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Transcript of Alcohol
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ALCOHOL
ETHYL ALCOHOL(Ethanol)
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ETHANOL
• PHARMACOKINETICS• absorption--more from intestine,peak level
after 30 min from empty stomach• Vd----0.5 -0.7L/kg• High first pass by gastric& liver ADH,lower in
females• Sequential hepatic oxidation to acetate 90-
98%• Zero order metabolism, supply of NAD+ rate
limiting step
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• Induces CYP 2E1• Vey small amount metab by catalase
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PHARMACOLOGICAL EFFECTS• CNS• Exact mechanism not known,may be GABA
receptor agonist,&blockade of NMDA recep• dose dependent CNS depression• Relieve anxiety, euphoria• behavioral disinhibition uncontrolled mood swings & emotional outbursts that may
have violent components • Toxic doses resp depression , coma
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• CVSHYPERTENSION Incr prevelance of hypertension(5---11%)cessation
more than30 gm alcohol associated with 2mmHg increase in systolic & diastolic BP,
i) increase in vascular reactivity due to release of Ca++
ii)inhibition of release of NO from endothelium
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• CARDIOMYOPATHY dose related hypokinesis ,free fatty acids reacts
enzymatically with ethanol forming fatty acid ethyl esters
50% patients of idiopathic cardiomyopathy are alcoholic
abstinence reverses myopathy CARDIAC ARRYTHMIAS supraventricular tachycardia, atrial fibrillation ,atrial
flutter , alcohol–dependents resistant to cardioversion
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• SERUM LIPOPROTEINS &EFFECT ON CVS 20----30 gm/day cardioprotective , 10---40% decreased risk of CHD&myocardial
infarction increased HDL,tissue plasminogen activator, decreased fibrinogen consumption ,STROKE cardiac arrythmias lead to thrombus formation, hypertension,acute rise may cause bleeding, head trauma
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• SKELETAL MUSCLES• Myomathy, dec muscle strength,• Heavy drinking may cause irreversible damage dec
glycogen stores ,reduced pyruvate kinase ,,reduction in muscle protein synthesis& type 11 fiber atrophy
BODY TEMPERATURE(hypothermia) i) Inc cutaneous& gastric blood flow,so a feeling of
warmth inc sweating, Rapid heat loss dec body temp ii)Heavy drinking depresses central temp-regulating
center,in winters chance of death due to hypothermia
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• DIURESISInhibits release of ADH,volume loading complements
diuresis tolerance develops to diuretic effect
GIT a)Esophageal reflux, barret’s esophagus,traumatic
rupture ,Mallory-Weiss tears,&esophageal cancer, b) disrupt gastric mucosal barrier,inc gastric secretions
due to stimulation of buccal & gastric nerves causing releaseof gastrin & histamineacute & chronic gastritis,
heavy driking directly damages the mucosa
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• C)malabsorption---leading to diarreha,rectal fissures,pruritis ani
• Structural & functional changes in intestines ,dec enzyme levels, flattened villi reversible after stopping alcohol
D)acute & chronic pancreatitis due to direct toxic metabolic effect on pancreatic cells
E)Fatty infiltration of liver,fibrosis,
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• VITAMINS & MINERALSHeavy drinkers have multiple nutritional deficiencies
to poor intake,&malabsorption/poor absorpt ion &impaired utilization
B-complex deficiency especially thiamine resulting in peripheral neuropathy , Wernicke’s
encephalopathy, Korsakoff’s psychosisVit A deficiency, decreased intake ,inc metabolism
due to enzyme ind, daily supplementation Vit E chronic alcohol intake inflicts oxidative
stress,antioxidant effect of alpha tocopherol may ameliorate hepatotoxicity
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• VIT D In liver cirrhosis not activated(hydroxylated)resulting in osteoprosisHypomagnesimea& dec intracellular levels of Mg disturb
cytoplasmic & mitochondrial bioenergetic pathways,leading to Ca++ overload & ischemia
SEXUAL FUNCTION initially increased libido,excessive long term use causes
i)impotence( in about 50% of patients), it provokes the desire but takes away funtion
ii) Testicular atrophy& infertility(direct effect on Leydig cell &depressed hypothalamic function)
iii)gynaecomastia, in alcoholic liver disease due to accelerated metabolism of testosterone
iv)Small ovaries without follicular development,dec libido,dec vaginal lubrication
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• HEMATOLOGICAL & IMMUNOLOGICAL EFFECTS• Microcytic anemia---blood loss & iron def• Normocytic anemia• Macrocytic anemia• Reversible thrombocytopenia,below 20,000/mm3• Dec T-cell production& migration ,dec formation of
immunoglobulins• Dec IL2 function,inc replication of HIV
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CLINICAL USES OAF ETHANOLRELIEF OF LONG LASTING PAINLOCAL INJECTION• Injection of dehydrated alcohol in close proximity
to a nerve or sympathetic ganglia to relieve long-lasting pain e.g trigeminal neuralgia, inoperable carcinoma
• ,lumbar paravertebral injection may destroy sympathetic ganglia& produces vasodilation,
relieve pain &promote healing of lesions in lower extrimities of patients with peripheral vascular disease
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TOLERANCE & DEPENDENCE
• Tolerance is defined as reduced behavioral or physiological response to the same dose of alcohol
• ACUTE TOLERANCE• Tolerance can be demonstrated by measuring
behavioral impairment at the same BAL( blood alcohhol level) on the asending limb of BAL-time curve (minutes after ingestion of alcohol) and on the descending limb of the curve as BALs are lowered by metabolism
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• CHRONIC TOLERANCE• seen in long term heavy drinkers &is dueto induction of
metabolizing enzymes&is mainly due to induction of metabolizing enzymes
• PHYSICAL DEPENDENCE• Elicitation of withdrawl syndrome when alcohol
consumption is terminated• SYMPTOMS• ImmediateSleep disturbance,sympathetic
stimulation,tremors and maybe seizures• Late delirium tremens characterized by
hallucination,delirium ,fever & tachycardia ,may be fatal
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• PSYCHOLOGICAL DEPENDENCE• Craving & drug seeking behavior.This may be due to
impairment of dopaminergic reward system thus resulting in increased intake in an attempt to regain activation of the system
• Prefrontal cortex is sensitive to alcohol abuse,• influencing decision making &emotion.This lack of
judjement and control causes obsessive alcohol consumption.
• Increase in NMDA-receptor function after chronic use& may contribute to CNS hyperexcitability &neurotoxicity after withdrawl
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• SYSTEMIC ADMINISTRATION• Methanol & ethylene glycol poisoning,methyl alcohol is metabolized toformaldehydeBy the enzyme ADH(alcoholdehydrogenase).Asethyl alcohol has more affinity ADH,it competes&replaces methylalcohol from enzyme bindingSite thus decreasing the rate of production offormaldehyde
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ACUTE ALCOHOL INTOXICATION
• ( Dpends upon the level of tolerance ,chronic alcoholics can tolerate high dose which may be fatal in non-addicts)
• Intoxicationat blood levels of 80mg/dl,motor vehical accidents greatly reduced at levels <50-80 mg/dl
• 20---30mg/dl increased reaction time ,diminished fine motor control,impaired judgment
• .>150mg/dl
• >400 mg/dl resp depression& death
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