Transcript Drugs and Drug Abuse

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General Issues
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More Specific Drugs and how they work
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Psychopharmacology – study of drugs and
behavior
 Drugs and behavior – PSY 459
 Clinical Psychopharmacology – PSY 565
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Psychoactive drugs – drugs that change the
way you feel
 All these must reach the brain!
1.
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To feel good
(positive reinforcement – likely cause DA
release!)
psychological dependence
**greatest amount of psychological
dependence occurs if the rewarding
effects of drugs happen very quickly after
behaviors associated with them.
drug rewards that happen very soon after a
behavior – strong positive reinforcement for
that behavior
ex. prep for heroin injection, crack smoking,
etc.
2. To avoid feeling bad (reduce withdrawal)
(negative reinforcement)
◦ chemical dependence-
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Often a combination of positive and negative
reinforcing effects or transition from positive
to negative……
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pharmacokinetics:
includes how the drug is taken in (absorption)
how it gets to the brain (distribution)
what it does in the brain (nt?;
pharmacodynamics)
how it is broken down (metabolism)
how it leaves the body (excretion)
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how a drug is taken into the body……
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for drugs of abuse - the more rapidly the drug
gets to the brain – the greater the abuse liability!
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oral
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injection
◦ subcutaneous
◦ intramuscular
◦ intravenous - reaches brain in ~ 10 secs
 quick response but also most dangerous
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inhalation - reaches brain in ~8 secs
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dermal – absorbed through the skin
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buccal or nasal membranes
1. cocaine – blocks reuptake of monoamine
neurotransmitters (most important DA)
2. nicotine
◦ acts as an agonist at nicotinic cholinergic receptors
3. alcohol
◦ works on virtually every neurotransmitter
4. metabolism (detoxification or breakdown)
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how a drug is broken down or made into inactive
forms
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mostly done by the liver – via enzymes!
5. excretion (elimination)
•
how a drug once broken down (or not) is
eliminated from body
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most psychoactive drugs metabolites excreted in
urine
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tolerance – either decreased effectiveness or
potency of a drug
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metabolic tolerance –
◦ enzyme induction enzymes – speed up a chemical reaction
◦ with repeated exposure, enzymes get better at
breaking down drug or liver makes more enzymes
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metabolic tolerance –
◦ enzyme induction- enzymes are either better at
breaking down drug or liver makes more of them
◦ implications?
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metabolic tolerance –
◦ enzyme induction
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cross tolerance – tolerance to one drug
results in tolerance to other drugs (usually
that need similar enzymes for breakdown)
◦ Implications:
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cross tolerance – tolerance to one drug
results in tolerance to other drugs (usually
that need similar enzymes for breakdown)
◦ Implications:
◦ Person shows up unconscious at ER and is an
alcoholic – given a barbiturate for surgery;
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tolerance can still occur when the amount of
drug reaching the brain/body is unchanged
pharmacodynamic or physiological tolerance
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pharmacodynamic or physiological tolerance
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“for every action, there is an equal and
opposite reaction (in your brain)”
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Use alcohol as an example –
Acutely – alcohol decreases glutamate activity
and increases GABA activity
Chronic alcohol -------- brain’s
compensatory response?
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upregulation of GLU receptors –
◦ increase the number or sensitivity of glutamate
receptors to compensate for decreased activity and
try to get activity back to normal levels….
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what happens during alcohol withdrawal?
◦ now have too many (or too sensitive) glutamate
receptors – overexcitation, seizures, etc.
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Use alcohol as an example –
Acutely – alcohol decreases glutamate activity
and increases GABA activity
Chronic alcohol -------- brain’s
compensatory response?
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down regulation of GABA receptors –
◦ to compensate for increased activity and try to get
activity back to normal levels…. – reduce n or
sensitivity of GABA receptors
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what happens during alcohol withdrawal?
◦ now have too few (or too insensitive) GABA
receptors – overexcitation, seizures, etc.
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the exposure of compensatory changes in
brain (and body perhaps) likely explain a
number of withdrawal symptoms (that are
often opposite of the effects that the drug
causes)
chemical see-saw
drug
Change from norm
chemical see-saw
heroin
constipation
The brain wants to rebalance the activity
heroin WD
diarrhea
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Drugs taken in the same environment can
also display tolerance associated with the
conditioned cues
ex. heroin
explanation – compensatory changes in brain
in EXPECTATION of drug
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most treatments do best with both
pharmacotherapy and behavioral therapy (of
some sort) but the data is still LOUSY!!!
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In terms of health –
Which drugs have the most significant health
effects (for the largest number of people)?
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KY issues?
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most treatments do best with both
pharmacotherapy and behavioral therapy (of
some sort) but the data is still LOUSY!!!
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Psychostimulants – increase arousal;
sympathetic nervous system
◦ cocaine
◦ amphetamines
 methamphetamine
 drugs used to treat ADD
 Ritalin (methylphenidate)
 Adderall (mixed salts amphetamine)
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naturally derived (often from plants)
◦ cocaine – comes from the coca plant
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synthetically derived (in the lab)
◦ amphetamine – synthesized in laboratories
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Cocaine – block reuptake (DA, NE)
◦ block the transporter
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amphetamines – block reuptake (actually
reverse the transporter) and stimulate
release!
methylphenidate – blocks reuptake
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stereotypic behavior
◦ repetitive behaviors
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Appetite suppression
◦ weight loss
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Possible aggression
◦ several descriptions of murder and other violent
offenses attributed to amphetamine intoxication
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Psychological dependence –
◦ very strong for drugs that are either smoked, or
injected IV
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Psychological dependence –
◦ very strong for drugs that are either smoked, or
injected IV
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Physical dependence◦ do we see a withdrawal syndrome?
◦ “cocaine crash” – cause less certain
cardiovascular
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respiratory
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increased risk for CVA
cardiac arrhythmia
increased blood pressure
chest pain
respiratory complications
difficulty breathing
CNS
CNS
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seizures
intracranial hemorrhages (strokes)
cocaine or amphetamine induced psychosis
formication
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produce relaxation, sleep and ultimately (for
some sedative hypnotics), unconsciousness
and death from respiratory depression if dose
is too high
alcohol, barbiturates, benzodiazepenes
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virtually all sedative hypnotic drugs work on
the GABA receptor to make GABA bind better
to its receptor!
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First written “recipe” for making beer – about
3000 BC (Egyptians)
fermenting fruit – sugar dissolved in H20 and
exposed to air – microorganisms (yeasts)
LOVE it
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http://videosift.com/video/Drunk-Animalsof-Africa-the-longer-version
Biphasic Alcohol Effects Scale
Stimulant scale
Elated
Talkative
Energized Up
Excited
Vigorous
Stimulated
Sedative scale
Inactive
Sedated
Down
Slow thoughts
Heavy head
Sluggish
Difficulty concentrating
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Alcoholism costs the nation $150 Billion /
annum
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many organ systems are affected including
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liver- fatty liver and cirrhosis
pancreas - pancreatitis
heart - cardiomyopathy
immune function - compromised
endocrine function - altered
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ethanol affects many NT
chronic ethanol is not good for CNS
◦ Wernicke’s – thiamine deficiency?
◦ Korsakoff’s – more permanent memory deficits
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affects many neurotransmitter systems
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inhibits glutamate activity
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enhances GABA activity
◦ R0-15-4513
Copyright © Allyn & Bacon 2007
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Psychological – perhaps some but certainly
not as strong as psychostimulants
Physical dependence – absolutely
◦ alcohol withdrawal – only withdrawal syndrome that
is potentially LETHAL if not done under medical
supervision!!!!
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First need to treat acute withdrawal
Then follow up with more long-term
strategies
◦ pharmacotherapies
◦ groups like Alcoholics Anonymous
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GABA
◦ a down regulation of GABA receptors
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Glutamate
◦ an upregulation of GLU receptors
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Treat with benzodiazepenes during WD
◦ reduces the risk of seizures
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probably 2nd most commonly used drug in US
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rewarding, pleasurable effects
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paradoxical effects on arousal
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decreased hunger and resulting weight
reduction
◦ how?
◦ biphasic effect with increased attention at lower
doses but decreased anxiety/arousal at higher
doses
◦ nt release and increased metabolism because of
sympathetic NS activation
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nACh receptors – nicotinic subtype of ACh
receptors
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Where are these receptors found?
◦ PNS
 autonomic ns – so can affect heart rate; blood
pressure, etc
 muscles – all postsynaptic receptors on muscles are
nicotinic!
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Where are these receptors found?
◦ PNS
 autonomic ns
 muscles
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biphasic effect
◦ low dose – stimulation; high dose – brief
stimulation followed by blockade of transmission
◦ (WHICH IS WHY NICOTINE IS SUCH A POTENT
POISON)
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OH YES!!!!!
Psychological Dependence
◦ nicotine produces strong psychological dependence
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Physical Dependence
◦ for regular smokers – nicotine produces strong
physical dependence
◦ TTFC – time to first cigarette –
 sometimes used as an indicator of dependence
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Pharmacotherapy◦ substitution therapy – provide nicotine via a safer
(and less rewarding route)
◦ intent is to reduce the positive reinforcing effects
AND provide negative reinforcement (ie reducing
withdrawal symptoms)
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Opioid based drugs
◦ heroin, morphine, oxycodone, methadone, etc
◦ activate endogenous opiate receptors
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treatment often uses substitution therapy
◦ methadone
◦ buprenorphine (
)
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hallucinogens – a mix of types of drugs
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some examples ◦ LSD like hallucinogens – work on 5HT neurons
◦ Amphetamine like hallucinogens – MDMA (Ecstasy)
– seems to have effects on serotonin (in some cases
it is neurotoxic to 5HT neurons)
◦ psychedelic anesthetics – PCP; ketamine
 work on the glutamate receptor