatic after 8 to 12 hours following an oral ingestion can be discharged.
    3) ADMISSION CRITERIA: Patients with hypotension and/or hemodynamically significant bradycardia should be admitted to an ICU or monitored setting. Because of the long duration of action, admission for 3 days or more is sometimes required.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing severe poisonings or following a significant ingestion.
    H) PITFALLS
    1) If a vasopressor is needed, avoid using dopamine, as it is likely to be ineffective due to presynaptic terminal depletion of catecholamines. Instead, use a direct-acting vasopressor (eg, norepinephrine). Avoid utilizing digitalis derivatives in cardiac failure; evidence or enhanced cardiac dysrhythmia production has been recorded when used in reserpine treated patients.
    I) PHARMACOKINETICS
    1) Plasma/blood concentrations are not well correlated to the activity of reserpine due to its irreversible binding to receptor sites. Reserpine, like other rauwolfia compounds, has a slow onset of action and sustained effects. Cardiovascular and CNS effects may persist following withdrawal of the drug. Maximum plasma concentrations after a single dose of 0.5 mg reserpine peaked after 2.5 hours. Absolute bioavailability of oral reserpine is approximately 50%. It is extensively bound (95%) to plasma proteins. Reserpine is almost completely metabolized in the body, and approximately 1% is excreted as unchanged drug in the urine. Following oral administration, an initial half-life of approximately 5 hours is followed by a terminal half-life of the order of 200 hours. Plasma levels can be measured up to 14 days after a single oral dose. Most of reserpine's pharmacologic action is due to depletion of stores of catecholamines and 5-hydroxytryptamine in many organs, including the brain and adrenal medulla.
    J) TOXICOKINETICS
    1) Plasma/blood concentrations are not well correlated to the activity of reserpine due to its irreversible binding to receptor sites. Symptomatology is usually delayed for 3 to 7 hours and may persist for 2 to 4 days. Based on its mechanism of action, the depression of sympathetic nerve function results in a decreased heart rate and a lower arterial blood pressure; these effects are likely exaggerated in overdose.
    K) DIFFERENTIAL DIAGNOSIS
    1) For hypotension and bradycardia, consider beta blocker, calcium channel blocker, alpha-2 agonist, and digoxin toxicity. Consider sedative hypnotic and CNS depressing plant ingestion in the setting of CNS depression. Opioids in overdose can also cause pinpoint pupils, hypotension and bradycardia.

Range Of Toxicity

    A) TOXICITY: RESERPINE: The highest known dose survived by a child is 1000 mg (age and sex not specified); a 20-month-old child survived a 200 mg dose. RAUWOLFIA ALKALOIDS: Children have survived rauwolfia alkaloid doses of up to 1000 mg (range 260 to 1000 mg).
    B) THERAPEUTIC DOSE: ADULT: RESERPINE: Hypertension: Initial: 0.5 mg/day orally for 1 to 2 weeks; Maintenance: 0.1 to 0.25 mg/day orally. Adjust dose as needed according to patient's response. Psychiatric Disorders: Initial: 0.5 mg daily; range 0.1 to 1 mg. Adjust dose as needed. RAUWOLFIA SERPENTINA: ADULT: Hypertension: 50 to 200 mg daily orally as a single dose or in 2 divided daily doses. PEDIATRIC: Reserpine is NOT typically recommended for use in children under 17 years; if the decision is made to treat a child, the dose is 20 mcg/kg/day orally, max 0.25 mg/day.

Clinical Effects

Summary Of Exposure

    A) USES: Rauwolfia alkaloids are used to treat hypertension. In addition, reserpine has been used to treat Raynaud's phenomenon, psychotic disorders, as radioprotective agent, and experimentally as a contraceptive. Rescinnamine, an ester alkaloid isolated from the root of Rauwolfia serpentina or R. vomitoria, has properties similar to reserpine. It has been used to treat hypertension. Reserpine and rescinnamine are the most active ester alkaloids (as hypotensive agents) of rauwolfia serpentine. Rauwolfia serpentina has been used by mouth as the powdered whole root. In India, a crude form of rauwolfia serpentina (eg, Sarpagandha) has been used for centuries to treat insomnia and certain forms of mental illness.
    B) PHARMACOLOGY: Reserpine and its congeners deplete catecholamines and serotonin peripherally and centrally from nerve terminal fibers. The resulting responses exhibit as CNS depression and peripheral sympatholysis.
    C) TOXICOLOGY: Overdose effects result from an exaggerated therapeutic response secondary to depletion of catecholamine and reflects parasympathetic effects. Peripheral responses are biphasic. Responses initially may result from catecholamine release, then depletion. Specific chemical compounds include alseroxylon, deserpidine, raubasine, rauwolfia serpentina, rescinnamine, and reserpine.
    D) EPIDEMIOLOGY: Reserpine and rauwolfia alkaloid exposures are extremely rare. No estimations on overdose exposures are available.
    E) WITH THERAPEUTIC USE
    1) Gastrointestinal events including nausea, vomiting and diarrhea have occurred. Dysrhythmias (in particular when used with digitalis or quinidine), bradycardia, and angina-like symptoms have been reported. Other events that have developed with therapeutic use of reserpine include: dyspnea, epistaxis, extrapyramidal tract symptoms, headache, dizziness, depression, drowsiness, and muscle aches. Drug withdrawal has been associated with the development of the delusional psychosis.
    F) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Typical overdose effects result from the reflex parasympathomimetic effect of reserpine. Symptoms are primarily related to CNS depression, coma, and ataxia; tachycardia, and initial hypertension, then hypotension. Peripheral responses are biphasic. Responses initially may result from catecholamine release, then depletion. Subsequent symptoms include hypothermia, pinpoint non-reactive pupils, facial flushing, nasal congestion, and excessive salivation. CNS depression can range from drowsiness, lethargy, mental depression to stupor and coma. Higher doses may produce cardiac dysrhythmias and an angina-like syndrome. Symptomatology is usually delayed for 3 to 7 hours and persists from 2 to 4 days. Gastrointestinal symptoms can include diarrhea and intense gastric acid secretion. Acute hematemesis and hemorrhagic gastritis have been described in patients receiving large parenteral and oral loading doses.
    2) SEVERE TOXICITY: Severe CNS toxicity can lead to stupor and coma. Higher doses may produce cardiac dysrhythmias and an angina-like syndrome. In severe overdose, hypotension, hypothermia, central respiratory depression and bradycardia can develop.

Vital Signs

    3.3.1) SUMMARY
    A) Although rarely reported, patients may initially demonstrate hypertension and tachycardia for up to one day (Loggie et al, 1967) followed by hypotension and bradycardia (McKown et al, 1963).
    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) HYPOTHERMIA has been reported after severe overdose due to the reflex parasympathomimetic effect of reserpine (Prod Info reserpine oral tablets, 2010; Loggie et al, 1967).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) MIOSIS: Non-reactive and pinpoint pupils occur frequently after overdose (Gosselin et al, 1984).
    2) CONJUNCTIVAL FLUSHING: Conjunctiva may appear flushed.
    3.4.5) NOSE
    A) WITH POISONING/EXPOSURE
    1) NASAL CONGESTION has been observed after overdose (Hubbard, 1955).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypotension and bradycardia may develop in severe overdose (Prod Info reserpine oral tablets, 2010).
    b) After 1 day of hypertension patients may experience hypotension and bradycardia. Hypotension was noted in 2 of 129 patients with a history of acute reserpine overdose (McKown et al, 1963).
    B) BRADYCARDIA
    1) WITH THERAPEUTIC USE
    a) Bradycardia may develop with reserpine therapy (Prod Info reserpine oral tablets, 2010).
    2) WITH POISONING/EXPOSURE
    a) Bradycardia may develop following a significant overdose of reserpine (Prod Info reserpine oral tablets, 2010).
    C) HYPERTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Based on limited data, patients may initially demonstrate hypertension and tachycardia for up to one day (Loggie et al, 1967).
    b) In a series of 3 inadvertent pediatric reserpine exposures (up to 25 mg ingested), they each developed progressive coma with general flaccidity, no deep tendon reflexes, right-sided third nerve palsy, and bilateral extensor plantar responses. This was associated with reduction in temperature, pulse, and blood pressure. Ten hours after ingestion, one patient (a 2-year-old) developed a blood pressure of 170/110 mmHg which remained elevated for 2 days. Catecholamines were noted to be increased in all three children in the first 24 hours following ingestion. Following supportive care, all 3 patients completely recovered (Loggie et al, 1967).
    D) CONDUCTION DISORDER OF THE HEART
    1) WITH THERAPEUTIC USE
    a) Dysrhythmias, especially when combined with digitalis or quinidine, may occur with reserpine therapy (Prod Info reserpine oral tablets, 2010).
    b) Higher doses may produce cardiac dysrhythmias and an angina-like syndrome. Symptomatology is delayed from 3 to 7 hours and may persist for 2 to 4 days. Digitalis may increase the incidence of dysrhythmias (Dick et al, 1962).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) RESPIRATORY INSUFFICIENCY
    1) WITH POISONING/EXPOSURE
    a) Central respiratory depression has been reported following severe reserpine overdose (Prod Info reserpine oral tablets, 2010).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) WITH THERAPEUTIC USE
    a) Depression, nervousness, paradoxical anxiety, dull sensorium and drowsiness have been observed with reserpine therapy (Prod Info reserpine oral tablets, 2010).
    2) WITH POISONING/EXPOSURE
    a) ADVERSE EFFECTS may commonly include depression (Walker & Mathis, 1981), drowsiness, lethargy, nightmares, and vertigo.
    B) COMA
    1) WITH POISONING/EXPOSURE
    a) CNS effects including coma, drowsiness, stupor, tremor and ataxia may occur 3 to 7 hours postingestion (Loggie et al, 1967; McKown et al, 1963). CNS depression occurred in 44% of symptomatic Rauwolfia ingestions, with coma in 1 patient (McKown et al, 1963).
    b) Coma may be long term, but mild, often allowing the patient to be aroused when needed (Gosselin et al, 1984).
    C) CATECHOLAMINE LEVEL - FINDING
    1) WITH POISONING/EXPOSURE
    a) PERIPHERAL RESPONSES are biphasic. Responses initially may demonstrate catecholamine release, then depletion.
    1) Theoretically, early symptoms of hypertension and tachycardia may occur up to one day after ingestion (Loggie et al, 1967).
    2) Following overdose flushing of the skin, conjunctival injection, and pupillary constriction should be anticipated due to reflex parasympathomimetic effects of reserpine. Hypotension, hypothermia, central respiratory depression, and bradycardia may develop in severe overdose (Prod Info reserpine oral tablets, 2010).
    D) EXTRAPYRAMIDAL DISEASE
    1) WITH THERAPEUTIC USE
    a) Rare parkinsonian syndrome and other extrapyramidal tract symptoms appear in patients being treated with reserpine (Prod Info reserpine oral tablets, 2010), particularly at higher doses (Stead & Wing, 1955).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) Nausea, vomiting, diarrhea, anorexia and hypersecretion may occur with therapeutic use of reserpine (Prod Info reserpine oral tablets, 2010).
    B) DIARRHEA
    1) WITH THERAPEUTIC USE
    a) Diarrhea may occur with therapeutic use of reserpine (Prod Info reserpine oral tablets, 2010).
    2) WITH POISONING/EXPOSURE
    a) Diarrhea may occur in overdose of reserpine (Prod Info reserpine oral tablets, 2010; Parker & Murphy, 1961).
    C) INDIGESTION
    1) WITH POISONING/EXPOSURE
    a) Increased salivation and gastric acid secretions may occur following overdose of reserpine (Prod Info reserpine oral tablets, 2010; Parker & Murphy, 1961).
    D) GASTROINTESTINAL HEMORRHAGE
    1) WITH THERAPEUTIC USE
    a) Acute hematemesis and hemorrhagic gastritis have been described in patients receiving large parenteral and oral loading doses (Duncan & Fleeson, 1959; Hollister, 1957).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) FLUSHING
    1) WITH POISONING/EXPOSURE
    a) Skin flushing was noted in 13% of Rauwolfia intoxications (McKown et al, 1963).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) ENGORGEMENT OF BREASTS
    1) WITH THERAPEUTIC USE
    a) Endocrine disorders causing breast engorgement, galactorrhea, and gynecomastia have been reported (Prod Info reserpine oral tablets, 2010).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) HYPERSENSITIVITY REACTION
    1) WITH THERAPEUTIC USE
    a) Purpura, rash and pruritus have been reported with reserpine therapy (Prod Info reserpine oral tablets, 2010).

Reproductive

    3.20.1) SUMMARY
    A) Reserpine crosses the placenta, and is excreted in breast milk.
    3.20.2) TERATOGENICITY
    A) CONGENITAL ANOMALY
    1) A woman who received reserpine (0.50 mg/day) during the first six weeks of gestation delivered a stillborn female with craniofacial, abdominal, and central nervous system malformations (Pauli & Pettersen, 1986).
    2) ANIMAL STUDIES
    a) RATS - Reserpine is teratogenic in rats after doses of 1 to 2 mg/kg intramuscularly or intraperitoneally in early pregnancy. In rabbits, pregnancy was interrupted after doses as low as 0.04 mg/kg (Technical Information, 1984).
    b) RATS - Pregnant rats treated with large doses of reserpine (0.375 mg/kg/day, or 0.75 mg/kg/day for days 12 to 15 of gestation) gave birth to pups that exhibited dose related effects on neurological development (Buelke-Sam et al, 1989).
    3.20.3) EFFECTS IN PREGNANCY
    A) FETAL DISTRESS
    1) Severe stuffy nose, lethargy, and respiratory depression may occur in infants of mothers ingesting these agents during pregnancy (Budnick et al, 1955).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Reserpine is excreted in breast milk. Serious adverse reactions are possible in nursing infants (Olin, 1990).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) A possible connection between reserpine and tumors of the breast in women remains controversial.
    3.21.3) HUMAN STUDIES
    A) BREAST CARCINOMA
    1) Several studies supporting the conclusion that reserpine increases the chance of developing breast tumors have been contradicted by studies finding no such relationship.
    a) A possible connection between reserpine therapy and increased breast cancer risk remains highly controversial (JEF Reynolds , 1991; Gilman et al, 1990).

Genotoxicity

    A) Genotoxic effects have included positive DNA damage, dominant lethal, sister chromatid exchange, and oncogenic transformation assays (von Poser et al, 1990; RTECS , 2002). Negative mutagenic and recombinogenic studies have also been reported (von Poser et al, 1990).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs.
    B) Obtain an ECG and institute continuous cardiac monitoring in symptomatic patients.
    C) Routine laboratory studies are not indicated; obtain studies as necessary.
    D) Plasma levels are generally not useful following an exposure.
    E) Epinephrine and norepinephrine urine levels may be elevated 1 to 2 days after an acute ingestion. Because reserpine is irreversibly bound to receptor sites, its concentration in plasma may have little to do with its pharmacological activity. Epinephrine and norepinephrine urine levels may be elevated 1 to 2 days subsequent to acute ingestion.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Reserpine binds irreversibly to receptor sites so that plasma levels cannot be consistently correlated with effect (Gilman et al, 1990).
    4.1.3) URINE
    A) URINARY LEVELS
    1) Epinephrine and norepinephrine urine levels may be elevated 1 to 2 days subsequent to acute ingestion (Ellenhorn & Barceloux, 1988).
    4.1.4) OTHER
    A) OTHER
    1) Obtain an ECG and institute continuous cardiac monitoring in symptomatic patients.

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) Patients with hypotension and/or hemodynamically significant bradycardia should be admitted to an ICU or monitored setting. Because of the long duration of action, admission for 3 days or more is sometimes required.
    B) The manufacturer recommends that patients who are symptomatic following a reserpine overdose should be observed for a minimum of 72 hours, due to the long duration of action (Prod Info reserpine oral tablets, 2010).
    6.3.1.2) HOME CRITERIA/ORAL
    A) Anyone with an intentional ingestion, symptoms other than mild vomiting or children who have ingested more than a "taste" amount of reserpine or rauwolfia alkaloids should be evaluated in a healthcare facility.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in managing severe poisonings or following a significant ingestion.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients who are asymptomatic after 8 to 12 hours following an oral ingestion can be discharged.

Monitoring

    A) Monitor vital signs.
    B) Obtain an ECG and institute continuous cardiac monitoring in symptomatic patients.
    C) Routine laboratory studies are not indicated; obtain studies as necessary.
    D) Plasma levels are generally not useful following an exposure.
    E) Epinephrine and norepinephrine urine levels may be elevated 1 to 2 days after an acute ingestion. Because reserpine is irreversibly bound to receptor sites, its concentration in plasma may have little to do with its pharmacological activity. Epinephrine and norepinephrine urine levels may be elevated 1 to 2 days subsequent to acute ingestion.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Gastrointestinal decontamination is not indicated due to the potential risk of CNS or respiratory depression. Do NOT induce emesis.
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) SUMMARY
    a) Gastrointestinal decontamination is typically not warranted following a minor exposure. Given the risk for CNS and respiratory depression, carefully monitor the patient's airway or secure the airway prior to administering activated charcoal.
    2) 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.
    3) 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) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY: Treatment is symptomatic and supportive. HYPOTENSION: Monitor vital signs. Infuse 10 to 20 mL/kg of isotonic fluid and keep the patient supine. Consider central venous pressure monitoring to guide further fluid therapy. HYPOTHERMIA: Use warming blankets to maintain or achieve normal body temperature.
    2) MANAGEMENT OF SEVERE TOXICITY: Treatment is symptomatic and supportive. Support respiratory and cardiovascular function. If hypotension persists, administer norepinephrine or epinephrine. Consider end-tidal CO2 monitoring for respiratory depression as well as advanced airway support including intubation and ventilation for respiratory insufficiency or failure. Avoid utilizing digitalis derivatives in cardiac failure; evidence of enhanced cardiac dysrhythmia production has been recorded when reserpine has been used simultaneously with digitalis derivatives.
    B) MONITORING OF PATIENT
    1) Monitor vital signs.
    2) Obtain an ECG and institute continuous cardiac monitoring in symptomatic patients.
    3) Routine laboratory studies are not indicated; obtain studies as necessary.
    4) Plasma levels are generally not useful following an exposure.
    5) Epinephrine and norepinephrine urine levels may be elevated 1 to 2 days after an acute ingestion. Because reserpine is irreversibly bound to receptor sites, its concentration in plasma may have little to do with its pharmacological activity. Epinephrine and norepinephrine urine levels may be elevated 1 to 2 days subsequent to acute ingestion.
    C) HYPOTENSIVE EPISODE
    1) Administer IV fluids and keep the patient supine. If a vasopressor is needed, avoid using dopamine, as it is likely to be ineffective due to presynaptic terminal depletion of catecholamines. Instead, use a direct-acting vasopressor (eg, norepinephrine, phenylephrine).
    2) 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).
    3) PHENYLEPHRINE
    a) MILD OR MODERATE HYPOTENSION
    1) INTRAVENOUS: ADULT: Usual dose: 0.2 mg; range: 0.1 mg to 0.5 mg. Maximum initial dose is 0.5 mg. A 0.5 mg IV dose can elevate the blood pressure for approximately 15 min (Prod Info phenylephrine HCl subcutaneous injection, intramuscular injection, intravenous injection, 2011). PEDIATRIC: Usual bolus dose: 5 to 20 mcg/kg IV repeated every 10 to 15 min as needed (Taketomo et al, 1997).
    b) CONTINUOUS INFUSION
    1) PREPARATION: Add 10 mg (1 mL of a 1% solution) to 500 mL of normal saline or dextrose 5% in water to produce a final concentration of 0.2 mg/mL.
    2) ADULT DOSE: To raise blood pressure rapidly; start an initial infusion of 100 to 180 mcg/min until blood pressure stabilizes; then reduce infusion to 40 to 60 mcg/min titrated to desired effect. If necessary, additional doses in increments of 10 mg or more may be added to the infusion solution and the rate of flow titrated to the desired effect (Prod Info phenylephrine HCl subcutaneous injection, intramuscular injection, intravenous injection, 2011).
    3) PEDIATRIC DOSE: Intravenous infusion should begin at 0.1 to 0.5 mcg/kg/min; titrate to the desired effect (Taketomo et al, 1997).
    c) ADVERSE EFFECTS
    1) Headache, reflex bradycardia, excitability, restlessness and rarely dysrhythmias may develop (Prod Info phenylephrine HCl subcutaneous injection, intramuscular injection, intravenous injection, 2011).
    D) HYPOTHERMIA
    1) Use warming blankets to maintain or achieve normal body temperature.
    E) CONTRAINDICATED TREATMENT
    1) Avoid utilizing digitalis derivatives in cardiac failure; evidence of enhanced cardiac dysrhythmia production has been recorded when reserpine has been used simultaneously with digitalis derivatives (Lown, 1961; Schreader, 1956; Dick et al, 1962).
    F) SEROTONIN SYNDROME
    1) Theoretically, serotonin syndrome may develop based on reserpine's mechanism of action. However, there have been no clinical reports of serotonin syndrome.
    2) SUMMARY
    a) Benzodiazepines are the mainstay of therapy. Cyproheptadine, a 5-HT antagonist, is also commonly used. Severe cases have been managed with benzodiazepine sedation and neuromuscular paralysis with non-depolarizing agents(Claassen & Gelissen, 2005).
    3) HYPERTHERMIA
    a) Control agitation and muscle activity. Undress patient and enhance evaporative heat loss by keeping skin damp and using cooling fans.
    b) MUSCLE ACTIVITY: Benzodiazepines are the drug of choice to control agitation and muscle activity. DIAZEPAM: ADULT: 5 to 10 mg IV every 5 to 10 minutes as needed, monitor for respiratory depression and need for intubation. CHILD: 0.25 mg/kg IV every 5 to 10 minutes; monitor for respiratory depression and need for intubation.
    c) Non-depolarizing paralytics may be used in severe cases.
    4) CYPROHEPTADINE
    a) Cyproheptadine is a non-specific 5-HT antagonist that has been shown to block development of serotonin syndrome in animals (Sternbach, 1991). Cyproheptadine has been used in the treatment of serotonin syndrome (Mills, 1997; Goldberg & Huk, 1992). There are no controlled human trials substantiating its efficacy.
    b) ADULT: 12 mg initially followed by 2 mg every 2 hours if symptoms persist, up to a maximum of 32 mg in 24 hours. Maintenance dose 8 mg orally repeated every 6 hours (Boyer & Shannon, 2005).
    c) CHILD: 0.25 mg/kg/day divided every 6 hours, maximum dose 12 mg/day (Mills, 1997).
    5) HYPERTENSION
    a) Monitor vital signs regularly. For mild/moderate asymptomatic hypertension, pharmacologic intervention is usually not necessary.
    6) HYPOTENSION
    a) Administer 10 to 20 mL/kg 0.9% saline bolus and place patient supine. Further fluid therapy should be guided by central venous pressure or right heart catheterization to avoid volume overload.
    b) Pressor agents with dopaminergic effects may theoretically worsen serotonin syndrome and should be used with caution. Direct acting agents (norepinephrine, epinephrine, phentolamine) are theoretically preferred.
    c) NOREPINEPHRINE
    1) PREPARATION: Add 4 mL of 0.1% solution to 1000 mL of dextrose 5% in water to produce 4 mcg/mL.
    2) INITIAL DOSE
    a) ADULT: 2 to 3 mL (8 to 12 mcg)/minute.
    b) ADULT or CHILD: 0.1 to 0.2 mcg/kg/min. Titrate to maintain adequate blood pressure.
    3) MAINTENANCE DOSE
    a) 0.5 to 1 mL (2 to 4 mcg)/minute.
    7) SEIZURES
    a) DIAZEPAM
    1) MAXIMUM RATE: Administer diazepam IV over 2 to 3 minutes (maximum rate: 5 mg/min).
    2) ADULT DIAZEPAM DOSE: 5 to 10 mg initially, repeat every 5 to 10 minutes as needed. Monitor for hypotension, respiratory depression and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after diazepam 30 milligrams.
    3) PEDIATRIC DIAZEPAM DOSE: 0.2 to 0.5 mg/kg, repeat every 5 minutes as needed. Monitor for hypotension, respiratory depression and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after diazepam 10 milligrams in children over 5 years or 5 milligrams in children under 5 years of age.
    4) RECTAL USE: If an intravenous line cannot be established, diazepam may be given per rectum (not FDA approved), or lorazepam may be given intramuscularly.
    b) LORAZEPAM
    1) MAXIMUM RATE: The rate of IV administration of lorazepam should not exceed 2 mg/min (Prod Info Ativan(R), 1991).
    2) ADULT LORAZEPAM DOSE: 2 to 4 mg IV. Initial doses may be repeated in 10 to 15 minutes, if seizures persist (Prod Info ATIVAN(R) injection, 2003).
    3) PEDIATRIC LORAZEPAM DOSE: 0.1 mg/kg IV push (range: 0.05 to 0.1 mg/kg; maximum dose 4 mg); may repeat dose in 5 to 10 minutes if seizures continue. It has also been given rectally at the same dose in children with no IV access (Sreenath et al, 2010; Chin et al, 2008; Wheless, 2004; Qureshi et al, 2002; De Negri & Baglietto, 2001; Mitchell, 1996; Appleton, 1995; Giang & McBride, 1988).
    c) RECURRING SEIZURES
    1) If seizures cannot be controlled with diazepam or recur, give phenobarbital or propofol.
    d) PHENOBARBITAL
    1) SERUM LEVEL MONITORING: Monitor serum levels over next 12 to 24 hours for maintenance of therapeutic levels (15 to 25 mcg/mL).
    2) ADULT PHENOBARBITAL LOADING DOSE: 600 to 1200 mg of phenobarbital IV initially (10 to 20 mg/kg) diluted in 60 mL of 0.9% saline given at 25 to 50 mg/minute.
    3) ADULT PHENOBARBITAL MAINTENANCE DOSE: Additional doses of 120 to 240 mg may be given every 20 minutes.
    4) MAXIMUM SAFE ADULT PHENOBARBITAL DOSE: No maximum safe dose has been established. Patients in status epilepticus have received as much as 100 mg/min until seizure control was achieved or a total dose of 10 mg/kg.
    5) PEDIATRIC PHENOBARBITAL LOADING DOSE: 15 to 20 mg/kg of phenobarbital intravenously at a rate of 25 to 50 mg/min.
    6) PEDIATRIC PHENOBARBITAL MAINTENANCE DOSE: Repeat doses of 5 to 10 mg/kg may be given every 20 minutes.
    7) MAXIMUM SAFE PEDIATRIC PHENOBARBITAL DOSE: No maximum safe dose has been established. Children in status epilepticus have received doses of 30 to 120 mg/kg within 24 hours. Vasopressors and mechanical ventilation were needed in some patients receiving these doses.
    8) NEONATAL PHENOBARBITAL LOADING DOSE: 20 to 30 mg/kg IV at a rate of no more than 1 mg/kg/min in patients with no preexisting phenobarbital serum levels.
    9) NEONATAL PHENOBARBITAL MAINTENANCE DOSE: Repeat doses of 2.5 mg/kg every 12 hours may be given; adjust dosage to maintain serum levels of 20 to 40 mcg/mL.
    10) MAXIMUM SAFE NEONATAL PHENOBARBITAL DOSE: Doses of up to 20 mg/kg/min up to a total of 30 mg/kg have been tolerated in neonates.
    11) CAUTION: Adequacy of ventilation must be continuously monitored in children and adults. Intubation may be necessary with increased doses.
    8) CHLORPROMAZINE
    a) Chlorpromazine is a 5-HT2 receptor antagonist that has been used to treat cases of serotonin syndrome (Graham, 1997; Gillman, 1996). Controlled human trial documenting its efficacy are lacking.
    b) ADULT: 25 to 100 mg intramuscularly repeated in 1 hour if necessary.
    c) CHILD: 0.5 to 1 mg/kg repeated as needed every 6 to 12 hours not to exceed 2 mg/kg/day.
    9) NOT RECOMMENDED
    a) BROMOCRIPTINE: It has been used in the treatment of neuroleptic malignant syndrome but is NOT RECOMMENDED in the treatment of serotonin syndrome as it has serotonergic effects (Gillman, 1997). In one case the use of bromocriptine was associated with a fatal outcome (Kline et al, 1989).
    G) ALPRAZOLAM
    1) Alprazolam reversed the reserpine-induced depression in 2 patients with compensated tardive dyskinesia. It is suggested that alprazolam may block increases in beta-adrenergic receptors in the brain caused by reserpine (Holt, 1984).

Abstracts

Case Reports

    A) INFANT
    1) A 20-month-old child who ingested 260 mg of reserpine was lethargic, but arousable, with flushed face, slowed reflexes, and nasal congestion. He recovered totally within 72 hours (Hubbard, 1955).
    B) PEDIATRIC
    1) Loggie et al (1967) reported on 3 children who accidently ingested up to 25 mg of reserpine. They subsequently developed progressive coma with general flaccidity, no deep tendon reflexes, right-sided third nerve palsy, and bilateral extensor plantar responses. This was associated with reduction in temperature, pulse, and blood pressure. Ten hours after ingestion, the blood pressure of 1 patient was noted to increase to 170/110 mmHg and remained elevated for 2 days. Catecholamines were noted to be increased in all 3 patients in the first 24 hours following ingestion. Each was treated with gastric lavage, saline enema, IV fluids and a warming blanket to control hypothermia. Within 18 hours, CNS function improved, but the patients' developed tremor and episodic clonic movements of the limbs. By 48 hours, each patient had completely recovered (Loggie et al, 1967).

Range Of Toxicity

Summary

    A) TOXICITY: RESERPINE: The highest known dose survived by a child is 1000 mg (age and sex not specified); a 20-month-old child survived a 200 mg dose. RAUWOLFIA ALKALOIDS: Children have survived rauwolfia alkaloid doses of up to 1000 mg (range 260 to 1000 mg).
    B) THERAPEUTIC DOSE: ADULT: RESERPINE: Hypertension: Initial: 0.5 mg/day orally for 1 to 2 weeks; Maintenance: 0.1 to 0.25 mg/day orally. Adjust dose as needed according to patient's response. Psychiatric Disorders: Initial: 0.5 mg daily; range 0.1 to 1 mg. Adjust dose as needed. RAUWOLFIA SERPENTINA: ADULT: Hypertension: 50 to 200 mg daily orally as a single dose or in 2 divided daily doses. PEDIATRIC: Reserpine is NOT typically recommended for use in children under 17 years; if the decision is made to treat a child, the dose is 20 mcg/kg/day orally, max 0.25 mg/day.

Therapeutic Dose

    7.2.1) ADULT
    A) SPECIFIC SUBSTANCE
    1) RESERPINE
    a) HYPERTENSION: Initial, 0.5 mg/day ORALLY for 1 to 2 wk; maintenance, reduce dose to 0.1 to 0.25 mg/day orally. Higher doses should be used with caution (Prod Info reserpine oral tablets, 2010).
    b) PSYCHIATRIC DISORDERS: Initial dosage: 0.5 mg daily, range 0.1 to 1.0 mg. Adjust dosage upward or downward according to patient response (Prod Info reserpine oral tablets, 2010).
    2) RAUWOLFIA SERPENTINA
    a) HYPERTENSION: Oral, 50 to 200 mg daily as a single dose or in 2 divided daily doses (USPDI , 2002).
    7.2.2) PEDIATRIC
    A) SPECIFIC SUBSTANCE
    1) RESERPINE
    a) Because of adverse effects, particularly including depression and lability, sedation and stuffy nose reserpine is not usually recommended as a step-2 drug in the treatment of hypertension (Prod Info reserpine oral tablets, 2010).
    b) ROUTE OF ADMINISTRATION
    1) ORAL: It is generally not recommended for use in children. If used the starting dose is 20 mcg/kg/day orally; max 0.25 mg/day (Prod Info reserpine oral tablets, 2010)
    2) NOTE: Parenteral dosage forms of reserpine are no longer available in the US.
    a) INTRAMUSCULAR: 0.07 mg/kg/dose given intramuscularly every 8 to 24 hours (Pagliaro & Levin, 1979; Cole, 1984).
    b) INTRAVENOUS: In pediatric patients (17 years and younger), it is recommended that reserpine be administered undiluted by direct intravenous push over 3 to 5 minutes. Intermittent and continuous infusions are not recommended. Patients should be monitored for hypotension (Anon, 1984).
    c) MAXIMUM DOSE: The maximum recommended intravenous dose for reserpine in pediatric patients (17 years and younger) is 4 milligrams/dose (Anon, 1984).

Minimum Lethal Exposure

    A) CASE REPORTS
    1) Two patients receiving large therapeutic doses of reserpine died of respiratory failure following electroshock therapy (Bracha & Hes, 1956; Foster & Gayle, 1955).

Maximum Tolerated Exposure

    A) CASE REPORTS
    1) PEDIATRIC
    a) RESERPINE: The highest known dose survived by a child is 1000 mg (age and sex not specified); a 20-month-old child survived a 200 mg dose (Prod Info reserpine oral tablets, 2004).
    b) Poisonings have been reported in children, with survival following oral dosages of 25 mg of reserpine, and 260 mg of Rauwolfia Alkaloids (Loggie et al, 1967; Hubbard, 1955), and 1000 mg (Hollister, 1966).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CONCENTRATION LEVEL
    a) Plasma/blood concentrations are not well correlated to the activity of reserpine due to its irreversible binding to receptor sites (Gilman et al, 1990).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) RESERPINE
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 5 mg/kg (RTECS , 2002a)
    2) LD50- (ORAL)MOUSE:
    a) Greater than 50 mg/kg (RTECS , 2002a)
    3) LD50- (INTRAPERITONEAL)RAT:
    a) 44 mg/kg (RTECS , 2002a)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Most of reserpine's pharmacologic action is due to depletion of stores of catecholamines and 5-hydroxytryptamine in many organs, including the brain and adrenal medulla. Depletion is slowest and less complete in the adrenal medulla compared to other tissues. The depression of sympathetic nerve function results in a decreased heart rate and a lower arterial blood pressure. The sedative and tranquilizing properties of reserpine are likely due to the depletion of catecholamines and 5-hydroxytryptamine from the brain (Prod Info reserpine oral tablets, 2010).

Toxicologic Mechanism

    A) Reserpine, like other rauwolfia compounds, produces both cardiovascular and CNS effects which may persist for a period of time following drug withdrawal. Acute poisoning is characterized by the reflex parasympathomimetic effects of reserpine. Based on its long acting effects, patients should be observed for at least 72 hours (Prod Info reserpine oral tablets, 2010).

Physicochemical

Physical Characteristics

    A) RESERPINE: colorless, crystalline powder
    B) ALSEROXYLON: reddish-brown amorphous powder
    C) RESCINNAMINE: white, pale buff, or cream odorless crystalline powder

Molecular Weight

    A) Varies

Animal Toxicology

Clinical Effects

    11.1.5) EQUINE/HORSE
    A) Intravenous administration of xylazine 200 mg and reserpine 12.5 mg to a 400 kg gelding resulted in trembling and sweating 8 hours later.
    1) Sinus bradycardia, heart block, miosis, upper eyelid ptosis, paraphimosis, and flatulence were observed on admission 12 hours postinjection. By 24 hours improvement was noted (Lloyd et al, 1985).
    B) Other signs of reserpine toxicosis in horses include violent colic-like behavior and abrupt recumbency. Clinical signs generally abate within 60 hours (Lloyd et al, 1985).

Range Of Toxicity

    11.3.1) THERAPEUTIC DOSE
    A) HORSE
    1) Doses effective in tranquilization range from 1 to 4 mg/450 kg parenterally (Earl, 1956).
    11.3.2) MINIMAL TOXIC DOSE
    A) HORSE
    1) Oral doses of 5 mg/450 kg have produced colic-like behavior (Earl, 1956). Parenteral doses of 10 mg have been tolerated (Tobin, 1978), while 12.5 mg produced marked toxicity (Lloyd et al, 1985).

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