Amphetamines and Cocaine

stimulants stimulate transmission of

epinephrine, norepinephrine, dopamine, serotonin, monoamines

types of amphetamines

natural, synthetic, amp-like

1887 - first synthesised

amphetamine absorption

oral (peak blood levels 30 min - 4 hours, depending on food in stomach and physical activity), inhalation (2.5 hours), IV (20 min)

cocaine absorption

IV (2-5 min), snorting (30-60 min, feel effects in 10-20 min)

distribution of amphetamines and cocaine

cross BBB, concentrate in kidneys and lungs (amphetamines) brain (cocaine)

neurophysiology of amphetamines and cocaine

act on monoamine system (DA, NE, serotonin)

cocaine action on monoamine system

reuptake blocker

amphetamine actions on monoamine system 

increases NT release, forces NT into synaptic cleft, reuptake blocker

effects in PNS

stimulate epinephrine synapses = fight or flight

CNS effects

increase dopamine = more motivation and motor activity, blocks APs = anaesthetic

effects of amphetamines and cocaine

vaso/bronchodilation, stereotyped behaviour and pending, amphetamine psychosis, formication, time underestimated, tunnelling of focus, anorectic actions

excretion of amphetamines

depends on urine pH

Half-life around 7-14 hours (acidic) and 16-34 hours (basic)

also excreted through sweat and saliva

metabolites in urine up to 1 week

excretion of cocaine

dependent on urine, half-life 45-76 minutes and metabolites in urine 24-36 hours

absorption of amphetamines

weak bases (pKa 9-10), ionised in digestive system, blood levels can be kept constant 

administration of cocaine

pKa 8.8, inhaled, oral, injected

conditioned behaviour in animals

increase SMA and stereotyped behaviours, rate dependency effect for punishment, mutilation and decreased food and water intake 

Self administration in animals

more reinforcing than other drugs for monkeys - will self administer lethal dose

self administration in humans

sporadic, depends on reason

discrimination

generalize to coke, MPH and MAO inhibitors but not caffeine, nicotine, BBTs and hallucinogens

tolerance

acute tolerance to coke rapidly disappears to subjective effects but not HR/BP

chronic tolerance leads to lethality, appetite suppression, sensitisation to stereotyped behaviour and psychosis

cocaine withdrawal

starts hours after last use, peaks 7-10 days, lasts weeks-months

amphetamine withdrawal

starts 24 hours from abstinence, crash phase, lasts 3-4 weeks

clinical uses of amphetamines/coke

amphetamines - ADHD (paradoxical effect), obesity, narcolepsy, cold/flu

coke - anaesthetic

pharmacotherapies include

modafinil, oral d-amphetamine, naltrexone

treatments include

detoxification, relapse. contingency management and community reinforcement

harmful effects of amphetamines

confusion, dizziness, punding, loss in limbic system, LT use leads to suicidal thinking

harmful effects of cocaine

jaundice, inflammation in nose, financial ruin, LT use leads to depression

Coke overdose phases

1. Excitement - headache, nausea, convulsions 2. Lose consciousness - cardiac failure and death

coke overdose can be treated by

diazepam (seizures), artificial respiration, chlorpromazine (antipsychotic)