43/44: Drugs of Abuse

Question 1

define drug abuse

Answer 1

consumption of drugs without medical approval or supervision to achieve strong feelings of euphoria and reward ; use of a drug in a manner detrimental to the health and well-being of the drug user, other individuals or society as a whole

Question 2

hallmark of drug addiction

Answer 2

compulsive drug use

Question 3

when drug is necessary for normal physiological functioning =

Answer 3

physical dependence

Question 4

pharmacokinetic v. pharmacodynamic tolerance

Answer 4

pharmacokinetic: increased drug metabolism results in decrease in the amount of available drug or duration of drug action at the target site
pharmacodynamic: CNS responds and adapts to presence of drug –> desensitization, down-regulation and/or internalization of receptors

Question 5

compulsive drug use to induce pleasure and/or an escape from reality despite negative consequences

Answer 5

addiction

Question 6

CNS mechanisms of psychological dependence

Answer 6

increased synaptic plasticity and DA release in the mesolimbic reward pathways

Question 7

t or f: all drugs of abuse are addictive

Answer 7

false

Question 8

all addictive drugs activate…

Answer 8

mesolimbic dopamine system –> reward pathway

Question 9

DA neurons from the ventral tegmentum project to…

Answer 9

amygdala
nculeus accumbens
prefrontal cortex
hippocampus

all part of reward pathway

Question 10

RR for CNS depressants and sedative/hypnotics

Answer 10

3

Question 11

ETOH is a depressant –> ________. Why do we use it?

Answer 11

produces sedation and sleep

low doses of ETOH cause suppression of inhibitory systems and mild euphoria, which facilitates social interactions by reducing behavioral inhibitions and self-consciousness

Question 12

basis for breathalyzer test

Answer 12

10% ETOH metabolized in GI tract and excreted through kidney and lungs

Question 13

elimination of ETOH from the blood follows

Answer 13

zero-order kinetics

rate of elimination is independent of time and concentration of ETOH (constant amount eliminated per unit time )

one drink/hr approx

Question 14

converts ETOH into acetaldehyde

Answer 14

alcohol dehyrogenase

part of alcohol metabolism

Question 15

converts acetaldehyde to acetic acid

Answer 15

aldehyde dehydrogenase

Question 16

MOA and use of disulfiram

Answer 16

inhibits ALDH and is used to encourag alcoholic to abstain from ETOH abuse

high acetaldehyde levels cause unpleasant rxns

Question 17

BAC is determined by the __ of ETOH ingestion

Answer 17

rate

0.08 by 2-4 drinks/hr

Question 18

12 oz beer = one drink = ___ liquor = ______ wine

Answer 18

1.5 oz liquor

5 oz wine

Question 19

ETOH MOA

Answer 19

1) potentiates effects of GABA at GABAa receptors (hyperpolarization)
2) inhibits glutamate-activated NMDA receptors –> ETOH related memory loss

Question 20

describe wernicke-korsakoff syndrome

Answer 20

aka wet brain or alcoholic encephalopathy

neurological condition associated with thiamine deficiency B1 in combination with excessive ETOH intake

observe: ocular disturbances, changes in mental state, memory impairment, and movement difficulties

Question 21

describe fetal alcohol syndrome

Answer 21

ETOH is powerful teratogen –> mental retardation, hyperactivity and antisocial behavior

no safe level of alcohol intake for preggers

Question 22

long-term ETOH consumption affect the following organs

Answer 22

• liver cirrhosis
• cardiovascular HTN, arrhythmias, etc
• inhibits ADH in kidney
• gastritis, cancer in GI tract, ulcers

Question 23

most common two-drug combination that results in drug-related death

Answer 23

cocaethylene = cocaine + ETOH

produced in liver –> intensifies cocaine’s euphoric effects

Question 24

what should be given to avoid wernicke-kosakoff syndrome

Answer 24

thiamine

Question 25

why give naltrexone for chronic alcoholism?

Answer 25

opioid antagonist that blocks reinforcing properties of ETOH and reduces the rate of relapse

Question 26

flunitrazepam =

Answer 26

date rape drug, benzodiazepine "roofie" tastesless when dissolve din a beverage, retrograde amnesia

Question 27

benzodiazepine receptor antagonist useful in treatment of overdose and in reversing the effects of long-acting benzodiazepines used in anesthesia

Answer 27

flumazenil

Question 28

MOA benzodiazepines and barbiturates

Answer 28

positive modulators of GABAa chloride channels ---> increase inhibition

Question 29

how do benzodiazepines and barbiturates work in the reward pathway?

Answer 29

activation of GABAa receptors on interneurons leads to decreased activity and reduced release of GABA --> disinhibiton of VTA DA neurons and activation of mesolimbic reward pathway

Question 30

MOA GHB

Answer 30

disinhibiton of DA neurons in VTA via GABAb receptors

Question 31

GHB causes...

Answer 31

``` euphoria enhanced sensory perceptoion sedation felling of social closeness amnesia "date rape drug" ```

Question 32

RR of addiction for psychostimulants

Answer 32

5

Question 33

"speedballing"

Answer 33

IV heroin and cocaine mixed together

Question 34

reward effects of cocaine

Answer 34

increased DA release in the nucleus accumbers

Question 35

cocaine produces these effects:

Answer 35

intense euphoric effect increased energy and libido also linked to cardiovascular toxicity!

Question 36

strongest psychological dependence of any drug

Answer 36

cocaine

Question 37

why might you prefer meth over cocaine?

Answer 37

price | and effects last 6-24 hrs compared to 20-30min with cocaine

Question 38

amphetamines lead to...

Answer 38

euphoria increased arousal reduced sleep

Question 39

common name for methylphenidate

Answer 39

ritalin

Question 40

"ecstasy" =

Answer 40

MDMA | evokes feeling of intimacy and empathy

Question 41

MOA MDMA

Answer 41

interferes with 5HT transporters to release 5HT from presynaptic terminals

Question 42

toxicity of MDMA **

Answer 42

hyperthermia and dehydration

Question 43

chronic abuse of psychostimulants can lead to ....

Answer 43

toxic psychosis that is indistinguishable from paranoid schizophrenia must be treated with antipsychotic agents (haloperidol or chlorpromazine)

Question 44

RR of addiction for psychedelics/hallucinogens

Answer 44

1

Question 45

lysergic acid diethylamide

Answer 45

LSD

Question 46

psilocybin =

Answer 46

magic mushroom

Question 47

ketamine =

Answer 47

special K

Question 48

phencyclidine =

Answer 48

PCP or angel dust

Question 49

MOA for LSD and psilocybin

Answer 49

release glutamate in cortex via thalmic excitation taget 5HT2a receptors

Question 50

is LSD addictive?

Answer 50

no does not stimulate mesolimbic doapmine release ---> no dependence or addiction and no withdrawal syndrome

Question 51

what type of anesthetic is ketamine?

Answer 51

dissociative (look awake but the pt doesn't remember anything)

Question 52

MOA ketamine and PCP

Answer 52

block NMDA type glutamate receptors; decrease activity of cortex and limbic system

Question 53

RR of addiction for opioids

Answer 53

4

Question 54

opiates =

Answer 54

morphine codeine heroin

Question 55

MOA of opioids

Answer 55

1) inhibition of GABAergic neurons vi aactivation of mu-opiod receptors leads to disinhibition of the VTA DA neurons causing euphoria 2) inhibition of VTA DA neurons via activation of kapp-opioid receptors (inhibitory) causes dysphoria

Question 56

used for emergency overdose of opioids

Answer 56

naloxone mu opioid receptor competitive antagonist that reverse the effects of morphine or heroin within minutes

Question 57

opioid abstinence syndrome

Answer 57

cessatiion of long-term opiate use leads to withdrawal with dysphoria, nausea and vomiting, lacrimation, flu-like, etc. subsides within 5 days

Question 58

used to treat opioid withdrawal and opioid addiction

Answer 58

methadone long-acting opioid agonist that has easier withdrawal symptoms

Question 59

mu opioid receptor antagonist used primarily for maintenance therapy

Answer 59

naltrexone

Question 60

RR of addiction for cannabinoids

Answer 60

2

Question 61

synthetic THC approved for treatment of chronic pain

Answer 61

dronabinol

Question 62

MOA THC

Answer 62

disinhibits DA neurons in the VTA via pre-synaptic cannabinoid receptors --> euphoria, relaxation and sense of well-being

Question 63

MOA nicotine

Answer 63

activation of nicotinic acetylcholine receptors on VTA projection neurons result in DA release in nucleus accumbens and PFC

Question 64

MOA varenicline

Answer 64

high affinity nACHR agonist that competes for binding with nicotine

Question 65

which is more addictive: shcedule I or V?

Answer 65

schedule I