HPEX 352 Stimulants - Cocaine and Amphetamine

Cocaine’s Mechanism: Complex; it blocks the reuptake of neurotransmitters dopamine, serotonin, and norepinephrine. GABA and glutamate have also been implicated in its effects.

Routes of Administration: Ingestion, insufflation, injection, inhalation.
Speed: Rapid absorption; peak effect typically occurs within seconds to minutes.
Duration: Short action duration of about 30 minutes.
Psychological Dependence: High potential due to rapid onset.
Physical Dependence: High potential due to short duration of action.

Metabolized by enzymes in the blood and liver.
Half-life: Approx. 1 hour for cocaine; major metabolites have half-lives of about 8 hours.
Active Metabolite: Nor-cocaine, detectable by urine drug screens; metabolites take about 3 days for complete elimination after moderate use.

Enzymatic Breakdown encompasses the transformation of cocaine into various metabolites like ecgonine methyl ester and benzoylecgonine by liver enzymes (CYP450-3A).

Local Anesthesia: Historical medical use since 1884, particularly for surgeries involving the nasal, laryngeal, and esophageal regions due to its vasoconstrictor properties and efficacy when absorbed by mucous membranes.

Chemical Structure: Methamphetamine is amphetamine double methylated; amphetamine is only methylated once.

Chemical Structure: Similar to catecholamine neurotransmitters, with the ability to increase their activity by stimulating release.
- Effects include dopamine, norepinephrine, and serotonin release. Methamphetamine can cross the blood-brain barrier more efficiently than ephedrine, leading to more pronounced central nervous system stimulation.

Dopamine Regulation: Addictive substances, including amphetamines, increase dopamine levels in synapses, enhancing pleasurable feelings. Addiction dynamics involve disruption of brain circuits controlling rewards and memory, leading to compulsive drug-taking behaviors.

Routes of Administration: Ingestion, insufflation, injection, inhalation.
Absorption Speed: Fast; peak effects generally occur within minutes.
Elimination Rate: Slow, with an extended duration of effect (6-12 hours) leading to potential for psychological and physical dependence.

Peak Effects Timing: Approximately 1.5 hours after oral ingestion, 5-20 minutes after nasal administration, and 5-10 minutes after intravenous injection or smoking.
Half-life: Ranges between 5-12 hours, with complete drug elimination taking about 2-3 days. Rapid tolerance (tachyphylaxis) may develop following high doses.

Smoking methamphetamine produces a high lasting 8-24 hours compared to 20-30 minutes for cocaine. Metabolism differs; methamphetamine persists in the brain longer due to a larger percentage remaining unchanged in the body.

Depression: Fast-acting antidepressant, formerly a main treatment from the 1950s to 60s, now often used in adjunctive therapy.
Weight Control: Historically, methamphetamine was FDA-approved for short-term weight management, with unclear long-term effects on obesity.
ADHD Treatment: Stimulants help reverse catecholamine deficits in ADHD, though concerns about abuse lead to exploration of alternatives; data indicates stimulants might protect against substance abuse.
Narcolepsy Treatment: Stimulants are employed to manage uncontrolled daytime sleepiness, with newer drugs such as modafinil showing lower abuse potential.