Examples of Drug transformations: the alcohols
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| 2 specific enzyme systems involved in the "usual" metabolism of ethanol and other n-alchohols | alcohol dehydrogenase, Acetaldehyde dehydrogenase
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| What is MEOS | Microsomal Ethanol Oxidizing System - mixed function oxidase, CYP2E1, CP1A2, CYP3A4. kicks in when ADH sys saturated
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| Genetic polymorphism for Alcohol Dehydrogenase | Some Asians have this, =enzyme w/ reduced activity and higher risk of alcoholism.
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| 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
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| Primary affected organ w/ ethanol | CNS
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| Primary affected organ w/ methanol | Retina
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| BAC 50-100 mg/dL symptoms | Sedation, relief of anxiety, subj high feeling, slowed reaction times
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| BAC 100-200 mg/dL symptoms | "Intoxication/drunk" slurred speech, impaired motor fxn, impaired judgement, disinhibited behavior, ataxia
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| BAC 200-300 mg/dL symptoms | "Falling down drunk" Most ppl vomit and become stuperous - not seen in chronic alcoholics
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| BAC 400+ mg/dL symptoms | coma is common
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| BAC 500+ mg/dL symptoms | Respiratory depression and death typical
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| Ethanol does what to GABA(a) mediated chloride influx in CNS? | increases
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| Ethanol opens what subtype of glutamate receptors? | NMDA (N-methyl-D-aspartate)
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| Alcoholic blackouts and hyper-excitability after withdrawal probably due to this | NMDA opening by ethanol, too much, inhibits NMDA receptor activation
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| What does binge drinking do to the heart | acutely decreases myocardial contractility, incr risk of atrial fibrillation
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| What does binge drinking to do brain and blood vessels | Incr risk of hemorrhagic stroke, acutely causes vasodilation.
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| 3 consequences of chronic EtOH consumption on Gastrointestinal system | Liver disease, chronic pancreatitis, GI bleeding (gastroesophageal varices worst), Malnutrition
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| 3 consequences of chronic EtOH consumption on Central Nervous System (CNS) | Tolerance and physical dependance, delirium tremens, Neurotoxicity, Wernicke-Korsakoff syndrom
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| What do you treat Delirium Tremens with? | Benzodiazepines, increase frequency of openings of the GABAa receptor channel = can also prevent DT
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| Neurotoxicity is common in long-term alcoholics. Sx? | usually symmetrical peripheral neuropathy of the "stocking-glove" variety
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| Which Sx of Wernicke-Korsakoff syndrome can be treated with thiamine/B1? | paralysis of external eye muscles, ataxia, confusion, devolving into coma and death
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| 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
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| 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
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| 3 consequences of chronic EtOH consumption on Endocrine System | 1)gynecomastia, testicular atrophy 2)depresses male fxn 3)Ascites, secondary hyperaldosteronism, hypoglycemia, ketosis.
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| Fetal Alcohol Syndrome common sx | intrauterine growth retardation, microcephaly, flattened facies, poor coordination, joint abnormalities, rarely: congenital heart defects.
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| Fetal Alcohol Syndrome is one of most common types of: | Mental retartdation and congenital malformaitons
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| 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)
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| What is the #2 cause of preventable morbidity and mortality in USA? | Ethanol - tobacco is #1
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| Drug you'd give to a chronic alcoholic who drinks a lot of methanol | Supporting respiration, bicarbonate and fluids
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| Brought to ED | hemodialysis and FOMEPIZOLE - alcohol dehydrogenase inhibitorm dialysis, folate (?)
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| Transferred to ICU | Benzodiazipine with fluids, electrolytes and thiamine: to prevent Wernicke Korsakoff syndrome (?)
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| Transferred to detox and rehab program | Taper benzodiazipine over several weeks. Add B-blocker and a-agonists(?)
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| 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.(?)
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