Acute effects of inhaled and i.v. cocaine on airway dynamics.
BACKGROUND
Wheezing has been reported by 32% of habitual smokers of crack cocaine, and several cases of crack-related acute exacerbations of asthma have been reported.


OBJECTIVE
To compare the acute effects of physiologically active doses of smoked cocaine base and, i.v. cocaine hydrochloride (HCl), a subphysiologic dose of cocaine base (smoked "placebo"), and i.v. saline solution placebo on bronchomotor tone, subjective level of intoxication, and cardiovascular responses in healthy habitual crack users.


METHODS
A single-blind crossover study in which the order of route of administration (inhaled vs i.v.) was random but placebo always preceded the active drug.


METHODS
Fourteen healthy, nonasthmatic current crack-smoking subjects, 34 to 48 years of age, with a history of previous i.v. cocaine use (1 to 12 times per lifetime).


METHODS
Heart rate, BP, self-rated level of intoxication (scale of 0 to 10), and measurements of airway resistance (Raw) and specific airway conductance (SGaw) were recorded during separate sessions before and 3 to 5, 10, 15, and 30 min after administration of smoked cocaine base (38.5 +/- 2.3 [SEM] mg), smoked placebo (2.3 +/- 0.9 mg cocaine base), i.v. cocaine HCl (30.0 +/- 2.0 mg), and i.v placebo (saline solution).


RESULTS
Both smoked active cocaine and i.v. cocaine HCl caused comparable, significant (p < 0.05) peak levels of acute intoxication (6.7 +/- 0.7 and 7.3 +/- 0.8, respectively) and increases in heart rate from baseline (29.6 +/- 2.9% and 21.4 +/- 3.7%, respectively, at 5 min). However, only smoked active cocaine caused significant decreases from baseline in SGaw (25.4 +/- 6.3% at 5 min), in contrast to nonsignificant changes after i.v. cocaine HCl (5.6 +/- 7.0% increase) and smoked placebo (10.2 +/- 6.0% decrease).


CONCLUSIONS
Smoked cocaine base, but not systemically administered cocaine HCl, causes acute bronchoconstriction that is probably mediated by local airway irritation and could account for reports of crack-induced wheezing and asthma attacks in nonasthmatic and asthmatic individuals, respectively.
Tashkin
D P
DP
Department of Medicine, UCLA School of Medicine 90024, USA.
Kleerup
E C
EC
Koyal
S N
SN
Marques
J A
JA
Goldman
M D
MD
D000280:Administration, Inhalation; D000328:Adult; D016084:Bronchoconstriction / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D016578:Crack Cocaine / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D015656:Respiratory Mechanics / Q000187:drug effects*
D016578:Crack Cocaine; D003042:Cocaine