Exam 3 - Amphetamines and Cocaine Flashcards
What accounted for the rise and fall of meth use?
its changes in potency
What are amphetamine and cocaine?
stimulants
What are amphetamines structurally similar to?
dopamine
Khat/Cathinone
- active components are cathinone and cathine
- stimulant properties similar to amphetamine and cocaine
Bath salts
- synthetic cathinone
- 10x more powerful than cocaine
- triggers release of dopamine
MDPV
- main ingredient in bath salts, detected in urine of users
- first synthesized in 1968 to counteract chronic fatigue
What are the desired effects of bath salts?
- euphoric high with a rush
- appetite suppression
- study aid
What are the adverse effects of bath salts?
- combative
- hallucinations
- hyperthermia
- anxious/paranoia
Ephedrine
- comes from ephedra
- only use today is anesthesiology to increase BP
- can be toxic/fatal when combined with other stimulants
- pseudoephedrine used in cough and cold medicines
Basic pharmacology of amphetamines
- absorption from GI tract is slow, I.V. is rapid
- methamphetamine is more potent than amphetamine
- amphet and metham are metabolized by liver at slow rate
What are amphetamines mechanism of action?
- release DA independently of an action potential, and also releases NE and DA
- block reuptake of NE and DA
- addiction comes from the release of DA in the mesolimbic pathway
What are the behavioral effects of amphetamines?
- confident
- highly alert/don’t sleep
- low appetite
- improves performance on simple repetitive tasks
What are the psychological effects of amphetamines?
- sympathomimetic agents - mimic actions of epinephrine
- sympathetic nervous system (increase HR, BP, RR, dilate pupils)
What are the therapeutic uses of amphetamines?
- narcolepsy
- obesity - suppresses appetite
- ADHD - causes release of DA in areas that control attention
Tolerance/Dependence of amphetamines
- reverse tolerance of motor effects
- withdrawal symptoms include: increased appetite/weight gain, decreased energy, increased need for sleep (amphets block REM)
Amphetamine psychosis
- psychotic reaction occurring in substantial number of high dose users
- resembles paranoid schizophrenia (hallucinations, behavioral disorganization, paranoia, formication - picking at skin)
Neurotoxicity of amphetamines
- neuronal death of both dopaminergic and serotonergic neurons in animal models
Cocaine
stimulant that comes from the coca plant
What were the leaves of E. coca used for historically? When was the active alkaloid isolated? What was this alkaloid named?
- increase endurance/stamina, promote sense of well being, induce euphoria
- 1850’s
- cocaine
Coca paste was combined with hydrochloric acid to form:
less potent, water soluble salt cocaine hydrochloride
Who typically uses cocaine? Why do they use it?
- young males that are typically dependent on other drugs
- tend to have coexisting psychopathology that they are self-medicating for
What are the two ways that cocaine is absorbed?
- snorted, slow absorption, low concentration in blood
- inhalation and IV, rapid absorption, high concentration in blood
Distribution of cocaine
- penetrates brain rapidly, initial brain concentrations exceed blood concentrations
- freely crosses the placental barrier
Metabolism and excretion of cocaine
- biological half-life of 20-90 minutes
- major metabolite is benzoylecgonine, makes cocaethylene
What does cocaine do?
- potent local anesthetic
- vasoconstrictor
What are the adverse effects of cocaine
- convulsions/seizures
- hemorrhagic stroke (vasocontrictor and also a stimulant)
- cardiac arrhythmias
What are some consequences of use of cocaine during pregnancy?
- everything that can happen to mom can happen to baby
- premature birth
- respiratory distress
- cerebral infarctions
- seizures
What are the 3 phases of withdrawal of cocaine?
- crash (1-14 days): intense craving, exhaustion, agitation
- withdrawal (1-10 weeks): intense craving, mod to severe depression, inability to feel normal pleasure
- extinction (months to years): cravings occurs by exposure to environment cues
Mechanism of action of cocaine
- blocks reuptake of DA, NE and 5-HT
Baseline DA release of reinforcing effects of psychostimulants
- b/c cocaine doesn’t cause release of DA, it depends on the baseline levels of DA
- body begins to compensate by releasing less and less DA
Neurotoxicity of cocaine
- damage axon terminals: change memory function
- predisposition to early onset dementia/parkinson’s
What are some medicinal treatments for cocaine dependency?
- dopaminergic agonists to treat withdrawal symptoms, relapse, and craving (disulfiram, antabuse)
- antidepressants (tricyclic like despiramine)
- Gamma-vinyl-GABA for anti-craving effects (inhibit endorphin areas that become excited w/ use)
What are some new approaches to cocaine dependency treatment?
- dopamine reuptake inhibitors to reduce craving and relapse
- cocaine vaccine: antibody that will bind to and inactivate cocaine, slow entry to brain and inhibit euphoria
- can be overridden by taking more cocaine
