Alcohol : ethanol and methanol
- 1. Ethanol and Methanol Dr. Sumit Kumar
- 2. Introduction Alcohols are hydroxy derivatives of aliphatic hydrocarbon Alcohol is manufactured by fermentation of sugars: • The major source of commercial alcohol is molasses • Starchy cereals when soaked produce malt which is then fermented by yeast to produce alcohol e.g. barley C6H12O6 2CO2 + 2C2H5OH
- 3. Introduction… Alcoholic beverages: Malted liquors: Obtained by fermentation of germinating cereals e.g: Beers, Stout. Wines: Produced by fermentation of natural sugars present in grapes and other fruits. Light wines: Alcohol content 9–12%, never exceed 15% Fortified wines: Port, Sherry (16–22%) Effervescent wines: Champagne (12-16%): Bottled before fermentation is complete
- 4. Spirits: These are distilled after fermentation • Alcohol content vary from 40–55%, and are standardized to 42.8% v/v or 37% w/w. • e.g. Rum, Gin, Whiskey, Brandy, Vodka, etc. Absolute alcohol: 99% w/w ethanol Rectified spirit: 90% w/w ethyl alcohol produced from fermented mollases Proof spirit: If whiskey is poured on gun powder and ignited it explodes, labelled to be of ‘proof strength’. 100% proof spirit is 49.29% w/w or 57.1% v/v alcohol.
- 5. Pharmacological properties Absorption, Distribution, and Metabolism: • After oral administration, ethanol is absorbed from the stomach and small intestine • In empty stomach peaks blood level in 30 minutes. Food delays gastric emptying & slows ethanol absorption. • Crosses blood brain barrier, placenta, concentration in brain is very near blood concentration. • first-pass metabolism begins from stomach and in liver by alcohol dehydrogenase (ADH), Aspirin increases ethanol bioavailability by inhibiting gastric ADH.
- 6. Metabolism: Metabolized by sequential hepatic oxidation, first to acetaldehyde by Alcohol dehydrogenase and then to acetic acid by aldehyde dehydrogenase (ALDH) NAD+ is required in each metabolic step, limiting ethanol metabolism to about 8-10g or 10 mL/hr and shifts to zero-order kinetics Small amount is also metabolized by hepatic cytochrome P450, CYP2E1 Excretion of alcohol occurs through kidney and lungs
- 7. Ratio of ethanol in end-expiratory alveolar air and blood is relatively constant Blood ethanol levels (BELs) in humans can be estimated readily by the measurement of alcohol levels in expired air Legally allowed BELs is below 80 mg% (80 mg /100 mL blood; 0.08% w/v)
- 8. INTERACTIONS Synergistic effect with anxiolytics, antidepressants, antihistaminics, hypnotics, opioids → marked CNS depression with motor impairment occurs Disulfiram-like reactions is shown by sulfonylurea, cefoperazone, or metronidazole when taken with alcohol Acute alcohol ingestion inhibits, while chronic intake induces CYP enzymes (especially CYP2E1) Alcohol enhaces hypoglycaemic action of insulin and sulfonylureas Alcohol when taken with aspirin and other nsaids cause more gastric bleeding
- 9. Effects Of Ethanol On Physiological Systems • Local actions: Irritant and counter irritant Rubefacient Astringent and antiseptic Antiseptic of 20-70% , above 90% antisepsis decreases
- 10. Effects Of Ethanol On Physiological Systems…….. CNS: Alcohol is a Neuronal Depressant 30–60 mg/dl : Excitation and Euphoria 80– 150 mg/dl: Mental clouding, altered thought, impairment of attention, memory, gait 150–200 mg/dl: Ataxic and drunk ‘blackouts’ occurs 200–300 mg/dl: Stupor and medullary centers are paralyzed and death may occur.
- 11. Neurohormonal mechanism of alcohol…
- 12. • Alcohol enhance GABA release at GABAA sites in the brain. • It also inhibits NMDA and kainate type of excitatory amino acid receptors (operating through cation channels). • Action of 5-HT on 5-HT3 inhibitory autoreceptor (having an intrinsic ion channel) is augmented. • Release and turnover of DA in brain is enhanced through β endorphin release in nucleus accumbens and an opioid receptor dependent mechanism. • Activity of membrane bound enzymes like Na+ K+ ATPase and adenylyl cyclase is also altered.
- 13. CVS Cardiac Arrhythmias: Abnormal cardiac conduction, Increase QT interval, Ventricular repolarization Atrial arrhythmias: Supraventricular tachycardia, atrial fibrillation, and atrial flutter Cardiomyopathy and strokes are also frequent Alcohol reduces risk of CHD • Increases in high-density lipoprotein (HDL) • Elevates levels of tissue plasminogen activator tPA
- 14. Decreased muscle strength • Heavy doses cause irreversible damage to muscle, reflected by increase in creatine kinase activity in plasma. • Muscle biopsies shows decreased glycogen stores Body Temperature • Ingestion of ethanol causes a feeling of warmth because alcohol enhances cutaneous and gastric blood flow. Diuresis • Alcohol inhibits the release of vasopressin (antidiuretic hormone) from the posterior pituitary gland, resulting in enhanced diuresis.
- 15. Respiration: • They irritate buccal and pharyngeal mucosa which may transiently stimulate respiration reflexly Vitamins and Minerals: Alcoholics often present with deficiencies owing to decreased intake, decreased absorption, or impaired utilization of nutrients. • Peripheral neuropathy • Korsakoff’s psychosis • Wernicke’s encephalopathy
- 16. Sexual Function: • Both acute and chronic alcohol lead to impotence in men. • Gynecomastia is associated with alcoholic liver disease • female have menstrual cycle abnormalities, ovaries often are small without follicular development Blood: • Mild anaemia is common in chronic alcoholics. • Megaloblastic anaemia occurring in chronic alcoholism is due to interference with folate metabolism.
- 17. GIT Esophageal reflux Barrett’s esophagus Traumatic rupture of the esophagus Mallory-weiss tears, and esophageal cancer Heavy alcohol disrupt the gastric mucosal barrier and cause acute and chronic gastritis. The primary effects are fatty infiltration of the liver, hepatitis, and cirrhosis. most common cause of both acute and chronic pancreatitis
- 19. Symptoms of acute acohol intoxication: 20-30 mg/dl : Increased reaction time, diminished fine motor control, impulsivity, and impaired judgment 80 mg/dl: Slurred speech, incoordination, unsteady gait, and impairments of attention 80-200 mg/dl: Greater cognitive deficits, potentially accompanied by aggressiveness, and anterograde amnesia >200 mg/dl: Nystagmus and unwanted falling asleep 300 mg/dl: Depressed vital signs, coma, and death. Symptoms are exacerbated and occur at a lower BEC when ethanol is taken along with other CNS depressants
- 20. Treatment of acute alcohol intoxication Treatment of acute alcohol intoxication is based on the severity of respiratory and CNS depression first priority is to maintain patent airway and prevent aspiration of vomitus. Tracheal intubation and positive pressure respiration Supportive treatment, • Maintenance of fluid and electrolyte balance • Correction of hypoglycaemia by glucose infusion • Thiamine (100 mg in 500 ml glucose solution infused i.v.) Should be added. Recovery can be hastened by haemodialysis.
- 21. Tolerance, Dependence, And Chronic Ethanol Use Tolerance is defined as a reduced behavioral or physiological response to the same dose of ethanol Physical dependence is demonstrated by appearance of a withdrawal syndrome when alcohol consumption is terminated. Symptoms and severity are determined by the amount and duration of alcohol consumption Include sleep disruption, autonomic nervous system (sympathetic) activation, tremors, and in severe cases, seizures. Delirium tremens: characterized by hallucinations, delirium, fever, and tachycardia. Another aspect of dependence is craving and drug-seeking behavior, often termed psychological dependence
- 22. Treatment Psychological and medical supportive measures are needed during withdrawal Currently, three drugs are approved in the U.S. for treatment of alcoholism: disulfiram (ANTABUSE), naltrexone (REVIA), and acamprosate Naltrexone: • Naltrexone blocks activation of dopaminergic pathways in the brain that are thought to be critical to reward. • Naltrexone helps to maintain abstinence by reducing the urge to drink • Nausea is the most common side effect, excessive dose causes liver damage, contraindicated in patient with liver failure and acute hepatitis
- 23. Acamprosate: • NMDA-receptor antagonist with modest GABAA receptor agonistic activity • Loose motion is a common side effect. Others are nausea, abdominal pain and itching Disulfiram: • It inhibits ALDH activity and causes blood acetaldehyde concentration to rise to 5-10 times • Within 5-10 minutes, signs and symptoms of acetaldehyde poisoning appears, face feels hot and flushed • Intense throbbing and pulsating headache is seen
- 24. 5-HT3 antagonist ondansetron and the antiepileptic topiramate have also shown some promise in treating alcoholism Benzodiazepines (chlordiazepoxide and diazepam) are given to prevent withdrawal. Naltrexone is used to reduce alcohol craving. Acamprosate used for maintenance therapy of alcohol abstinence
- 25. Clinical use of Ethanol As antiseptic Rubefacient and counterirritant for sprains, joint pains Astringent action of alcohol is utilized in antiperspirant and aftershave lotions Intractable neuralgias (trigeminal and others), severe cancer pain. Injection of alcohol round the nerve causes permanent loss of transmission To treat methanol poisoning
- 26. foetal alcohol syndrome: Intrauterine and postnatal growth retardation Low IQ Microcephaly, Cranio-facial and other abnormalities, Susceptibility to infections. Increases incidence of miscarriage, Stillbirths Low Birth-weight babies
- 27. Methanol One carbon alcohol, methanol (CH3 OH), is also known as methyl and wood alcohol • Paint removers, • Shellac, and • Antifreeze • Added to industrial-use ethanol to mark it unsafe for human consumption. An important industrial reagent and solvent found in products such as
- 28. Methanol Methanol is a CNS depressant Toxic effects of methanol are largely due to formic acid A blood level >50 mg/dl methanol is associated with severe poisoning 15 ml of methanol causes blindness fatal dose : 75–100 ml
- 29. Treatment of Methanol Poisoning Keep the patient in a quiet, dark room; protect the eyes from light Supportive measures to maintain ventilation and BP i.v. Sod. bicarbonate infusion to Combat acidosis Pot. chloride infusion to treat hypokalemia Ethanol (10% in water) is administered through a nasogastric tube, loading dose of 0.7 ml/kg is followed by 0.15 ml/kg/hour. Fomepizole a specific inhibitor of alcohol dehydrogenase and drug of choice for methanol poisoning loading dose of 15 mg/kg i.v. followed by 10 mg/kg every 12 hours till serum methanol falls below 20 mg/dl Folate therapy, leucovorin 50 mg injected 6 hourly
- 30. Thank you
Editor's Notes
- #11: At 30-60mg/dl Hesitation, caution, self-criticism and restraint are lost first. Mood and feelings are altered; anxiety may be allayed 80– 150 mg/dl Though, alcohol can produce anaesthesia, margin of safety is narrow