General Issues

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General Issues




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Presentations text content in General Issues

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General IssuesMore Specific Drugs and how they work

Drugs and Drug Abuse

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Psychopharmacology – study of drugs and behaviorDrugs and behavior – PSY 459Clinical Psychopharmacology – PSY 565Psychoactive drugs – drugs that change the way you feelAll these must reach the brain!

Psychopharmacology

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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.

Why do people take psychoactive (particularly illicit) drugs?

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drug rewards that happen very soon after abehavior – strong positive reinforcement forthat behavior ex. prep for heroin injection, crack smoking, etc.

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2. To avoid feeling bad (reduce withdrawal) (negative reinforcement) chemical dependence-

Why do people take drugs?

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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)

Important issues related to how and why we take drugs

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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.......

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oralinjectionsubcutaneous intramuscularintravenous - reaches brain in ~ 10 secsquick response but also most dangerousinhalation - reaches brain in ~8 secsdermal – absorbed through the skinbuccal or nasal membranes

routes of administration

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1. cocaine – blocks reuptake of monoamine neurotransmitters (most important DA)2. nicotineacts as an agonist at nicotinic cholinergic receptors3. alcoholworks on virtually every neurotransmitter

ex of pharmacodynamics –

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4. metabolism (detoxification or breakdown)how a drug is broken down or made into inactive formsmostly done by the liver – via enzymes!

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5. excretion (elimination)how a drug once broken down (or not) is eliminated from bodymost psychoactive drugs metabolites excreted in urine

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tolerance – either decreased effectiveness or potency of a drug

Tolerance, Dependence, Withdrawal, etc……

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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

Mechanisms for Tolerance

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metabolic tolerance –enzyme induction- enzymes are either better at breaking down drug or liver makes more of themimplications?

Mechanisms for Tolerance

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metabolic tolerance –enzyme inductioncross tolerance – tolerance to one drug results in tolerance to other drugs (usually that need similar enzymes for breakdown) Implications:

Mechanisms for Tolerance

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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;

Mechanisms for Tolerance

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tolerance can still occur when the amount of drug reaching the brain/body is unchangedpharmacodynamic or physiological tolerance –

What if amount of drug reaching brain/body is unchanged?

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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?

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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……

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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….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?

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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……

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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 receptorswhat 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?

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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)

Explanation for various withdrawal symptoms

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chemical see-saw

drug

Change from norm

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heroin

constipation

chemical see-saw

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The brain wants to rebalance the activity

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heroin WD

diarrhea

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Drugs taken in the same environment can also display tolerance associated with the conditioned cuesex. heroinexplanation – compensatory changes in brain in EXPECTATION of drug

Environmental Tolerance

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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?

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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?

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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?

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Psychostimulants – increase arousal; sympathetic nervous systemcocaineamphetaminesmethamphetaminedrugs used to treat ADDRitalin (methylphenidate)Adderall (mixed salts amphetamine)

Some categories of psychoactive drugs

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naturally derived (often from plants)cocaine – comes from the coca plantsynthetically derived (in the lab)amphetamine – synthesized in laboratories

psychoactive drugs

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Cocaine – block reuptake (DA, NE)block the transporteramphetamines – block reuptake (actually reverse the transporter) and stimulate release!methylphenidate – blocks reuptake

how do psychostimulants work?

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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 amphetamine

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Psychological dependence – very strong for drugs that are either smoked, or injected IV

What about dependence?

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Psychological dependence – very strong for drugs that are either smoked, or injected IVPhysical dependence-do we see a withdrawal syndrome?“cocaine crash” – cause less certain

What about dependence?

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cardiovascularincreased risk for CVAcardiac arrhythmiaincreased blood pressurerespiratorychest pain respiratory complicationsdifficulty breathingCNS

Medical Side Effects and Consequences of Cocaine and Amphetamine Abuse

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CNS

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 highalcohol, barbiturates, benzodiazepenes

Sedative Hypnotics and Anxiolytics (anxiety reducers)

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virtually all sedative hypnotic drugs work on the GABA receptor to make GABA bind better to its receptor!

how do they work?

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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

A bit of history about alcohol

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http://videosift.com/video/Drunk-Animals-of-Africa-the-longer-version

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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 / annummany organ systems are affected includingliver- fatty liver and cirrhosispancreas - pancreatitisheart - cardiomyopathyimmune function - compromisedendocrine function - altered

Consequences of Alcoholism

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ethanol affects many NTchronic ethanol is not good for CNSWernicke’s – thiamine deficiency?Korsakoff’s – more permanent memory deficits

Effects on the CNS

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affects many neurotransmitter systemsinhibits glutamate activity enhances GABA activityR0-15-4513

how does alcohol work in the CNS?

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Copyright © Allyn & Bacon 2007

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Psychological – perhaps some but certainly not as strong as psychostimulantsPhysical dependence – absolutelyalcohol withdrawal – only withdrawal syndrome that is potentially LETHAL if not done under medical supervision!!!!

Dependence?

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First need to treat acute withdrawalThen follow up with more long-term strategiespharmacotherapiesgroups like Alcoholics Anonymous

Treating Alcohol Dependence

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GABAa down regulation of GABA receptorsGlutamatean upregulation of GLU receptorsTreat with benzodiazepenes during WD reduces the risk of seizures

Alcohol withdrawal

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probably 2nd most commonly used drug in US

Nicotine!

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Why do so many people start and continue to smoke when we know there are such significant health risks?

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rewarding, pleasurable effectshow?paradoxical effects on arousalbiphasic effect with increased attention at lower doses but decreased anxiety/arousal at higher dosesdecreased hunger and resulting weight reductionnt release and increased metabolism because of sympathetic NS activation

What are the behavioral effects of nicotine?

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nACh receptors – nicotinic subtype of ACh receptors

How does nicotine exert behavioral effects?

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Where are these receptors found?PNSautonomic ns – so can affect heart rate; blood pressure, etc muscles – all postsynaptic receptors on muscles are nicotinic!

How does nicotine exert behavioral effects?

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Where are these receptors found?PNSautonomic 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?

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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?

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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)

How do we treat nicotine dependence?

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Opioid based drugsheroin, morphine, oxycodone, methadone, etcactivate endogenous opiate receptors treatment often uses substitution therapy methadone buprenorphine ( )

Pharmacodynamics of Other Drugs

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hallucinogens – a mix of types of drugs

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

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