Pharmacology of alcohol

introduction, uses, manifacturing, mechanisam of action, pharmacological action, pharmacokinetic, disulfiram

1. Presented by Miss. Ashvini Vijay Govande Assistant Professor Kandhar College of Pharmacy, Kandhar PHARMACOLOGY OF ALCOHOL

2. Content Introduction Uses of alcohol How alcohol Manufactured Mechanism of action Pharmacological action Pharmacokinetics

3. Introduction Alcohol is a chemical name for a group of compound that contain a hydroxyl group (-OH) bonds to carbon atom. The alcohol consumed by human is ethyl alcohol or ethanol. Structural formula is C2H5OH / C2H6O. It is clear colourless liquid rapidly absorbed from git tract and distributed throughout the body.

4. Uses of alcohol As antiseptic As astringent Bactericidal and antifungal activity Topical disinfectant Appetite stimulator Rubifacient and counter irritant for sprains and joint pain Alcohol sponges reduce body temperature Reflex stimulation in fainthing and hysteria To treat methanol posioning Solvent and preservative in pharmaceutical preparation Primary ingredient in alcoholic beverages

5. How alcohol Manufactured It is manufactured by fermentation process. Fermentation is a biochemical process through which yeast converts sugar to alcohol. C6H12O6 2(CH3-CH2-OH) + 2CO2

6. Mechanism of action It affects a large number of membrane protein that participate in signalling pathway including neurotransmitter receptor , enzyme and ion channel. Alcohol mainly affects on CNS It affects on neurotransmission by glutamate and gamma aminobutyric acid (GABA) the main excitatory and inhibitory neurotransmitter in CNS.

7. Continue.... Fig- a Fig-b

8. Continue.... Actions of the brain’s glutamate system (Fig-a). In the presence of alcohol, the activity of the N-methyl- Daspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-isoxazole-4-proprionic acid receptors (AMPARs), is inhibited, reducing cation entry into the cell. As a result, the activity of the neuron is reduced and no or fewer nerve signals are generated. Actions of the brain’s γ- aminobutyric acid (GABA) system(Fig-b). In the presence of ethanol, GABA activity is enhanced, resulting in greater Cl influx into the postsynaptic neuron and, consequently, greater inhibition of the neuron.

9. Pharmacological action CNS- At small doses- Alcohol causes sedation, relief of anxiety At moderate doses- Inhibit attention and information processing skill as well as motor skills At higher doses - slurred speech, ataxia, impaired judgement and disinhibited behaviour (intoxication or drunkenness) Chronic drinker- who are tolerant to effect of alcohol, required higher conc. for their effect and causes marked intoxication/coma

10. Continue.... 2) CVS- At small doses- Cutaneous vasodilation , flushing At moderate doses- Tachycardia and mild rise in BP At large doses- Vasodilatation due to direct vascular smooth muscle dilation and vasomotor centre depression 3) Body temp. – Feeling of warmth due to cutaneous blood flow is increased

11. Continue.... 4 ) Smooth muscle- Ethanol is a vasodilator It produces vasodilation effect by two mechanisam - Depression of vasomotor center Direct smooth muscle relaxation caused by its metabolite, acetaldehyde It also relaxes uterus so it was used intravenously for the suppression of premature labor before the availability of more effective and safer uterine relaxant.

12. Continue.... 5) Liver- Liver diseases is most common cmplications of alcohol abuse Alcohol induces liver damage due to production of its metabolite acetaldehyde This acetaldehyde radialy reacts with proteins, lipids and other comp. leads to impaired in mitochondrial function. Chronic alcoholics increases fat accumulation in liver severe liver damage and cirrhosis

13. Continue.... 6) GIT- Dilute alcohol at low doses- stimulate GI secretion Higher doses- inhibit GI secretion Long term ingestion of high conc.- Esophageal varices and bleeding, erosive gastritis, diarrhea and malabsorption of neutrients and vitamins. Increases risk of tumors in the GI system as well as in other tissues including lungs and breast. 7) Sex- Decreases sexual performance

14. Pharmacokinetic Absorption- Absorbed from GIT (rapidly absorbe from small intestine and colon but slowly absorbed from stomach) The maximum blood conc. Is reached within 30 min. Can be absorbed from lungs Can be absorbed from skin

15. Continue.... Distribution- Uniformly distributed throughout the tissue and body fluid The volume of distribution of ethanol is approximate total body water (0.5-0.7L/kg) Rapidly crosses placenta for the exposure to fetus It cross BBB rapidly

16. Continue.... Excretion- Through lungs and urine Metabolism- About 90% alcohol is metabolised in liver The metabolite product of alcohol is acetaldehyde

17. Continue.... Fig. Metabolism of alcohol

18. Drug-Drug interaction Alcohol enhance the hepatotoxic effect of acetaminophen and gastric irritating effects of NSAIDs, thus increasing the risk for development of gastritis and upper GI bleeding. Alcohol enhances the sedation effect of antihistamines and produces significant CNS depression. Chronic alcoholics interfere with metabolism of certain drugs due to enhanced levels of liver enzyme.

19. Disulfiram It is a carbamate derivative used as an alcohol deterrent. It is nontoxic sub. when administered alone but when ingested after administration of alcohol it immediately alter the metabolism of alcohol. Disulfiram inhibit oxidation of acetaldehyde so blood acetaldehyde conc. are increased and causes an unpleasent reaction of facial flushing, systemic vasodilatation, respiratory difficulty, nausea, hypotension and other symptoms. It act by inhibiting aldehyde dehydrogenase (ALDH).

20. Thank you