International Programme on Chemical safety
Poisons Information Monograph 139
Nervous system; anesthetics;
local; esters of benzoic acid (N01BC01)
Ecgonine methyl ester benzoate;
Kokain; Kokan; Kokayeen;
Bernies; Blow; Burese;
C; Cadillac of drugs;
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
1.4.2 Other numbers
CAS cocaine hydrochloride: 53-21-4
1.5 Main brand names, main trade names
mélange de Bonain
1.6 Main manufacturers / importers
Merck (Germany); Stepan Chemical Company (Mazwood,
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.
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
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. PHYSICO-CHEMICAL PROPERTIES
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).
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).
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
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
colourless or white
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)
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
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
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).
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
The recommended dose is between 1 and 3
milligrams per kilogram (Loper, 1989; Reynolds, 1989).
No data available
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. ROUTES OF EXPOSURE
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 &
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).
The intra-ocular route is not used therapeutically.
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,
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).
6.1 Absorption by route of exposure
Cocaine is absorbed by all routes of administration, but
the proportion absorbed depends on the route (Haddad &
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;
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 &
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
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).
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
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;
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. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
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,
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.,
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
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).
7.2.1 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,
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).
No data available.
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.,
No data available.
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
There are metabolic interactions with other local
anaesthetics, cholinesterase inhibitors and cytotoxic drugs
(Fleming et al., 1990).
7.7 Main adverse effects
8. TOXICOLOGICAL ANALYSIS AND BIOMEDICAL INVESTIGATIONS
9. CLINICAL EFFECTS
9.1 Acute poisoning
Acute intoxication causes intense agitation,
convulsions, hypertension, rhythm disturbance,
coronary insufficiency, hyperthermia, rhabdomyolysis,
and renal impairment.
Intestinal ischaemia has been described.
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
9.1.4 Eye contact
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
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
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.,
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
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).
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 &
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 &
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
The following have been described with chronic
intravenous abuse or inhalation:
- precordial pain, of unknown aetiology in 80% of
- arterial hypertension;
- ventricular and supraventricular tachyarrhythmias,
- acute coronary insufficiency and myocardial
- digital, renal, intestinal and spinal cord
- dilated cardiomyopathy and myocarditis, rupture of
the ascending aorta;
- 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).
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).
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,
184.108.40.206 Peripheral Nervous System
Local anaesthesia, muscular
paralysis and abolition of reflexes occur
(Baschard & Richard, 1984).
220.127.116.11 Autonomic Nervous System
Cocaine can cause tachycardia,
arterial hypertension, vomiting, "cocaine
fever", and occasionally
18.104.22.168 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.,
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
hyperbilirubinaemia, anti-hepatocellular necroses have
been described (Guérin et al., 1989).
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.
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,
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
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).
22.214.171.124 Acid-Base Disturbance
Acid-base disturbances are caused
by hypoxia in cocaine addicts, particularly
when there are repeated convulsions (Bismuth
et al., 1989).
126.96.36.199 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
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 &
9.4.14 Other clinical effects
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).
Subjects who are deficient in pseudocholinesterase can
die suddenly after cocaine.
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).
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
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
- the patient should be placed in a calm environment;
- hyperthermia should be corrected by undressing;
- hydration should be sufficient to induce a diuresis and
- 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
- 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).
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
(Caruana et al., 1984; Bismuth et al., 1989; Baud, 1991; Marc
et al., 1992).
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
There is no specific antidote.
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. ILLUSTRATITIVE CASES
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. ADDITIONAL INFORMATION
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.
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
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
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,
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.
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
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
Finalised and edited by Dr MO Rambourg: February 1999
Cocaine (PIM 139F, French)