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PYB260 > Week 7 - Amphetamines & Cocaine > Flashcards

Week 7 - Amphetamines & Cocaine Flashcards

1
Q

what are stimulants

A

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

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2
Q

ampethamine

A

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)

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3
Q

cocaine

A
  • 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
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4
Q

oral administration of amphetamines

A
  • ionized in digestive system (slower rate of absorption)
  • blood levels can be kept constant
  • medical uses
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5
Q

injection and inhalation of amphetamines

A
  • more potent than oral
  • rush
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6
Q

oral administration of cocaine

A
  • sucking coca leaves
  • mix leaves with lime to decrease ionization (increases absorption)
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7
Q

different methods of inhalation of cocaine

A
  • ‘tooting’: inhaling vapor from heated powder
  • freebasing - seperates cocaine from hydrochloride
  • crack (cocaine hydrochloride and sodium bicarbonate; cocaine base)
  • snorting powdered salt (cocaine hydrochloride)
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8
Q

absorption - amphetamines

A
  • 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)
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9
Q

absorption - cocaine

A
  • 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
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10
Q

distribution

A

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

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11
Q

Excretion - amphetamines

A
  • 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
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12
Q

excretion - cocaine

A
  • 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
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13
Q

neurophysiology

A

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)

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14
Q

neurophysiology - amphetamines

A
  • 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)
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15
Q

neurophysiology - cocaine

A

1 effect only - reuptake blocker

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16
Q

stimulants on the body

A
  • increased heart rate and blood pressure
  • vasodilation
  • bronchodilation

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

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17
Q

stimulants on sleep

A
  • prevents sleep
  • insomnia
  • suppression of REM sleep
18
Q

stimulants on mood

A
  • 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)
19
Q

stimulants on behaviour

A
  • stereotyped behaviour
  • punding at high doses
20
Q

stimulants on mental disturbance

A
  • 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
21
Q

stimulants on sensory effects

A
  • increased visual acuity (CFF) & auditory acuity
  • time underestimated (seems longer than usual)
22
Q

stimulants on performance

A
  • 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
23
Q

stimulants on athletic performance

A
  • 1% improvement on swimming & track performance
  • banned substance
24
Q

stimulants on appetite

A

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

25
Q

Unconditioned behaviour in animals

A
  • increased spontaneous motor activity - low and intermediate doses
  • stereotyped behaviour
  • auto-mutilation - higher doses
  • decreased food and water
26
Q

conditioned behaviour

A
  • 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
27
Q

discrimination

A
  • 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
28
Q

self-administration in humans

amphetamines

A
  • sporadic (run-abstinence cycle)
  • depends on reason for taking the drug
  • ‘speed freaks’
29
Q

self-administration in humans

cocaine

A
  • sporadic (run-abstinence cycle)
  • usually mixed with other drugs (speedball or mixed with depressants)
30
Q

self-administration in animals

A
  • 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
31
Q

Acute tolerance

A
  • cocaine - disappears rapidly (>24hrs)
  • to subjective effects but not BP & HR
32
Q

chronic tolerance

A
  • appetite supression - 2 weeks
  • HR & BP
  • lethal effects
  • no tolerance to effects on sleep
  • reverse tolerance (sensitization) to stereotyped behaviour & psychosis
33
Q

withdrawal

A
  • 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
34
Q

amphetamines clinical uses

A
  • 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
35
Q

cocaine clinical uses

A

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

36
Q

harmful effects - amphetamines

A
  • 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)
37
Q

harmful effects - cocaine

A
  • 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
38
Q

harmful effects on reproduction

A
  • 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)
39
Q

overdose - cocaine

A
  • muscle weakness
  • respiratory depression
  • cardiovascular effects - sudden-death
40
Q

2 phases of overdose for cocaine

caine reaction

A
  1. excitement followed by headache, nausea, vomiting, convulsions
  2. lose consciousness, respiratory depression, cardiac failure, death (hypoxic brain damage risk)
41
Q

overdose treatment

A
  • diazepam (controls seizures)
  • artifical respiration (control breathing)
  • chlorpromazine (antipsychotic) an antagonist to toxic effects of cocaine
42
Q

treatment

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

PYB260 (10 decks)

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