1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Brand names, Trade names
   1.6 Manufacturers, Importers
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First aid measures and management principles
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Properties of the substance Colour State/Form Description
      3.3.2 Properties of the locally available formulation
   3.4 Other characteristics
      3.4.1 Shelf-life of the substance
      3.4.2 Shelf-life of the locally available formulation
      3.4.3 Storage conditions
      3.4.4 Bioavailability
      3.4.5 Specific properties and composition
   4.1 Indications
      4.1.1 Indications
      4.1.2 Description
   4.2 Therapeutic dosage
      4.2.1 Adults
      4.2.2 Children
   4.3 Contraindications
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Other
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination by route of exposure
   7.1 Mode of action
      7.1.1 Toxicodynamics
      7.1.2 Pharmacodynamics
   7.2 Toxicity
      7.2.1 Human data Adults Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
   7.7 Main adverse effects
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection Toxicological analyses Biomedical analyses Arterial blood gas analysis Haematological analyses Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens Toxicological analyses Biomedical analyses Arterial blood gas analysis Haematological analyses Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens Toxicological analyses Biomedical analyses Arterial blood gas analysis Haematological analyses Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material Simple Qualitative Test(s) Advanced Qualitative Confirmation Test(s) Simple Quantitative Method(s) Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens Simple Qualitative Test(s) Advanced Qualitative Confirmation Test(s) Simple Quantitative Method(s) Advanced Quantitative Method(s) Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis Blood, plasma or serum Urine Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomed. investigations etc.
   8.5 Overall Interpretation etc.
   8.6 References
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological CNS Peripheral nervous system Autonomic nervous system Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary Renal Other
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ear, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic Acid-base disturbances Fluid and electrolyte disturbances Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Other
   9.6 Summary
   10.1 General principles
   10.2 Relevant laboratory analyses
      10.2.1 Sample collection
      10.2.2 Biomedical analysis
      10.2.3 Toxicological analysis
      10.2.4 Other investigations
   10.3 Life supportive procedures etc.
   10.4 Decontamination
   10.5 Elimination
   10.6 Antidote treatment
      10.6.1 Adults
      10.6.2 Children
   10.7 Management discussion
   11.1 Case reports from literature
   11.2 Internally extracted data on cases
   11.3 Internal cases
   12.1 Availability of antidotes
   12.2 Specific preventive measures
   12.3 Other
    1.  NAME
        1.1  Substance
        1.2  Group
        1.3  Synonyms
        1.4  Identification numbers
             1.4.1  CAS number
             1.4.2  Other numbers
        1.5  Brand names, Trade names
        1.6  Manufacturers, Importers
             To be completed by local centre
    2.  SUMMARY
        2.1  Main risks and target organs
             The main risks associated with reserpine poisoning are 
             central nervous system depression , the development of 
             psychiatric depression, cardiovascular toxicity, and 
             gastrointestinal irritation.
             The main target organs are the central nervous system, 
             cardiovascular system, and gastrointestinal tract.
        2.2  Summary of clinical effects
             The clinical effects include sedation and lethargy, 
             which can rarely progress to coma, and gastrointestinal 
             irritation which includes nausea, vomiting, and abdominal 
             cramping. Gastrointestinal irritation can be severe and 
             result in ulceration, perforation, and hemorrhage. 
             Psychiatric depression can be severe and lead to suicidal 
             thoughts and there can be nightmares, and vertigo. 
             Cardiovascular effects include hypotension and bradycardia. 
             Nasal congestion and flushing are also frequent.  Hypothermia 
             has also been described. These effects are generally more 
             common with poisonings, oral daily reserpine doses greater 
             than 0.5 mg.
             The most commonly reported effects were facial flushing, 
             lethargy which rarely progressed to coma, hypotension and 
             bradycardia. Death has been described from hypotension in 2 
        2.3  Diagnosis
             The diagnosis of reserpine toxicity is primarily based 
             on a history of reserpine ingestion.  The potential for 
             reserpine toxicity should be considered in cases where there 
             is no specific history of ingestion but there is potential 
             access to reserpine, the presence of hypertension treated 
             with unknown medications, or the use of unidentified herbal 
        2.4  First aid measures and management principles
             The management of reserpine toxicity should be based 
             primarily on supportive care of the patient's respiratory and 
             cardiovascular function.  The airway should be protected and 
             oxygenation adequate.  Blood pressure should be adequate for 
             tissue perfusion.  Gastrointestinal decontamination with 
             activated charcoal should be undertaken and the patient 
             monitored until symptoms of toxicity resolve.  If hypotension 
             occurs and does not respond to the administration of 
             intravenous fluid, the administration of a direct acting 
             vasoconstrictor such as phenylephrine, norepinephrine, or 
             metaraminol is recommended, based on the catecholamine 
             depleting action of reserpine.
        3.1  Origin of the substance
             An alkaloid from the roots of certain species of 
             Rauwolfia, family Apocynacea, usually Rauwolfia serpintina or 
             R. Vomitoria. Reserpine can also be synthesized.
             (USPC, 1989)
        3.2  Chemical structure
             Methyl 11, 17 alpha-dimethoxy-18 beta (3,4,5-trimethoxy 
             benzolyl) reserpate
        3.3  Physical properties
             3.3.1  Properties of the substance
                             White or pale buff to slightly 
                             yellow coloured.  Darkens slowly on exposure 
                             to light when powder, more rapidly when in 
                             (USPC, 1989)
                             Small crystals or crystalline 
                             (USPC, 1989)
                             The pure alkaloid obtained from 
                             Rauwolfia serpentina.  A odorless, light 
                             coloured crystalline powder which is 
                             insoluble in water, freely soluble in 
                             chloroform and acetic acid, and very slightly 
                             soluble in alcohol and ether.  The pKa is 
                             6.6.  In solution it unstable in the presence 
                             of alkali.
                             (USPC, 1989)
             3.3.2  Properties of the locally available formulation
                    To be added by local centres
        3.4  Other characteristics
             3.4.1  Shelf-life of the substance
                    To be added by local centres
             3.4.2  Shelf-life of the locally available formulation
                    To be added by local centres
             3.4.3  Storage conditions
                    Store in airtight containers, protect from 
                    (USPC, 1989)
             3.4.4  Bioavailability
                    The reported bioavailability after oral 
                    ingestion is approximately 50%.
                    (Reynolds, 1993)
             3.4.5  Specific properties and composition
                    No information available
    4.  USES
        4.1  Indications
             4.1.1  Indications
             4.1.2  Description
                    Raynaud's phenomenon
                    Possibly for prevention of attacks of familial 
                    Mediterranean fever
                    Possibly for treatment of thyroid storm not responsive 
                    to standard therapy
                    Historically reserpine has also been used for the 
                    treatment of schizophrenia and tardive dyskinesia, 
                    however, these uses are not used in current clinical 
                    (USPC, 1989; Reynolds, 1993)
        4.2  Therapeutic dosage
             4.2.1  Adults
                    Hypertension: oral doses of 0.1 mg or 0.25 mg 
                    daily, usually in conjunction with an oral 
                    Raynaud's phenomenon: oral doses of 0.1 mg to 0.25 mg 
                    Note: doses of 0.5 mg daily or greater are associated 
                    with an increased frequency of depression and 
                    psychiatric adverse effect.
                    (USPC, 1989; Reynolds, 1993)
             4.2.2  Children
                    Hypertension: 0.005 mg/kg to 0.020 mg/kg body 
                    weight daily, in 1 or 2 divided doses.
                    (USPC, 1989)
        4.3  Contraindications
             1)  Absolute
             Psychiatric depression
             Active peptic ulcer disease
             Ulcerative colitis
             Parkinson's disease
             Hypersensitivity to any rauwolfia alkaloid
             2)  Relative contraindications where the use of reserpine 
             should be undertaken with caution and started with lower 
             Elderly patients
             Cardiac arrhythmias
             Myocardial infarction
             Renal insufficiency
             (USPC, 1989; Reynolds, 1993)
        5.1  Oral
             The most common route of administration and 
             (McKown, et al, 1963; Pfeifer, et al, 1976)
        5.2  Inhalation
             No data available
        5.3  Dermal
             No data available
        5.4  Eye
             No data available
        5.5  Parenteral
             Intramuscular injection has been used for the urgent 
             treatment of hypertension.  Intra-arterial injection has been 
             described in Raynaud's syndrome, but appears to be 
             ineffective. (Surwit, et al, 1983; Reynolds, 1993)
        5.6  Other
             No data available
    6.  KINETICS
        6.1  Absorption by route of exposure
             The reported bioavailability is approximately 50% to 70% 
             after oral ingestion.  Absorption is relatively rapid, with 
             peak concentrations achieved approximately 1 to 2 hours after 
             administration of an oral solution.  Slower absorption, with 
             peak concentrations at 2 to 4 hours has also been reported. 
             (Maass, et al, 1969; Reynolds, 1993)
        6.2  Distribution by route of exposure
             The volume of distribution has not been reported.  It is 
             widely distributed into the brain, liver, spleen, kidney, and 
             adipose tissue.  Reserpine binds to red blood cells and in 
             the peripheral neuron at its site of action.  It is reported 
             not to bind to plasma protein. (Maass, et al, 1969; USPC, 
             1989)  Reserpine crosses the placental barrier, and is found 
             in breast milk. (Briggs, et al, 1986; Ellenhorn & Barceloux, 
             1988; USPC, 1989; Reynolds, 1993)  An initial half-life of 
             distribution of approximately 4 to 5 hours is observed after 
             oral administration. (Maass, et al, 1969)
        6.3  Biological half-life by route of exposure
             Reserpine can be described using a two compartmental 
             pharmacokinetic model.  The elimination half-life ranges from 
             45 to 168 hours in plasma.  Because of binding to red blood 
             cells, the terminal elimination half-life is longer when 
             whole blood levels is measured, and has been reported to be 
             386 hours. (Maass, et al, 1969)  The half-life is longer in 
             patients with renal insufficiency.  Zsoter and associates 
             (1973) observed that the elimination half-life was 
             significantly prolonged in patients with creatinine clearance 
             values of less than 10 mL/min.
        6.4  Metabolism
             Hepatic metabolism accounts for less than 50% of the 
             elimination of reserpine, with the remainder being eliminated 
             in the faeces, and some unmetabolized reserpine and 
             metabolites being eliminated in the urine. (USPC, 1989)  In 
             man, metabolites are methylreserpate and trimethoxybenzoic 
             acid. (Maass et al, 1969) Metabolism may be more important 
             with intramuscular administration.(Zsoter, et al, 1973)
        6.5  Elimination by route of exposure
             The elimination of reserpine and its metabolites in the 
             faeces ranges from 30% after intramuscular administration to 
             approximately 60% after oral administration, primarily as 
             unmetabolized reserpine, over a 4 day period after the 
             administration of 0.25 mg to 0.50 mg doses. (Maass et al, 
             1969; Zsoter et al, 1973)  Over the same time period 
             approximately 8% of the administered dose was recovered in 
             the urine, primarily as the trimethoxybenzoic acid 
        7.1  Mode of action
             7.1.1  Toxicodynamics
                    The mechanism of reserpine's toxic effects is 
                    similar to the mechanism of it's pharmacologic 
                    effects.  Reserpine inhibits normal sympathetic 
                    activity in both the CNS and peripheral nervous system 
                    by binding to catecholamine storage vesicles. This 
                    prevents the normal storage of catecholamines and 
                    serotonin in the nerve cell, with the result being 
                    catecholamine depletion. Reserpine has also been 
                    described as inhibiting catecholamine synthesis by 
                    blocking the uptake of dopamine into the storage 
                    vesicle.  (Ellenhorn & Barceloux , 1989; Gilman et al, 
             7.1.2  Pharmacodynamics
                    Reserpine inhibits normal sympathetic activity 
                    by decreasing the storage of catecholamines at the 
                    pre-synaptic, CNS, and peripheral neuron.  Reserpine 
                    binds to the storage vesicles, causing catecholamines 
                    to leak into the synapse so that they are not 
                    available for release when the pre-synaptic neuron is 
                    stimulated.  The process appears to affect serotonin 
                    storage in a similar manner.
                    These actions result in a reduction in both cardiac 
                    output and peripheral vascular resistance with long 
                    term therapy, which takes approximately 3 weeks to 
                    develop after the initiation of therapy.  Heart rate 
                    and renin concentrations decrease, and there is sodium 
                    and water retention. (Gilman, et al, 1990)
        7.2  Toxicity
             7.2.1  Human data
                             There are few reported cases of 
                             reserpine poisoning in adult patients.  In a 
                             series of 151 cases reported from the United 
                             States from 1959 to 1960 only 4% were adults. 
                             Nausea, vomiting, hypotension, sedation, and 
                             coma were described in these patients. 
                             (McKown et al, 1963)  It would be expected 
                             that poisoned adults would have bradycardia, 
                             facial flushing, and the other symptoms 
                             associated with reserpine poisoning in 
                             Psychiatric depression is historically the 
                             most important adverse effect associated with 
                             the chronic administration of reserpine for 
                             the treatment of hypertension.  The 
                             depression is most common with daily doses of 
                             0.5 mg or greater, and the frequency is 
                             significantly decreased when the dose is 0.25 
                             mg or lower.  The depression is often severe, 
                             can occur in patients without a prior history 
                             of depressive illness, and may last for 
                             months after reserpine is discontinued. 
                             (Anon, 1976)
                             Most of the reported cases of 
                             reserpine poisoning have been in children. 
                             In the series of cases reported by McKown and 
                             associates (1963), 142 of the 151 cases of 
                             rauwolfia poisoning were in children less 
                             than 13 years of age.  Approximately 40% of 
                             the cases had some symptoms, Mild CNS 
                             depression such as lethargy or sedation was 
                             the most common symptom, and facial flushing 
                             the next most common.  Hospitalization for 
                             toxicity was needed in 24 of the 142 
                             pediatric cases.  Nausea, vomiting, 
                             hypotension and vertigo were also described. 
                             Loggie and associates (1967) reported that 
                             during the period of 1962 to 1965 there were 
                             no cases of serious toxicity in 225 reports 
                             of accidental ingestion.
                             Individual cases of toxicity include 
                             information about potential doses of 
                             reserpine ingested and the time course of 
                             toxicity.  A 20 month-old-male who ingested 
                             260 mg reserpine had symptoms of lethargy, 
                             flushing, rapid pulse rate and slowed 
                             respiration. Within 21 hours the symptoms had 
                             primarily resolved without any specific 
                             therapy other than a cathartic.  A mild 
                             leucocytosis resolved within 2 weeks. 
                             (Hubbard, 1955)  Three cases of reserpine 
                             ingestion in children between 30 months and 4 
                             years of age, who ingested doses of reserpine 
                             as large as 25 mg (2 cases), and an unknown 
                             dose (1 case), demonstrated a wide range of 
                             toxicity.  All cases had some lethargy and 
                             CNS depression which progressed to coma. 
                             Bradycardia and hypothermia was also 
                             documented in all cases, while the youngest 
                             child also had an episode of hypertension and 
                             tachycardia starting about 10 hours after 
                             ingestion. (Loggie, et al, 1968)
             7.2.2  Relevant animal data
                    No data available
             7.2.3  Relevant in vitro data
                    No data available
        7.3  Carcinogenicity
             There does not appear to be an association between 
             reserpine administration and cancer. Three studies in the mid 
             1970's reported an increased risk of breast cancer in female 
             patients who had taken reserpine for the treatment of 
             hypertension.  After these studies, an additional 9 studies 
             concluded that there was no increase in the risk of breast 
             cancer associated with reserpine therapy.  It appears that a 
             flaw in the initial study designs resulted in an exclusion 
             bias which may have falsely suggested a positive relationship 
             between reserpine use and breast cancer.  (Horwitz & 
             Feinstein, 1985)
             Studies in rats and mice using doses at least 100 fold 
             greater than the usual human dose have demonstrated an 
             increased incidence of mammary fibroadenomas, malignant 
             tumors of the seminal vesicles, and malignant adrenal 
             medullary tumors, (USPC, 1989)
        7.4  Teratogenicity
             Reserpine administered in large doses has been 
             demonstrated to be teratogenic in rats and guinea pigs. 
             (USPC, 1989)  There are no controlled studies in humans.  In 
             48 cases of mothers who had taken reserpine during their 
             first trimester of pregnancy, the incidence of birth defects 
             was 8%, higher than expected, although no major types of 
             malformations were seen.  There was no increased risk of 
             birth defects in women who ingested reserpine at any time 
             during their pregnancy. (Briggs, et al, 1986)
        7.5  Mutagenicity
             Recent studies have suggested a lack of mutagenic, 
             genotoxic, and recombinogenic effects. (von Poser, et al, 
        7.6  Interactions
             The following drugs have been reported to interact with 
             Alcohol and CNS depressant drugs - increased sedation
             Nonsteroidal antiinflammatory drugs - increased risk of 
             gastric irritation
             Drugs with antimuscarinic actions - increased gastric acid 
             Beta-adrenergic blocking agents - additive beta adrenergic 
             Bromocriptine - increased serum prolactin and decreased 
             bromocriptine activity
             Digitalis glycosides - possible increase in bradycardia and 
             Quinidine - possilbe increase in arrhythmias
             Estrogens - decrease antihypertensive effects of 
             Drugs causing extrapyramidal adverse effects - potentiate 
             extrapyramidal activity
             Antihypertensive agents- hypotension
             Levodopa - decreased efficacy of levodopa
             Monoamine oxidase inhibitors - increased CNS depression or 
             increased blood pressure and CNS stimulation
             Sympathomimetics - decreased effects of reserpine
             (Ellenhorn & Barceloux, 1988; USPC, 1989; Reynolds, 
        7.7  Main adverse effects
             The main adverse effects described with the therapeutic 
             administration of reserpine include lethargy and sedation, 
             psychiatric depression, hypotension, nausea, vomiting, 
             abdominal cramping, gastric ulceration, nightmares or vivid 
             dreams, bradycardia, and bronchospasm (in asthmatics)  Much 
             less common are symptoms of skin rash or itching, 
             Parkinsonian effects, and thrombocytopenia.  Adverse effects 
             are more common with daily doses of reserpine of 0.5 mg or 
             greater.  The lethargy and sedation is more common when other 
             CNS depressant drugs are being used concurrently.
             Adverse reactions were reported in 26 of 231 hospitalized 
             patients who received reserpine (Pfeifer et al, 1976)  Three 
             reactions after intramuscular reserpine doses of 0.5 mg or 
             greater were considered life-threatening (hypotension in 2 
             patients, cerebral edema in 1 patient), but no deaths were 
             attributed to reserpine.  Bronchospasm has been described 
             when reserpine is administered to asthmatics, and may be 
             relatively common (Segal, 1970)  A case of withdrawal 
             psychosis has been described (Samuels & Taylor, 1989). 
             (Pfeifer, et al, 1976; USPC, 1989; Reynolds, 1993)
        8.1  Material sampling plan
             8.1.1  Sampling and specimen collection
            Toxicological analyses
            Biomedical analyses
            Arterial blood gas analysis
            Haematological analyses
            Other (unspecified) analyses
             8.1.2  Storage of laboratory samples and specimens
            Toxicological analyses
            Biomedical analyses
            Arterial blood gas analysis
            Haematological analyses
            Other (unspecified) analyses
             8.1.3  Transport of laboratory samples and specimens
            Toxicological analyses
            Biomedical analyses
            Arterial blood gas analysis
            Haematological analyses
            Other (unspecified) analyses
        8.2  Toxicological Analyses and Their Interpretation
             8.2.1  Tests on toxic ingredient(s) of material
            Simple Qualitative Test(s)
            Advanced Qualitative Confirmation Test(s)
            Simple Quantitative Method(s)
            Advanced Quantitative Method(s)
             8.2.2  Tests for biological specimens
            Simple Qualitative Test(s)
            Advanced Qualitative Confirmation Test(s)
            Simple Quantitative Method(s)
            Advanced Quantitative Method(s)
            Other Dedicated Method(s)
             8.2.3  Interpretation of toxicological analyses
        8.3  Biomedical investigations and their interpretation
             8.3.1  Biochemical analysis
            Blood, plasma or serum
            Other fluids
             8.3.2  Arterial blood gas analyses
             8.3.3  Haematological analyses
             8.3.4  Interpretation of biomedical investigations
        8.4  Other biomed. investigations etc.
        8.5  Overall Interpretation etc.
        8.6  References
        9.1  Acute poisoning
             9.1.1  Ingestion
                    Poisoning with reserpine most commonly results 
                    in lethargy, sedation, and infrequently results in 
                    coma.  Other effects include psychiatric depression, 
                    hypothermia, facial flushing, nausea, vomiting, 
                    abdominal cramping, and cardiovascular toxicity 
                    including hypotension and bradycardia. (McKown, et al, 
                    1963; Loggie, et al, 1967)
             9.1.2  Inhalation
                    No data available
             9.1.3  Skin exposure
                    No data available
             9.1.4  Eye contact
                    No data available
             9.1.5  Parenteral exposure
                    After intramuscular injection of therapeutic 
                    doses of reserpine, hypotension, bronchospasm, 
                    lethargy and sedation have occurred. These effects are 
                    most commonly secondary to larger doses (0.5 mg or 
                    greater), and are not expected to be any different 
                    than the adverse effects associated with oral 
                    reserpine administration.
                    (Pfeifer, et al, 1976; Segal, 1969)
             9.1.6  Other
                    No data available
        9.2  Chronic poisoning
             9.2.1  Ingestion
                    The development of psychiatric depression, 
                    which can be severe, and gastric ulceration and 
                    hemorrhage are the most severe adverse effects of 
                    chronic reserpine therapy.  Nasal congestion, dry 
                    mouth, diarrhoea, abdominal pain, lethargy, 
                    Parkinsonian features, breast enlargement, 
                    galactorrhoea, impotence, sodium retention, peripheral 
                    oedema, and weight gain have been reported much less 
                    commonly. (Anon, 1976; USPC, 1989; Reynolds, 
             9.2.2  Inhalation
                    No data available
             9.2.3  Skin exposure
                    No data available
             9.2.4  Eye contact
                    No data available
             9.2.5  Parenteral exposure
                    The administration of intramuscular reserpine 
                    results in adverse effects similar to those seen with 
                    oral administration.  They are more commonly reported 
                    following intramuscular injection because of the 
                    larger doses administered and the increased 
                    bioavailability associated with this route (Pfeifer, 
             9.2.6  Other
                    No data available
        9.3  Course, prognosis, cause of death
             Symptoms of toxicity develop over the first 4 hours 
             after ingestion.  Symptoms generally resolve over 18 to 24 
             hours. Approximately 15% of the children described by McKown 
             et al (1963) required admission to the hospital for 
             observation.  The prognosis is generally very good, and 
             patients recover without sequelae (Hubbard, 1955; Loggie et 
             al, 1967).
             The psychiatric depression can take months to resolve (Anon, 
             Two deaths following reserpine poisoning have been reported 
             in the Russian literature.  Both cases were adults who died 
             of cardiovascular collapse and multi-organ system failure in 
             the first few days after ingestion.  One patient was known to 
             have ingested 5.0 mg of reserpine.  (Landyshev, et al, 1969; 
             Rogal, et al, 1989)
        9.4  Systematic description of clinical effects
             9.4.1  Cardiovascular
                    Cardiovascular effects associated with 
                    reserpine poisoning are relatively uncommon, with only 
                    2 cases of hypotension reported in a total of 151 
                    patients. (McKown, et al, 1963)  Bradycardia is also 
                    described, and there is one case of tachycardia and 
                    hypertension which developed approximately 10 hours 
                    after ingestion. (Loggie et al, 1967)  Angina-like 
                    symptoms, and dysrrhythmias are possible when 
                    reserpine is administered to patients taking a 
                    digitalis glycoside, quinidine, or procainamide. 
                    (Ellenhorn & Barceloux, 1988).
             9.4.2  Respiratory
                    Upper respiratory bronchospasm and nasal 
                    congestion may occur.
             9.4.3  Neurological
                             The most common symptoms with 
                             poisoning are lethargy and sedation, which 
                             occurred in 44% of 151 rauwolfia poisonings. 
                             (McKown, et al, 1963).  Coma is much less 
                             common.  A decrease in body temperature may 
                             develop. With poisonings, psychiatric 
                             depression may occur, however, it is more 
                             commonly described with chronic reserpine 
                             use.  Additional CNS effects include 
                             nightmares and vivid dreams, vertigo, 
                             headache, dizziness, nervousness, anxiety, 
                             and rarely deafness.  (Ellenhorn & Barceloux, 
                             1988). The development of extrapyramidal 
                             symptoms including dystonia and Parkinson's 
                             symptoms is reported, though it is not clear 
                             whether these develop after poisonings, or 
                             only with chronic therapy. (Haddad & 
                             Winchester, 1983)  Tardive dyskinesia has 
                             also been suggested, though cases are not 
                             identified in the literature. (Bacher & 
                             Lewis, 1984).  There is a case of reserpine 
                             withdrawal psychosis which developed over 1 
                             week after a 66 year old female ceased the 
                             daily ingestion of 3 mg of reserpine. 
                             (Samuels & Taylor, 1989)  Reserpine lowers 
                             the seizure threshold, however, clonic 
                             seizures have been described in only one case 
                             (Loggie et al, 1967)
            Peripheral nervous system
                             The effects of reserpine on the 
                             peripheral nervous system catecholamine 
                             stores would be expected to diminish the 
                             responsiveness of the reserpine poisoned 
                             patients to indirect acting vasoconstrictors 
                             such as dopamine.  Direct acting agents such 
                             as phenylephrine, metaraminol, and 
                             norepinephrine are suggested as 
                             vasoconstrictors for the treatment of 
                             hypotension which is unresponsive to 
                             intravenous fluids. (Reynolds, 
            Autonomic nervous system
                             No direct effects are described. 
                             The development of gastrointestinal 
                             ulceration is described as being due to 
                             increased gastric acid secretion which could 
                             be due to changes in autonomic nervous system 
                             function.  (Reynolds, 1993)
            Skeletal and smooth muscle
                             Gastric cramping is described. 
                             Muscle weakness can also occur. (USPC, 
             9.4.4  Gastrointestinal
                    Abdominal cramping, nausea, vomiting.  Gastric 
                    ulceration and hemorrhage are less common.  (USPC, 
                    1989; Reynolds, 1993)
             9.4.5  Hepatic
                    No data available
             9.4.6  Urinary
                             No data available
                             Painful or difficult urination is 
                             described as a rare adverse effect of chronic 
                             therapy. (USPC, 1989)
             9.4.7  Endocrine and reproductive systems
                    Chronic therapy is associated with breast 
                    engorgement and galactorrhoea.  Gynaecomastia, 
                    increased prolactin concentrations, decreased libido 
                    and impotence are also potential adverse effects of 
                    chronic therapy.  It is not known whether these 
                    effects occur with acute poisonings. (Reynolds, 
             9.4.8  Dermatological
                    Facial flushing, rashes, and pruritis. 
                    (Reynolds, 1993)
             9.4.9  Eye, ear, nose, throat: local effects
                    Nasal congestion, sialorrhoea, slight decrease 
                    in color vision, conjunctival injection, lachrymation, 
                    and miosis. (USPC, 1989; Reynolds, 1993)
             9.4.10 Haematological
                    Thrombocytopenic purpura (Reynolds, 1993)
             9.4.11 Immunological
                    Angioimmunoblastic lymphadenopathy (Ellenhorn 
                    & Barceloux, 1988)
             9.4.12 Metabolic
           Acid-base disturbances
                             No data available
           Fluid and electrolyte disturbances
                             Sodium and water retention with the 
                             development of edema. (Reynolds, 1993)
                             No data available
             9.4.13 Allergic reactions
                    There is cross sensitivity with reserpine 
                    among the different rauwolfia substances.  Reports of 
                    allergic reactions were not identified.  (USPC, 1989)
             9.4.14 Other clinical effects
                    Not identified
             9.4.15 Special risks
                    The administration of reserpine at the end of 
                    pregnancy can cause nasal congestion, respiratory 
                    distress, cyanosis, poor feeding, and lethargy in the 
                    newborn infant.
                    Reserpine is accepted therapy during breastfeeding 
                    based on the recommendations of the American Academy 
                    of Pediatrics.  (Briggs et al, 1986.)
        9.5  Other
             Most reserpine poisonings were reported in the 1960's, 
             and there are few recently described cases.  Toxicity is 
             generally not severe and results most commonly in lethargy 
             and sedation, and gastrointestinal irritation.  Hypotension, 
             usually mild and not requiring treatment, mild hypothermia, 
             and bradycardia are less frequently seen.  Psychiatric 
             depression is more likely to occur with chronic therapy with 
             doses of 0.5 mg or greater daily, as are the majority of the 
             other reported adverse and toxic effects of reserpine. 
             Facial flushing also occurs in poisonings.
        9.6  Summary
        10.1 General principles
             The patient should be assessed to determine that the 
             airway is clear, oxygenation is adequate, and the blood 
             pressure and heart rate are compatible with adequate tissue 
             perfusion.  Patients with a recent ingestion may benefit from 
             activated charcoal. The patient should be observed until 
             symptoms resolve.  Treatment of symptoms such as bradycardia 
             and hypotension should follow the general principles of 
             supportive care.  The use of atropine and H2-histamine 
             receptor antagonists may be considered for treatment of 
             gastric hyperacidity.
        10.2 Relevant laboratory analyses
             10.2.1 Sample collection
                    Laboratory analysis for the presence of 
                    reserpine in urine or blood has not been demonstrated 
                    to be useful in the management of the poisoned 
             10.2.2 Biomedical analysis
                    There are no specific laboratory analyses 
                    which would be required as part of the assessment and 
                    management of reserpine toxicity.
             10.2.3 Toxicological analysis
                    Reserpine assays are not generally performed, 
                    and it is unlikely that they would be of benefit in 
                    the management of reserpine toxicity.
             10.2.4 Other investigations
                    A history of the ingestion of reserpine or 
                    other rauwolfia alkaloids, the presence of 
                    hypertension which may be treated by reserpine, or 
                    access to reserpine is the most useful information 
                    when assessing the likelihood of reserpine poisoning 
                    as a diagnosis.
        10.3 Life supportive procedures etc.
             The patient should be evaluated to determine that the 
             airway is clear, breathing and circulation are adequate, and 
             observed until clinical signs of toxicity have resolved, 
             Symptomatic bradycardia can be treated with atropine. 
             Hypotension is treated initially with intravenous fluids.  If 
             vasopressor drug therapy is necessary, norepinephrine, 
             phenylephrine, or metaraminol would be more likely to be 
             effective, based on the mechanism of reserpine's toxicity 
             (Reynolds, 1993)
        10.4 Decontamination
             If the patient has symptoms of reserpine toxicity upon 
             presentation for treatment, or a history of the ingestion of 
             reserpine as a poisoning or overdose, gastrointestinal 
             decontamination may be considered.  Activated charcoal 
             administration would likely be of benefit in the first few 
             hours after ingestion, however, there is no data available to 
             indicate that reserpine is adsorbed to activated charcoal, or 
             is beneficial in the treatment of reserpine ingestions.  It 
             is probably less likely that ipecac syrup or gastric lavage 
             would be useful in treatment.
        10.5 Elimination
             There is no evidence that forced diuresis, changing 
             urinary pH, and other measures such as hemodialysis or 
             hemoperfusion are effective in increasing reserpine 
             elimination from the body. These treatments are not 
             recommended for the treatment of reserpine poisonings.
        10.6 Antidote treatment
             10.6.1 Adults
             10.6.2 Children
        10.7 Management discussion
        11.1 Case reports from literature
             Case 1.  A 20 month old boy ingested 260 mg of 
             reserpine, and was discovered to be lethargic, and flushed 
             with slowed respirations, a rapid pulse rate, and temperature 
             of 101.4 F four hours later.  He was treated with two 
             teaspoonfuls of magnesia magma and observed.  He was 
             lethargic, had facial flushing, nasal congestion, and was 
             otherwise normal the next day. (Hubbard 1956)
             Case 2.  A 3 year old female ingested an unknown dose of 
             reserpine which could have been as large as 25 mg.  She was 
             drowsy and had a mild decrease in temperature to 95.5 o F 
             measured rectally.  She had no other findings and her heart 
             rate, respiration, and blood pressure remained normal.  She 
             recovered over the next 48 hours without specific therapy. 
             (Loggie et al, 1967)
             Case 3.  A 2 year old male, the brother of Case 2 above, also 
             presented after ingestion of an unknown dose of reserpine 
             which could have been as large as 25 mg.  He was drowsy and 
             had constricted pupils upon presentation to the hospital, 
             with a normal temperature, pulse, respiratory rate, and blood 
             pressure. Over the next 7 hours he became more lethargic and 
             was comatose 9 hours after presentation.  He had a rectal 
             temperature of 96.4 o F, and his blood pressure decreased to 
             95/60 mmHg.  An hour later his blood pressure had increased 
             to 170/110 mmHg and remained elevated for approximately a day 
             and one half.  He had tremor and episodic clonic movements of 
             his arms and legs during this time. The boy's mental status 
             started to improve about 18 hours after ingestion, and had 
             returned to normal 10 hours later.  Gastric lavage and a 
             saline enema were administered when the boy was admitted to 
             the hospital, and maintenance doses of intravenous fluids 
             administered over the first 36 hours. (Loggie et al, 
        11.2 Internally extracted data on cases
             To be entered by each centre
        11.3 Internal cases
             To be entered by each centre
        12.1 Availability of antidotes
        12.2 Specific preventive measures
        12.3 Other
        Anon. (1976) Severe depression caused by reserpine.  Med Lett 
        Drugs Ther, 18(4):19-20.
        Briggs GG, Freeman RK, Yaffe SJ. eds. (1986)  Drugs in pregnancy 
        and lactation - a reference guide to fetal and neonatal risk, 2nd 
        ed. Baltimore, MD, Williams and Wilkins, pp402/r-403/r.
        Bacher NM & Lewis HA (1984) Reserpine and tardive dyskinesia.  Am 
        J Psychiatry, 141(5): 719.
        Ellenhorn MJ & Barceloux DG  (1988) Medical toxicology -Diagnosis 
        and treatment of human poisoning,  New York, Elsevier , 
        Gilman AF, Rall WT,  Nies AD, Taylor P, editors, (1990)   Goodman 
        and Gilman's The Pharmacologic Basis of Therapeutics, 8th ed, 
        Pergamon Press, New York, New York, 1990, pp795.
        Haddad LM & Winchester JF (1983)  The clinical management of 
        poisoning and drug overdose. WB Saunders Co, Philadelphia, 
        Horwitz RI & Feinstein AR  (1985)  Exclusion bias and the false 
        relationship of reserpine and breast cancer.  Arch Intern Med, 
        145: 1873-1875.
        Hubbard BA  (1955) Reserpine.  JAMA, 157:468.
        Landyshev IuS, Pronina EI, Markelov IP  (1969) [Fatal case of 
        reserpine poisoning.]  Klin Med Mosk, 47(10): 141-142 (in 
        Loggie JMH, Saito H, Kahn I, Fenner A, Gaffney TE  (1967) 
        Accidental reserpine poisoning:  clinical and metabolic effects. 
        Clin Pharmacol Therap, 8:  692-695.
        Maass AR, Jenkins B, Shen Y, Tannenbaum P  (1969)  Studies on 
        absorption, excretion, and metabolism of  3H-reserpine in man. 
        Clin Pharmacol Ther, 10:  366-377.
        McKown CH, Verhulst HL, Crotty JJ  (1963)  Overdosage effects and 
        danger from tranquilizing drugs.  JAMA, 185(6): 425-430.
        Pfeifer HJ, Greenblatt DJ, Koch-Weser J  (1976)  Clinical toxicity 
        of reserpine in hospitalized patients:  a report from the Boston 
        collaborative drug surveillance program.  Am J Med Sci, 271(3): 
        Reynolds JEF ed. (1993) Martindale, the extrapharmacopoeia, 30th 
        ed. London, the Pharmaceutical Press, pp386-387.
        Rogal PP, Rakitin VA, Boichak MP, Gusarov AI, Ivachev VG  (1989) 
        [Fatal reserpine poisoning]  Sud Med Ekspert, 32:  51-52. (in 
        Samuels AH & Taylor AJ  (1989)  Reserpine withdrawal psychosis. 
        Aus NZ J Psych, 23:  129-130.
        Segal MS  (1969)  Bronchospasm after reserpine.  N Eng J Med, 
        281(25):  1426-1427.
        Surwit Rs, Gilgor RS, Duvie M, Allen LM, Neal JA  (1983) 
        Intra-arterial reserpine for Raynaud's syndrome.  Arch Dermatol, 
        119:  733-735.
        The United States Pharmacopeial Convention, Inc.(1989)  Rauwolfia 
        alkaloids (systemic).  In The United States Pharmacopeia Drug 
        Information for the Health Care Professional.  Volume 1A, 9th 
        edition, Rockville, MD, pp 2091-2096.
        von Poser C, Andrade HH, da Silva KV, Henriques AT, Henriques JA 
        (1990)  Genotoxic, mutagenic and recombinogenic effects of 
        rauwolfia alkaloids.  Mutat Res, 232(1):  37-43.
        Zsoter TT, Johnson  GE, DeVeber GA, Paul H  (1973)  Excretion and 
        metabolism of reserpine in renal failure.  Clin Pharmacol Ther, 
        14(3):  325-330.
    14. AUTHOR(S), ETC.
        Dr. S. Lall, New Delhi
        Reviewer, Dr. Wm A. Watson, Kansas City
        Reviewed at INTOX-9, Cardiff, Wales, Sept, 1996

    See Also:
       Toxicological Abbreviations
       Reserpine  (IARC Summary & Evaluation, Supplement7, 1987)
       Reserpine (IARC Summary & Evaluation, Volume 10, 1976)
       Reserpine (IARC Summary & Evaluation, Volume 24, 1980)