Synthesis: methamphetamine can be readily synthesized via simple reactions using readily available chemicals and over-the-counter cold medicines (ephedrine, pseudoephedrine)
Methamphetamine synthesis carries significant risks of explosion
Methamphetamine synthesis can result in the exposure of children to toxic byproducts
Routes of Methamphetamine Exposure
Intravenous (IV) Methamphetamine Injection: less common (route of abuse in 7% of cases)
Oral Methamphetamine Ingestion: less common (route of abuse in 3% of cases)
“Body Stuffing”: ingestion of methamphetamine packets to avoid arrest
“Body Packing”: concealment of large quantities of methamphetamine for transport
Intentional Ingestion
Therapeutic Methamphetamine Administration
Attention Deficit Disorder with Hyperactivity (ADHD)
Narcolepsy (see Narcolepsy, [[Narcolepsy]]): off-label use
Obesity (see Obesity, [[Obesity]]): short-term treatment
Methamphetamine Smoking: most common method of abuse (route of abuse in 68% of cases)
Methamphetamine Nasal Insufflation (“Snorting”): common (route of abuse in 31% of cases)
“Body Packing”: concealment of large quantities of methamphetamine for transport
Urethral Methamphetamine Insertion
Urethral Methamphetamine Abuse
Pharmacology
Methamphetamine is a Phenethylamine Sympathomimetic Amine: substitutions on the phenethylamine ring structure determine the degree of central nervous system penetration, degree of degradation by monoamine oxidase, receptor binding affinity, and the variety of clinical effects
Amphetamine (alpha methyl phenethylamine) has single methyl group at the alpha position on the carbon chain
Methamphetamine has a second methyl group on the carbon chain: this increases lipophilicity and its central nervous system activity
Methamphetamine is an Indirect Neurotransmitter Which Moves into Cytoplasmic Vesicles in Presynaptic Adrenergic Neurons -> Displacement of Epinephrine, Norepinephrine, Dopamine, and Serotonin into the Cytosol: as cytosolic concentrations of these neurotransmitters increase, they diffuse out of neuron and into the synapse -> activation of postsynaptic receptors
Increased Expression and Activity of Tyrosine Hydroxylase: enzyme which is responsible for synthesizing dopamine
Monoamine Oxidase (MAO) Inhibition
Decreased Expression of Dopamine Transporters on Cell Surface
Inhibition of Monoamine Transporters
Reversal of Transport of Neurotransmitters Through Plasma Membrane Transporters
Epidemiology: excessive tooth decay is common with chronic methamphetamine abuse (and is more severe in those who use the drug intravenously than in those who use the drug by smoking/ingestion/inhalation)
Bupropion ((Wellbutrin, Zyban) (see Bupropion, [[Bupropion]]) [MEDLINE]
Selegiline ((Anipryl, L-Deprenyl, Eldepryl, Emsam, Zelapar) (see Selegiline, [[Selegiline]]): metabolized to l-methamphetamine
False-Negative: as urine toxicology screens are dependent upon renal clearance of methamphetamine, it may fail to detect the drug if insufficient time has elapsed for drug to be excreted in the urine
Clinical Manifestations
General Comments: variably ranges from asymptomatic to frank sympathomimetic crisis
Hypotension/Shock (see Hypotension, [[Hypotension]]): precipitous cardiovascular collapse may rapidly occur in patients with severe agitation (especially when restrained to avoid harm to themselves or others)
Physiology: likely results from neurotransmitter depletion, metabolic acidosis, and dehydration
Prognosis: shock is a poor prognostic factor [MEDLINE]
Myocardial Ischemia/Infarction (MI) (see Coronary Artery Disease, [[Coronary Artery Disease]])
Epidemiology: may occur with either acute and chronic methamphetamine abuse
Barotrauma: associated with forceful inhalation (however, the incidence of barotrauma is far lower than that observed with crack cocaine abuse for unclear reasons)
Benzodiazepines (see Benzodiazepines, [[Benzodiazepines]]): have been used
References
Subarachnoid and intracerebral hemorrhage associated with necrotizing angiitis due to methamphetamine abuse–an autopsy case. Neurol Med Chir (Tokyo) 1991; 31:49–52
Fatal and nonfatal methamphetamine intoxication in the intensive care unit. J Toxicol Clin Toxicol. 1994;32(2):147-55 [MEDLINE]
GC-MS determination of amphetamine and methamphetamine in human urine for 12 hours following oral administration of dextro-methamphetamine: lack of evidence supporting the established forensic guidelines for methamphetamine confirmation. J Anal Toxicol. 1995;19(7):581 [MEDLINE]
