Alcohol (1) PDF

Alcohol Ethyl Alcohol [Ethanol] Alcohol Ethanol is one of the oldest drugs recognized by man and is the primary alcohol present in beers, wines and distilled spirits. Ethanol is a clear, colorless liquid that has a very slight pleasant odor....

Alcohol Ethyl Alcohol [Ethanol] Alcohol Ethanol is one of the oldest drugs recognized by man and is the primary alcohol present in beers, wines and distilled spirits. Ethanol is a clear, colorless liquid that has a very slight pleasant odor. Source: From fermentation of sugar. Ethyl Alcohol [Ethanol] Alcohol Uses: Beverages: e.g. wines and whisky. Over — the counter products: - Mouth washes. - Aftershave lotions. - Hair sprays. - Cough and cold preparations. Solvent Ethyl Alcohol [Ethanol] Alcohol Pharmacokinetics of ethanol: Absorption: Major (80%) (from small intestine) Minor (20%) (From stomach & large intestine) Distribution: - To all tissues and body fluids, and parallels the water content of each. - Passes the blood brain barrier. - Passes placenta. Metabolism: 90-98% of the absorbed ethanol is removed from the body by enzymatic oxidation primarily in the liver but to a lesser extent in the kidney. Ethyl Alcohol [Ethanol] Alcohol Pharmacokinetics of ethanol: Excretion: 2-10% Ethanol excreted unchanged through. - Urine. - Breath. - Small amounts can be detected in sweat, tears, bile, gastric juice and other secretions. Ethyl Alcohol [Ethanol] Alcohol Conditions of poisoning: Accidental: - Addicts. - Children. -Workers. Homicidal: to facilitate rape & robbery (as barbiturates). Suicidal: rare Ethyl Alcohol [Ethanol] Alcohol Mechanism of action:  CNS: depression is the principal effect of ethanol. Ethanol exerts its action through direct effect on neuronal membrane possibly due to inhibition of Na- K- ATP. The effect of ethanol on the CNS is directly proportional to the blood concentration.  Peripheral: Vasodilatation false sensation of heat (Central thermal auto regulation is inhibited, so temperature is low).  Ethanol metabolism leads to significant decrease in NAD/ NADH ratio in the liver. This results in: - Significant hypoglycemia partly due to inhibition of gluconeogenesis - Reduction in the metabolism of glycerol, resulting in accumulation of fat in the liver. - Accumulation of lactic acid & ketoacids [metabolic acidosis]. Ethyl Alcohol [Ethanol] Alcohol Toxic dose: - Generally, 0.7g/kg of pure ethanol will produce a blood level of 100mg/dL which is considered legally intoxicated. - The level sufficient to cause deep coma or respiratory depression is highly variable, depending on the individual’s degree of tolerance to ethanol. Although levels above 300 mg/dL usually causes coma in novice drinkers, chronic alcoholics may awake with levels of 500-600 mg/dL or higher. Ethyl Alcohol [Ethanol] Alcohol Clinical presentation: Depends on blood Ethanol level 1) Mild toxicity: [stage of excitation] - Blood alcohol level ranges between 0.05 - 0.15%. - There is Inhibition of centers which control judgment & behaviors. - Euphoria. - Talkativeness and behavioral changes. Ethyl Alcohol [Ethanol] Alcohol Clinical presentation: 2) Moderate toxicity: [stage of incoordination] - Blood alcohol level ranges between 0.15 - 0.3%. Motor incoordination: - Drunkard (staggering) gait. - Tremors of hands. - Slurred speech. - Decreased motor skills. Diaphragm: Sudden contraction - Hiccough. Eyes: Diplopia. GIT: vomiting. Skin: flushed (alcohol flush). Ethyl Alcohol [Ethanol] Alcohol Clinical presentation: 3) Severe toxicity: [stage of seizures & coma] - Blood alcohol level is more than 0.5%. - Severe depression of medullary centers. Seizures. Shock: - Temperature ( ) - B.P ( ) - Pulse (rapid & weak). - Resp. (rapid & shallow). Breath: Alcoholic smell. Pupil : McEwen’s sign [constricted pupil that dilate on pinching the skin of face or neck]. Coma with respiratory depression. Cause of death : Central asphyxia. Ethyl Alcohol [Ethanol] Alcohol Investigations:  Rapid tests  Chemical analysis  Blood chemistry Ethyl Alcohol [Ethanol] Alcohol Investigations:  Rapid tests: Finger to nose test. To walk along a straight line. Buttoning and unbuttoning.  Chemical analysis: to detect alcohol in: Breath [Breath analyser] used by police. It is simple colorimetric test that gives relative accurate approximation of the blood alcohol level. Urine. Blood.  Blood chemistry: There is ketoacidosis. Ethyl Alcohol [Ethanol] Alcohol Treatment:  Supportive measures [ABCs] see general toxicology. Top priority should include care of respiration (insure patent airway, oxygen therapy and assisted ventilation if necessary).  GIT Decontamination Gastric lavage by NaHCo3 , leave strong coffee in the stomach at the end of lavage. Activated charcoal not bind Ethanol so not used Elimination of the absorbed poison Forced alkaline diuresis [see general toxicology] Haemodialysis is very effective (Ethanol has small Vd & low molecular weight). It is indicated in: Severe intoxication, Acid-base and /or electrolyte disturbance. Ethyl Alcohol [Ethanol] Alcohol Treatment:  Antidotes: No specific antidote, but Vit B6 may accelerate ethanol metabolism through stimulation of alcohol dehydrogenase enzyme.  Symptomatic: Metabolic acidosis: NaHCo3 Hypoglycemia: 10-50% dextrose solution IV. Hypothermia: Warming the patient. Shock : fluid expansion and dobutamine. Methyl Alcohol [Methanol] “Wood alcohol” Alcohol Methanol is the alcohol with the simplest structure, but the one most likely to cause serious human toxicity. Source: From distillation of wood. Uses: It is used to adulterate ethyl alcohol [cheap, tax free] Solvent, fuel, paint remover, household cleaners. Methyl Alcohol [Methanol] “Wood alcohol” Alcohol Pharmacokinetics of methanol: Absorption: Rapidly and completely absorbed from the GIT. Inhalation and cutaneous absorption are also reported. Distribution: - As Ethanol. - Distributed mainly to optic nerve. Metabolism: (90% in liver) Excretion: - Mainly through liver, other routes include kidneys and lungs. NB: Metabolism (1/7- 1/5 that of ethanol) & Excretion of Methanol is slower than Ethanol [Cunmulation] Methyl Alcohol [Methanol] “Wood alcohol” Alcohol Conditions of poisoning: Mainly: Accidental: - Drinking adulterated Ethanol. - Children. - Workers. Methyl Alcohol [Methanol] “Wood alcohol” Alcohol Mechanism of action: CNS depressant (more than Ethanol) G.I.T irritation Metabolic acidosis due to accumulation of formic acid (six times more toxic than methanol) and lactic acid which is generated by lowering of hepatic NAD/NADH ratios). Ocular toxicity (formic acid inhibits cytochrome oxidase in the optic nerve resulting in cellular ischemia and obligatory anaerobic metabolism). Methyl Alcohol [Methanol] “Wood alcohol” Alcohol Clinical presentations: Visual : Visual blurring, ocular pain, papilledema, optic atrophy and irreversible blindness (25% of the cases). Metabolic Acidosis : Moderate to severe, is secondary to the toxic metabolites of methanol. It is responsible for the tachypnea (air hunger), confusion. headache and weakness. Severe metabolic acidosis may produce life threatening hyperkalemia. Gastrointestinal: Vomiting, abdominal cramps and dehydration. Methyl Alcohol [Methanol] “Wood alcohol” Alcohol Clinical presentations: CNS: - Disorientation, Stupor and Coma: It is caused by acidosis and accumulation of formic acid in the CSF. - Convulsions (serious). - Encephalopathy. - Respiratory Depression follows air hunger (acidotic breathing). It is correlated with severity of acidosis and coma. Shock Due to depression of VMC, severe vomiting and myocardial depression secondary to acidosis and hyperkalemia. Methyl Alcohol [Methanol] “Wood alcohol” Alcohol Investigations: Serum methanol level. Fundus Examination and Visual Evoked Potential: Initial and serial examinations are essential to assess optic nerve affection. Arterial blood gases and serum electrolytes to monitor acidosis and hyperkalemia. Cause of death : Central asphyxia Methyl Alcohol [Methanol] “Wood alcohol” Alcohol Treatment:  Supportive measures [ABCs] Oxygen, Airway, Breathing, Circulation support.  GIT Decontamination Gastric lavage by NaHCO3. Activated charcoal not bind Methanol so not used.  Elimination of the absorbed poison:- Forced alkaline diuresis Haemodialysis is indicated in: History of ingesting 30ml [0.4mg/Kg] Methanol blood level > 20 mg / dL Visual symptoms. Severe metabolic acidosis. Methyl Alcohol [Methanol] “Wood alcohol” Alcohol Treatment:  Antidotes: Ethanol: - It compete with methanol for alcohol dehydrogenase enzyme (higher affinity to ethanol), to inhibit its metabolism to its toxic metabolites -Dose: l gm/kg/30min of 10% solution, followed by 0.5 gm/kg/4 hours to maintain blood ethanol at l00-l50mg/dL 4-methyl pyrazole (4-MP): - Strong inhibitor of alcohol dehydrogenase enzyme, blocking methanol metabolism to its toxic metabolites, and allowing methanol to be excreted as parent compound. - Advantages: It doesn’t cause CNS depression like ethanol. - Dose: 15mg/kg. Methyl Alcohol [Methanol] “Wood alcohol” Alcohol Treatment: Folinic acid (leucovorin) and folic acid: - For conversion of formic acid to Co2 & H20. -Dose: 50mg/4hrs IV.  Symptomatic: Metabolic acidosis: NaHCo3 Hypoglycaemia: 10-50% dextrose solution IV. Hypothermia: Warming the pateint. Shock : fluid expansion and dobutamine. Convulsions: Diazepam.