PSYCH 265 1st Edition Lecture 17Outline of Last Lecture I. Barbiturate withdrawal II. Barbiturate vs. benzodiazepinesIII. Withdrawal from benzoIV. Chemical properties of ethanolV. Absorption of ethanolVI. Distribution of ethanolVII. BACVIII. Metabolism of ethanolIX. Metabolism & excretionX. Pharmacogentetics of EthanolXI. Ethnic Differences in ADHXII. Ethnic Differences in ALDHXIII. DisulfiramOutline of Current Lecture I. Ethanol action at GABA(A) Chloride Channel receptor complexII. Ethanol action at NMDA receptorIII. Central effects of ethanolIV. Enzyme inducing effects of ethanolV. Endocrine effects of ethanolVI. Gastrointestinal effectsVII. Synergistic CNS depressionVIII. Effects on liverIX. Effects on immune systemX. Effects on nervous systemXI. Alcohol related cancersXII. Tolerance Current Lecture-Ethanol Action at the GABA(A) Chloride Channel Receptor ComplexoAlcohol binds to the GABA(A) site and amplifies the effects of GABA, probably by increasing the duration that chloride channel is open, thus prolonging the chloride ion influxoIncreased chloride ion influx results in hyperpolarization (neural inhibition)oAlcohol, therefore, enhances GABA neuronal inhibition and mimics the effects of GABAThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.-Ethanol Action at the NMDA Receptor oAlcohol also binds to the NMDA receptor for glutamate (Glue) and reduces the sodium and calcium ion influxoAction reduces the excitatory effect of glutamate on NMDA receptor oCoupled together with the enhanced GABA effect, this enhances the neuronal inhibitory effect of alcohol -Shakespeare the pharmacologist oMacbeth, Act 2 Scene 3Porter -Central effects of ethanol-Enzyme inducing effects of ethanol oMEOS=microsomal ethanol oxidizing system oAlternate pathway for oxidizing ethanol to acetaldehyde oUsually active after consumption of lots of ethanol oInvolves part of cytochrome P450 enzyme family, some of which are inaudible -Endocrine Effects of ethanoloEthanol inhibits release of antidiuretic hormone, resulting in excessive production of urine oIncrease in blood sugar after consumption of ethanol may cause overproduction of insulin which may enhance the effects of anti-diabetic medicationsoInterferes with how body absorbs calcium, which can predispose heavy drinkers in osteoporosis oHeavy male drinkers can experience loss of testosterone, resulting in erectile dysfunctionand emotional changes oHeavy drinking also may be responsible for easy bruising or acne-Gastrointestinal effects of ethanoloModerate consumption of alcohol stimulates digestive juices and acid secretion oLow-dose alcohol accelerates gastric emptying oHigh-dose ethanol delays gastric emptying and slows bowel motility oExcessive ethanol damages the lining of the stomach, leading to inflammation of the stomach, gastritis oEthanol facilitates development of oraopharyngeal, esophageal, gastric and colon cancer -Synergistic CNS depression -The most important drug interaction in CNS pharmacology -Effects of ethanol on the LiveroCirrhosis is most widely recognized medical complication of chronic alcoholism oGrave and irreversible condition characterized by a progressive replacement of healthy liver tissue with scars, which can lead to liver failure and death -Effects of ethanol on the immune system oExcess alcohol consumption may suppress immune system, causing increased susceptibility to certain diseasePneumonia Tuberculosis Hepatitis B and C Septicemia -Effects of ethanol on nervous system oWernicke encephalopathy and Korsakoff syndrome are different conditions Both are due to brain damage caused by lack of vitamin B1oLack of vitamin B1 is common in alcoholics whose bodies can utilize ethanol as food (calorigenic) but lack vitamins oKoraskoff syndrome develops as wernicke symptoms subside oWernicke encephalopathy causes damage in the thalamus and hypothalamus oKoraskoff psychosis results from permanent damage to areas of brain involved with memory oSymptoms of WernickeConfusion & loss of mental activity that can progress to coma and death Ataxia and leg tremor Vision changes (abnormal eye mvmt, double vision, eyelid drooping)oSymptoms of koraskoff syndrome Inability to form new memories Loss of memory can be servereConfabulation Hallucinations -Alcohol-related cancersoAcetaldehyde is probably carcinogen oSome individuals are less likely to consume large amounts of alcohol, when they do drink, their risk for developing certain cancers is higher than drinkers who are exposed to less acetaldehyde during alcohol metabolism oDrinking too much alcohol can increase the risk of developing certain cancers including cancers of mouth, esophagus, throat, liver, breast, colon, rectum -Tolerance to ethanol oBehavioral toleranceBehavioral compensation for effects of ethanol oPharmacokinetic tolerance Induction of cytochrome P450 enzymes that can break down ethanol oPharmacodynamic tolerance Adaptive changes in drug targets that make them less responsive to the