alcohol Flashcards
alcohol potency
not very potent, one dose is about 14g
12oz beer, 5 oz wine, 1.5 oz of liquor
consumption of 14g results in BAC 30 mg/decileter
basic pharm of ethanol
absorption
pharmacokinetics small, water soluble molecule which is absorbed rapidly after oral admin (primarily absorbed from small intestine
Rate of absorption influenced by ethanol concentration, rate of consumption and composition of gastric contents
absorption is decreased if gastric emptying is delayed
ethanol distribution
distributed to total body water (Vd approximates volume of total body water ~1L/Kg
distribution depends on degree of tissue vascularization
freely membrane permeable
metabolism of ethanol
90-98% of ethanol is metabolized to acetaldehyde, with significant 1st pass effect in liver
2 major paths of metabolism
1. alcohol dehydrogenase (ADH)- 1’ pathway for ethanol oxidation–> acetylaldehyde (Rate limiting step) in liver but other tissues, kinetics of ethanol elimination by this path are zero order (10 g/ hr in 70 kg person)
ADH inhibited by FOMEPIZOLE
- microsomal ethanol oxidizing system (MEOS/MFOS)
High Km- little contribution at concentrations below 100 mg/dl, induced in alcoholics (CYP2E1)- influences metabolism of other drugs
acetylaldehyde metabolism
mitochondrial aldehyde dehydrogenase (ALDH)
oxidizes acetylaldehyde to acetate, genetic polymorphism, inhibition by
DISULFIRAM
major metabolic consequences of ethanol metabolism
increased NADH/NAD+ ratio (result of ADH action) inhibits TCA cycle; accumulation of acetyl CoA, promotion of lactic acidosis, accumulation of ketones can exacerbate lactic acidosis
Increased NADP+/decreased NADH ratio (result of MEOS action) limited regeneration of GSH
Increased acetaldehyde: generation of protein and DNA adducts, inhibits microtubules
excretion of ethanol: 2-10% excreted as ethanol through the lungs and urine
MOA of ethanol in the CNS
affects function of several ion channels, especially GABA receptor-ligand gated Cl-channel and inhibits NMDA inhibits NMDA receptor-ligand gated cation channel
Disturbs balance between excitatory and inhibitory neurotransmission
Ethanol is a dose dependent CNS depressent
alcohol/drug interaction
CNS depressants are additive: barbituates; benzodiaziepines; opiods; neuroleptics
Interaction with drug metabolism: acute high doses can inhibit Cyp mediated metabolism of some drugs
chronic ethanol use induces CYP2E1, therefore accelerates metobolism of some drugs
acetaminophen toxicity: worse in alcoholics (GSH depleted)
ethanol as food
7.1 cal/gram, 100 cal/drink, heavy ethanol –> hypoglycemia (insulin secretion), alcohol- induced ketoacidosis (increase in serum ketones)
GIT and chronic alcohol use
alcoholic liver disease, steatosis (fatty liver), hep C (co morbid), alcoholic cirrhosis
Chronic gastritis, pancreatitis, diarrhea, malabsorption of vitamins
NS and chronic alchohol use
tolerance and physical dependence (Adaptive neuronal changes, metabolic tolerance)
Dependence (Psychological dependence cravings), physical dependence (withdrawal is dangerous can get seizures
neurotoxicity: neuralgias and peripheral nerve injuries, cerebral/cerebellar atrophy, wernickes encephalopathy, korsakoffs psychosis, psychiatric disorders
teratogenic effects (FAS)
associated with chronic maternal alcohol abuse
Complex syndrome characterized by growth deficiencies, microcephaly, poor coordination, facial abnormalities and minor joint abnormalities
direct inhibitory effect on ebryonic cell proliferation
severity is dose dependent and minimum dose is not known
management of acute intoxication
diagnosis based on blood ethanol concentration, lethal concentration (above 400 mg/dl)
goal– prevention of severe respiratory depression and aspiration of vomitus
metabolic alterations may require treatment of dehydration, hypoglycemia, ketosis, and/or electrolyte imbalance
management of alcohol withdrawal syndrome
withdrawal: syndrome- agitation, anxiety, insomnia, seizures, mood swings
severity- proportional to degree and duration of alcohol use
objectives of drug therapy- prevention of seizures, delerium, and arrhythmias
benzodiazepines- Diazepam, chlordiazepoxide (gradual reduction of dose tapering off)
atenolol: B- blocker to prevent cardiac arrythmias
pharmacotherapy of alcoholism
naltrexone- reduces urge to drink, increases control, MOA- opioid receptor antagonist, best together with psychosocial therapy
acamprosate- decreases drinking frequency and reduces relapse in abstinent individuals, MOA: GABA mimetic, well tolerated - primary side effect is diarrhea
disulfiram: aversion therapy, therapeutic use, MOA:inhibition of aldehyde dehydrogenase, pharmacologic effects- acetylaldehyde syndrome, not effective
