Transcript Psychopharmacology

Psychopharmacology
• psychopharmacology – study of drugs and
behavior
• Drugs and behavior – PSY 459
• some general concepts and issues
• psychoactive drugs – change the way you
feel
Why do people take psychoactive
(particularly illicit) drugs?
1. 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.
Why do people take drugs?
2. To avoid feeling bad (reduce withdrawal)
(negative reinforcement)
– chemical dependence
Important issues related to how
and why we take drugs
• pharmacokinetics:
• includes drug absorption, distribution,
metabolism and drug excretion
– absorption – how we take drugs into the body
– distribution - how the drug reaches its primary
site of action
– metabolism - how our body breaks drugs
down
– excretion - how we eliminate drugs
pharmacokinetics.......
how a drug is taken into the body……
-
for drugs of abuse - the more rapidly the
drug gets to the brain – the greater the
abuse liability!
routes of administration
• oral
• injection
– subcutaneous
– intramuscular
– intravenous - reaches brain in ~ 10 secs
• quick response but also most dangerous
• inhalation - reaches brain in ~8 secs
• dermal – absorbed through the skin
• buccal or nasal membranes
pharmacokinetics.......
2. absorption –
all drugs that change how we feel must
be able to cross the blood brain barrier
3. pharmacodynamics
-
how does drug produce its effects on
behavior (ie what neurotransmitter or
neurotransmitters are affected)
ex of pharmacodynamics –
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)
•
how a drug is broken down or made into
inactive forms
•
mostly done by the liver – via enzymes!
Tolerance, Dependence,
Withdrawal, etc……
• tolerance – either decreased effectiveness
or potency of a drug
Mechanisms for Tolerance
• 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
Mechanisms for Tolerance
• metabolic tolerance –
– enzyme induction- enzymes are either better
at breaking down drug or liver makes more of
them
– implications?
Mechanisms for Tolerance
• metabolic tolerance –
– enzyme induction
• cross tolerance – tolerance to one drug
results in tolerance to other drugs (usually
that need similar enzymes for breakdown)
– Implications:
Mechanisms for Tolerance
• 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;
What if amount of drug reaching
brain/body is unchanged?
• tolerance can still occur when the amount
of drug reaching the brain/body is
unchanged
• pharmacodynamic or physiological
tolerance –
What if amount of drug reaching
brain/body is unchanged?
• pharmacodynamic or physiological
tolerance –
“for every action, there is an equal and opposite
reaction (in your brain)”
Ways that the brain may try and
compensate……
• Use alcohol as an example –
• Acutely – alcohol decreases glutamate
activity and increases GABA activity
• Chronic alcohol -------- brain’s
compensatory response?
How might the brain try and
compensate for this change if it is
chronic?
• 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….
How might the brain try and
compensate for this change if it is
chronic?
• 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….
• what happens during alcohol withdrawal?
– now have too many (or too sensitive)
glutamate receptors – overexcitation,
seizures, etc.
How might the brain try and
compensate for this change if it is
chronic?
• 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
How might the brain try and
compensate for this change if it is
chronic?
• 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
• what happens during alcohol withdrawal?
Explanation for various withdrawal
symptoms
• 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
brain response
chemical see-saw
heroin
constipation
heroin WD
diarrhea
Environmental Tolerance
• 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
5. excretion (elimination)
•
how a drug once broken down (or not) is
eliminated from body
•
most psychoactive drugs metabolites
excreted in urine