Pharmacology of alcohols - satya

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an informative lecture on pharmacology of alcohols with juicy quotes and fantastic pics.... <3 .... satya

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Pharmacology of alcohols - satya

  1. 1. The first glass is for myself, the secondfor my friends, the third for goodhumour, and the fourth for myenemies….
  2. 2. PHARMACOLOGY OFALCOHOLS DR. V. SATHYANARAYANAN MD PROFESSOR OF PHARMACOLOGY
  3. 3. INTRODUCTION• Alcohol refers to ethyl alcohol or ethanol• Manufactured by fermentation of sugars• Major source of commercial alcohol – molasses (byproduct of sugar industry)
  4. 4. ALCOHOLIC BEVERAGES• BEERS- fermentation of germinating cereals• Alcohol content is 3 – 6 %• WINES: Fermentation of natural sugars as present in grapes and other fruits• Undistilled light wines 9 – 12 %• Fortified wines – port, sherry 16 – 22 % alcohol• Effervescent wines – champagne 12 – 16% alcohol• RUM, GIN, WHISKEY, BRANDY, VODKA• Alcohol content 40 – 45%
  5. 5. ALCOHOLIC BEVERAGES• Taste, flavor, value•  presence of higher ethers, higher alcohols, aldehydes, esters, volatile oils which are formed during ‘maturation’ of ‘maturation the beverage
  6. 6. PHARMACOLOGICAL ACTIONS CNS• CNS depressant• The features at lower concentration • (30-100mg/dl) are• Excitation, euphoria• Altered mood & feelings• Loss of social inhibitions• Relieve anxiety
  7. 7. Alcohol removes inhibitions –like that scared little mouse who got drunk andshook his whiskers and shouted: "Now bringon that damn cat!"”
  8. 8. PHARMACOLOGICAL ACTIONS With increasing concentration (100 – 150mg/dl)• Mental clouding• Disorganization of thought• Impairment of memory• Alteration of perception• Drowsiness• Loss of self-control
  9. 9. PHARMACOLOGICAL ACTIONS With high concentrations (150 – 200mg/dl ) Make the person sloppy • ataxic • drunk….!!
  10. 10. One reason I don’t drink is that I wantto know when I am having a goodtime…….
  11. 11. PHARMACOLOGICAL ACTIONS• 200 – 300mg/dl  stupor• above this • unconsciousness,• Paralysis of medullary centres,• death• ( due to respiratory depression )
  12. 12. ALCOHOL• Driving is dangerous• Impaired performance• Obliteration of fine discrimination, precise movements• Increased errors
  13. 13. Don’t drink and drive, you might hit abump and spill your drink…..
  14. 14. PHARMACOLOGICAL ACTIONS• Induce sleep –• poor quality &• early morning awakening• Disorganized sleep architecture Raises pain threshold & alters reaction to it
  15. 15. PHARMACOLOGICAL ACTIONS• Exerts anticonvulsant action  followed by lowering of threshold• Precipitate seizures in epileptics• Tolerance• Chronic alcohol abuse damages brain neurons
  16. 16. CVS• Tachycardia,• mild rise in BP• Large doses: Decrease BP• Chronic alcoholism • Hypertension,• Arrhythmias• Regular intake of small to moderate amounts  Increase HDL, decrease LDL cholesterol
  17. 17. A cross – eyed cop arrests three cross-eyeddrunks. He turns to the first cross-eyed drunk andsays, “What’s your name?” And the second cross-eyed drunk says,“Miles MacDuffy”. The cross-eyed cop says, “I wasn’t talking toyou” And the third cross-eyed drunk says, “I didn’tsay anything!”
  18. 18. BODY TEMPERATURE • Produces Sense of warmth due to cutaneous and gastric vasodilatation • increases heat loss in cold surroundings • may be harmful • High doses depress temperature regulating center
  19. 19. RESPIRATION• Brandy or whisky are reputed as respiratory stimulants• Irritate buccal and pharyngeal mucosa – transiently stimulate respiration• Don’t depend on this, because Directly Depresses respiratory centre
  20. 20. GIT• Irritant  Increases gastric secretion• Appetizer• Vomiting, mucosal congestion and gastritis• Decrease tone of LES  increase reflux•• Chronic alcoholism  chronic gastritis• Altered bowel movement• Acute pancreatitis
  21. 21. LIVER • Causes accumulation of fat in liver • Liver enlargement, • fatty degeneration, • cirrhosis • Induces microsomal enzymes
  22. 22. SKELETAL MUSCLE• Allays fatigue• Chronic intake • Myopathy, weakness
  23. 23. KIDNEY • Diuresis (decreases ADH ) • Does not impair renal function
  24. 24. SEX• Reputed as an aphrodisiac• Induces aggressive sexual behavior• but impairs performance• Chronic  impotence,• testicular atrophy,• gynaecomastia,• infertility
  25. 25. ENDOCRINE• Moderate  hyperglycemia and other sympathetic effects• Acute intoxication  hypoglycemia (inhibition of gluconeogenesis , depletion of hepatic glycogen)
  26. 26. LOCAL ACTION• Astringent• Antiseptic – ( maximum at 70% )• Rubefacient• Counterirritant• Applied topically has a cooling effect• Cause Irritation,• burning sensation if applied to delicate skin
  27. 27. MECHANISM OF ACTION• Promotes GABAA receptor mediated synaptic inhibition (through chloride channel opening)• Inhibits NMDA receptors and kainate receptors• Promoting the function of 5HT3 receptor• Indirectly reduce neurotransmitter release by inhibiting neuronal Ca2+ channels• block uptake of adenosine• Enhanced turnover of NA in brain• Alteration of activity of Na+K+ ATPase and adenyl cyclase• PKC, PKA mediated alteration of phosphorylation
  28. 28. PHARMACOKINETICS• Absorption from intestines is very fast.• Limited first pass metabolism  stomach and liver• From skin – minimal (adults) significant (infants)• Widely distributed• Crosses BBB efficiently• Freely crosses placental barrier• 98% oxidized in liver• Excreted through kidneys and lungs
  29. 29. PHARMACOKINETICSEthyl Alcohol AldehydeAlcohol Acetaldehyde Acetate CO2+H2O dehydro- dehydro- genase genase• Metabolism follows zero order kinetics• 10ml of absolute alcohol / hour is degraded in unit time, irrespective of blood concentration• Rate of consuming drinks governs whether a person will get drunk
  30. 30. INTERACTIONS• Synergizes with hypnotics,• antipsychotics,• antidepressants,• antihistamines,• opioids  marked CNS depression  chances of accidents• Acute alcohol inhibits phenytoin, tolbutamide metabolism• chronic alcohol induces microsomal enzymes hasten the metabolism of other drugs
  31. 31. INTERACTIONS• Disulfiram like reaction with• sulfonylureas (chlorpropamide)• Cefaperazone• metronidazole• Aspirin + alcohol more gastric bleeding• Alcohol + insulin, sulfonylureas  enhances hypoglycemia• Alcoholics more prone to paracetamol toxicity
  32. 32. “Alcohol may be mans worst enemy,but the bible says love your enemy…..”
  33. 33. FOOD VALUE• Requires no digestion• Metabolized rapidly• Energy yielding substrate : 7 Cal/g, Cal/g•  cannot be stored• Who Take alcohol suffer from nutritional deficiencies• Alcohol is an imperfect and expensive food
  34. 34. CONTRAINDICATIONS• Peptic ulcer• GERD• Epilepsy• Severe liver disease• Unstable personalities
  35. 35. CONTRAINDICATIONS • Pregnancy  fetal alcohol syndrome - • IUGR, • low IQ, • Microcephaly, • facial, other abnormalities, • infections, • miscarriage, • stillbirths, • low birth-weight babies
  36. 36. GUIDELINES FOR SAFE DRINKING • 1 – 2 drinks per day is usually safe • > 3 drinks / day  associated with adverse health effects…. • Do not drive or engage in hazardous activities after drinking • Do not drink if an interacting drug has been taken lower for women… • Safe limits are • 1 drink = 50ml of spirits = 400ml of beer = 150ml of wine = 18 – 20g alcohol
  37. 37. TOXICITY• Side effects of moderate drinking: nausea, vomiting, flushing, hangover, traffic accidents• Acute alcoholic intoxication:• Gastritis, Hypotension, Collapse• Respiratory depression• Hypoglycemia• Coma• Death• Fatal blood alcohol concentration  > 400 mg/dl
  38. 38. TREATMENT• Gastric lavage,• maintain patent airway and• take steps to prevent aspiration of vomitus• Fluid and electrolyte balance• Correction of hypoglycemia  Glucose infusion• Thiamine 100mg in 500ml of glucose i.v infusion• Check and correct blood potassium and phosphate• Insulin + fructose drip  accelerate alcohol metabolism• In severe cases • Positive pressure respiration,• Haemodialysis
  39. 39. A JOKE ON BARBARA Barbara Beanbag has been tomarket and is walking homecarrying a duck. A drunk comes staggering alongin the other direction, stops andsays, “Hey! What are youdoing with that pig?” Barbara looks at him coldly andreplies, “This is not a pig, it’s aduck!”“I know”, says the drunk, “I wastalking to the duck!”
  40. 40. I stopped drinking, but only when Isleep.
  41. 41. CHRONIC ALCOHOLISM• Tolerance develops• Psychic dependence,• Physical dependence occurs only on heavy and round the clock drinking• associated with nutritional deficiencies• Impaired mental, physical performance
  42. 42. A JOKE ON DEATH demonstrate• A biology teacher wished to harmful effects of alcohol on living organisms. he showed them a beaker with pond water full of worms. When he added some alcohol into the beaker the worms doubled-up and died.• "Now," he said, "what do you learn from this?”• An eager student gave his answer.• "Well the answer is obvious," he said "if you drink alcohol, youll never have worms."
  43. 43. COMPLICATIONS • Polyneuritis, pellagra, anemia • Tremors, seizures, loss of brain mass • Wernicke’s encephalopathy, Korsakoff ’s psychosis. • Cirrhosis of liver • Impotence, infertility , gynacomastia • Hypertension, cardiomyopathy, CHF, arrhythmias • Stroke • Malignancy • Immune function is depressed • teratogenicity
  44. 44. WITHDRAWAL SYNDROME• Consists of anxiety, sweating, tremor• Impairment of sleep, confusion• Hallucinations• Delirium tremens• Convulsions and collapse.
  45. 45. TREATMENT• Psychological and medical supportive measures• Benzodiazepines (Diazepam, chlordiazepoxide) preferred for substitution therapy• Naltrexone, nalmefene - To prevent relapse of alcoholism, alcohol craving during withdrawal• Acomprostate (NMDA antagonist and GABA agonist) prevent relapse• Ondansetron (5 HT3 antagonist) , topiramate• Clonidine, propranolol  reduces sympathetic activity• Baclofen, rimonabant useful in alcohol withdrawal
  46. 46. CLINICAL USES• As antiseptic• Rubefacient and counterirritant for sprains, joint pains etc• To prevent bedsores• To reduce body temperature in fever• Intractable neuralgias, severe cancer pain  injection around the nerve• Appetite stimulant and carminative (50ml of 7 – 10% alcohol)• Methanol poisoning
  47. 47. DISULFIRAM• In inhibits the enzyme aldehyde dehydrogenase irreversibly.• Alcohol  acetaldehyde // acetate  CO2 + H2O• When alcohol is ingested after disulfiram, the concentration of acetaldehyde increases• Aldehyde syndrome (Flushing, burning sensation, headache, sweating, uneasiness, tightness in chest, dizziness, vomiting, visual disturbances, mental confusion, fainting, circulatory collapse) duration 1 – 4 hrs• Used as an aversion technique in chronic alcoholics Who have desire to leave the habit• Sensitization to alcohol develops after 2 – 3hrs after 1st dose, lasts for 7 – 14 days
  48. 48. DISULFIRAM• Treatment should be given in hospital• ADR: Rashes, metallic taste, nervousness, malaise, abdominal upset• Contraindication: Physical dependence to alcohol• D/I: Inhibit CP450 enzymes  prolongs half life of many drugs
  49. 49. When I read about the evils of drinking,I gave up reading.
  50. 50. Always remember that I have taken moreout of alcohol than alcohol has taken out ofme….
  51. 51. METHYL ALCOHOL• Methyl alcohol is used to denature ethyl alcohol• Accidental mixing of methanol  alcoholic beverages methanol poisoning on ingestion• Methanol  formaldehyde  formic acid• follows zero order kinetics, t ½ - 20 – 60 hrs• CNS depressant• Formic acid  toxic effects• Blood level of > 50mg/dl methanol  severe poisoning• 15ml of methanol  blindness• 30ml of has caused  death• Fatal dose 75 -100ml
  52. 52. MANIFESTATIONS• Takes 30 hrs to appear• Vomiting, headache, epigastric pain, headache pain• uneasiness, dyspnoea, bradycardia, hypotension,• blurring of vision, blindness, delirium and vision coma• Acidosis  due to formic acid• Specific toxicity  Retinal damage• Death is due to respiratory failure
  53. 53. TREATMENT• Keep the patient in a dark, quiet room• protect eyes from light• Gastric lavage with sodium bicarbonate ( within 2 hrs of ingesting methanol )• ABC• Supportive measures• IV sod. bicarbonate infusion (prevents retinal damage and other symptoms)• Ethanol (10% in water) by nasogastric tube• 0.7ml/kg followed by 0.15ml/kg/hour drip• Continue Treatment for several days
  54. 54. TREATMENT• Take care of Hypoglycemia• Fomepizole (4 – methylpyrazole)  (specific inhibitor of alcohol dehydrogenase) 15mg/kg I.V loading dose followed by 10mg/kg every 12 hrs – not available commercially in india• Folate therapy: calcium leucovorin 50 mg injected 6 th hourly (enhance formate oxidation )• Potassium Chloride infusion – (hypokalemia due to NaHCo3• haemodialysis
  55. 55. ETHYLENE GLYCOL POISONING• Industrial solvent, coolant, antifreeze• Sporadically seen• Specially in children• Ethylene glycol  glycoaldehyde  glycolic acid• Intoxication similar to ethanol• Acidosis, cardiopulmonary complication, renal tubular necrosis Treatment: Fomepizole (orphan drug) Ethanol
  56. 56. Mrs. Meyerowitz is having tea with Mrs. Abramowitz.“These cookies of yours are too delicious,” raves Mrs. deliciousMeyerowitz, “I have already had five of them.”“Seven,” smiles Mrs. Abramowitz, “but who is counting?”
  57. 57. I like whiskey. I respect it. I always did, andthat is why I never drink it…..!

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