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Pharm 1 (block2) S6

Examples of Drug transformations: the alcohols

2 specific enzyme systems involved in the "usual" metabolism of ethanol and other n-alchohols alcohol dehydrogenase, Acetaldehyde dehydrogenase
What is MEOS Microsomal Ethanol Oxidizing System - mixed function oxidase, CYP2E1, CP1A2, CYP3A4. kicks in when ADH sys saturated
Genetic polymorphism for Alcohol Dehydrogenase Some Asians have this, =enzyme w/ reduced activity and higher risk of alcoholism.
Genetic polymorphism for Acetaldehyde Dehydrogenase Majority of Asians - single gene mutation, greatly reduces activity. Develop higher than normal serum acetaldehyde conc=fascial flushing, nausea, headache, dizziness and vomiting. Same symptoms as disulfiram. If persist, very high risk of liver disease
Primary affected organ w/ ethanol CNS
Primary affected organ w/ methanol Retina
BAC 50-100 mg/dL symptoms Sedation, relief of anxiety, subj high feeling, slowed reaction times
BAC 100-200 mg/dL symptoms "Intoxication/drunk" slurred speech, impaired motor fxn, impaired judgement, disinhibited behavior, ataxia
BAC 200-300 mg/dL symptoms "Falling down drunk" Most ppl vomit and become stuperous - not seen in chronic alcoholics
BAC 400+ mg/dL symptoms coma is common
BAC 500+ mg/dL symptoms Respiratory depression and death typical
Ethanol does what to GABA(a) mediated chloride influx in CNS? increases
Ethanol opens what subtype of glutamate receptors? NMDA (N-methyl-D-aspartate)
Alcoholic blackouts and hyper-excitability after withdrawal probably due to this NMDA opening by ethanol, too much, inhibits NMDA receptor activation
What does binge drinking do to the heart acutely decreases myocardial contractility, incr risk of atrial fibrillation
What does binge drinking to do brain and blood vessels Incr risk of hemorrhagic stroke, acutely causes vasodilation.
3 consequences of chronic EtOH consumption on Gastrointestinal system Liver disease, chronic pancreatitis, GI bleeding (gastroesophageal varices worst), Malnutrition
3 consequences of chronic EtOH consumption on Central Nervous System (CNS) Tolerance and physical dependance, delirium tremens, Neurotoxicity, Wernicke-Korsakoff syndrom
What do you treat Delirium Tremens with? Benzodiazepines, increase frequency of openings of the GABAa receptor channel = can also prevent DT
Neurotoxicity is common in long-term alcoholics. Sx? usually symmetrical peripheral neuropathy of the "stocking-glove" variety
Which Sx of Wernicke-Korsakoff syndrome can be treated with thiamine/B1? paralysis of external eye muscles, ataxia, confusion, devolving into coma and death
Many sx improve with tx thiamine in W-K, but what usually doesn't? most pt don't fully recover their memory = Korsakoff's psychosis
3 consequences of chronic EtOH consumption on Cardiovascular System (CV) 1)dilated cardiomyopathy-->heart failure 2)atrial dysrhythmias (afib) and vfib 3)HTN 4)Anemia and other blood dyscrasias
3 consequences of chronic EtOH consumption on Endocrine System 1)gynecomastia, testicular atrophy 2)depresses male fxn 3)Ascites, secondary hyperaldosteronism, hypoglycemia, ketosis.
Fetal Alcohol Syndrome common sx intrauterine growth retardation, microcephaly, flattened facies, poor coordination, joint abnormalities, rarely: congenital heart defects.
Fetal Alcohol Syndrome is one of most common types of: Mental retartdation and congenital malformaitons
3 consequences of chronic EtOH consumption on Immune systems 1)depressed hematopoeisis 2)different for acute/chronic but =incr risk of infections (pulmonary-tubercular and fungal) 3)Incr risk of cancer (oral cavity, pharynx, larynx, esophagus, liver)
What is the #2 cause of preventable morbidity and mortality in USA? Ethanol - tobacco is #1
Drug you'd give to a chronic alcoholic who drinks a lot of methanol Supporting respiration, bicarbonate and fluids
Brought to ED hemodialysis and FOMEPIZOLE - alcohol dehydrogenase inhibitorm dialysis, folate (?)
Transferred to ICU Benzodiazipine with fluids, electrolytes and thiamine: to prevent Wernicke Korsakoff syndrome (?)
Transferred to detox and rehab program Taper benzodiazipine over several weeks. Add B-blocker and a-agonists(?)
Begins chronic oral tx for alcoholism Naltrexone (unless also taking opiod or active liver disease); Acamprosate (except if severe renal impairment); Combo of naltrexone/acamprosate or disulfiram/acamprosate.(?)
Created by: akenney



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