More Specific Drugs and how they work Drugs and Drug Abuse Psychopharmacology study of drugs and behavior Drugs and behavior PSY 459 Clinical Psychopharmacology PSY 565 Psychoactive drugs drugs that change the way you feel ID: 568377
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General IssuesMore Specific Drugs and how they work
Drugs and Drug AbuseSlide2
Psychopharmacology – study of drugs and behaviorDrugs and behavior – PSY 459
Clinical Psychopharmacology – PSY 565
Psychoactive drugs – drugs that change the way you feelAll these must reach the brain!
PsychopharmacologySlide3
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.
Why do people take psychoactive (particularly illicit) drugs?Slide4
drug rewards that happen very soon after a
behavior – strong positive reinforcement for
that behavior ex. prep for heroin injection, crack smoking, etc. Slide5
2. To avoid feeling bad (reduce withdrawal)
(negative reinforcement)
chemical dependence-
Why do people take drugs?Slide6
Often a combination of positive and negative reinforcing effects or transition from positive to negative……Slide7
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)
Important issues related to how and why we take drugsSlide8
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!
pharmacokinetics.......Slide9
oral
injection
subcutaneous intramuscularintravenous - reaches brain in ~ 10 secsquick response but also most dangerous
inhalation - reaches brain in ~8 secs
dermal – absorbed through the skin
buccal or nasal membranes
routes of administrationSlide10
1. cocaine – blocks reuptake of monoamine neurotransmitters (most important DA)
2. nicotine
acts as an agonist at nicotinic cholinergic receptors3. alcoholworks on virtually every neurotransmitter
ex of pharmacodynamics – Slide11
4. metabolism (detoxification or breakdown)
how a drug is broken down or made into inactive forms
mostly done by the liver – via enzymes!Slide12
5. excretion (elimination)
how a drug once broken down (or not) is eliminated from body
most psychoactive drugs metabolites excreted in urineSlide13
tolerance – either decreased effectiveness or potency of a drug
Tolerance, Dependence, Withdrawal, etc……Slide14
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 ToleranceSlide15
metabolic tolerance –
enzyme induction- enzymes are either better at breaking down drug or liver makes more of them
implications?
Mechanisms for ToleranceSlide16
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 ToleranceSlide17
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;Mechanisms for ToleranceSlide18
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?Slide19
pharmacodynamic or physiological tolerance –
“for every action, there is an equal and opposite reaction (in your brain)”
What if amount of drug reaching brain/body is unchanged?Slide20
Use alcohol as an example –
Acutely – alcohol decreases glutamate activity and increases GABA activity
Chronic alcohol -------- brain’s compensatory response? Ways that the brain may try and compensate……Slide21
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?Slide22
Use alcohol as an example –
Acutely – alcohol decreases glutamate activity
and increases GABA activityChronic alcohol -------- brain’s compensatory response?
Ways that the brain may try and compensate……Slide23
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?now have too few (or too insensitive) GABA receptors – overexcitation, seizures, etc.
How might the brain try and compensate for this change if it is chronic?Slide24
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)
Explanation for various withdrawal symptomsSlide25
chemical see-saw
drug
Change from normSlide26
heroin
constipation
chemical see-sawSlide27
The brain wants to rebalance the activitySlide28
heroin WD
diarrheaSlide29
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 drugEnvironmental ToleranceSlide30
most treatments do best with both pharmacotherapy and behavioral therapy (of some sort) but the data is still LOUSY!!!
How good are we at treating drug addiction?Slide31
Specific Drugs or Drug Categories
In terms of health –
Which drugs have the most significant health effects (for the largest number of people)?KY issues?Slide32
most treatments do best with both pharmacotherapy and behavioral therapy (of some sort) but the data is still LOUSY!!!
How good are we at treating drug addiction?Slide33
Psychostimulants – increase arousal; sympathetic nervous systemcocaine
amphetamines
methamphetaminedrugs used to treat ADDRitalin (methylphenidate)Adderall (mixed salts amphetamine)
Some categories of psychoactive drugsSlide34
naturally derived (often from plants)cocaine – comes from the coca plant
synthetically derived (in the lab)
amphetamine – synthesized in laboratoriespsychoactive drugsSlide35
Cocaine – block reuptake (DA, NE)block the transporter
amphetamines – block reuptake (actually reverse the transporter) and stimulate release!
methylphenidate – blocks reuptakehow do psychostimulants work?Slide36
stereotypic behavior
repetitive behaviors
Appetite suppressionweight lossPossible aggressionseveral descriptions of murder and other violent offenses attributed to amphetamine intoxication
Behavioral effects of cocaine and/or amphetamineSlide37
Psychological dependence – very strong for drugs that are either smoked, or injected IV
What about dependence?Slide38Slide39Slide40Slide41Slide42
Psychological dependence – very strong for drugs that are either smoked, or injected IV
Physical dependence-
do we see a withdrawal syndrome?“cocaine crash” – cause less certainWhat about dependence?Slide43
cardiovascular
increased risk for CVA
cardiac arrhythmiaincreased blood pressurerespiratorychest pain respiratory complicationsdifficulty breathing
CNS
Medical Side Effects and Consequences of Cocaine and Amphetamine AbuseSlide44
CNS
seizures
intracranial hemorrhages (strokes)cocaine or amphetamine induced psychosisformicationSlide45
produce relaxation, sleep and ultimately (for some sedative hypnotics), unconsciousness and death from respiratory depression if dose is too high
alcohol, barbiturates, benzodiazepenes
Sedative Hypnotics and Anxiolytics (anxiety reducers)Slide46
virtually all sedative hypnotic drugs work on the GABA receptor to make GABA bind better to its receptor!
how do they work?Slide47
First written “recipe” for making beer – about 3000 BC (Egyptians)
fermenting fruit – sugar dissolved in H20 and exposed to air – microorganisms (yeasts) LOVE it
A bit of history about alcoholSlide48
http://videosift.com/video/Drunk-Animals-of-Africa-the-longer-versionSlide49
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
Slide50
Alcoholism costs the nation $150 Billion / annum
many organ systems are affected including
liver- fatty liver and cirrhosispancreas - pancreatitisheart - cardiomyopathy
immune function - compromised
endocrine function - altered
Consequences of AlcoholismSlide51
ethanol affects many NTchronic ethanol is not good for CNS
Wernicke’s – thiamine deficiency?
Korsakoff’s – more permanent memory deficitsEffects on the CNSSlide52
affects many neurotransmitter systems
inhibits glutamate activity
enhances GABA activityR0-15-4513
how does alcohol work in the CNS?Slide53
Copyright © Allyn & Bacon 2007Slide54
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!!!!Dependence?Slide55
First need to treat acute withdrawal
Then follow up with more long-term strategies
pharmacotherapiesgroups like Alcoholics AnonymousTreating Alcohol DependenceSlide56
GABAa down regulation of GABA receptors
Glutamate
an upregulation of GLU receptorsTreat with benzodiazepenes during WD reduces the risk of seizures
Alcohol withdrawalSlide57
probably 2nd most commonly used drug in US
Nicotine!Slide58
Why do so many people start and continue to smoke when we know there are such significant health risks?Slide59
rewarding, pleasurable effects
how?
paradoxical effects on arousalbiphasic effect with increased attention at lower doses but decreased anxiety/arousal at higher doses
decreased hunger and resulting weight reduction
nt release and increased metabolism because of sympathetic NS activation
What are the behavioral effects of nicotine?Slide60
nACh receptors – nicotinic subtype of ACh receptors
How does nicotine exert behavioral effects?Slide61
Where are these receptors found?
PNS
autonomic ns – so can affect heart rate; blood pressure, etc muscles – all postsynaptic receptors on muscles are nicotinic! How does nicotine exert behavioral effects?Slide62
Where are these receptors found?
PNS
autonomic ns musclesbiphasic effectlow dose – stimulation; high dose – brief stimulation followed by blockade of transmission
(WHICH IS WHY NICOTINE IS SUCH A POTENT POISON)
How does nicotine exert behavioral effects?Slide63
OH YES!!!!!
Psychological Dependence
nicotine produces strong psychological dependencePhysical Dependencefor regular smokers – nicotine produces strong physical dependenceTTFC – time to first cigarette – sometimes used as an indicator of dependence
Does Nicotine Produce Dependence?Slide64
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)
How do we treat nicotine dependence?Slide65
Opioid based drugsheroin, morphine, oxycodone, methadone, etc
activate endogenous opiate receptors
treatment often uses substitution therapy methadone buprenorphine ( )
Pharmacodynamics of Other DrugsSlide66
hallucinogens – a mix of types of drugs
some examples -
LSD like hallucinogens – work on 5HT neuronsAmphetamine like hallucinogens – MDMA (Ecstasy) – seems to have effects on serotonin (in some cases it is neurotoxic to 5HT neurons)psychedelic anesthetics – PCP; ketaminework on the glutamate receptor