6. ALCOHOL.pptx

Pharmacology of Alcohols Ethyl alcohol & Methyl alcohol Learning Objectives • Know alcohol – Its Types and sources – Pharmacokinetics • Explain Pharmacological actions of alcohol – Uses – Acute and chronic intoxication and management • Describe Methanol poisoning and its management Alcohols •...

Pharmacology of Alcohols Ethyl alcohol & Methyl alcohol Learning Objectives • Know alcohol – Its Types and sources – Pharmacokinetics • Explain Pharmacological actions of alcohol – Uses – Acute and chronic intoxication and management • Describe Methanol poisoning and its management Alcohols • Methanol (CH3OH) Wood alcohol • Ethanol (CH3CH2OH) Grain alcohol • Ethylene Glycol (CH2OHCH2OH) Polyhydric alcohol Synthesis & types of alcohols • Fermentation of sugars • Commercial sources: – Mollases: a bye product of sugar industry • Starchy cereals= maltoses – Maltoses are fermented by yeast • Types: – Malted: germinating cereals- beer, stouts – Wines: fermentation of sugars (light wines, fortified wines and effervescent wines (champagne)) – Spirits: distilled after fermentation- Rum, Gin, Whiskey, Brandy, Vodka etc. Pharmacokinetics of alcohols • Rapid absorption from duodenum • Blood alcohol concentration (BAC) depends on: – Volume, concentration, Rate of drinking, Food, Gastric emptying and Hepatic first pass – Distribution: into Total Body Water • Gender Differences in body composition – Women have less alcohol dehydrogenase than men; Metabolizes alcohol slower – Women have a lower proportion of total body water compared to men Metabolis m of ethanol Pharmacological actions • Local actions: – Astringent and Antiseptic • CNS – Ethanol is a sedative-hypnotic agent – Primarily affects the Reticular Activating system – Mechanism of CNS action involves: • Potentiates GABA receptor • inhibits Glutamate/NMDA receptor neurotransmission • Induces release of endogenous opiates Pharmacological actions: CVS, Body Temp and Respiration • CVS: – Large doses: myocardial and vasomotor centre depression and there is fall in BP – Chronic alcoholism: hypertension, arrhythmias • Blood: – raises HDL levels and decreases LDL oxidation • Body temperature: – Warmth due to vasodilatation – High doses depress temperature regulating centre • Respiration: – Depresses respiratory centre Pharmacological actions: GIT and Liver • GIT: – Dilute alcohol: strong stimulant of gastric secretion – Higher concentrations: inhibit gastric secretion • Liver: – mobilizes peripheral fat and increases fat synthesis in liver – Chronic alcoholism: • oxidative stress in the liver and causes cellular necrosis Pharmacological actions: SKM, Kidney and endocrine • Skeletal muscle: – Chronic alcoholism: Weakness and myopathy • Kidney: – Diuresis • Sex: – Reputed aphrodisiac – Chronic alcoholism: impotence and infertility • Endocrine effects: – Moderate amounts: hyperglycaemia due to Adr release – Acute intoxication: hypoglycaemia BAC and clinical effects Interactions with Alcohols • Synergism: – antidepressants, antihistaminics, hypnotics, opioids • Disulfiram like reactions: – chlorpropamide, metronidazole and cefoperazone • With Insulin and sulfonylureas: – alcohol enhances hypoglycaemia acutely • With Aspirin: – more gastric bleeding Alcohols: Contraindications • • • • Peptic ulcer Epileptics Severe liver diseases Unstable personalities: – may abuse and become excessive drinkers • Pregnant women: – moderate drinking: foetal alcohol syndrome Clinical Uses • External application: – Antiseptic, antiperspirant and aftershave lotions. – Alcoholic sponges to reduce body temperature in fever. – Prevention of bedsores • Internal uses: – Appetite stimulant and carminative – Intractable neuralgias, severe cancer pain – To ward off cold – Methanol poisoning Acute alcoholic intoxication • Acute alcoholic intoxication: – Hypotension, hypoglycaemia, collapse, respiratory depression, coma and death • Treatment: – ABCD, Gastric lavage – Correction of hypoglycaemia and electrolyte balance – Insulin + fructose drip – Recovery can be hastened by haemodialysis – Thiamine to protect Wernicke-Korsakoff syndrome – Analeptics should not be used Chronic alcoholism • Tolerance: subjective and behavioral effects – pharmacokinetic • Dependence: – Psychic dependence: even with moderate drinking – Physical dependence: on heavy and round the clock drinking – Withdrawal syndrome: • anxiety, sweating, tremor, impairment of sleep, confusion, hallucinations, delirium tremens, convulsions and collapse. Chronic alcoholism: Treatment • Benzodiazepines: – Chordiazepoxide, diazepam • Long acting opioid antagonist: – Naltrexone • NMDA antagonist and probably GABA agonist: Acamprostate Aldehyde Dehydrogenase Inhibitor: Disulfiram • Disulfiram: – Acetaldehyde concentration rises • Distressing symptoms (aldehyde syndrome): – Flushing, throbbing headache, perspiration – dizziness, vomiting, visual disturbances – mental confusion, postural fainting and CVS collapse • Duration of the syndrome: 1- 4 hours • Used only as an aversion technique in chronic alcoholics Acamprostate • Alcohol inhibits the activity of receptors known as NMethy-D-aspartate receptors (or NMDARs), causing the brain to create more NMDARs • Absence of alcohol, or no inhibition of the receptor, causes these receptors to be overly active and cause symptoms such as delirium tremens (DT). • Acamprosate is thought to reduce glutamate surges that excite NMDARs. • This property makes Acamprosate useful in treating the withdrawal symptoms in alcoholics. • Acamprosate has also been shown in some studies to act as a neuro-protectant and protect neurons from damage caused by alcohol withdrawal Methanol • Methanol’s toxic metabolites: – formaldehyde and formic acid • Well absorbed from GI tract – peak levels attained 30-90 min after ingestion • Blood levels: – >50 mg/dl: severe poisoning – Fatal dose: 75—100 ml – 15 ml methanol can cause blindness Methanol metabolis m Methanol poisoning: Treatment • Keep in a quiet, dark room; protect the eyes from light • Gastric lavage with Sod. bicarbonate • Combat acidosis – Pot. chloride infusion: if hypokalemia • Ethanol 100 mg/dl in blood • Haemodialysis • Specific inhibitor of alcohol dehydrogenase: – Fomepizole Notes Notes