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
Management of Chronic Alcoholism
Disulfiram
Naltrexone
Sedative/Hypnotics RR=
RR = 3 moderately addictive
Most commonly abused benzo’s (2)
Diazepam
Alprazolam
Flunitrazepam
rohypnol
date rape drug
tasteless when dissolved in a beverage
60 Hour detection window
Flumazenil
BENZO ANTAGONIST
treatment of overdose and reversing effects of long acting benzo’s
Overall mechanism of benzo’s and barbiturates as drugs of abuse
DISINHIBITION OF VTA DOPAMINE neurons
ACTIVATION OF MESOLIMBIC REWARD PATHWAY
GHB
activates reward pathway
causes amnesia
also used as date rape drug
Psychostimulants
RR = ?
cocaine amphetamine methamphetamine methylphenidate MDMA
RR = 5
Cocaine associated with what positive effects?
linked to what major negative effect?
intense euphoria
increase energy
increased libido/self confidence
linked to CARDIOVASCULAR TOXICITY
Cocaine has what characteristic?
STRONGEST PSYCHOLOGICAL DEPENDENCE
Methamphetamine effects last?
Also has what?
6 to 24 hours vs 30 to 60 mins of cocaine
sympathomimetic activity
Cocaine MOA
blocks DA RE-UPTAKE
INCREASES SYNAPTIC RELEASE
Amphetamines MOA
cause VESICLE RELEASE OF DA AND NE
REVERSE DA transporter
Methylphenidate used for? (2)
ADHD
Narcolepsy
MDMA MOA
Causes?
interferes with 5-HT TRANSPORTERS to release 5-HT
significant depletion of 5-HT for 24 hrs
Toxicity of MDMA
acute - HYPERTHERMIA AND DEHYDRATION
chronic - neurotoxicity and irreversible brain damage
Long term use of psychostimulants causes?
TOXIC PSYCHOSIS
INDISTINGUISHABLE FROM PARANOID SCHIZOPHRENIA
Psychedelics (4)
RR =
Lysergic acid diethylamide
Psiolcybin
Ketamine
Phencyclidine
RR = 1
LSD and Psylocibin effects
MOA?
key receptor?
hallucinations, illusions, paranoia, euphoria, or depression
RELEASE GLUTAMATE in CORTEX via THALAMIC EXCITATION
target 5-HT-2a receptors –> INCREASES CALCIUM
Negative effects of LSD and Psylocibin
Flashbacks
Bad trips
Rapid tolerance
No dependence or addiction
Ketamine and PCP MOA
block NMDA-YPE GLUTAMATE RECEPTORS
DECREASE ACTIVITY OF CORTEX AND LIMBIC SYSTEM
Opioids RR
RR = 4
Most commonly abused opioids (4)
codeine
heroin
morphine
oxycodone
Naloxone
emergency overdose treatment
Naltrexone
primarily for MAINTENANCE THERAPY
longer acting, slower onset
Methadone
strong opioid agonist
MILDER WITHDRAWAL SYMPTOMS
Dronabinol
SYNTHETIC THC approved for chronic pain treatment
Cannabinoids RR
RR = 2
THC/Cannabinoids MOA
DISINHIBITS DA NEURONS in VTA via PRE-SYNAPTIC CANNABINOID RECEPTORS
likely involves removing GABA-A inhibition
Cannabinoids effects
euphoria
relaxation
sense of wellbeing
Treatments for nicotine addiction (3)
transdermal patch
bupropion
varenicline
