cocaine (Depsocaine, Eritroxilina)
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Introduction
Ecgonine methyl ester benzoate.
Indications
- topical anesthetic for mucous membranes
- unlawfully used as a recreational drug
Dosage
- may be given by means of cotton application, packs, spray or instilled into a cavity
- maximal single dose of 150 mg
Solution: 4%.
Pharmacokinetics
- rapidly absorbed from all sites of application
- maximal local anesthetic effect occurs with 5 minutes
- duration of local anesthetic effect: 35-45 minutes
- metabolized by the liver; excreted in the urine
- elimination 1/2life 1 hour
- benzoylecgonine is the major detectable metabolite
elimination via liver
1/2life = 1.0 hours
Adverse effects
- common (> 10%)
- CNS stimulation, loss of smell & taste,
- chronic rhinitis, nasal congestion
- less common (1-10%)
- 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]
- nervous system
- nervousness, restlessness, agitation
- euphoria, excitement
- tremor
- seizures
- stroke, especially hemorrhagic stroke
- respiratory system
- tachypnea
- barotrauma
- bronchospasm
- non-cardiac pulmonary edema
- pulmonary hemorrage
- respiratory failure
- eyes
- cardiac
- other
- hyperthermia
- renal tubular acidosis type-1
- rhabdomyolysis
- destruction of the osteocartilaginous structures of the nasal cavity due to necrotizing inflammation[11] (images)
- cocaine adulterated with levamisole (most cocaine)[13]
Management of toxicity:
- ventricular arrhythmias may respond to 1 ampule of NaHCO3
- aspirin to prevent thrombosis
- intravenous benzodiazepines & nitrates for hypertension & chest pain[12]
- calcium channel blockers* may diminish vasoconstriction
- calcium channel blockers* & benzodiazepines may lower heart rate, blood pressure & myocardial oxygen demand[5][10]
- seizure control - benzodiazepine
- use of beta blockers is controversial
- leads to unopposed alpha activity & vasoconstriction
- labetalol:
- combined alpha & beta block (alpha-1/beta potency is 1/7)
- use is controversial
- selective beta blockers may be useful for chest pain[9]
- analogy to treatment of pheochromocytoma crisis
* calcium channel blocker should be paired with benzodiazepine[13]
- drug adverse effects of analeptics
- drug adverse effects of antidepressants
- drug adverse effects of psychotropic agents
- drug adverse effects of sympathomimetic(s)
Drug interactions
- lidocaine may increase risk of seizures (+ studies in rats)
- calcium channel blockers may increase risk of seizures (+ studies in rats)
- MAO inhibitors
- epinephrine
- drug interaction(s) of antidepressant in combination with GLP1-agonist
- drug interaction(s) of benzodiazepines with antidepressants
- drug interaction(s) of antidepressants with benzodiazepines
- drug interaction(s) of NSAIDs with antidepressants
- drug interaction(s) of antidepressant with opiates
Laboratory
- specimen:
- methods:
- methods: specimen: sensitivity
- presence of cocaine & benzoylecgonine can generally be detected for 48-72 hours
- using GC/MS, cocaine metabolites have been detected up to 3 weeks after use
- interferences:
- methaqualone may interfere with some GLC procedures
- labs with Loincs
cocaine & benzoylecgonine (active metabolite) detected
HPLC: high-performance liquid chromatography
GC-MS: gas chromatography-mass spectroscopy
Mechanism of action
- a central stimulant
- local anesthetic
- causes vasoconstriction
- blocks reuptake of dopamine & norepinephrine at pre- ganglionic sympathetic nerves
- directly facilitates dopamine release from CNS neurons
- indirectly leads to release of epinephrine & norepinephrine from the adrenal medulla
- leads to hyperadrenergic state
- cardiac effects
- tachycardia
- hypertension
- proarrhythmic state
- positive inotropic effect at low doses, but negative inotropic effect at higher doses
- increased myocardial oxygen demand
More general terms
- tropane
- sympathomimetic (alpha & beta agonists)
- atypical antidepressant
- analeptic (CNS stimulant)
- local anesthetic
Additional terms
- cocaine abuse
- cocaine in urine
- pheochromocytoma; paroxysmal hypertension; adrenal medullary paraganglioma; chromoffinoma
Component of
References
- ↑ Merck Index 11th ed #2411
- ↑ Research Biochemicals International 1993-94 catalog
- ↑ Goldfrank's Toxicologic Emergencies, 6th ed, Goldfrank et al eds, Appleton & Lang, Stamford, CT, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 5.0 5.1 5.2 Medical Knowledge Self Assessment Program (MKSAP) 11, 16. American College of Physicians, Philadelphia 1998, 2012
- ↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
- ↑ Department of Veterans Affairs, VA National Formulary
- ↑ Daubert GP, Emergency Medicine, University of California, Davis
- ↑ 9.0 9.1 Rangel C et al. beta-blockers for chest pain associated with recent cocaine use. Arch Intern Med 2010 May 24; 170:874. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20498415
- ↑ 10.0 10.1 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: https://www.ncbi.nlm.nih.gov/pubmed/18347214
- ↑ 11.0 11.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26962731 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMicm1503043
- ↑ 12.0 12.1 Finkel JB, Marhefka GD Rethinking cocaine-associated chest pain and acute coronary syndromes. Mayo Clin Proc. 2011 Dec;86(12):1198-207. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22134939 Free PMC article. Review.
- ↑ 13.0 13.1 13.2 13.3 13.4 13.5 NEJM Knowledge+ Psychiatry
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=446220
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2826
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5760
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5871
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5315982
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=135184
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=656832
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=165375
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=83826
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=517282