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General Issues

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.

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General Issues






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Slide1

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?Slide38
Slide39
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Slide41
Slide42

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