Clinical Textbook of Addictive Disorders 3rd ed - R. Frances, S. Miller, A. Mack (Guilford, 2005) WW

9. Cocaine and Stimulants 197When cocaine is administered repeatedly over a short period of time, acute tolerancecan develop to the sympathomimetic effects of cocaine. In contrast, theeffects of cocaine mediated by its local anesthetic action do not appear bluntedby anesthesia or susceptible to acute tolerance. In addition to the effects ofcocaine alone, the metabolites of cocaine may also contribute to cocaine’sacute and chronic cardiovascular toxicity, and both licit and illicit drugs used incombination with cocaine might potentially alter its cardiovascular effects(Schindler, 1996).With chronic administration, higher cocaine doses appear to induce tolerance,while lower doses may induce sensitization to cocaine’s sympathomimeticeffects. Chronic cocaine use is associated with multiple cardiovascular conditions,including myocardial infarction, aortic dissection, left ventricularhypertrophy, arrhythmias, sudden death, and cardiomyopathy (Frishman, DelVecchio, Sanal, & Ismail, 2003).CNS manifestations of cocaine exposure include seizures, status epilepticus,cerebral hemorrhage, and transient ischemic attacks. Cocaine may producehyperpyrexia through direct effects on thermoregulatory centers. Depressionof the medullary centers may result in respiratory paralysis, and suddendeath may be caused by respiratory arrest, myocardial infarction or arrhythmia,or status epilepticus (Cregler & Mark, 1986). Migraine-like headaches havebeen associated with cocaine withdrawal and may be linked to serotonin dysregulation(Satel & Gawin, 1989). Rhabdomyolysis is a complication ofcocaine use. When it is accompanied by acute renal failure, severe liver dysfunction,and disseminated intravascular coagulation, the fatality rate is high(Roth, Alarcon, Fernandez, Preston, & Bourgoignie, 1988).Other difficulties associated with chronic cocaine use include weight loss,dehydration, nutritional deficiencies (particularly of vitamins B 6, C, and thiamine),and endocrine abnormalities. Neglect of self-care may be evident,including dental caries and periodontitis exacerbated by bruxism. Addicts maymedicate their pain with cocaine or other mood-altering drugs and seek medicalattention only after prolonged existence of their problem(s).Adulterants also play a role in the development of medical complications.Local anesthetics and stimulants may increase cocaine’s inherent toxicity byincreasing the risk of hypertension and cardiovascular complications. Sugars,though relatively benign, may encourage development of bacteria that becomesproblematic when injected intravenously.Other complications of cocaine may be due to the route of administration.Intestinal ischemia caused by vasoconstriction and reduced blood flow in themesenteric vasculature from catecholamine stimulation of alpha receptors hasbeen reported after oral cocaine ingestion (Texter, Chou, Merrill, Laureton, &Frohlich, 1964). Emergency room patients have required surgical correction oftheir intestinal perforations, after smoking crack cocaine. The chronologicalrelationship between crack consumption and gastrointestinal perforation indi-