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Uses 1- Ingredient for many tinctures, elixirs, spirits 2- Cosmetic industry: perfumes, aftershaves, colognes 3- Solvent 4- Antidote 5- Wide recreational (prohibited in Libya) use - Beers 3-6% - Wines 10-12% - Distilled beverages (Whisky, Vodka..) 20-60%
Absorption: 20% stomach &80% upper small intestine. GASTRIC EMPTYING • INCREASED • Tolerance to the alcohol. • Gastrectomy. • Type of beverage. • DECEASED • Presence of food in the stomach (milk & carbohydrates). • Drugs (e.g. atropine). • Emotional state. • Solutions with concentrations above 20% are absorbed slowly , inhibit gastric peristalsis and cause pylorospasm.
Blood Concentration • Alcohol in blood can be detected after 5 min • Maximum concentration within 30-90 min. • One unit alcohol increases blood level in females more than that in males because of: • Smaller body mass in women • Higher fats & lesser fluids in the body. • Diminished “first-pass” metabolism of alcohol in the gastric mucosa because of lesser alcohol dehydrogenase
Bioavailability Destroyed in gut Not absorbed Destroyed by gut wall Destroyed by liver Dose to systemic circulation
Peak blood ethanol concentrations develop more slowly after rapid ingestion due to the irritant properties of ethanol. • Little difference in rate of absorption of the same dose of ethanol administered in the form of different alcoholic beverages. • This is important for forensic considerations, i.e., blood ethanol concentration is not significantly influenced by the type of alcoholic beverage consumed.
Distribution & Equilibrium • Alcohol enters various organs of the body as well as spinal fluid, urine, and pulmonary alveolar air, etc. • Alcohol is distributed in body water. Tissues rich in water take up more alcohol than those rich in fat do. • Equilibrium between tissues and blood takes place within 1-2 hours. Elimination • About 10% of alcohol are excreted as such mainly through urine and breath and only negligible amount in sweat and faeces.
Metabolism in the liver First Step 1- About 90% of the ingested alcohol are oxidized in the cytoplasm by alcohol dehydrogenase. 2- Catalase system: peroxisomes & mitochondria. 3- Microsomal ethanol-oxidizing system: smaller amount of alcohol is converted to acetaldehyde. Second step metabolism of acetaldehyde, which is converted to acetate by the effect of aldehydedehydrogenaseand the presence of NAD as cofactor. Ethanol Acetaldehyde acetate H2O + CO2
Acetaldehyde might be responsible for alcohol intoxication and addiction: • Flushers (Chinese & some other Asians) differ from other non-flushers in that addiction is lesser among them but this not a fact as American Indians are more alcoholic than other ethnic groups. • Acetaldehyde combines with norepinephrine, epinephrine, and serotonin to make substances similar in structures to plant alkaloids that cause addiction such as morphine.
Metabolic adaptation (Tolerance) • Besides CNS adaptation, alcoholics (in the absence of liver disease) often have an increased rate of blood alcohol clearance. • This is called metabolic tolerance Suggested mechanisms include: • Induction of ADH. • Increased reoxidation of NADH • Induction of CYP2E1 (the most active cytochrome P450 for oxidizing ethanol). Clearance: rate of chemical elimination from the body per unit of time.
Blood Alcohol Curve • Alcohol concentration rises steeply to a distinct maximum (absorption phase). Peak concentration is reached after 30-90 minutes (average 60 minutes). • Irregularly curved fall due to a period of diffusion within the tissues to equilibrium (15-30 minutes). • The BAC then falls progressively in linear fasion (elimination phase).
Blood Alcohol Curve Fluctuations due to metabolism 30-90 min15-30 min (Diffusion) Absorption Elimination
Time of consumption Type of alcoholic beverage Presence of food in stomach Factors that Affect Alcohol Absorption
Alcohol is an example of Zero-order kinetics Zero-order reaction First-order reaction The reaction proceeds at a rate that is dependent on the concentration dA/dt = KA1 • The reaction proceeds at a constant rate and is independent of the concentration . dA/dt = KA0
10000 Zero Order Elimination 1000 Plasma Concentration 100 10 1 0 1 2 3 4 5 6 Time logCt = logCo - Kel . t 2.303
Forensic Significance of Zero-order kinetics • The rate of elimination of ethanol is 15-20 mg/dl/hour • At very high concentrations >200mg% over 12 hours are required to eliminate 200mg%.
Limits of blood alcohol content (BAC) • In Libya, alcohol is prohibited. • The alcohol level at which a person is considered to be legally impaired varies by country. • The list below gives limits by country. These are typically BAC limits for the operation of a vehicle.
Criminal Code of Canada reports legal limit for ethanol as 80 milligrams per 100 millilitres of blood (80 mg%). • Also expressed as 0.08 g/100 ml blood. Serum/Plasma versus Whole Blood Serum contains more alcohol than whole blood by a factor of 1.12:1. Serum level 112 mg% = 100 mg% in whole blood.
Mode of Action • Direct effect by its lipid solubility, interacts with membrane lipoproteins. 1- Depression of CNS. • Releasing inhibition: euphoric effect. • Acts on the frontal lobe, psychic area, cerebellum, spinal cord, and finally the medulla. • Inhibits (1) higher nervous centers (control conduct & judgment), (2) motor centers (3) the vital organs. • The effect on the spinal cord leads to initial increase in deep tendon reflexes.
Reward Brain System Alcohol ↑ dopamine transmission → Pleasurable effects
Movement: Slower, Inaccurate, Random • Impairment of mental function: • interfering with the speed of perception • Interfering with the mental processing slower learning, decreased focusing, concentration, judgment, discrimination, and thinking. 2- Acid-base disturbances: HIGH ANION GAP METABOLIC ACIDOSIS 3- Hypoglycemia (or hyperglycemia). Hypoglycemia most common. 4- Hypothermia
CLINICAL MANIFESTATIONS Phase I: Excitation (50-150 mg/100ml) • Excitement, euphoria, and increased confidence • Talkative and argues on every point • Inhibition of self-control. • Face is flushed and the conjunctiva is injected • Pupils are dilated with sluggish light and accommodation reactions. • Judgment is impaired while mental alertness can be retained.
Phase II: Incoordination (Confusion) BAC up to 300mg/100ml. • Important for medicolegal purposes • Incoordination of thought, speech, and action • Pupils are dilated and react sluggishly to light and accommodation • Sense of perceptions and skilled movements are affected • Ataxia. • There may be hangover due to brain edema, toxic effects of alcohol on the brain, GIT, and liver.
Phase III: Coma (Narcosis) BAC is more than 300mg/100ml. • Motor and sensory cells are deeply affected. • Speech becomes thick and slurring • Incoordination is more marked the person staggers and falls • Gradually, he enters into coma and cannot be awakened by deep stimuli and reflexes are abolished. • Pupils may be constricted.
Clinical Diagnosis Serum level (mg/100ml) = Osmolar gap x 4.6
Analysis of BAC • Breath Tests • Field Sobriety Tests • Blood Tests
Infrared Breath Test uses infrared wavelengths to test for alcohol or other interferences in the breath Fuel Cell Test converts fuel (alcohol) and oxygen into a measurable electric current Other breath testsInfrared and Fuel Cell Breath Tests
Field Sobriety Tests • Horizontal Gaze Nystagmus • Involuntary eye jerk as eye moves horizontally • Walk and Turn (divided attention tasks) • One-Leg Stand
Collection and preservation of blood • Use nonalcoholic disinfectant like • Povidone-iodine (Betadine) • Benzalkonium chloride (Zepiran) • Mercuric chloride • Stored in airtight container with anticoagulant and preservative under refrigeration
Pathological Alcohol intoxication (mania a potu) • Rare • Extraordinary severe response • Marked by apparently senseless violent behavior, usually followed by exhaustion, sleep and amnesia for the episode. • It is used by criminals to form legal defense against their criminal activities.
TREATMENT • ABC: IV dextrose & 100 mg of thiamine. • Gastric lavage in noncomatose patients, if the patient comes early after the ingestion. The lavage should be done, at the beginning, with plain water, from which a sample should be sent for chemical analysis. The next wash will be done by NaHCO3. This will prevent further absorption and help for acidosis.
Maintain body temperature, especially in cold weather. • Others causes of coma should be excluded. • Treat acidosis if ABG results show low pH. • Hemodialysis or hemoperfusion may be considered in severe cases.
CHRONIC ALCOHOLISM • Daily use of large amounts of alcohol for adequate functioning. • Regular heavy drinking limited to weekends. • Long periods of sobriety interspersed with binges of heavy alcohol intake lasting for weeks or months.
CHRONIC ALCOHOLISM • Associated behaviors as: • Inability to stop drinking: Repeated efforts to control or reduce excessive drinking or restricting drinking to certain times • Binges (remaining intoxicated for at least 2 days). • The continuation of drinking despite a Binges. • Amnestic periods for events while intoxicated (blackouts). • The continuation of drinking despite a serious physical disorder that the person knows is exacerbated by alcohol use. • The drinking of nonbeverage alcohol such as fuel. • Impaired social and occupational functioning
Complications of Alcohol Withdrawal 1- Withdrawal Seizures 2- Impending delirium Tremens: common alcohol withdrawal syndrome. Mild to moderate agitation, tremor, insomnia, loss of blood pressure control. Acute alcoholic hallucinations, with auditory hallucinations. Generalized tremor the most is the most obvious feature of the illness. 3- Delirium Tremens • Most severe form of withdrawal syndrome. • A medical emergency. • Due to severe cortical and brainstem hyperexcitability, cerebral edema, and increased pressure of CSF. • Onset follows 3-5 days after cessation of drinking. • Mortality is 20% if untreated, usually as a result of an intercurrent medical illness such as pneumonia, renal disease, hepatic insufficiency, pancreatitis, or heart failure.
Forensic Considerations • Time lag from consumption to peak level determined by factors affecting absorption. • Ethanol elimination rates; genetic, sex, age, Wt. • Partition ratio: differences between blood, breath, and urine ratios. • Fluctuations and anomalies: factors that change in blood levels of alcohol due to changes in absorption and elimination.
Postmortem appearance • External: congestion of conjunctiva, odor of alcohol around mouth and nose. • Internal: congestion of GIT, pulmonary and cerebral edema, congestion of other viscera. • In chronic alcoholism there may be additional features: • Fatty or cirrhotic liver • Degenerative changes in the brain.
Also called wood alcohol obtained by destructive distillation of wood. • Widely used as solvent and found in paint, varnish • Used as Antifreeze • Surgical spirit: Ethanol & Methanol.
Methanol Uses • Gas Line Antifreeze 100% • Windshield washer fluid 30% • Varnish removers • Fuel for food warming 3-70% • Industrial uses
Mechanism of toxicity • Methanol is slowlymetabolized by ADH to formaldehyde and subsequently by aldehyde dehydrogenase to formic acid (formate). • Systemic acidosis is caused by the formic acid as well as by lactic acid, while blindness is caused primarily by formate. • Both ethanol and methanol compete for the enzyme alcohol dehydrogenase; the preference of this enzyme for metabolizing ethanol forms the basis for ethanol therapy in methanol poisonings
