exam 5 watts alcohol Flashcards
where is alcohol absorbed?
10% in stomach and the rest in intestine
limited by gastric emptying
increases acid release
what is the distribution of alcohol?
distributed in TBW
58% in men
48% in women
What kinetics does alcohol follow?
Alcohol follows a zero order PK
ADH is the rate limiting step
how is alcohol metabolized?
90% in liver
ADH, MEOS involving CYP2E1, ALDH
gluronidation
what is ADH?
alcohol dehydrogenase
enzyme in liver and brain
men have higher levels
what is fomepizole?
ADH inhibitor used to treat alcohol poisoning
slows fomation of formaldehyde and toxic metabolites so liver has more time to metabolize
what is ALDH?
aldehyde dehydrogenase
ALDH1B1 and ALDH2 are important in metabolism of alcohol
SNP ALDH2*2 reduces activity
what are heterozygous and homozygous ALDH2*2?
heterozygous can drink
homozygous cannot drink
what is disulfrim?
irreversible inhibitor of ALDH
used to treat alcoholism
makes bad symptoms when taking alcohol
effects last up to 14 days
What the channels involved in alcohol action?
ligand-gated ion channels:
GABA-a receptors (allosteric activator of inhibitory neurotransmitters)
NMDA receptors
alpha7 nicotinic receptors
what neurotransmitters are released with alcohol use?
opioid (enkephalins)
DA
S
NE
ACh
increases CNS and blood ACTH
what is the legal driving limit BAC?
0.08 BAC or 80mg%
0.1 BAC is 100mg/dl
What are actions at low levels of alcohol?
Euphoria, dishibition, talkative: 30-80mg/dL
Analgesia (60-90mg/dL)
What are actions at intermediate levels of alcohol?
CNS stimulation (mood swings + depression): 80-120mg/dl
CNS depression: 100-200mg/dl
Slurred speech, ataxia, sedation, loss of motor control
what are pharmacological effects of alochol at high concentrations?
300-500mg/dl
coma
death
what the the CV effects of acute alcohol use?
Vasodilation, warm, flush, decreased BP, increased HR
what the the CV effects of moderate alcohol use?
risk of CAD
can increase HDL
what the CV effects of chornic alcohol use?
Heart problems: arrhythmias, HTN, hemostasis
what are physiological effects of alcohol consumption?
Thermoregulation: Hypothermia
GI: increased acid secretion, chronic gastritis
what are the long term ADRs of alcohol consumption?
liver: increased fat metabolism, fatty liver leading to cirrhosis, vitamin deficiencies
blood: mild anemia, gastritis, alcohol folic acid deficiency
cancer: liver
what are some drug interactions of alcohol?
Cns depressants: opioid, atipsychotics, antihistamines, sedative hypnotics
ALDH inhibitors: disulfiram, antimicrobials, sulfonylureas
APAP
aspirin
how do you manage acute intoxication?
prevent respiratory depression
prevent aspiration of vomit
how is alcohol teratogenic?
fetal alcohol syndrome
lowers testosterone and sperm quality
what are the treatments to alcoholism?
disulfiram: ALDH inhibitor that cause bad reaction to alcohol
camprosate: NMDA antagonist and GABA agonist
naltrexone: opioid receptor antagonist to prevent relapse
pts with 118G respond better to what drug?
naltrexone
what are off label drugs used to treat alcoholism?
topiramate: inhibits glutamate
baclofen: stimulates GABA
varenicline: nicotinic acetylcholine receptor partial agonist
