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Ephedrine

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS
      1.4.2 Other numbers
   1.5 Main brand names
   1.6 Main manufacturers and/or importers
2. SUMMARY
   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. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Colour
      3.3.2 State/form
      3.3.3 Description
   3.4 Other characteristics
      3.4.1 Shelf-life of the substance
      3.4.2 Storage conditions
4. USES
   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. ROUTES OF EXPOSURE
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Other
6. KINETICS
   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. PHARMACOLOGY AND TOXICOLOGY
   7.1 Mode of action
      7.1.1 Toxicodynamics
      7.1.2 Pharmacodynamics
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 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. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
         8.1.3.6
   8.2 Toxicological analyses and their interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple qualitative test(s)
         8.2.1.2 Advanced qualitative confirmation test(s)
         8.2.1.3 Simple quantitative method(s)
         8.2.1.4 Advanced quantitative method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple qualitative test(s)
         8.2.2.2 Advanced qualitative confirmation test(s)
         8.2.2.3 Simple quantitative method(s)
         8.2.2.4 Advanced quantitative method(s)
         8.2.2.5 Other dedicated method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall interpretation of all toxicological analyses and toxicological investigations
9. CLINICAL EFFECTS
   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
         9.4.3.1 CNS
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 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
         9.4.12.1 Acid base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Other
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Life supportive procedures and symptomatic/specific treatment
   10.3 Decontamination
   10.4 Enhanced elimination
   10.5 Antidote treatment
      10.5.1 Adults
      10.5.2 Children
   10.6 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from literature
12. ADDITIONAL INFORMATION
   12.1 Specific preventive measures
   12.3 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S) DATA (INCLUDING EACH UPDATING), COMPLETE ADDRESSES



    Ephedrine

    International Programme on Chemical Safety
    Poisons Information Monograph 209
    Pharmaceutical

    1.  NAME

        1.1  Substance

             Ephedrine

        1.2  Group

        1.3 Synonyms

             Ephedrinum;
             Hydrated ephedrine,
             Eedrynum hidratum;
             Ephedrina;
             Ma-huang;

        1.4  Identification numbers

             1.4.1  CAS

                    229-42-3 (anhydrous)

             1.4.2  Other numbers

                    50906-05-3 (hemihydrate)
                    ATC codes: R01AA03
                               S01FB02

        1.5  Main brand names

             Amidrin; Daral; Fluidin; Kidargol; Rhinamide; Tedral;
             Tenfril; Vicks decongestive cough syrup

        1.6  Main manufacturers and/or importers

             Farmacéutica Uruguaya
             Lab. Andrómaco
             Roussel-Labur

    2.  SUMMARY

        2.1  Main risks and target organs

             Cardiovascular: heart and arterial vessels
             CNS stimulation
             Chronic use can lead to tolerance with dependence

        2.2  Summary of clinical effects

             Digestive disorders: nausea, vomiting.
             Cardiovascular impairment: tachycardia, severe hypertension
             and secondary myocardial infarction and/or stroke.
             Central effects: anxiety, tremor, irritability,
             hallucinations, psychotic states, seizures, intracerebral
             haemorrhage.
             Metabolic dysfunction: hyperglycaemia, hypokalaemia
             (intracellular shift).

        2.3  Diagnosis

             Diagnosis is based on history and/or the presence of
             nausea, vomiting, tachycardia, headache, elevated blood
             pressure. Ephedrine and its metabolites can be analyzed in
             blood and urine by gas chromatography.

        2.4  First aid measures and management principles

             Gastrointestinal decontamination
             Supportive and symptomatic care; administration of
             propranolol in patients with severe arterial
             hypertension.

    3.  PHYSICO-CHEMICAL PROPERTIES

        3.1  Origin of the substance

             Ephedra species (particularly E. sinica) contain chiefly
             two alkaloids: ephedrine and pseudoephedrine, which is a
             stereoisomer of ephedrine.  Ephedra species have been used as
             a source of ephedrine; ephedrine is also prepared
             synthetically.
    
             Ephedra is sold as a traditional Chinese medicinal herb under
             the name Ma-huang.
             (Parfitt, 1999)

        3.2  Chemical structure

             Molecular formula:
    
             C10 H15 NO1
    
             Molecular mass: 165.2
    
             Structural name:
             (1R,2S)-2-methylamino-1-phenylpropan-1-ol

        3.3  Physical properties

             3.3.1  Colour

                    Colourless or white

             3.3.2  State/form

                    Solid-crystals
                    Solid-powder

             3.3.3  Description

                    Bitter taste; odourless or slight aromatic
                    odour.  In warm weather it slowly volatilizes.  The
                    anhydrous substance melts at 36°C and the hemihydrate
                    melts at 42°C. It is a weak base, with a pKa = 9.6 
                    Ephedrine decomposes with light.  Solutions in oil can
                    have a garlicky odour.  It is soluble in water (1 in
                    20) and in alcohol, chloroform, ether, glycerol, olive
                    oil and in liquid paraffin (Windholz, 1983).
    
                    Ephedrine and its optical isomer pseudoephedrine are
                    structurally very similar to methamphetamine. In
                    illicit drug laboratories simple dehydrogenation is
                    used to make methamphetamine from ephedrine (Kelley
                    1998).

        3.4  Other characteristics

             3.4.1  Shelf-life of the substance

             3.4.2  Storage conditions

                    Protect from light.
                    Temperatures must not exceed 8EC in containers.

    4.  USES

        4.1  Indications

             4.1.1  Indications

             4.1.2  Description

                    The most important uses are:
                    -  as a  bronchodilator
                    -  nasal decongestant

                    -  other uses:   syndrome of Stokes-Adams; as a
                                     mydriatic and hypertensor in the
                                     spinal-anesthesia. It is also used as
                                     an herbal diet supplement under the
                                     name "Ma-huang" as an anorectic and
                                     CNS stimulant. 

        4.2  Therapeutic dosage

             4.2.1  Adults

                    15 to 60 mg of ephedrine hydrochloride or
                    sulphate 3 or 4 times  daily as a bronchodilator
                    

             4.2.2  Children

                    500 (g/kg body weight of ephedrine
                    hydrochloride or sulphate 3 or 4 times daily (Parfitt,
                    1999).

        4.3  Contraindications

             Cardiovascular disease; hypertension; hyperthyroidism;
             phaeochromocytoma and closed angle glaucoma.  Ephedrine
             should not be given in patients being treated with MAOI (or
             have stopped treatment in the last 14 days) (Dukes, 1988;
             Parfitt, 1999; Dawson et al., 1995). It should be used with
             caution in patients with prostatic enlargement or with renal
             impairment

    5.  ROUTES OF EXPOSURE

        5.1  Oral

             Abuse of ephedrine-containing diet pills is a common
             occurrence (MMWR, 1996).

        5.2  Inhalation

             Ephedrine salts are used as nasal drops or sprays in the
             relief of nasal congestion associated with cold or rhinitis.
             Ephedrine can be abused by the nasal route by subjects who
             have developed dependence to its vasoconstrictive effect
             (Bismuth, 2000).

        5.3  Dermal

             As an ointments well absorbed.

        5.4  Eye

             Eye-drops at 0.1% are effective in congestion of
             conjunctival allergy.

        5.5  Parenteral

             Subcutaneous or intramuscular injections.

        5.6  Other

    6.  KINETICS

        6.1  Absorption by route of exposure

             Ephedrine is readily and completely absorbed from the
             gastrointestinal tract; plasma peak concentrations are
             reached an hour after ingestion
             A single oral dose of 24 mg produced an average peak plasma
             concentration of 0.10 mg/L (Goldfrank, 1990).

        6.2  Distribution by route of exposure

             The volume of distribution is about 3L/kg; patients with
             toxicity are not good candidates for haemodialysis (Kelley
             1998).

        6.3  Biological half-life by route of exposure

             It has a plasma half-life ranging from 3 to 6 hours
             depending on urinary pH (Parfitt, 1999).
             No change in half-life from that seen with therapeutic dosing
             was observed in an otherwise healthy patient with massive
             overdose (Snook et al., 1992).
             The ephedrine concentrations in three fatalities were 3.49;
             7.85 and 20.5 mg/L (Ellenhorn, 1988).

        6.4  Metabolism

             Only a small amount of ephedrine is metabolized in the
             liver.

        6.5  Elimination by route of exposure

             It is largely excreted unchanged in the urine, with some
             deaminated metabolites and N-demethylated metabolites.
             Elimination is enhanced in acid urine.
             (Parfitt, 1999)
             Less than 10% of ephedrine is excreted as norephedrine. In
             normal subjects 70-80% of a dose is eliminated unchanged in
             the urine within 48 hours. 4% is present as norephedrine
             (Baselt and Cravey 1995)

    7.  PHARMACOLOGY AND TOXICOLOGY

        7.1  Mode of action

             7.1.1  Toxicodynamics

                    Ephedrine can produce stimulation at the
                    adrenergic receptors and neuronal norepinephrine
                    release (Kelley 1998).

             7.1.2  Pharmacodynamics

                    Ephedrine has both alpha- and beta-adrenergic
                    activities, and both direct and indirect effects on
                    receptors. It raises blood pressure both by increasing
                    cardiac output and inducing peripheral
                    vasoconstriction (Shufman et al., 1994; Parfitt,
                    1999).
                    It can produce bronchodilation. In local application
                    it causes pupils dilation. The main metabolic effects
                    in overdose are hyperglycaemia and hypokalaemia. 
                    Ephedrine is a centrally acting respiratory stimulant
                    and can increase motor activity.

        7.2  Toxicity

             7.2.1  Human data

                    7.2.1.1  Adults

                             The ephedrine concentrations in
                             three fatalities were 3.49, 7.85, and
                             20.5mg/L (Kelley 1998). However survival at
                             levels of 23mg/L has been reported (Baselt
                             and Cravey 1995)

                    7.2.1.2  Children

             7.2.2  Relevant animal data

             7.2.3  Relevant in vitro data

        7.3  Carcinogenicity

             No data available

        7.4  Teratogenicity

             No data available

        7.5  Mutagenicity

             No data available

        7.6  Interactions

             A serotonin syndrome has been reported in a patient
             taking paroxetine and an over-the-counter cold medicine
             containing ephedrine (Skop et al., 1994).
             Combination of ephedrine and a MAOI can produce
             life-threatening reactions (Dawson et al., 1995). It should
             also be avoided in patients undergoing anaesthesia with
             cyclopropane, halothane or other volatile anaesthesia. An
             increased risk of arrhythmias may occur if given to patients
             receiving cardiac glycosides, quinidine or tricyclic
             antidepressants, ergot alkaloids, oxytocin (Parfitt
             1999).

        7.7  Main adverse effects

             Central effects of sympathomimetic agents include:
             tremor, fear, anxiety, confusion, irritability, insomnia, and
             psychotic states. Paranoid psychosis, delusions and
             hallucinations may also follow ephedrine overdose.
    
             Effects on the cardiovascular system are complex:
             vasoconstriction, hypertension, or hypotension and
             bradycardia, tachycardia, palpitations, cardiac arrest.
    
             It can cause local ischaemia in chronic topical use (Parfitt,
             1999).

    8.  TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

        8.1  Material sampling plan

             8.1.1  Sampling and specimen collection

                    8.1.1.1  Toxicological analyses

                    8.1.1.2  Biomedical analyses

                    8.1.1.3  Arterial blood gas analysis

                    8.1.1.4  Haematological analyses

                    8.1.1.5  Other (unspecified) analyses

             8.1.2  Storage of laboratory samples and specimens

                    8.1.2.1  Toxicological analyses

                    8.1.2.2  Biomedical analyses

                    8.1.2.3  Arterial blood gas analysis

                    8.1.2.4  Haematological analyses

                    8.1.2.5  Other (unspecified) analyses

             8.1.3  Transport of laboratory samples and specimens

                    8.1.3.1  Toxicological analyses

                    8.1.3.2  Biomedical analyses

                    8.1.3.3  Arterial blood gas analysis

                    8.1.3.4  Haematological analyses

                    8.1.3.5  Other (unspecified) analyses

                    8.1.3.6

        8.2  Toxicological analyses and their interpretation

             8.2.1  Tests on toxic ingredient(s) of material

                    8.2.1.1  Simple qualitative test(s)

                    8.2.1.2  Advanced qualitative confirmation test(s)

                    8.2.1.3  Simple quantitative method(s)

                    8.2.1.4  Advanced quantitative method(s)

             8.2.2  Tests for biological specimens

                    8.2.2.1  Simple qualitative test(s)

                    8.2.2.2  Advanced qualitative confirmation test(s)

                    8.2.2.3  Simple quantitative method(s)

                    8.2.2.4  Advanced quantitative method(s)

                    8.2.2.5  Other dedicated method(s)

             8.2.3  Interpretation of toxicological analyses

        8.3  Biomedical investigations and their interpretation

             8.3.1  Biochemical analysis

                    8.3.1.1  Blood, plasma or serum

                             "Basic analyses"

                             "Dedicated analyses"

                             "Optional analyses"

                    8.3.1.2  Urine

                             "Basic analyses"

                             "Dedicated analyses"

                             "Optional analyses"

                    8.3.1.3  Other fluids

             8.3.2  Arterial blood gas analyses

             8.3.3  Haematological analyses

                    "Basic analyses"

                    "Dedicated analyses"

                    "Optional analyses"

             8.3.4  Interpretation of biomedical investigations

        8.4  Other biomedical (diagnostic) investigations and their
             interpretation

        8.5  Overall interpretation of all toxicological analyses and
             toxicological investigations

    9.  CLINICAL EFFECTS

        9.1  Acute poisoning

             9.1.1  Ingestion

                    Early clinical manifestations of ingestion of
                    high doses of ephedrine consist of nausea and
                    vomiting, followed by insomnia, cardiac arrhythmia,
                    myocardial ischemia, agitation, psychosis and
                    seizures.

             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

                    The parenteral use of ephedrine may cause
                    intracerebral haemorrhage as a result of a rise in
                    arterial pressure.  Ventricular arrhythmias have been
                    described (Ellenhorn 1988).

             9.1.6  Other

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    Neurological symptoms that have been described
                    include  headache, anxiety, tremor, insomnia,
                    dizziness, seizures (MMWR, 1996). Several cases of
                    psychosis have been reported (Roxanas & Spalding,
                    1977; Shufman et al., 1994; Copwell, 1995; Doyle &
                    Kargin, 1996; Jacobs & Kirsch, 2000).
                    Cardiovascular disorders associated with the chronic
                    use of ephedrine may include chest pain, hypertension,
                    arrhythmia, myocardial infarction, cerebral vascilitis
                    and stroke (MMWR, 1996).

             9.2.2  Inhalation

                    No data available

             9.2.3  Skin exposure

                    Local applications of ephedrine may cause
                    contact dermatitis (Tomb et al., 1991).

             9.2.4  Eye contact

                    No data available.

             9.2.5  Parenteral exposure

                    The intravenous use of ephedrine causes similar
                    effects as oral ingestion.

             9.2.6  Other

                    The vasoconstrictive effects of ephedrine
                    applied topically as nasal spray or drops may cause
                    local ischaemia (Parfitt, 1999).

        9.3  Course, prognosis, cause of death

             Early clinical manifestations of ephedrine overdose
             consist of nausea and vomiting, followed by headache,
             agitation, anxiety, tremor, seizures, tachycardia and
             hypertensive crisis. Severe rise in blood pressure may
             produce cerebral haemorrhage and myocardial infarction.
             Ventricular arrhythmia may progress to cardiac arrest and
             death. Although fatalities have been reported the prognosis
             is usually good (Burkhart, 1992; Snook et al., 1992; MMWR,
             1996; Backer et al., 1997; Theoharides, 1997; Hedetoft et
             al., 1999).

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    The most common symptoms are arterial
                    hypertension and tachycardia; ventricular arrhythmia,
                    chest pain, myocardial infarction, ischaemic or
                    haemorrhagic stroke, cardiac arrest may rarely occur
                    (Burkhart, 1992; Snook et al., 1992; MMWR, 1996;
                    Parfitt, 1999; Matthews et al., 1997; Hedetoft et al.,
                    1999)

             9.4.2  Respiratory

                    Respiratory stimulation, bronchodilation,
                    pulmonary oedema apnea (Parfitt, 1999).

             9.4.3  Neurological

                    9.4.3.1  CNS

                             CNS stimulation: anxiety, agitation,
                             tremor, mental confusion, hallucinations,
                             mania, paranoid psychosis may occur;
                             convulsions have been reported.

                             (Roxanas & Spalding, 1977; Snook et al.,
                             1992; Shufman et al., 1994; Copwell, 1995;
                             Doyle & Kargin, 1996; Jacobs & Kirsch,
                             2000).

                    9.4.3.2  Peripheral nervous system

                             No data available.

                    9.4.3.3  Autonomic nervous system

                             Ephedrine causes stimulation of the
                             sympathetic nervous system acting on both
                             alpha and beta receptors. Symptoms include
                             tachycardia, arterial hypertension, tremor,
                             sweating, mydriasis.

                    9.4.3.4  Skeletal and smooth muscle

                             Ephedrine produces relaxation of
                             smooth muscle. In overdose it may also cause
                             rhabdomyolysis (Salmon and Nicholson
                             1988)

             9.4.4  Gastrointestinal

                    Nausea and vomiting are common.

             9.4.5  Hepatic

                    No data available.

             9.4.6  Urinary

                    9.4.6.1  Renal

                             No data available.

                    9.4.6.2  Other

                             Ephedrine relaxes the vesical
                             detrusor muscle, and increases contraction of
                             the vesical sphincter (alpha agonist action),
                             and can produce acute retention of urine
                             (Parfitt, 1999).

             9.4.7  Endocrine and reproductive systems

                    Inhibition of insulin secretion.

             9.4.8  Dermatological

                    No data available

             9.4.9  Eye, ear, nose, throat: local effects

                    Chronic administration of nasal drops or spray
                    can result in rebound nasal congestion and rhinorrhoea
                    (Parfitt, 1996; Bismuth, 2000).

             9.4.10 Haematological

                    Leukopenia.

             9.4.11 Immunological

                    No data available.

             9.4.12 Metabolic

                    9.4.12.1 Acid base disturbances

                             Metabolic acidosis.

                    9.4.12.2 Fluid and electrolyte disturbances

                             Hypokalaemia resulting from
                             intracellular shift.

                    9.4.12.3 Others

                             Hyperglycaemia.

             9.4.13 Allergic reactions

                    Contact dermatitis after local application.
                    Sensitization and systemic allergic reactions (severe
                    eczema) have been reported after oral administration
                    (Audicana et al., 1991; Tomb et al., 1991).

             9.4.14 Other clinical effects

             9.4.15 Special risks

                    Ephedrine is present in breast-milk in
                    sufficient concentrations to be harmful to the baby,
                    and is contraindicated in women who are
                    breast-feeding. Patients with ischaemic heart disease,
                    hypertension, acute angle glaucoma, hyperthyroidism,
                    prostatic enlargement, or taking MAOI antidepressants
                    should also avoid ephedrine.

        9.5  Other

             Chronic use can lead to tolerance with dependence.
             Ephedrine abuse is a common occurrence and has been
             associated with several deaths (Roxanas & Spalding, 1977;
             Copwell, 1995; Doyle & Kargin, 1996; Gualtieri & Harris,
             1996; MMWR, 1996; Theoharides, 1997; Jacobs & Kirsch,
             2000).

        9.6  Summary

    10. MANAGEMENT

        10.1 General principles

             Establish airway patency, breathing and circulation. 
             Establish baseline blood pressure and pulse.
             Treatment is primarily supportive.
             ECG monitoring is necessary. Monitor urine output.
             Gastrointestinal decontamination may be indicated
             There is no antidote.

        10.2 Life supportive procedures and symptomatic/specific treatment

             Severe hypertension and tachycardia should be treated
             with the intravenous administration of a short-acting,
             selective beta-blocker such as esmolol (Burkhart, 1992;
             Bismuth, 2000). (Care should be taken as hypertension may be
             aggrevated with use of beta-blockers owing to unopposed
             alpha-agonist effects). Alternative treatments for
             hypertension include nitroprusside or nitroglycerin infusion
             In the treatment of ventricular dysrhythmias, lidocaine or
             bretylium may be required.
             Convulsions require administration of intravenous
             diazepam.

        10.3 Decontamination

             Gastric lavage may be performed within 2 hours of
             ingestion but can also increase intracranial pressure. Emesis
             is contra-indicated
             Administration of activated charcoal.

        10.4 Enhanced elimination

             Maintenance of adequate urine output is essential;
             although ephedrine elimination is best achieved in acidic
             urine, however the risk of this procedure in this setting
             probably outweighs the potential benefits (Kelley 1998);
             there is no evidence of the usefulness of forced diuresis,
             hemodialysis or peritoneal dialysis in enhancing ephedrine
             elimination.

        10.5 Antidote treatment

             10.5.1 Adults

             10.5.2 Children

        10.6 Management discussion

    11. ILLUSTRATIVE CASES

        11.1 Case reports from literature

             A 20 y-o woman ingested 300 diet pills containing a
             total of 7.5 g of ephedrine in a suicide attempt. She
             presented to the ED two hours post ingestion, with a HR of
             116, BP 146-60 mmHg, she was agitated and anxious, with
             tremor and vomiting. Treatment included gastric lavage,
             activated charcoal, and 1 mg propranolol. Serum ephedrine
             level was 22.8 nanog/mL (therapeutic range: 0.04-0.08
             nanog/mL) at 90 minutes post ingestion. The patient made an
             uneventful recovery (Snook et al., 1992).
    
             After ingesting 17500 mg of ephedrine, a 29 y-o female
             developed a BP of 168-106. Her BP was 124-90 five minutes
             after IV propranolol (Burkhart, 1992).
    
             A 19 y-o woman ingested 1000 mg of ephedrine in combination
             with 10000 mg of caffeine. She developed severe toxic
             manifestations from the heart, CNS, muscles, liver and
             kidneys leading to multiorgan failure, cardiac arrests and
             died subsequently of cerebral oedema on the fourth day of
             hospitalization (Hedetoft et al., 1999).
    
             A 57 y-o woman had been taking a usual dose of ephedrine for
             bronchial asthma (50 mg 3 times a day) for more than 30
             years. When her husband died she developed depression, for
             which she tried to use ephedrine as an antidepressant,
             increasing the dose to 500 to 1000 mg a day over the course
             of half a year. She developed paranoid psychosis with
             delusions of persecution and auditory hallucinations.
             Recovery was rapid after ephedrine was gradually reduced to
             200 mg a day (Shufman et al., 1994)

    12. ADDITIONAL INFORMATION

        12.1 Specific preventive measures

        12.3 Other

    13. REFERENCES

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        Corres L (1991) Sensitization to ephedrine in oral anticatarrhal
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        Backer R, tautman D, Lowry S, Harvey CM, Poklis A (1997) Fatal
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        Bacelt RC, Cravey RH. (1995) Disposition of toxic drugs and
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        Bismuth C Ed. (2000) Toxicologie clinique, 5čme Ed, Flammarion,
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        Burkhart KK (1992) Intravenous propranolol reverses hypertension
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        Toxicol, 30: 109-114
    
        Copwell RR (1995) Ephedrine-induced mania from an herbal diet
        supplement. Am J Psychiatry, 152: 647
    
        Dawson JK, Earnshaw SM, Graham CS (1995) Dangerous monoamine
        oxidase inhibitor interactions are still occurring in the 1990's.
        J Accid Emerg Med, 12: 49-51
    
        Doyle H & Kargin M (1996) Herbal stimulant containing ephedrine
        has also caused psychosis. BMJ, 313: 756
    
        Dukes, MNG (1988) Meylers Side effects of drugs, 11th ed.,
        259-260.
    
        Ellenhorn MJ, Barceloux DG (1988)  Medical Toxicology - Diagnosis
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        Hedetoft C, Jensen CH, Christensen MR, Christensen O (1999) Fatal
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        Ma-huang. Psychosomatics, 41: 58-62
    

        Kelley MT (1998). Chapter 39 Sympathiomimetics. In Clinical
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        pp1082-1083
    
        Matthews G, Smolinske S, White S (1997) Ephedrine-related stroke
        in a teenager. Clin Toxicol, 35: 555 (abstract)
    
        MMWR Morb Mortal Wkly Rep (1996) Adverse events associated with
        ephedrine-containing products-Texas, December 1993-September 1995.
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        Parfitts K. (1999) The Extra Pharmacopoeia, 31 Ed, The
        pharmaceutical Press, London
    
        Roxanas MG & Spalding J (1977) Ephedrine abuse psychosis. Med J
        Aust, 2: 639-640
    
        Salmon J, Nicholson D. DIC and rhabdomyolysis following
        pseudoephedrine overdose. Am J Emerg Med 1988;6:545-546
    
        Shufman NE, Witztum E, Vass A (1994) Ephedrine psychosis.
        Harefuah, 127: 166-8, 215
    
        Skop BP, Finkelstein JA, Mareth TR, Magoon MR, Brown TM (1994) The
        serotonin syndrome associated with paroxetine, an over-the-counter
        cold remedy and vascular disease. Am J Emerg Med, 12: 642-644
    
        Snook C, Otten M, Hassan M (1992) Massive ephedrine overdose: case
        report and toxicokinetic analysis. Vet Human Toxicol, 34: 335
        (abstract)
    
        Theoharides TC (1997) Sudden death of a healthy college student
        related to ephedrine toxicity from a Ma-huang-containing drink. J
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        Tomb RR, Lepoittevin JP, Espinassouze F, Heid E, Foussereau J
        (1991) Systemic contact dermatitis from pseudoephedrine, Contact
        Dermatitis, 24: 86-88
    
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        Co., Inc.

    14. AUTHOR(S), REVIEWER(S) DATA (INCLUDING EACH UPDATING), COMPLETE
        ADDRESSES

        Author:     Dr Mabel Burger
    
        Address:    CIAT - Piso  7E
                    Hospital de Clinicas
                    Avenida Italia s/n
                    Montevideo
                    Uruguay
    
                    Tel:     (598 2)  80 40 00
                             (598 2)  47 03 00
    
                    Fax:     (598 2)  47 03 00
    
        Date:                July 1991
    
        Update:     MO Rambourg Schepens, September 2000
    
        Reviewed at INTOX 12, Erfurt, Germany, November 2000
        Reviewers M. Balali-Mood, W. Temple, B. Groszek, N. Langford.