Drugs of Abuse Flashcards
Hallmark of drug addiction
COMPULSIVE DRUG USE - due to brain alterations associated with chronic exposure
Two Types of Dependence
Physical
Psychological
Physical dependence - DEPENDENCE
when drug is NECESSARY FOR NORMAL PHYSIOLOGICAL FUNCTION
Two Tolerance types
pharmocokinetic - associated with METABOLISM
pharmacodynamic - DESENSITIZATION/down regulation/increased receptor internalization
Psychological Dependence - ADDICTION
high risk of?
compulsive drug use to induce pleasure/escape from realitY DESPITE NEGATIVE CONSEQUENCES
relapse
Relative Risk of Addiction
1 - non-addictive 2 - slightly 3 - moderate 4 - addictive 5 - highly
Addictive nature of drugs comes from effects on what two areas?
ventral tegmentum
reward pathway
DOPAMINERGIC
Ventral Tegmentum acts on what four main areas in the reward pathway?
amygdala
nucleus accumbens
pre-frontal cortex
hippocampus
Three mechanisms of increasing DA release
activation of Gi protein-coupled receptors - blocks GABA-ergic
Activation of ionotropic receptors or ion channels
Targeting DOPAMINE TRANSPORTER
CNS/Depressants
RR =
Alcohol
Benzo’s
Barbiturates
GHB
RR=3
Ethanol effects?
sedation, sleep, suppression of inhibitory systems, mild euphoria
Ethanol pharmacokinetics
rapidly and completel absorbed from GI tract
BLOOD BRAIN BARRIER AND PLACENTA ARE FREELY PERMEABLE
Ethanol metabolism
Elimination kinetics?
90% LIVER
10% GI tract
Excreted through KIDNEY AND LUNGS
ZERO ORDER ELIMINATION
Why do women have higher blood EtOH than men for same dose?
DECREASES first pass metabolism
LOWER total body water
3 enzymes of alcohol metabolism
ALCOHOL DEHYDROGENASE
MICROSOMAL ETHANOL-OXIDIZING SYSTEM
ALDEHYDE DEHYDROGENASE
Fomepizole
alcohol dehydrogenase inhibitor
treats methanol and ethylene glycol poisoning
Disulfiram
aldehyde dehydrogenase inhibitor
ecnourages alcoholics to abstain of EtOH
EtOH Mechanism of Action
POTENTIATES GABA AT GABA-A receptors
Also INHIBITS GLUTAMATE ACTIVATED NMDA RECEPTORS
Wernicke-Korsakoff Syndrome
vitamin B1 deficiency associated with excessive alcohol intake
Cocaine and Alcohol
liver combines them to make COCAETHYLENE
produces an intensification of cocaine’s euphoric effects
most common two drug combination that causes death