psychostimulants lesson 19. psychostimulants n cocaine l alkaloid from coca plant n amphetamines...
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Psychostimulants
Lesson 19
Psychostimulants Cocaine
alkaloid from coca plant Amphetamines (synthetics)
similar fx & mechanismsall related to ephedrine (ephedra)dl-amphetamine: methamphetamineMDMA (Ecstasy) ~
Cocaine: Local Anesthetic
Pharmacokinetics Inject SC
Half-life: 1 hr Numbing < 2 min Peak effects: 15-20 minutes
Pharmacodynamics Blocks Na+ channels Constricts blood vessels ~
Cocaine: Psychostimulant Pharmacokinetics p.o.
ineffective for cocaine effective for amphetamine analogs onset: 30 minutes / peak 2-3 hrs
Intranasal onset 3-4 minutes peak effects: 15-20 minutes ~
CocainePharmacokinetics
Inhalation (smoking) & IV injection Onset: < 2 min
For both routes Euphoria Crash Craving
Powerful positive RFT short delay high magnitude ~
Pharmacokinetics: Metabolism
Cocaine By cholinesterases Blood & Liver Half-life: 1 hr
Amphetamines In liver, much excreted unchanged Half-life: 7-30 hrs ~
Tachyphylaxis brief & transient tolerance reuse within minutes - hours
Tolerance Lower doses
Sensitization repeated use over days ~
Psychostimulant Pharmacokinetics
Psychostimulant Pharmacology
Indirect agonists: DA, NE, 5-HT
DA - reinforcing effects in nucleus accumbens Euphoria
Rate of change of blood levels Amphetamine
Primary effects on reuptake Also NT & MAO function ~
Physiological Effects
Sympathomimetic Heart
Low doses: decrease HR Moderate: HR & BP High: cardiac arrhythmia, failure
Body temperature Low doses: decrease moderate & high: increase ~
Physiological Effects
Restlessness Sleep: interferes with REM Vomiting Breathing is facilitated Depresses cortical activity ~
Psychostimulant Neurotoxicity
DA neurotoxicity; DA transporters amphetamine methamphetamine
5-HT neurotoxicity methamphetamine MDA MDMA (Ecstasy)
Single high dose ~
Psychotomimetic Effects
Prolonged use Schizophrenia-like psychosis
Paranoia Hallucinations: parasitosis delusions
Methamphetamine earlier developing may persist for days, weeks ~
Lethality
Cocaine Oral: 500 mg Nasal: 150-300 mg
Amphetamine/Methamphetamine toxic effects: 15 mg in novices lethal 500-1700 mg
Inhalation (smoked): much lower ~
Early•Agitation•Depression•Anorexia•High Craving
Middle•Depression •Fatigue•Insomnia•No craving
Late•Exhaustion•Hypersomnolence•Hyperphagia•No Craving
Phase 1: Crash9 hrs - 4 days
Phase 2: Withdrawal1 - 10 weeks
Early•Normal sleep•Normal mood•Low anxiety•Low craving
Middle & Late•Anhedonia•Anergia•Anxiety•High Craving & conditioned cues
Phase 3: Extinctionindefinite
•Normal hedonic response•Normal mood•Episodic craving•Conditioned cues trigger craving
AbstinenceBinge
Relapse
Cocaine Abstinence Syndrome
Gawin & Kleber (1986)
Cocaine Abuse: Animals
Self-administration Will work hard to get
progressive FR6400
Continuous access: Weight loss Self-mutilation
parasitosis? Death within 2 weeks ~