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cocaine (Depsocaine, Eritroxilina)

Ecgonine methyl ester benzoate. Indications: 1) topical anesthetic for mucous membranes 2) unlawfully used as a recreational drug Dosage: 1) may be given by means of cotton application, packs, spray or instilled into a cavity 2) maximal single dose of 150 mg Solution: 4%. Pharmacokinetics: 1) rapidly absorbed from all sites of application 2) maximal local anesthetic effect occurs with 5 minutes 3) duration of local anesthetic effect: 35-45 minutes 4) metabolized by the liver; excreted in the urine 5) elimination 1/2life 1 hour 2) benzoylecgonine is the major detectable metabolite Adverse effects: 1) common (> 10%) - CNS stimulation, loss of smell & taste, - chronic rhinitis, nasal congestion 2) less common (1-10%) a) cardiac - tachycardia with higher doses - bradycardia with lower doses - hypertension - ventricular dysrhythmias - chest pain (common) - myocardial ischemia 6% - coronary vasospasm common - myocardial infarction (rare) - may occur in young patients with normal coronary arteries - thrombosis - vasoconstriction - increased myocardial oxygen demand - intravenous benzodiazepines & nitrates [13] - aortic dissection [5] b) nervous system - nervousness, restlessness, agitation - euphoria, excitement - tremor - seizures - stroke, especially hemorrhagic stroke c) respiratory system - tachypnea - barotrauma - bronchospasm - non-cardiac pulmonary edema - pulmonary hemorrage - respiratory failure d) eyes - mydriasis - ulceration & sloughing of corneal epithelium 3) other - hyperthermia - renal tubular acidosis type-1 - rhabdomyolysis - destruction of the osteocartilaginous structures of the nasal cavity due to necrotizing inflammation [11] (images) - nasal septum perforation - erythema of nasal mucosa 4) cocaine adulterated with levamisole (most cocaine) [13] - cocaine-associated vasculitis - reticulated purpuric skin lesions on ears & extremities - thrombosis, leukocytoclastic vasculitis [13] - neutropenia [13] Management of toxicity: 1) ventricular arrhythmias may respond to 1 ampule of NaHCO3 2) aspirin to prevent thrombosis 3) intravenous benzodiazepines & nitrates for hypertension & chest pain [12] 4) calcium channel blockers* may diminish vasoconstriction 5) calcium channel blockers* & benzodiazepines may lower heart rate, blood pressure & myocardial oxygen demand [5,10] 6) seizure control - benzodiazepine 6) use of beta blockers is controversial a) leads to unopposed alpha activity & vasoconstriction b) labetalol: 1] combined alpha & beta block (alpha-1/beta potency is 1/7) 2] use is controversial c) selective beta blockers may be useful for chest pain [9] 7) analogy to treatment of pheochromocytoma crisis * calcium channel blocker should be paired with benzodiazepine [13] Drug interactions: 1) lidocaine may increase risk of seizures (+ studies in rats) 2) calcium channel blockers may increase risk of seizures (+ studies in rats) 3) MAO inhibitors 4) epinephrine Laboratory: 1) specimen: a) serum, plasma (heparin, EDTA); store on ice; assay immediately b) urine: (random); store at 8 degrees C if not assayed immediately 2) methods: a) serum/plasma: RIA, GLC, HPLC, GC-MS b) urine: EIA, GLC, FPIA, HPLC, GC-MS 3) methods: specimen: sensitivity a) EMIT: urine: 200-300 ng/mL b) RIA: urine/blood: 5-100 ng/mL c) HPLC: serum/urine: 200-300 ng/mL d) GC-MS: serum/urine: 200-300 ng/mL 4) presence of cocaine & benzoylecgonine can generally be detected for 48-72 hours 5) using GC/MS, cocaine metabolites have been detected up to 3 weeks after use 6) interferences: -> methaqualone may interfere with some GLC procedures 7) labs with Loincs - cocaine in specimen - cocaine in hair - cocaine in body fluid - cocaine in bile fluid - cocaine in blood - cocaine in meconium - cocaine in saliva - cocaine in serum/plasma - cocaine in stool - cocaine in urine - cocaine in vitreous fluid cocaine & benzoylecgonine (active metabolite) detected RIA: radioimmunoassay HPLC: high-performance liquid chromatography GC-MS: gas chromatography-mass spectroscopy Mechanism of action: 1) a central stimulant 2) local anesthetic 3) causes vasoconstriction 4) blocks reuptake of dopamine & norepinephrine at pre- ganglionic sympathetic nerves 5) directly facilitates dopamine release from CNS neurons 6) indirectly leads to release of epinephrine & norepinephrine from the adrenal medulla 7) leads to hyperadrenergic state 8) cardiac effects a) tachycardia b) hypertension c) proarrhythmic state d) positive inotropic effect at low doses, but negative inotropic effect at higher doses e) increased myocardial oxygen demand

Interactions

drug interactions drug adverse effects (more general classes)

Related

cocaine abuse cocaine in urine pheochromocytoma; paroxysmal hypertension; adrenal medullary paraganglioma; chromoffinoma

General

analeptic (CNS stimulant) atypical antidepressant local anesthetic sympathomimetic (alpha & beta agonists) tropane

Properties

SIZE: hcl salt = 339.82 G/M MISC-INFO: elimination route LIVER MW 122-124 C {HCL_SALT} C17 H21 N O4 1/2life 1.0 HOURS toxic-range >1000 NG/ML

Database Correlations

PUBCHEM correlations

References

  1. Merck Index 11th ed #2411
  2. Research Biochemicals International 1993-94 catalog
  3. Goldfrank's Toxicologic Emergencies, 6th ed, Goldfrank et al eds, Appleton & Lang, Stamford, CT, 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Medical Knowledge Self Assessment Program (MKSAP) 11, 16. American College of Physicians, Philadelphia 1998, 2012
  6. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
  7. Department of Veterans Affairs, VA National Formulary
  8. Daubert GP, Emergency Medicine, University of California, Davis
  9. Rangel C et al. beta-blockers for chest pain associated with recent cocaine use. Arch Intern Med 2010 May 24; 170:874. PMID: 20498415
  10. McCord J, Jneid H, Hollander JE et al Management of cocaine-associated chest pain and myocardial infarction: a scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology. Circulation. 2008 Apr 8;117(14):1897-907 PMID: 18347214
  11. Stelten BM, Post B IMAGES IN CLINICAL MEDICINE. Midline Destructive Lesions in a Cocaine User N Engl J Med 2016; 374:969. March 10, 2016 PMID: 26962731 http://www.nejm.org/doi/full/10.1056/NEJMicm1503043
  12. Finkel JB, Marhefka GD Rethinking cocaine-associated chest pain and acute coronary syndromes. Mayo Clin Proc. 2011 Dec;86(12):1198-207. PMID: 22134939 Free PMC article. Review.
  13. NEJM Knowledge+ Psychiatry

Component-of

cocaine/diacetylmorphine (speedball)