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 Main brand names, main trade names
   1.6 Main 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 principle
   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
   4.1 Indications
      4.1.1 Indications
      4.4.2 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 and excretion
   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
   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 Gastro-intestinal
      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 Disturbance 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 Life supportive procedures and symptomatic/specific treatment
   10.3 Decontamination
   10.4 Elimination
   10.5 Antidote Treatment
      10.5.1 Adults
      10.5.2 Children
   10.6 Management discussion
   11.1 Case reports from literature
   12.1 Specific preventive measures
   12.2 Other

    International Programme on Chemical safety
    Poisons Information Monograph 139

    1.  NAME

        1.1  Substance


        1.2  Group

             Nervous system; anesthetics;
             local; esters of benzoic acid (N01BC01)

        1.3  Synonyms

             (-)-cocaine; ß-cocaine;
             Ecgonine methyl ester benzoate;
             L-cocaine; Methylbenzoylecgonine;
             cocaina; Erytroxylin;
             Kokain; Kokan; Kokayeen;
             Neurocaïne; Bernice;
             Bernies; Blow; Burese;
             C; Cadillac of drugs;
             Carrie; Cecil; 
             Champagne of drugs; Charlie;
             Cholly; Coke; Corine;
             Crack; Dama blanca;
             Eritroxilina; Flake; Girl;
             Gold dust; Green gold; 
             Happy dust; Happy trails;
             Her; Jam; Lady;
             Leaf; Nose candy; 
             Pimp's drug; Rock; She;
             Snow; Star dust; 
             Star-spangled powder; Toot; 
             White girl; White lady; 
             liquid lady (alcohol + cocaine); 
             speed ball (heroine + cocaine)

        1.4  Identification numbers

             1.4.1  CAS number

                    50-36-2 (cocaine)

             1.4.2  Other numbers

                    CAS cocaine hydrochloride: 53-21-4
                    ATC codes: 


        1.5  Main brand names, main trade names

             mélange de Bonain 

        1.6  Main manufacturers / importers

             Merck (Germany); Stepan Chemical Company (Mazwood,
             New-Jersey, USA) 

    2.  SUMMARY

        2.1  Main risks and target organs

             The target organs are Central Nervous System (CNS) and
             the Cardio-vascular (CV) system.
             Abuse of cocaine leads to strong psychological

        2.2  Summary of clinical effects

             Effects depend on the dose, the other substances taken,
             the route of administration and individual
             In low doses acute intoxication causes euphoria and
             Larger doses cause hyperthermia, nausea, vomiting, abdominal
             pain, chest pain, tachycardia, ventricular arrhythmia,
             hypertension, extreme anxiety, agitation, hallucination,
             mydriasis. These can be followed by CNS depression with
             irregular respirations, convulsions, coma, cardiac
             disturbances, collapse and death.
             Chronic intoxication produces euphoria, agitation
             psychomotor, suicidal ideation, anorexia, weight loss,
             hallucinations and mental deterioration.
             A withdrawal syndrome with severe psychiatric effects can
             occur (euphoria, depression).
             Physical signs of withdrawal have been described.

        2.3  Diagnosis

             Clinical features:
             Acute cocaine poisoning produces signs similar to acute
             amphetamine poisoning: psychiatric disturbance (agitation,
             hallucinations), neurological effects (mydriasis,
             convulsions), cardiovascular problems (tachycardia, raise in
             blood pressure, arrhythmia and acute coronary insufficiency)
             and respiratory difficulties (cardio-respiratory arrest).
             When agitation, convulsions, acute coronary insufficiency are
             seen in a young patient without previous cardiovascular
             problems, cocaine poisoning should be suspected.
             Headaches may be due to stroke or transient ischemic attack
             or to intra-cerebral or subarachnoid haemorrhage. Spontaneous
             cerebral haemorrhage can occur in normotensive subjects.
             Laboratory: by detection of urinary metabolites of cocaine.

        2.4  First aid measures and management principle

             In case of ingestion, gastric emptying, may provoke
             convulsions and is dangerous. Ipecac should not be used.
             Treatment of acute intoxication is symptomatic.
             If there are convulsions or agitation, 2.5 to 5 mg diazepam
             by slow intravenous injection can be given, and repeated
             every 10 to 15 minutes up to a maximum of 30 mg; in status
             epilepticus, thiopentone with intubation and mechanical
             ventilation is used.
             In acute psychiatric disturbance, 2 to 5 mg haloperidol
             intramuscularly may be required.
             Betablockers may correct cardiac arrhythmia but may aggravate
             coronary or systemic vasoconstriction. Antiarrhythmic and
             cardioversion can be used but intravenous lidocaine should be
             avoided because it can provoke convulsions.
             Severe arterial hypertension can be corrected with
             intravenous nitroprusside, phentolamine or labetolol, or with
             oral nifedipine.
             Myocardial ischemia is treated in the usual manner with
             nitrates and betablockers, or calcium channel blockers.
             Hyperthermia is treated by removal of clothing, a calm
             atmosphere and cooling blanket.
             Cardio-respiratory resuscitation may be required.
             Cardiovascular collapse is treated by molar sodium lactate if
             the QRS complex is wider than 120 milliseconds and by the
             cautious administration of catecholamines (dopamine or
             Monitoring of CPK activity is required because
             cocaine-induced rhabdomyolysis and hypotension pose a high
             risk of acute renal failure and require treatment.


        3.1  Origin of the substance

             Cocaine is one of 14 alkaloids extracted from the leaves
             of 2 species of coca: Erythroxylum coca (found in South
             America, central America, India and Java) and Erythroxylum
             novogranatense (in South America).
             Local manufacture:
             The leaves are steeped in alkaline, sulphuric acid, paraffin
             or other solvents:  the mixture forms a thick brown paste,
             "coca paste", which contains 40 to 91% cocaine. 
             Subsequently, the alkaloids are precipitated with sodium
             carbonate and then dissolved in dilute hydrochloric acid to
             produce cocaine hydrochloride containing 40% cocaine. 
             Extraction of cocaine hydrochloride with ether in aqueous or
             alkaline solution produces "freebase" or "crack", which
             contains 85 to 90% of pure cocaine (Jeri, 1984; Ellenhorn &
             Barceloux, 1988; Farrar & Kearns, 1989; Goldfrank, 1990).
             Pharmaceutical manufacture:
             Cocaine is a semi-synthetic drug obtained from ecgonine, a
             product of the saponification of coca alkaloids; the ecgonine
             is esterified with methyl alcohol in the presence of an
             excess of chlorine.  It is made from the resulting methyl
             ecgonine by treatment with benzoic anhydride (Dorvault,
             Street cocaine used by addicts can be mixed with a number of
             diluants ("cut"), and these include amphetamines,
             anti-histamines, benzocaine, inositol, lactose, lidocaine,
             mannitol, opiods, phencyclidine, procaine, sugars,
             tetracaine, and sometimes arsenic, caffeine, quinidine, and
             even flour or talc.  These adulterants can themselves be the
             cause of poisoning (Cregler, 1986; Van Viet et al.,

        3.2  Chemical structure

             Chemical names: 
             (1R,2R,3S,5S)-2-Methoxycarbonyltropan-3-yl benzoate;
             1aH, 5aH-tropane-2ß-carboxylic acid 3ß-hydroxy-methyl ester
             3-tropanylbenzoate-2-carboxylic acid methyl ester; 
             octane-2-carboxylic acid methyl ester;

             Molecular Weight= 303.4
             Molecular formula: C17 H21 N O4
             (Clarke, 1986; Reynolds, 1989)

        3.3  Physical properties

             3.3.1  Colour

                    Cocaine hydrochloride:
                    colourless or white
                    Cocaine freebase:

             3.3.2  State/form

                    Cocaine hydrochloride:

                    Cocaine freebase:

             3.3.3  Description

                    Cocaine hydrochloride:
                    Hygroscopic odourless bitter tasting crystals
                    Solubility in water:  200 grams per 100 mLs
                    In alcohol:  25 grams per 100 mLs
                    In ether:  insoluble
                    Melting point:  197°C
                    1% solution is of neutral pH (Pharmacopée française,
                    1982; Clarke, 1986; Dorvault, 1987)
                    Cocaine freebase:
                    Slightly volatile, anhydrous, bitter tasting crystals
                    Solubility in water:  0.17 grams per 100 mL
                    In alcohol:  15.4 grams per 100 mL
                    In ether:  28.6 grams per 100 mL
                    Melting point 98°C 
                    Boiling point 187 to 188°C
                    pH:  alkaline
                    (Budavari, 1989)
                    Street cocaine used by addicts can be mixed with a
                    number of diluents ("cut"), and these include
                    amphetamines, anti-histamines, benzocaine, inositol,
                    lactose, lidocaine, mannitol, opioids, phencyclidine,
                    procaine, sugars, tetracaine, and sometimes arsenic,
                    caffeine, quinidine, and even flour or talc.

        3.4  Other characteristics

             3.4.1  Shelf-life of the substance

                    No data

             3.4.2  Storage conditions

                    Cocaine hydrochloride should be kept in a
                    tightly shut recipient away from light and moisture
                    (Pharmacopée française, 1982; Reynolds, 1989).

    4.  USES

        4.1  Indications

             4.1.1  Indications

             4.4.2  Description

                    Cocaine hydrochloride is now used only for
                    anaesthesia of the respiratory tract (Baschard &
                    Richard, 1984; Clarke, 1986; Goldfrank, 1990; Goodman
                    & Gilman, 1990), though concentrations of 1 to 20%
                    were in the past used as anaesthesia for the middle
                    ear, pharynx, larynx, mucosae of the nose, urinary
                    tract and rectum, the cornea and the iris.
                    The value of cocaine in analgesic mixtures (such as
                    "the Brompton cocktail") used for terminal care is
                    controversial, and current opinion does not favour it
                    (Ellenhorn & Barceloux,  1988; Fleming et al., 1990).
                    The major use of cocaine at present is as an illegal
                    drug of abuse.

        4.2  Therapeutic dosage

             4.2.1  Adults

                    The recommended dose is between 1 and 3
                    milligrams per kilogram (Loper, 1989; Reynolds, 1989).

             4.2.2  Children

                    No data available

        4.3  Contraindications

             Cocaine hydrochloride should not be used intra-ocularly,
             because it can provoke corneal ulceration (Goodman & Gilman,
             1990). Solutions of cocaine should not be applied to burnt or
             abraded skin or tissue supplied by terminal arterioles,
             because of the risks of ischaemia and tissue necrosis.


        5.1  Oral

             The use of oral cocaine in analgesic mixtures intended
             for terminal care is controversial and not at present
             recommended (Ellenhorn & Barceloux, 1988; Fleming et al.,
             1990). Cocaine can be abused by the oral or sublingual route
             (Cregler, 1986), and drug smugglers, called "mules" or "body
             packers", sometimes swallow the product in packages of
             variable composition (for example, condoms) which may leak or
             rupture and cause massive intoxication (Ellenhorn &
             Barceloux, 1988).

        5.2  Inhalation

             There is no therapeutic use for this route.
             Crack cocaine is abused by inhaling the vapour from
             cigarettes (in which it is mixed with tobacco or marijuana)
             or after heating in a device called a cocaine pipe. Coco
             paste can also be smoked.
             Most drug abusers at present take cocaine by the nasal route,
             and cocaine hydrochloride can be "sniffed" or "snorted" in
             "lines" on a flat surface such as a mirror. This route leads
             to pulmonary complications (Jéri, 1984; Cregler & Mark, 1987;
             Derlet, 1989; Haddad & Winchester, 1990).

        5.3  Dermal

             Not described.

        5.4  Eye

             The intra-ocular route is not used therapeutically.

        5.5  Parenteral

             There is no therapeutic use for parenteral cocaine
             Drug abusers inject cocaine hydrochloride subcutaneously,
             intramuscularly or intravenously alone or with heroin ("speed
             ball") or with other drugs (Jeri, 1984; Cregler & Mark,

        5.6  Other

             Cocaine can also be administered rectally, vaginally,
             and urethrally (Cregler, 1986). Cocaine has been used
             therapeutically for local anaesthesia of the upper
             respiratory tract (Fleming et al., 1990).

    6.  KINETICS

        6.1  Absorption by route of exposure

             Cocaine is absorbed by all routes of administration, but
             the proportion absorbed depends on the route (Haddad &
             Winchester, 1990).
             After oral administration, cocaine appears in blood after
             about 30 minutes, reaching a maximum concentration in 50 to
             90 minutes (Clarke, 1986).
             In acid medium, cocaine is ionised, and fails to cross into
             cells. In alkaline medium, there is less ionisation and the
             absorption rapidly increases. (Ellenhorn & Barceloux,
             By the nasal route, clinical effects are evident 3 minutes
             after administration, and last for 30 to 60 minutes, the peak
             plasma concentration being around 15 minutes.
             By oral or intra-nasal route, 60 to 80% of cocaine is
             absorbed (Ellenhorn & Barceloux, 1988; Stinus, 1992).
             By inhalation, the absorption can vary from 20 to 60%, the
             variability being related to secondary vasoconstriction.
             Freebase does not undergo first-pass hepatic metabolism, and
             plasma concentrations rise immediately to 1 to 2 mg per
             litre. The effects on the brain occur very rapidly, after
             about 8 to 12 seconds, are very violent ("flash"), and last
             only 5 to 10 minutes (Burnat & Le Brumant-Payen, 1992;
             Stinus, 1992).
             By the intravenous route blood concentrations rise to a peak
             within a few minutes (Clarke, 1986).

        6.2  Distribution by route of exposure

             Cocaine is distributed within all body tissues, and
             crosses the blood brain barrier (Ellenhorn & Barceloux,
             In large, repeated doses, it is probably accumulated in the
             central nervous system and in adipose tissue, as a results of
             its lipid solubility (Cone & Weddington, 1989).
             The volume of distribution is, according to different
             authors, between 1 and 3 litres per kilogram (Clarke, 1986;
             Ellenhorn & Barceloux, 1988; Baselt, 1989).
             Cocaine crosses the placenta by simple diffusion, and
             accumulates in the fetus after repeated use (Finster &
             Pedersen, 1991).

        6.3  Biological half-life by route of exposure

             The observed half life depends on the route of
             administration, dosage, and individual subject. It is of the
             order of 0.7 to 1.5 hours (Clarke, 1986). After oral
             administration, it appears to be 0.8 hours (Baselt, 1989),
             nasal administration, 1.25 hours (Baselt, 1989; Ellenhorn &
             Barceloux, 1988), parenteral administration 0.7 to  0.9 hours

             (Ambre et al., 1988; Ellenhorn & Barceloux, 1988; Burnat & Le
             Brumant-Payen, 1992).
             For therapeutic doses there is no tolerance to the effects of
             cocaine, but when used in abuse it may lead to dose
             escalation to obtain the same euphoriant effects
             (psychological tolerance); and there are anecdotal cases of
             abusers taking more than the recognised lethal dose
             (Ellenhorn & Barceloux, 1988).

        6.4  Metabolism

             Cocaine metabolism takes place mainly in the liver,
             within 2 hours of administration. The rate of metabolism
             varies according to plasma concentration (Baselt, 1989;
             Haddad & Winchester, 1990).
             There are 3 routes of bio-transformation:
             -  the major route is hydrolysis of cocaine by hepatic and
                plasma esterases, with loss of a benzoyl group to give
                ecgonine methyl ester. Esterase activity varies
                substantially from one subject to another (Fleming et al.,
             -  the secondary route is spontaneous hydrolysis, probably
                non-enzymatic, which leads to benzoylecgonine by
                demethylation (Fleming et al., 1990).
             The final degradation of cocaine, which is a sequel to both
             the principle and secondary routes of metabolism, leads to
             ecgonine (Burnat & Le Brumant-Payen, 1992).
             N-demethylation of cocaine is a minor route leading to
             norcocaine (Fleming et al., 1990). 
             The principle metabolites are therefore benzoylecgonine,
             ecgonine methyl ester, and ecgonine itself, which are
             inactive; and norcocaine which is active, and may be relevant
             after acute intoxication (Baselt, 1989; Burnat & Le
             Brumant-Payen, 1992).
             In the presence of alcohol, a further active metabolite,
             cocaethylene is formed, and is more toxic then cocaine itself
             (Nahas et al., 1992).
             The rate of cocaine metabolism is reduced in pregnant women,
             aged men, patients with liver disease, and those with
             congenital choline esterase deficiency (Cregler, 1986;
             Slutsker, 1992).

        6.5  Elimination and excretion

             1 to 9% of cocaine is eliminated unchanged in the urine,
             with a higher proportion in acid urine. The metabolites
             ecgonine methyl ester, benzoylecgonine, and ecgonine are
             recovered in variable proportions which depend on the route
             of administration (Clarke, 1986).
             At the end of 4 hours, most of the drug is eliminated from
             plasma, but metabolites may be identified up to 144 hours
             after administration (Ellenhorn & Barceloux, 1988).

             Unchanged cocaine is excreted in the stool and in saliva
             (Clarke, 1986; Cone & Weddington, 1989).
             Cocaine and benzoylecgonine can be detected in maternal milk
             up to 36 hours after administration, and in the urine of
             neonates for as much as 5 days. (Chasnoff et al., 1987,
             Freebase cocaine crosses the placenta, and norcocaine
             persists for 4 to 5 days in amniotic fluid, even when it is
             no longer detectable in maternal blood (Stinus, 1992).


        7.1  Mode of action

             7.1.1  Toxicodynamics

                    The main target organs are the central nervous
                    system and cardiovascular system. Effects depend on
                    the dose, other substances taken, the route of
                    administration, and individual susceptibility (Jeri,
                    Cardiovascular effects:
                    the mechanism of cardiovascular toxicity is unclear.
                    Increased circulating catecholamine concentrations
                    cause excessive stimulation of alpha- and
                    beta-adrenoceptors (Derlet, 1989). The cardiovascular
                    effects are dose-dependent. At low doses there is
                    vagal stimulation with bradycardia (Baschard &
                    Richard, 1984). At moderate doses, because of
                    adrenergic stimulation, there is a rapid increase in
                    cardiac output, myocardial oxygen consumption, and
                    blood pressure (followed by a fall).
                    This may have several consequences:
                    -   there is a risk of myocardial infarction, both the
                        subjects with coronary atheroma and those with
                        normal coronary arteries (when it is unclear if
                        the mechanism is thrombosis, embolism, or
                    -   there is a risk of spontaneous cerebral
                        haemorrhage, which may occur even in subjects with
                        normal blood pressure. This may be a consequence
                        of arterial malformation, ischaemia, arterial
                        vasoconstriction, cerebral vasculitis, cardiac
                        rhythm disturbance, or myocardial infarction
                        (Cregler & Mark, 1987; De Broucker et al., 1989;
                        Derlet, 1989; Isner & Chokshi, 1989; Stenberg et
                        al., 1989; Guérin et al., 1990; Kloner et al.,
                    -   at very high doses, cocaine can cause cardiac
                        arrest by a direct toxic effect on the

                    Cocaine can cause intestinal ischaemia or gangrene.
                    The intestinal vasculature contains alpha receptors,
                    which are stimulated by norepinephrine, leading to an
                    increase in arterial resistance, intense vaso
                    constriction, and a reduction in cardiac output (for
                    example, in body packers).
                    Action on the central nervous system:
                    the neurotoxic actions of cocaine are complex and
                    involve several sites and mechanisms of action.
                    Euphoria, confusion, agitation, and hallucination
                    result from an increase in the action of dopamine in
                    the limbic system (Nahas et al., 1987). Cortical
                    effects lead to pressure of speech, excitation, and a
                    reduced feeling of fatigue; stimulation of lower
                    centres leads to tremor and tonic-clonic convulsion;
                    brain stem effects lead to stimulation and then
                    depression of the respiratory vasomotor and vomiting
                    Cocaine causes hyperthermia as a result of 2
                    mechanisms: the increase in muscular activity and a
                    direct effect on thermal regulatory centres (Baschard
                    & Richard, 1984; Goodman & Gilman, 1990).
                    The visceral effects on liver and kidney are due to
                    dopaminergic action of cocaine, or its metabolites, or
                    to impurities (Guérin et al., 1989). The abrupt
                    increase intra-alveolar pressure can cause alveolar
                    rupture and pneumomediastinum.
                    Rhabdomyolysis occurs as a result of several different
                    mechanisms: direct effect on muscle and muscle
                    metabolism, tissue ischaemia, the effects of drugs
                    taken with cocaine, such as alcohol and heroin (Roth
                    et al., 1988; Skluth et al., 1988; Singhal et al.,

             7.1.2  Pharmacodynamics

                    The principle effects of cocaine are the result
                    of its sympathetic action: cocaine prevents the
                    re-uptake of dopamine and noradrenaline, which
                    accumulate and stimulate neuronal receptors (Amin et
                    al., 1990; Kloner et al., 1992).
                    At the same time, the release of serotonin a
                    "sedative" neurotransmitter, is inhibited (Derlet,
                    The inhibition of catecholamine re-uptake does not
                    explain the duration of action of cocaine, which may
                    also result from an increase in calcium flux,
                    potentiating cellular responses and causing receptor
                    hypersensitivity.  There may also be a direct effect
                    on peripheral organs (Fleming et al., 1990; Goldfrank,

                    Applied locally, cocaine blocks neuronal transmission:
                    this results in a powerful local anaesthetic action at
                    the level of sensory nerve terminals (Derlet, 1989;
                    Lange et al., 1989; Goodman & Gilman, 1990; Kloner et
                    al., 1992).
                    Anabolic experiments have shown that there is no true
                    physical tolerance to the effects of cocaine, but a
                    very marked psychic tolerance which leads animals to
                    auto-inject cocaine to obtain the desired
                    psychological effects, even though this may lead to
                    death (Stinus, 1992).

        7.2  Toxicity

             7.2.1  Human data


                             Lethal doses are estimated at 0.5 to
                             1.3 grams per day by mouth; 0.05 to  5 grams
                             per day by the nasal route, 0.02 grams of
                             cocaine by the parenteral route (Baschard &
                             Richard, 1984; Haddad & Winchester, 1990;
                             Burnat & Le Brumant-Payen, 1992).
                             Cocaine addicts can tolerate doses up to 5
                             grams per day.
                             Toxic effects can be manifest with plasma
                             concentrations equal to or above 0.50 mg per
                             litre; deaths have been reported with
                             concentrations of 1 mg per litre (Clarke,


                             No data.

             7.2.2  Relevant animal data

                    The LD50 for the rabbit is 15 mg per kilogram
                    by the intravenous route, and 50 mg per kilogram by
                    the nasal route; the intravenous LD50 for the rat is
                    17.5 mg per kilogram (Budavari, 1989).

             7.2.3  Relevant in vitro data

                    Experiments on animal heart tissue show a
                    direct, reversible, depressant effect of cocaine on
                    ventricular myocardium (Chokshi et al., 1989).
                    Experiments on rats prove that alcohol potentiates the
                    toxic effects of cocaine (Nahas et al., 1992).

        7.3  Carcinogenicity

             No data available.

        7.4  Teratogenicity

             The studies in animals are contradictory (Shepard, 1986;
             Ellenhorn & Barceloux, 1988). A recent meta-analysis shows an
             increase in congenital malformation rate in the offspring of
             cocaine-users, particularly for abnormalities of the limbs,
             the genito-urinary tract, and the cardiovascular,
             neurological, and digestive systems (Kain et al.,

        7.5  Mutagenicity

             No data available.

        7.6  Interactions

             Patients with choline esterase deficiency may develop
             severe reactions (Ellenhorn & Barceloux, 1988).
             Interactions can occur with adrenaline, alpha- and
             beta-blockers, vasoactive amines, antidepressants,
             chlorpromazine, guanethidine, indomethacin, monoamine oxidase
             inhibitors, methyldopa, naloxone, psychotropic medicines, and
             reserpine (Reynolds, 1989; Fleming et al., 1990; Carlan et
             al., 1991).
             There are metabolic interactions with other local
             anaesthetics, cholinesterase inhibitors and cytotoxic drugs
             (Fleming et al., 1990).

        7.7  Main adverse effects

             Not applicable.



        9.1  Acute poisoning

             9.1.1  Ingestion

                    Acute intoxication causes intense agitation,
                    convulsions, hypertension, rhythm disturbance,
                    coronary insufficiency, hyperthermia, rhabdomyolysis,
                    and renal impairment.
                    Intestinal ischaemia has been described.

             9.1.2  Inhalation

                    Acute intoxication causes intense agitation,
                    convulsions, hypertension, rhythm disturbance,
                    pulmonary oedema with acute respiratory distress
                    syndrome, coronary insufficiency, hyperthermia,
                    rhabdomyolysis, and renal impairment.

             9.1.3  Skin exposure

                    Not applicable.

             9.1.4  Eye contact

                    Not applicable.

             9.1.5  Parenteral exposure

                    Acute intoxication causes intense agitation,
                    convulsions, hypertension, pulmonary oedema with acute
                    respiratory distress syndrome, coronary insufficiency,
                    hyperthermia, rhabdomyolysis, and renal

             9.1.6  Other

                    By the intranasal route, acute intoxication
                    causes intense agitation, convulsions, hypertension,
                    rhythm disturbance, pulmonary oedema, stroke, coronary
                    insufficiency, hyperthermia, rhabdomyolysis, and renal

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    Chronic ingestion of cocaine can cause thoracic
                    pain, changes on the electrocardiogram with transient
                    elevation of the ST segments and re-polarisation
                    abnormalities; and convulsions (Zimmerman et al.,
                    1991). Erosion of the teeth has been noted with
                    chronic oral ingestion (Krutchkoff et al.,

             9.2.2  Inhalation

                    During inhalation of "crack", chest pain with
                    changes on the electrocardiogram (re-polarisation
                    abnormalities and transient ST segment elevation), and
                    convulsions can occur (Zimmerman et al., 1991).
                    Reversible cardiomyopathy with hypotension, hypoxaemia
                    and tachycardia, has been described (Chokshi et al.,
                    1989). A number of other symptoms have been described,

                    though their aetiology is not always clear. Cough,
                    black or blood-stained sputum, dyspnoea, thoracic
                    pain, spontaneous pneumothorax, spontaneous
                    pneumomediastinum, and asthma (in a few cases) or
                    immunoallergic lung disease, have been described.
                    Pulmonary granulomas and fibrosis, bronchiolitis
                    obliterans, and isolated arterial hypertension have
                    also been observed (Kevorkian & Guérin, 1993).
                    Chronic cocaine intoxication causes anorexia, which
                    leads to weight loss, physical exhaustion, behavioural
                    problems, and depression.

             9.2.3  Skin exposure

                    Application of cocaine to skin or mucous
                    membrane can cause necrotic lesions.

             9.2.4  Eye contact

                    Repeated application of cocaine can cause
                    necrotic lesions.

             9.2.5  Parenteral exposure

                    Cocaine addicts can develop HIV infection and
                    AIDS as a result of sharing needles and syringes
                    (Burnat & Le Brumant-Payen, 1992; Rubin & Neugarten,
                    1992; Kevorkian & Guérin, 1993).

             9.2.6  Other

                    Intranasal administration of cocaine can cause
                    necrosis and perforation of the nasal septum, atrophy
                    of the nasal mucosa, chronic sinusitis, and anosmia
                    (Baschard & Richard, 1984; Burnat & Le Brumant-Payen,

        9.3  Course, prognosis, cause of death

             In patients who are moderately poisoned, the symptoms
             have often spontaneously resolved before emergency admission,
             and most patients leave hospital within 36 hours (Rubin &
             Neugarten, 1992).
             Serious cocaine intoxication evolves in 3 phases:
             -  an early phase of stimulation,
             -  a second phase of hyper-stimulation with tonic-clonic
                convulsions, tachyarrhythmias, and dyspnoea,
             -  a third phase of depression of the central nervous system,
                with loss of vital function, paralysis, coma, and
                respiratory and circulatory collapse.

             Two-thirds of deaths occur within 5 hours of administration,
             and one-third within one hour after absorption of the drug,
             whatever the route of administration.
             Important factors include:
             -  the quantity absorbed,
             -  the rapidity with which the serum concentration
             -  the occurrence of hyperthermia secondary to
             -  the prior cardiovascular state of the patient: large
                intravenous doses of cocaine can cause immediate death as
                a result of arrhythmia, myocardial infarction, circulatory
                failure, or direct myocardial depression (Goodman &
                Gilman, 1990).
             Also recognized are acute pulmonary complications (acute
             respiratory distress syndrome) which can lead to death within
             a few hours of poisoning by the parenteral route. Post mortem
             examination often reveals intra-alveolar haemorrhage
             (Baschard & Richard, 1984).
             The occurrence of convulsions, which are secondary to cardiac
             effects (particularly ventricular fibrillation or
             tachycardia), can appear whatever the dose absorbed, and are
             responsible for one-third of the deaths.
             Chronic intoxication by cocaine leads to anorexia, weight
             loss, physical exhaustion, behavioural problems, and

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    The following have been described with chronic
                    intravenous abuse or inhalation:
                    -  precordial pain, of unknown aetiology in 80% of
                    -  palpitation;
                    -  arterial hypertension;
                    -  tachycardia;
                    -  ventricular and supraventricular tachyarrhythmias,
                       atroventricular block;
                    -  acute coronary insufficiency and myocardial
                    -  digital, renal, intestinal and spinal cord
                    -  dilated cardiomyopathy and myocarditis, rupture of
                       the ascending aorta;
                    -  asystole;
                    -  circulatory collapse;
                    -  endocarditis affecting the tricuspid valve;
                    -  superficial thrombophlebitis;

                    -  electrocardiographic changes: widening of the QRS
                       complex, re-polarisation changes, ST segment
                    (Baschard & Richard, 1984; Cregler & Mark, 1987;
                    Wiener & Putman, 1988; Derlet, 1989; Guérin et al.,
                    1990; Zimmermann et al., 1991).

             9.4.2  Respiratory

                    The following features have been observed:
                    cough, chest pain, haemoptysis, dark sputum, dyspnoea,
                    cyanosis, pneumothorax, surgical (subcutaneous)
                    emphysema, pneumopericardium, spontaneous
                    pneumomediastinum, non-cardiogenic pulmonary oedema,
                    and cardiogenic pulmonary oedema secondary to acute
                    coronary insufficiency, rhythm disturbance, or
                    Death has occurred from renal insufficiency and from
                    acute respiratory distress syndrome (Baschard &
                    Richard, 1984; Cregler & Mark, 1987).
                    During chronic poisoning, the following have been
                    pulmonary fibrosis and granulomatosis, bronchiolitis
                    obliterans, and isolated pulmonary hypertension. There
                    are also non-specific complications: inhalation
                    pneumonia, related to reduced consciousness; pulmonary
                    abscesses secondary to infective endocarditis; and
                    pulmonary complications related to AIDS. There are a
                    few cases reported of asthma and of immunoallergic
                    lung disease (Kevorkian & Guérin, 1993).

             9.4.3  Neurological


                             The following consequences have been
                             described: tremor, headaches, transient
                             ischaemic attacks, cerebrovascular ischaemia
                             or haemorrhage, intracerebral and
                             subarachnoid haemorrhage, intracerebral
                             infarction; syncopy, epileptic fits, optic
                             neuritis, mental confusion and insomnia,
                             intellectual stimulation, mania, pressure of
                             speech, agitation, excitement, anxiety,
                             irritability, euphoria, depression, suicidal
                             ideation; visual hallucination,
                             hallucinations of parasites leading to
                             scratching; paranoia, irrational fear,
                             persecution complex, "acting out", psychotic
                             states, destruction of the personality; and
                             anorexia leading to weight loss and physical
                             exhaustion (Baschard & Richard, 1984;

                             Cregler, 1986; Bismuth et al., 1989; De
                             Broucker et al., 1989; Goldfrank, 1990;
                             Guérin et al., 1990; Vaille, 1990; Stinus,

            Peripheral Nervous System

                             Local anaesthesia, muscular
                             paralysis and abolition of reflexes occur
                             (Baschard & Richard, 1984).

            Autonomic Nervous System

                             Cocaine can cause tachycardia,
                             arterial hypertension, vomiting, "cocaine
                             fever", and occasionally

            Skeletal and smooth muscle

                             Contraction of facial, digital and
                             intestinal smooth muscle occurs. There may be
                             myalgia and muscular weakness, and
                             rabdomyolysis (Cregler, 1986; Bismuth et al.,
                             1989; Herzlich & Arzura, 1989; Brody et al.,

             9.4.4  Gastro-intestinal

                    Anorexia leading to weight loss and physical
                    exhaustion occur; as do nausea, vomiting, diarrhoea,
                    abdominal pain, and intestinal ischaemia (Burnat & Le
                    Brumant-Payen, 1992). Drug smugglers ("mules" or "body
                    packers") can develop intestinal obstruction from

             9.4.5  Hepatic

                    Hepatocellular insufficiency,
                    hyperbilirubinaemia, anti-hepatocellular necroses have
                    been described (Guérin et al., 1989).

             9.4.6  Urinary


                             Both acute renal insufficiency
                             secondary to rhabdomyolysis, and renal
                             infarction, have been described (Cregler,
                             1986; Roth et al., 1988; Van Viet et al.,


                             Haematuria, glycosuria, and
                             proteinuria are seen.

             9.4.7  Endocrine and Reproductive Systems

                    In small doses, cocaine delays ejaculation and
                    orgasm, increases libido, and improves sexual
                    performance. In large and repeated doses, impotence
                    and complete loss of libido occur.

             9.4.8  Dermatological

                    In therapeutic doses, cocaine has a local
                    anaesthetic action, and application to the skin and
                    mucous membranes (eye, nose) can cause necrotic
                    lesions. Hallucinations of parasites can lead to
                    scratching. Crack smokers can lose eye lashes and
                    eyebrows, as a result of the hot vapours which burn
                    them. Cocaine can also provoke porphyria (Cregler,
                    1986; Dick, 1987).

             9.4.9  Eye, ear, nose, throat, local effects

                    The contact of cocaine with the cornea leads to
                    ulceration and prevents its therapeutic use as an eye
                    During acute intoxication, local action can cause
                    pupillary dilation, anaesthesia, and vasoconstriction
                    of mucous membranes.
                    During chronic intranasal intoxication, there may be:
                    deformity, atrophy, necrosis, perforation of the nasal
                    septum or base of the tongue or epiglottis, retraction
                    of the palette, chronic sinusitis, a change in the
                    voice, anosmia, and blindness.
                    Dental erosion can follow oral cocaine ingestion.
                    (Baschard & Richard, 1984; Cregler, 1986; Bezmalinovic
                    et al., 1988; Deutsch & Millard, 1989; Krutchkoff et
                    al., 1990; Vaille, 1990; Burnat & Le Brumant-Payen,

             9.4.10 Haematological

                    Disseminated intravascular coagulation has
                    been observed in subjects: platelet aggregation and
                    thromboxane A2 levels are increased and prostacyclin
                    inhibited by cocaine (Roth et al., 1988; Guérin et
                    al., 1989).

             9.4.11 Immunological

                    Opportunist infections such as cerebral
                    mycosis, and infectious lung disease, have been
                    described in intravenous cocaine users, who have no
                    other pre-disposing factors; needle sharing,
                    prostitution and homosexuality greatly increase the
                    risk of infection with HIV in cocaine addicts
                    (Cregler, 1986; Kevorkian & Guérin, 1993).

             9.4.12 Metabolic

           Acid-Base Disturbance

                             Acid-base disturbances are caused
                             by hypoxia in cocaine addicts, particularly
                             when there are repeated convulsions (Bismuth
                             et al., 1989).

           Fluid and electrolyte disturbances

                             Electrolyte disturbances are the
                             consequence of vomiting and 


                             Poor nutrition, failure to adhere
                             to therapeutic regimes, a sensitivity to
                             epinephrine which mobilises glucose cause
                             abnormalities of glucose homeostasis in
                             patients who repeatedly consume cocaine
                             (Cregler, 1986).

             9.4.13 Allergic Reactions

                    Asthma and an immunoallergic lung disorder
                    have been described in some subjects without preceding
                    asthma or atopy, during prolonged crack intoxication;
                    the relevant allergen may be cocaine itself, or
                    excipients in inhaled preparations (Kevorkian &
                    Guérin, 1993).

             9.4.14 Other clinical effects

                    No data

             9.4.15 Special risks

                    Pregnancy: cocaine causes uterine
                    hypercontractility, a reduced uterine blood flow, and
                    placental vasoconstriction. Thus, women cocaine
                    addicts can develop hypertension of pregnancy,

                    spontaneous abortion, placental abruption, premature
                    delivery, and complications at delivery (Burnat & Le
                    Brumant-Payen, 1992; Kain et al., 1992).
                    Risks in the fetus: the offspring of mothers who are
                    cocaine addicts has an increased risk of
                    genito-urinary, cardiovascular, gastrointestinal, and
                    neurological malformations; even a single exposure to
                    cocaine during pregnancy can lead to cerebral
                    infarction or haematoma, or to failure of development
                    of the blood supply or nerve supply to fetal
                    In the new-born: ventricular tachycardia, cerebral
                    infarction, convulsion, hypertension, and unilateral
                    hypotonia are seen with increased frequency. Sudden,
                    unexplained death in the babies of cocaine addicted
                    mothers can occur during the first few weeks of life
                    (Cregler, 1986; Chavez et al., 1989; Kain et al.,
                    Breast feeding: cocaine and benzoylecgonine are
                    found in maternal milk up to 36 hours after the use of
                    cocaine (Chasnoff et al., 1987).
                    Enzyme deficiencies:
                    Subjects who are deficient in pseudocholinesterase can
                    die suddenly after cocaine.

        9.5  Other

             Cocaine use causes hypersensitivity of the autonomic
             nervous system and changes to the structure and function of
             the brain; there is very marked psychological dependence
             without physical dependence or tolerance, because the same
             dose causes the same psychological effects. Nonetheless,
             cocaine abuse can lead to the consumption of increasingly
             large quantities to obtain euphoriant effects; there are
             anecdotal cases of addicts taking doses above the theoretical
             lethal dose. Addicts can take cocaine at intervals of 10 to
             45 minutes during the course of a "run", which may last for
             several days, when there is loss of control of the frequency
             and duration of the pleasurable phase (Ellenhorn & Barceloux,
             1988; Stinus, 1992).
             Withdrawal syndrome:
             there are 3 distinct phases:
             -  when the drug wears off, 15 to 30 minutes after the last
                dose, there is a "crash" when the addict becomes
                dysphoric, depressed, irresistibly sleepy, agitated, and
                anxious with a strong desire ("craving") for cocaine,
             -  after about 2 hours, there is a phase of sleeping and
                exhaustion so intense that even the desire for cocaine is
                unable to overcome it;
             -  during the next several weeks there is a period of
                dysphoria, anhedonia, depression and "extinction" or
                "cocaine blues".

        9.6  Summary


        10.1 General Principles

             The treatment of cocaine poisoning varies according to
             the clinical severity; most patients do not require admission
             to hospital, because symptoms resolve rapidly and
             spontaneously. The emergency treatment of severe
             intoxications requires the maintenance of vital functions,
             and the treatments of complications due to cocaine, or to
             adulterants of the drug. There is no antidote.
             The measurement of serum creatine kinase activity is
             necessary to detect rhabdomyolysis; but neither the creatine
             kinase nor the electrocardiogram necessarily give information
             on the likelihood of chest pain being due to myocardial
             infarction (Amin et al., 1990; Brody et al., 1990; Guérin et
             al., 1990). Plain abdominal x-rays may show evidence of
             packets of cocaine.

        10.2 Life supportive procedures and symptomatic/specific treatment

             Vital function, particularly cardiorespiratory
             function, has to be maintained. According to the
             circumstances this may require:
             -  electrocardiographic monitoring of arrhythmias;
             -  intubation and assisted ventilation;
             -  alkalinisation with sodium bicarbonate;
             -  reversal of cardiovascular collapse with molar sodium
                lactate if the QRS complex is wider than 120 milliseconds
                and by the cautious administration of catecholamines
                (dopamine or norepinephrine)
             If creatine kinase is elevated above 10,000 international
             units per litre then rehydration, diuresis with frusemide,
             and alkalinisation of the urine have been advised, and
             haemodialysis may be required (Guérin et al., 1989).
             Symptomatic treatment of moderately severe cases requires the
             following measures:
             -  the patient should be placed in a calm environment;
             -  hyperthermia should be corrected by undressing;
             -  hydration should be sufficient to induce a diuresis and
                prevent rhabdomyolysis;
             -  moderate doses of diazepam (5 to 10 mg intravenously,
                which may have to be repeated after 10 minutes) if there
                are convulsions or severe agitation;
             -  ventilation with the administration of thiopentone or
                clonazepam may be necessary to control status
             -  neuroleptics such as haloperidol (2 to 5 mg
                intramuscularly) may be required for psychosis or

             -  arterial hypertension may require diazoxide, phentolamine,
                labetalol or sodium nitroprusside for its control;
             -  arrhythmias: betablockers may correct cardiac arrhythmias
                but may aggravate coronary or systemic vasoconstriction;
                antiarrhythmics, cardioversion and over-pacing can be used
                but intravenous lidocaine should be avoided because it can
                provoke convulsions;
             -  dexamethasone and positive pressure of ventilation may be
                required in the case of alveolar haemorrhage.
             (Baschard & Richard, 1984; Bismuth et al., 1989; Derlet,
             1989; Bouchi et al., 1992).

        10.3 Decontamination

             Gastric lavage is dangerous because of sudden
             occurrence of convulsion, and syrup of ipecacuanha is even
             worse, because the effects can be delayed, and the subject
             meanwhile may lose consciousness. Activated charcoal is
             For drug smugglers ("mules" or "body packers"), gentle
             laxatives (avoid liquid paraffin) and activated charcoal are
             recommended rather than endoscopy, which risks rupturing the
             sachets, leading to massive acute intoxication. Repeat x-rays
             are required to be certain that all packets have been
             eliminated. Intestinal irrigation with polyethylene glycol
             has been used. Surgical intervention is requrired only in
             exceptional cases.
             (Caruana et al., 1984; Bismuth et al., 1989; Baud, 1991; Marc
             et al., 1992).

        10.4 Elimination

             Given the large volume and distribution and short half
             life of cocaine, there is no role for methods of increasing
             the rate of elimination.

        10.5 Antidote Treatment

             10.5.1 Adults

                    There is no specific antidote.

             10.5.2 Children

                    There is no specific antidote.

        10.6 Management discussion

             The following drugs have been suggested in the
             literature for treating the syndrome of intense adrenergic

             amitriptyline, propranolol, labetalol, calcium channel
             blocking drugs, and phentolamine (an alpha-1 receptor
             Combination of diazepam and enalaprilat or diazepam and
             propranolol has also been used to prevent both cardiovascular
             and neurological disturbance.
             Withdrawal symptoms have been treated with amantadine, and
             dopamine agonist such as bromocriptine.
             There may be a place for dantrolene in treating the muscular
             hypertonia, hyperthermia, and rhabdomyolysis that occur in
             cocaine poisoning. Heparin and fresh frozen plasma have been
             shown to be ineffective in treating the rhabdomyolysis.
             (Dackis & Gold, 1985; Cregler, 1986; Trouvé et al., 1988;
             Fox, 1989; Pike, 1989; Baud, 1991).
             Research in this field includes neurobiological studies of
             the effects of the drug, and the development of experimental
             models of cocaine dependence with a view to developing
             treatments for cocaine addiction (Beckeman et al.,


        11.1 Case reports from literature

             Local application of 30 mg of cocaine in a 14 month old
             child prior to bronchoscopy caused mydriasis, agitation,
             euphoria, tachypnoea, tremor, and flushing. The child was
             treated with rectal diazepam, intramuscular meperidine
             (pethidine) and rectal methohexitone (methohexital); it had
             recovered 18 hours after exposure (Schou et al., 1987).


        12.1 Specific preventive measures

             Providing the public with information to contradict the
             myths surrounding cocaine: that it is benign, aphrodisiac,
             and does not cause dependence.

        12.2 Other

             Treatments suggested for chronic intoxication include:
             a programme of detoxification; maintainence treatment; self
             control methods; exercise sessions and abstainence programmes
             and tranquillizers. Relapse is possible many years after
             cessation of drug taking, and some teams suggest providing
             support for as long as 5 years (Jeri, 1984).


        Ambre J, Ruo TI, Nelson J & Belknap S (1988) Urinary
        excretion of cocaine, benzoylecgonine, and ecgonine methyl ester
        in humans. J Anal Toxicol, 12: 301-306.
        Amin M, Gabelman G, Karpel J & Buttrick P (1990) Acute myocardial
        infarction and chest pain syndromes after cocaine use. Am J
        Cardiol, 66: 1434-1437.
        Baschard P & Richard D (1984) La cocaïne. Act Pharm, 212:
        Baselt RC (1989) Disposition of toxic drugs and chemicals in man,
        2nd ed, Davis, California, Biomedical publications, 208-213.
        Baud F (1991) Drogues. Intoxications aiguës et chroniques,
        principes du traitement d'urgence. Rev Prat, 41(15): 1412.
        Beckman KJ, Parker RB, Hariman RJ, Gallastegui JL, Javaid JI &
        Bauman JL (1991) Hemodynamic and electrophysiological actions of
        cocaine. Circulation, 83 (5): 1799-1807.
        Bezmalinovic Z, Gonzalez M & Farr C (1988) Oropharyngeal injury
        possibly due to free-base cocaine. N Engl J Med, 319 (21):
        Bismuth C, Baud FJ, Conso F, Fréjaville JP & Garnier R (1989) 
        Toxicologie clinique, 5ème éd, Paris, éd. Médecine-Sciences
        Flammarion, p 116.
        Bouchi J, El Asmar B, Couetil JP, Gédéon E & Bouchi N (1992)
        Hémorragie alvéolaire après inhalation de cocaïne. Presse Med, 21
        (22): 1025-1026.
        Brody SL, Wrenn KD, Wilber MM & Slovis CM (1990) Predicting the
        severity of cocaïne-associated rhabdomyolysis. Ann Emerg Med, 19:
        Brody SL, Slovis & Wrenn KD (1990) Cocaine related medical
        problems: consecutive series of 233 patients. Am J Med, 88:
        Burnat P & Le Brumant-Payen C (1992) Intoxication par la cocaïne.
        Lyon Pharm, 43 (3): 149-156.
        Budavari S ed. (1989) The Merck Index: an encyclopedia of
        chemicals, drugs and biologicals, 11th ed. Rahway, New Jersey,
        Merck and Co, Inc.

        Carlan SJ, Stromquist C, Angel JL, Harris M & O'Brien WF (1991)
        Cocaine and indomethacin: fetal anuria, neonatal edema and
        gastrointestinal bleeding. Obstet and Gynecol, 78 (3):
        Caruana DS, Weinbach B, Goerg D & Gardner LB (1984) Cocaine-packet
        ingestion. Diagnosis, management and natural history. Ann Intern
        Med, 100 (1): 73-74.
        Chasnoff IJ, Lewis DE & Squires L (1987) Cocaine intoxication in a
        breast-fed infant. Pediatrics, 80 (6): 836-838.

        Chasnoff IJ, Lewis DE, Griffith DR & Willey S (1989) Cocaine and
        pregnancy: clinical and toxicological implications for the
        neonate. Clin Chem, 35 (7): 1276-1278.
        Chavez GF, Mulinare J & Cordero JF (1989) Maternal cocaine use
        during early pregnancy as a risk factor for congenital urogenital
        anomalies. JAMA, 262 (6): 795-798.
        Chokshi SK, Moore R, Pandian NG & Isner JM (1989) Reversible
        cardiomyopathy associated with cocaine intoxication. Ann Intern
        Med, 111 (12): 1039-1040.
        Clarke EGC (1986) Clarke's isolation and identification of drugs
        in pharmaceuticals, body fluids, and post-mortem materials, 2nd
        ed, London, The Pharmaceutical Press.
        Cone EJ & Weddington WW (1989) Prolonged occurrence of cocaine in
        human saliva and urine after chronic use. J Anal Toxicol, 13:
        Cregler LL, Mark H (1987) [Risques cardiovasculaires et cocaïne].
        J Intern Med, 100 (suppl): 6-8.
        Cregler LL (1986) Medical complications of cocaine abuse. N Engl J
        Med, 315 (23): 1495-1500.
        Dackis CA & Gold MS (1985) Bromocriptine as treatment of cocaine
        abuse. Lancet, 18 mai: 1151-1152.
        De Broucker Th, Verstichel P, Cambier J & De Truchis P (1989)
        Accidents neurologiques après prise de cocaïne. Presse Med, 18
        (10): 541-542.
        Derlet RW (1989) Cocaine intoxication. Postgrad Med, 86 (5):
        Deutsch HL & Millard DR (1989) A new cocaine abuse complex. Arch
        Otolaryngol Head Neck Surg, 115: 235-237.

        Dick AD (1987) Cocaine and acute porphyria. Lancet, 8568 (2):
        Dorvault F (1987) L'officine, XXIIème édition, éd. Vigot, Paris,
        pp 368-371.
        Ellenhorn MJ ed. & Barceloux DG ed. (1988) Medical Toxicology:
        diagnosis and treatement of human poisoning. New York, Elsevier
        science publishing compagny, Inc., 644-661. 
        Farrar HC & Kearns GL (1989) Cocaine: clinical pharmacology and
        toxicology. J Pediatr, 115 (5): 665-675.
        Finster M & Pedersen H (1991) Maternal and fetal effects of
        cocaine abuse. Adv Biosciences, 80: 233-238.
        Fleming JA, Byck R & Barash PG (1990) Pharmacology and therapeutic
        applications of cocaine. Anesthesiology, 73: 518-531.
        Fox AW (1989) More on rhabdomyolysis associated with cocaine
        intoxication.  N Engl J Med, 321 (18): 1271.
        Goldfrank LR (1990) Management of acute neuropsychiatric
        manifestations of cocaine intoxication. Intensive Care and
        Emergency Medicine, 10 ed. J. L Vincent, Springer-Verlag.
        Goldfrank LR, Flomenbaum NE, Lewin NA, Weisman RS & Howland MA ed.
        (1990) Goldfrank's toxicologic emergencies, 4th ed, Prentice-Hall
        Goodman LS & Gilman A ed (1990) Goodman and Gilman's: the
        pharmacological basis of therapeutics, 8th ed., New-York, Pergamon
        Guérin JM, Barbotin-Larrieu F, Lutsman C & Lerebours F (1990)
        Intoxication par la cocaïne: les complications cardio-vasculaires.
        Concours Médical, 112 (36): 3251-3253.
        Guérin JM, Barbotin-Larrieu F, Lutsman C & Aoula D (1989)
        Complications neurologiques de l'intoxication par la cocaïne.
        Concours Médical, 111 (19): 1603-1605.
        Guérin JM, Barbotin-Larrieu F, Lutsman C & Aoula D (1989)
        Complications viscérales multiples lors d'une intoxication par la
        cocaïne. Rev  Med Interne, 10: 561-562
        Haddad LM & Winchester JF (1990) Clinical management of poisoning
        and drug overdose, 2nd ed, Philadelphia, London, Montreal,
        Toronto, Sidney, Tokyo, WB Saunders Company Inc.

        Herzlich B & Arsura E (1989) Acute rhabdomyolysis associated with
        cocaine intoxication. N Engl J Med, 320 (10): 667-668. 
        Isner JM & Chokshi SK (1989) Cocaine and vasospasm. N Engl J Med,
        312 (23): 1604-1606.
        Jeri FR (1984) La fumerie de pâte de coca dans certains pays
        d'Amérique latine: une forme de toxicomanie grave et soutenue.
        Bulletin des stupéfiants, 1984, 25 (2): 17-34.
        Kain ZN, Kain TS & Scarpelli EM (1992) Cocaine exposure in utero:
        perinatal development and neonatal manifestations. Review. J
        Toxicol Clin Toxicol, 30 (4): 607-636.
        Kevorkian JP & Guérin JM (1993) Complications pulmonaires de
        l'intoxication par la cocaïne. Concours Médical, 115 (07);
        Kloner RA, Hale S, Alker K & Rezkalla S (1992) The effects of
        acute and chronic cocaine use on the heart. Circulation, 85 (2):
        Krutchkoff DJ, Eisenberg E, O'Brien JE & Ponzillo JJ (1990)
        Cocaine induced dental erosions. N Engl J Med, 8: 408.
        Lange RA, Cigarroa RG, Yancy CW, Willard JE, Popma JJ, Sills MN,
        MacBride W, Kim AS & Hillis LD (1989) Cocaine-induced
        coronary-artery vasoconstriction. N Engl J Med, 321 (23):
        Loper KA (1989) Clinical toxicology of cocaine. Med Toxicol
        Adverse Drug Exp, 4 (3): 174-185.
        Marc B, Baud FJ, Maison-Blanche P, Leporc P, Garnier M & Gherardi
        R (1992) Cardiac monitoring during medical management cocaine body
        packers. J Toxicol Clin Toxicol, 30 (3): 387-397.
        Nahas G, Latour C & Trouvé R (1992) Potentialisation des effets
        toxiques aigus de la cocaïne par l'alcool éthylique. Bull Acad
        Natl Med, 176 (2): 193-197.
        Nahas G, Trouvé R, Manger W, Vinyard C & Goldberg S (1987) Cocaïne
        et toxicité des neurotransmetteurs endogènes. Bull Acad Nat Med,
        171 (6): 669-673
        Pharmacopée Française (1982) 10ème éd, Paris, Maisonneuve S. A.
        Pike RF (1989) Cocaine withdrawal. An effective three-drug
        regimen. Postgrad Med, 85 (4); 115-121.

        Reynolds ed. (1989) Martindale the Extra Pharmacopoeia, 29th ed.
        Londres, The Pharmaceutical Press.
        Roth D, Alarcon FJ, Fernandez JA, Preston RA & Bourgoignie JJ
        (1988) Acute rabdomyolysis associated with cocaine intoxication. N
        Engl J Med, 319 (11); 673-677.
        Rubin RB & Neugarten J (1992) Medical complications of cocaine:
        changes in pattern of use and spectrum of complications. J Toxicol
        Clin Toxicol, 30 (1): 1-12.
        Schou H, Krogh B & Knudsen F (1987) Unexpected cocaine
        intoxication in a fourteen month old child following topical
        administration. J Toxicol Clin Toxicol, 25 (5): 419-422.
        Shepard TH (1986) Catalog of teratogenic agents, 5th ed,
        Baltimore, London, the John's Hopkins University Press.
        Singhal PC, Rubin RB, Peters A, Santiago A & Neugarten J (1990)
        Rhabdomyolysis and acute renal failure associated with cocaine
        abuse. J Toxicol Clin Toxicol, 28 (3): 321-330.
        Skluth HA, Clark JE, Ehringer GL (1988) Rhabdomyolysis associated
        with cocaine intoxication. Drug Intelligence and Clinical
        Pharmacy, 22: 778-780.
        Slutsker L (1992) Risks associated with cocaine use during
        pregnancy. Obstet Gynecol, 79 (5): 778-789.
        Stenberg RG, Winniford MD, Hillis LD, Dowling GP & Buja LM (1989)
        Simultaneous acute thrombosis of two major coronary arteries
        following intraveinous cocaine use. Arch Pathol Lab Med, 113:
        Stinus L (1992) La dépendance à la cocaïne. Rev Prat, 6 (179):
        Trouvé R, Sitbon M, Latour C & Nahas G (1988) Combinaison
        enalaprilat + valium comme antidote de l'intoxication cocaïnique.
        J Toxicol Clin Exp, 8 (1): 61.
        Vaille C (1990) Cécité due à la cocaïne. Presse Med, 19 (10):

        Van Viet H, Chevalier P, Sereni C, Bornet Ph, Bautier P, Degos CF
        & Rullière R (1990) Accidents neurologiques liés à l'usage de la
        cocaïne.  Presse Med, 19 (22): 1045-1049.
        Welch RD, Todd K, Krause GS (1991) Incidence of cocaine-associated
        rhabdomyolysis. Ann Emerg Med, 20 (2): 154-157.

        Wiener MD & Putman CE (1988) [Douleur thoracique chez un
        cocaïnomane]. JAMA, 13 (170): 1017-1019.
        Zimmermann JL, Dellinger RP & Majid PA (1991) Cocaine-associated
        chest pain. Ann Emerg Med,  611 (330): 33-37.

    14. AUTHORS

        Authors:  Dr Anne Claustre
                    Dr Isabelle Bresch-Rieu
                    Nathalie Fouilhé, Interne 
                    Unité de Toxicologie Clinique et Centre Anti-Poisons
                    (Docteur V Danel)
                    Service de Médecine Interne et Toxicologie (Pr JL
                    Debru), Hopital Albert-Michallon BP 217 38043 GRENOBLE
                    CEDEX FRANCE
                    Tél. 33 4 76 76 56 46
                    Fax 33 4 76 76 56 70
        Date: April 1993
        Peer review: Cardiff, United Kingdom, February  1994 (Dr
        C. Alonzo, Dr V. Danel, Dr J. de Kom, Dr R. Ferner, Dr A. Furtado
        Rahde, Dr J. Hodgson, Dr Z. Kolacinski, Dr P. Myrenfors)
        Translation from French to English: R Ferner, MO Rambourg Schepens
        First revision and update: Drs V Danel, R Ferner, MO Rambourg
        Schepens (1998)
        Finalised  and edited by Dr MO Rambourg: February 1999

    See Also:
       Toxicological Abbreviations
       Cocaine (PIM 139F, French)