Week 7 - Amphetamines & Cocaine Flashcards
what are stimulants
drugs which stimulate transmission of monoamines or biogenic amines (can be known as sympathomimetic)
ampethamine
Natural:
- ephedrine
Synthetic:
- d-amphetamine (dex-amphetamine/dexedrine)
- l-amphetamine (benzedine; adderall)
- methylamphetamine (meth/speed)
amphetamine-like stimulants:
- methylphenidate (ritalin)
- pipradrol
weak bases (pKa = 9-10)
cocaine
- extracted from leaf of coca plant native to south america
- cathinone (khat) extracted from african shrub
- synthetics: methcathinon (jeff, cat); buproprion (Zyban)
pKa = 8.7
oral administration of amphetamines
- ionized in digestive system (slower rate of absorption)
- blood levels can be kept constant
- medical uses
injection and inhalation of amphetamines
- more potent than oral
- rush
oral administration of cocaine
- sucking coca leaves
- mix leaves with lime to decrease ionization (increases absorption)
different methods of inhalation of cocaine
- ‘tooting’: inhaling vapor from heated powder
- freebasing - seperates cocaine from hydrochloride
- crack (cocaine hydrochloride and sodium bicarbonate; cocaine base)
- snorting powdered salt (cocaine hydrochloride)
absorption - amphetamines
- oral - determined by food in stomach & physical activity
-> peak blood levels within 30 mins - 4 hrs - inhalation (smoked)/intranasal (snorted) ~2.5 hrs
- I.V. - peak blood level ~ 20 mins (subjective effects sooner)
absorption - cocaine
- IV crack - 2-5 mins
- inhalation (snorting) - 30-60 mins (10-20 mins subjective effects)
- freebasing & crack - not studied - since un-ionized should be extremely rapid absorption
distribution
amphetamines & cocaine cross the BBB and concentrate in kidneys and lungs (amphetamine) & brain (cocaine)
Excretion - amphetamines
- depends on pH of urine: more basic = more reabsorption
- 30-50% excreted unchanged/rest metabolized by liver
- 1/2 life = 7-14 hours if acidic urine & 16-34 hours if basic
- also excreted through sweat and saliva
- metabolites can also be active with long half lives, can detect in urine ~ 1 week
excretion - cocaine
- excreted faster than amphetamines
- 1/2 life = 45-75 mins, also dependent on urine pH
- metabolites may be present in urine 24-36 hrs after single admin
- also present in hair
neurophysiology
both classes of drugs act on the monoamine synapses, but mechanisms differ
PNS: stimulate epinephrine synapses - fight or flight response
CNS: multiple effects
1. increased dopamine in nacc (reinf & motiv)
2. increased dopamine in nigrostriatal system (motor activity)
3. cocaine also blocks action potentials, therefore local anaesthetic
- procaine (novocaine)
neurophysiology - amphetamines
- effect on synapses using 5HT, E, NE & DA (esp. DA)
3 effects:
1. causes NTs to leak into synaptic cleft
2. increases NTs released due to action potentials
3. block reuptake (& inhibit MAO activity)
neurophysiology - cocaine
1 effect only - reuptake blocker
stimulants on the body
- increased heart rate and blood pressure
- vasodilation
- bronchodilation
side effects:
- headaches
- dry mouth
- upset stomach
methamphetamine has fewer PNS effects
stimulants on sleep
- prevents sleep
- insomnia
- suppression of REM sleep
stimulants on mood
- improves mood (2-5 hrs)
- decreased fatigue/ increase energy
- rush (IV and smoking routes; snorting cocaine)
- followed by depression/crash
- acute tolerance to pleasureable effects
- cocaine has shorter-acting effects (<10-20 mins ‘ pleasureable)
stimulants on behaviour
- stereotyped behaviour
- punding at high doses
stimulants on mental disturbance
- amphetamine psychosis or ‘monoamine psychosis’ (hallucinations, delusions, hostility/violence, paranoia)
- disappears in a few days with no lasting effects (most people)
- at high doses cocaine can also induce psychosis
- formication - feeling of bugs crawling on skin
stimulants on sensory effects
- increased visual acuity (CFF) & auditory acuity
- time underestimated (seems longer than usual)
stimulants on performance
- increased endurance
- fatigue effects decrease = improved reaction time and coordination (esp complex tasks)
- increased vigilance and attention
- most effects seen on simple or learned performance vs novel performance tasks; narrowing or tunneling of attentional focus
stimulants on athletic performance
- 1% improvement on swimming & track performance
- banned substance
stimulants on appetite
anorectic effects
- increased other motoric behaviour
- stimulation of areas of the hypothalamus
- decrease dopamine midbrain activation to sweet rewards
increased metabolism & decreased food intake = weight loss
Unconditioned behaviour in animals
- increased spontaneous motor activity - low and intermediate doses
- stereotyped behaviour
- auto-mutilation - higher doses
- decreased food and water
conditioned behaviour
- rate dependency effect ( increased low-rate behaviours, decreased high-rate behaviours); doesn’t apply to punished behaviour
- operant effects of cocaine not as significant as amphetamines
discrimination
- amphetamines can create dissociation
- amphetamines and cocaine discriminate from saline but not as easily as with barbituates or benzos
- amphetamine generalizes to cocaine, methylphenidate and some monoamine inhibitors
- amphetamines do not really generalize to caffeine, nicotine, barbituates, hallucinogines
self-administration in humans
amphetamines
- sporadic (run-abstinence cycle)
- depends on reason for taking the drug
- ‘speed freaks’
self-administration in humans
cocaine
- sporadic (run-abstinence cycle)
- usually mixed with other drugs (speedball or mixed with depressants)
self-administration in animals
- cocaine administration by rats
- more reinforcing than any other drug (particularly in monkeys)
- erratic pattern of administration
- monkeys will self-administer lethal dose
- increase by stress, prior experience, caffeine heroin and alcohol
Acute tolerance
- cocaine - disappears rapidly (>24hrs)
- to subjective effects but not BP & HR
chronic tolerance
- appetite supression - 2 weeks
- HR & BP
- lethal effects
- no tolerance to effects on sleep
- reverse tolerance (sensitization) to stereotyped behaviour & psychosis
withdrawal
- depression - within 1/2 hr for cocaine & hrs for amphetamines
- dose dependent severity
- REM rebound, frequent awakenings
- long term cocaine use can cause on-going depression; may be treated with anti-depressants
- long term amphetamine use can lead to suicidal thinking/attempts; may present as if clinically depressed, with changed sleep and appetite
amphetamines clinical uses
- ADHD - can cause a paradoxical effect and suggests ADHD due to deficiency in NE and DA function
- obesity - tolerance to effects in 2 weeks therefore continue to increase dose
- narcolepsy - few side effects, no tolerance to sleep effects
- some cold and flu preparations
cocaine clinical uses
synthetic preparations of cocaine like substance
- local anaesthetic ( in nose and mouth to ease discomfort, dental work)
harmful effects - amphetamines
- restlessness, confusion, dizziness
- punding, stereotyped behaviour
- paranoid psychosis
- internal bleeding & strokes from increased BP
- cessating may induce suicidal depression and sleep disturbance (REM rebound)
- brain damage from ruptured blood vessels in the brain
- lifestyle effects (HIV/AIDS, hepatitis from IV, immune functioning from nutritional deficiences, sleep disturbance)
harmful effects - cocaine
- jaundice/liver disease
- inflammation & ulcers in the nose (damage to septum)
- cocaine runs (financial problems)
- paranoia, hallucinations, cravings, antisocial behaviour, attention & concentration probs, blurred vision, weight loss
harmful effects on reproduction
- increased sexual activity (prolong erection, delay ejaculation; enhance female libido)
- continuous high doses of cocaine: disinterest
- birth abnormalities
- ‘crack babies’ (retardation, premature, abruptio placentae, behavioural problems)
overdose - cocaine
- muscle weakness
- respiratory depression
- cardiovascular effects - sudden-death
2 phases of overdose for cocaine
caine reaction
- excitement followed by headache, nausea, vomiting, convulsions
- lose consciousness, respiratory depression, cardiac failure, death (hypoxic brain damage risk)
overdose treatment
- diazepam (controls seizures)
- artifical respiration (control breathing)
- chlorpromazine (antipsychotic) an antagonist to toxic effects of cocaine
treatment
- detoxification
- strong probability of relapse due to intense craving
- pharmacotherapies (antidepressants, modafinil, oral d-amphetamine, naltrexone)
- behavioural therapies (contingency management, community reinforcement)
