Pharmacology of Alcohol and Drugs of Abuse - Linger Flashcards
most commonly abused drug in world
ethanol
75% adults in US
use alcohol
only 8% become disorder
ethanol PK
amphipathic - hydrophilic and hydrophobic
first pass metabolism
zero order kinetics
BAC sedation, high, slower rxn time
50-100
BAC impaired motor fxn, slurred speech, ataxia
100-200
BAC emesis, stupor
200-300
BAC coma
300-450
BAC resp depression and death
> 500
0.08% BAC
= 80mg/dL blood alcohol concentration
tolerance
decrease in responsiveness to drug following repeated exposure
can happen in acute alcohol consumption
sensitization
reverse tolerance
increase in responsiveness to drug following repeated exposure
with cocaine
drugs sedative hypnotics
class B - benzos and newer drugs - plateau
class A - barbs, alclhol, older sedative hypnotic - linear - to coma
enzyme of alcohol metabolism
alcohol dehydrogenase (ADH)
aldehyde DH (ALDH)
microsomal ethanol oxidizing system (MEOS)
-CYP450s
enzyme mutations
hyperactive AHD
low active ALDH
accumulate of acetaldehyde
adverse effects
disulfram
inhibit ALDH
aka anabuse
fomepizole
inhibit ADH
tx - methanol OD - so don’t metabolize it
ethanol vs. methanol
ethanol higher affinity for ADH
tx of methanol poisoning
acetaldehyde
toxic - from alcohol metabolism
metabolize 1 mol of ethanol
need 2 mol NAD+
saturate enzymes quickly - zero-order kinetics
tx of alcohol intox
resp support gastric lavage - naloxone (short acting) fluid replacement short acting benzo thiamine (prevent wernicke) glucose
mostly supportive
receptors for ethanol
NMDA - glutamate - excitation (memory impairment)
-ethanol decrease NMDA
GABA-A - inhibition
-ethanol increase NMDA
liver and alcohol
fatty liver > hepatitis > cirrhosis > liver failure
CV and alcohol
cardiomyopathy HF arrhythmia HTN stroke coronary heart disease
cancer and alcohol
increased risk
-mouth, pharynx, esophagus, liver
CNS and alcohol
altered expression - NMDA and GABA-A receptors
tolerance to alcohol
has a limit
still get resp depression
tx for seizure in alcohol OD
diazepam - fasting acting - IV
diazepam vs. oxazepam
diazepam - fast and IV
oxazepam - slow and PO
thiamine
prevents wernicke encephalopathy
alcohol withdrawal syndrome
anxiety, insomnia, tremor, palps, nausea, anorexia
go away days
may persist for months
delirium tremens
tachy, HTN, low grade fever, tremor, diaphoresis, delirium, agitation
with alcohol withdrawal
detox from alcohol
benzos
long acting benzos
diazepam and chlordiazepoxide
cause liver damage
short acting benzos
lorazepam and oxazepam
for pt with liver disease
tx of alcohol depedence
naltrexone acamprosate disulfiram - anabuse topiramate ondansetron
naltrexon
longer acting
opioid receptor antagonist
reducing craving and relapse rates - alcohol dependence
acamprosate
weak NMDA antagonist
GABA-A agonist
reduce short and long term relapse rates alcohol dependence
disulfiram
inhibit ALDH
- discomfort in pt who drunk alcohol
- accumulation of adehyde
abuse
pattern of substance use leading to significant impairment
dependence
compulsive use of substance despite significant problems resulting from such use
psych
physio
psych dependence
addiction
physical dependence
dependence - withdrawal syndrome occurs
withdrawal
evidence of physical dependence
drugs of abuse in brain
mesolimbic dopamine system
VTA
MFB - medial forebrain bundle - DA neurons
sensitization
with cocaine
more higher response to same dose over time
drugs of abuse on GPCRs
opioids
cannabinoids
GHB
hallucinogens - LSD, mescaline, psilocybin
drugs of abuse on monoamine transporters
cocaine
amphetamines
ecstasy
drugs of abuse on ion channels
nicotine alcohol benzos dissociative anesthetics - phencyclidine and ketamine inhalants
GABA
inotropic
cocaine
inhibit DAT
methadone
long acting opioid used for substitution therapy
buprenorphine
mix agonist/antagonist
smoking cessation
bupropion - antidepressant
varenicline
partial neuronal nAChR agonist
-for smoking cessation only
suicidal ideation
lozenge
nicotine dependence
adverse of lots of methanol
blindless
tx - fomepizole or ethanol and sodium bicarb
benzo antagonist
flumazenil
spike alcohol
benzo
