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A. Pharmacologic Actions [2,3] navigator

  1. Similar to amphetamines
    1. Inhibits catecholamine reuptake: norepinephrine, dopamine, epinephrine
    2. Leads to elevated levels of sympathetic neurotransmitters
    3. May show slight increase in release of norepinephrine
  2. Potent Vasoconstriction
    1. Mediated primarily through alpha-adrenergic receptors
    2. Increases release of endothelins
    3. Reduces production of nitric oxide (potent vasodilator)
    4. Prevents cutaneous vasodilation
  3. Other Acute Cardiac Effects
    1. alpha and/or ß-adrenergic effects
    2. Increased blood pressure
    3. Increased heart rate
    4. All lead to increased cardiac oxygen consumption
  4. Chronic Cardiac Effects
    1. Myocardial ischemia - silent and/or with angina
    2. Accelerated atherosclerosis
    3. Myocarditis
    4. Cardiomyopathy - dilated and hypertrophic
    5. Arrhythmias
    6. Hypertension
    7. Aortic dissection
    8. Endocarditis
  5. Inhibit sodium channels, primarily in the heart
    1. Widening of QRS interval
    2. Prolongation of QT interval
  6. Induces Hyperthermia: Impairs sweating and cutaneous vasodilation
  7. Psychotropic effects correlate closely with inhibition of dopamine uptake
  8. Local (usually topical) anesthetic effects
  9. Nasal Septal Collapse [21]
    1. May be mistaken for vasculitis
    2. May induce transient anti-neutrophil cytoplasmic antibodies (ANCA)
    3. May be mistaken for Wegener's granulomatosis or glomerulonephritis
  10. Methamphetamine abuse symptoms similar to cocaine [22]
    1. Highly addictive synthetic sympathomimetic
    2. Ingestion, smoked, snorted, or injected
    3. Anorexia, insomnia, tachycardia, tachypnea, hypertension, hyperthermia, seizures
    4. Hemorrhagic and ischemic strokes and renal failure have occurred
    5. CNS effects include anxiety, agitation, paranoia, delirium, psychosis
    6. Metabolized by CYP2D6; drugs that compete with CYP2D6 can increase levels
    7. Therapies similar to cocaine abuse but avoid haloperidol (CYP2D6 inhibitor)

B. Evaluation of Cocaine Abusenavigator

  1. High suspicion in young persons with
    1. Unexplained weight loss
    2. Evidence of cardiac ischemia
    3. Poor or declining performance at school or work
    4. Later stages - becoming antisocial
  2. Abuse of cocaine highly associated with HIV and Hepatitis B and C Virus infections
  3. Use with heroin intravenously is called a "speedball"
  4. Symptoms
    1. Duration of "high" from cocaine is <30 minutes
    2. High is followed typically by a "down" lasting hours (or until another dose of cocaine)
    3. Major "upper" feelings are excitement, hyper-speech, omnipotence
    4. Anxiety, agitation, paranoia, hallucinations (auditory and visual), delirium
    5. Frank seizures (stroke) may also occur
    6. Tachycardia, hypertension, and/or high fevers with no other obvious cause
    7. Markedly reduced appetite; may lead to substantial weight loss
    8. Severe headaches, pupillary dilation, eye watering occur as well
    9. Epistaxis, septal perforation, sinusitis also occur with intranasal abuse
  5. Psychiatric Abnormalities
    1. >70% of cocaine abusers have personality disorders
    2. Confusion is prominant in nearly all patients
    3. Psychosis with severe agitation is common in acute overdoses
    4. Chronic use can lead to hallucinations
  6. Intake of Cocaine
    1. Snorting - intranasal (most popular)
    2. Solid (crack) or freebase can be smoked
    3. Intravenous injection
    4. Subcutaneously (popping)
  7. Toxin screen in blood and urine (metabolite benzoylecgonine) is gold standard for therapy

C. Acute Medical Effects of Cocaine Abusenavigator

  1. Main effects leading to serious problems due to vasospasm and sympathomimetic activity
  2. Severe peripheral vasoconstriction with hypertension
    1. May cause hypertensive emergency
    2. Usually with tachycardia
  3. Myocardial Ischemia and Infarction (MI) [11,15,18]
    1. Vasoconstriction (primarily cardiac) and platelet activation
    2. Chronotropic and inotropic activities of cocaine greatly increase cardiac oxygen demand
    3. Cocaine stimulates endothelial damage and atherosclerosis as well
    4. Exacerbated by pre-existing coronary artery disease, smoking, and alcoholism
    5. Smoking greatly increases risk of cocaine induced MI
    6. Creatine kinase (CK) elevations are not useful for evaluation of cocaine-induced MI
    7. Troponin I or T elevations are required to assess cocaine-induced ischemia
    8. CK elevations without troponin I or T increases are not due to cardiac ischemia
    9. In patients with acute symptoms, 9-12 hours observation is sufficient to ensure low risk for complications [19]
  4. Other Cardiac Effects [12,15,18]
    1. Acute ventricular dysfunction and frank heart failure [10]
    2. Aortic dissection - uncommon, likely related to severe, acute HTN
    3. Hemopericardium
    4. Atrial Arrhythmias: sinus tachycardia, sinus bradycardia, supraventricular tachycardia
    5. Ventricular Arrhythmias: AIVR, ventricular tachycardia and fibrillation, TDP
    6. Heart Block: bundle branch block (BBB), complete heart block, asystole
    7. Brugada pattern can occur (right BBB, ST semgnet elevation in V1, V2, V3)
  5. Rhabdomyolysis
    1. Likely related to vasoconstriction
    2. Significant serum CK occur in rhabdomyolysis
  6. Acute Renal Failure
    1. Vasoconstriction is a primary contributor
    2. Exacerbated by rhabdomyolysis and myoglobinuria
  7. Hyperthermia [2]
    1. Cocaine impairs sweating
    2. Impairs cutaneous vasodilation
    3. Reduces heat perception
  8. Central Nervous System
    1. Induces cerebral vasoconstriction (detectable on MRI angiography) [4]
    2. Very low doses of cocaine induce these vasocontrictive events
    3. Seizures and Strokes have been reported
  9. Pupillary Dilatation
  10. Risk for spontaneous abortion increased 1.4 fold [7]

D. Acute Therapy [19] navigator

  1. Supportive therapy is mainstay for acute treatment of overdose
  2. Sedation
    1. Benzodiazepines are often very effective and are used first line
    2. Antipsychotics may be required and are second line
  3. Treatment of Cocaine-Induced Cardiac Ischemia [11,15]
    1. All patients receive oxygen and aspirin
    2. Intravenous nitrates are vasodilators of choice
    3. Sedation is critical using above agents
    4. Calcium blockers are moderately effective and can be used for slowing heart rate
    5. Calcium blockers iv may be preferred in patients with coronary artery spasm
    6. ß-blockers are contraindicated due to increase in cocaine induced vasosconstriction [3]
    7. Thrombolytics are generally reserved for resistant cases and used with caution
    8. Phentolamine (alpha-adrenergic antagonist) can be used for refractory HTN, ischemia
    9. Patients with no signs of acute ischemia over 9-12 hours may be safely discharged [19]
  4. Hypertensive Emergency [3]
    1. Nitroprusside (Nipride®) - caution with renal failure or rhabdomyolysis
    2. Phentolamine is preferred, may be combined with nitroglycerin
  5. Benzodiazepines preferred over opiates to sedate patient
  6. Morphine is useful for pain in cases of cocaine induced ischemia

E. Chronic Cocaine Abuse [17,20]navigator

  1. Dysphoria / Anxiety
  2. Sleep Disorders
  3. Sexual Disorders
  4. Psychosis
  5. Myocardial Infarction
  6. Stroke - hemorrhagic and thromboembolic
  7. Hepatotoxicity - usually with severe cocaine overdose, often with rhabdomyolysis [8]
  8. Cognitive deficiency and delay in cocaine-exposed infants [16]
  9. Treatment of Chronic Abuse
    1. Prevention of relapse
    2. Psychological support
    3. Detoxification Programs and Self-Help Groups
    4. Behavioral Therapy - mixed results; better if patients' significant others involved
    5. Acupuncture did not reduce cocaine abuse [14]
    6. To date, no effective agents to substantially prevent relapse
  10. Medications for Chronic Abuse
    1. Desipramine - only effective for depressed patients (no effect on abstinance)
    2. Seretonin reuptake inhibitors are not effective
    3. Flupentixol - dopamine receptor antagonist, may be effective in chronic abuse
    4. Buprenorphine - a mixed opiate agonist/antagonist; may have some efficacy

References navigator

  1. Acute Reactions to Drugs of Abuse. 2002. Med Let. 44(1125):21 abstract
  2. Crandall CG, Vongpatanasin W, Victor RG. 2002. Ann Intern Med. 136(11):785 abstract
  3. Cocaine. 1996. Med Let. 38(974):43
  4. Kaufman MJ, Levin JM, Ross MH, et al. 1998. JAMA. 279(5):376 abstract
  5. Holden R and Jackson MA. 1996. Lancet. 347:1052 abstract
  6. Henry JA, Fallon JK, Kicman AT, et al. 1998. Lancet. 351(9118):1784 abstract
  7. Ness RB, Grisso JA, Hirschinger N, et al. 1999. NEJM. 340(5):333 abstract
  8. Jonas MM and Graeme-Cook FM. 2001. NEJM. 344(8):591
  9. Schneider RK, Levenson JL, Schnoll SH. 2001. Ann Intern Med. 134(5):387 abstract
  10. Missouris CG, Swift PA, Singer DRJ. 2001. Lancet. 357(9268):1586 abstract
  11. Hollander JE. 1995. NEJM. 333(19):1267 abstract
  12. Nallamothu BK, Saint S, Kolias TJ, Eagle KA. 2001. NEJM. 345(5):359 abstract
  13. Reneman L, Booij J, de Bruin K, et al. 2001. Lancet. 358(9296):1864 abstract
  14. Margolin A, Kleber HD, Avants SK, et al. 2002. JAMA. 287(1):55 abstract
  15. Lange RA and Hillis LD. 2001. NEJM. 345(5):351 abstract
  16. Singer LT, Arendt R, Minnes S, et al. 2002. JAMA. 287(15):1952 abstract
  17. Mendelson JH and Mello NK. 1996. NEJM. 334(15):965 abstract
  18. Kloner RA and Rezkalla SH. 2003. NEJM. 348(6):487 abstract
  19. Weber JE, Shofer FS, Larkin L, et al. 2003. NEJM. 348(6):510 abstract
  20. Kosten TR and O'Connor PG. 2003. NEJM. 348(18):1786 abstract
  21. Cami J and Farre M. 2003. NEJM. 349(10):975 abstract
  22. Rowshani AT, Schot LJ, ten Berge IJM. 2004. Lancet. 363(9411):782 (Case Report) abstract
  23. Methamphetamine Abuse. 2004. Med Let. 46(1188):62 abstract