Week 7 - Amphetamines & Cocaine

Question 1

what are stimulants

Answer 1

drugs which stimulate transmission of monoamines or biogenic amines (can be known as sympathomimetic)

Question 2

ampethamine

Answer 2

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)

Question 3

cocaine

Answer 3

• 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

Question 4

oral administration of amphetamines

Answer 4

• ionized in digestive system (slower rate of absorption)
• blood levels can be kept constant
• medical uses

Question 5

injection and inhalation of amphetamines

Answer 5

• more potent than oral
• rush

Question 6

oral administration of cocaine

Answer 6

• sucking coca leaves
• mix leaves with lime to decrease ionization (increases absorption)

Question 7

different methods of inhalation of cocaine

Answer 7

• ‘tooting’: inhaling vapor from heated powder
• freebasing - seperates cocaine from hydrochloride
• crack (cocaine hydrochloride and sodium bicarbonate; cocaine base)
• snorting powdered salt (cocaine hydrochloride)

Question 8

absorption - amphetamines

Answer 8

• 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)

Question 9

absorption - cocaine

Answer 9

• 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

Question 10

distribution

Answer 10

amphetamines & cocaine cross the BBB and concentrate in kidneys and lungs (amphetamine) & brain (cocaine)

Question 11

Excretion - amphetamines

Answer 11

• 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

Question 12

excretion - cocaine

Answer 12

• 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

Question 13

neurophysiology

Answer 13

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)

Question 14

neurophysiology - amphetamines

Answer 14

• 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)

Question 15

neurophysiology - cocaine

Answer 15

1 effect only - reuptake blocker

Question 16

stimulants on the body

Answer 16

• increased heart rate and blood pressure
• vasodilation
• bronchodilation

side effects:
- headaches
- dry mouth
- upset stomach
methamphetamine has fewer PNS effects

Question 17

stimulants on sleep

Answer 17

• prevents sleep
• insomnia
• suppression of REM sleep

Question 18

stimulants on mood

Answer 18

• 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)

Question 19

stimulants on behaviour

Answer 19

• stereotyped behaviour
• punding at high doses

Question 20

stimulants on mental disturbance

Answer 20

• 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

Question 21

stimulants on sensory effects

Answer 21

• increased visual acuity (CFF) & auditory acuity
• time underestimated (seems longer than usual)

Question 22

stimulants on performance

Answer 22

• 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

Question 23

stimulants on athletic performance

Answer 23

• 1% improvement on swimming & track performance
• banned substance

Question 24

stimulants on appetite

Answer 24

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

Question 25

Unconditioned behaviour in animals

Answer 25

- increased spontaneous motor activity - low and intermediate doses - stereotyped behaviour - auto-mutilation - higher doses - decreased food and water

Question 26

conditioned behaviour

Answer 26

- 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

Question 27

discrimination

Answer 27

- 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

Question 28

self-administration in humans | amphetamines

Answer 28

- sporadic (run-abstinence cycle) - depends on reason for taking the drug - 'speed freaks'

Question 29

self-administration in humans | cocaine

Answer 29

- sporadic (run-abstinence cycle) - usually mixed with other drugs (speedball or mixed with depressants)

Question 30

self-administration in animals

Answer 30

- 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

Question 31

Acute tolerance

Answer 31

- cocaine - disappears rapidly (>24hrs) - to subjective effects but not BP & HR

Question 32

chronic tolerance

Answer 32

- appetite supression - 2 weeks - HR & BP - lethal effects - no tolerance to effects on sleep - reverse tolerance (sensitization) to stereotyped behaviour & psychosis

Question 33

withdrawal

Answer 33

- 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

Question 34

amphetamines clinical uses

Answer 34

- 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

Question 35

cocaine clinical uses

Answer 35

synthetic preparations of cocaine like substance - local anaesthetic ( in nose and mouth to ease discomfort, dental work)

Question 36

harmful effects - amphetamines

Answer 36

- 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)

Question 37

harmful effects - cocaine

Answer 37

- 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

Question 38

harmful effects on reproduction

Answer 38

- 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)

Question 39

overdose - cocaine

Answer 39

- muscle weakness - respiratory depression - cardiovascular effects - sudden-death

Question 40

2 phases of overdose for cocaine | caine reaction

Answer 40

1. excitement followed by headache, nausea, vomiting, convulsions 2. lose consciousness, respiratory depression, cardiac failure, death (hypoxic brain damage risk)

Question 41

overdose treatment

Answer 41

- diazepam (controls seizures) - artifical respiration (control breathing) - chlorpromazine (antipsychotic) an antagonist to toxic effects of cocaine

Question 42

treatment

Answer 42

- detoxification - strong probability of relapse due to intense craving - pharmacotherapies (antidepressants, modafinil, oral d-amphetamine, naltrexone) - behavioural therapies (contingency management, community reinforcement)