ALCOHOL
Alcohol is a substance which is not much important for its therapeutic use but extremely important for its worldwide use/abuse and a lot of controversies.
- Used since ancient time.
- Alcohols are the hydroxy derivatives of aliphatic hydrocarbons, i.e.
- – CH3OH: Methyl alcohol
- – C2H5OH: Ethyl alcohol
- Production of alcohols require sugar, water, yeast, and warm atmosphere.
- Ethyl alcohol (alcohol in general) is a mono-hydroxy alcohol manufactured by fermentation of sugars (any high carbohydrate content substance, i.e. grapes, grains, etc.)
- It is a colorless, volatile, inflammable liquid. The ethanol content of various alcoholic beverages ranges from 4–55%.
- For industrial use: It is chiefly manufactured by organic synthesis from ethylene.
Ethanol (Ethyl Alcohol)
- It has limited therapeutic value
- Alcohol abuse (chronic alcoholism) and major socioeconomics are the major diseases (not intoxication).
- Alcohol drinkers can be divided into:
- Social drinkers
- Social heavy drinkers (about 50% intoxicated)
- Alcoholics (habitual drinkers)
BEVERAGE: Liquor for drinking
- Absolute alcohol: 99% w/w ethanol (dehydrated alcohol)
- Rectified spirit: 90% w/w ethanol
- Proof spirit: Old term, [gun powder + whisky] ignited
- – Explodes: Proof strength
- – If not explodes: water is present (diluted)
- 100% proof spirit: 49.29% v/v or 57.1% w/w alcohol.
- Wines
- Light wines: (9–12% alcohol)—Claret, Cider, etc.
- Fortified wines: (16–22% alcohol)—Distilled alcohol added port and sherry.
- Effervescent wines: (12–16% alcohol)—Champagne [bottled before complete fermentation]
- Spirit: Distilled after fermentation, i.e. Rum, Gin, Whisky, Brandy, Vodka, etc.
- Blood alcohol concentration and clinical effect50–100 mg/dL: Sedation, Euphoria, increased retention time100–200 mg/dL: Ataxia/impaired motor functions, slurred speech impaired short term memory.200–300 mg/dL: Emesis/Staper200–400 mg/dL: Coma> 500 mg/dL: Respiratory depression and death
- In USA Adult blood level of 80–100 mg/dL, permitted for driving. (See Fig. 11.1.1)
Pharmacokinetics
- Alcohol (C2H5OH), is water soluble and is rapidly/completely absorbed (80% from the small Intestine).
- Absorption increases in empty stomach, while decreases with food and with other factors.
- After drinking, it can be detected in blood within 5 minutes.
- Its maximum absorption occurs within 30 to 60 minutes. Time varies from person to person.
- Peak plasma concentration attain within 2 hours.
- Distribution occurs throughout the body. Early equilibrium is achieved at that part (organ) of the body with high blood flow, i.e. lung, liver, kidney and brain.
Test for drunk
- Expiratory air concentration × 2000 = Blood concentration
- Urine concentration × 77 = Blood concentration.
- 100 mg% = legally drunk
- Metabolism: Alcohol is metabolized in the liver (>90%) by oxidation. First by alcohol dehydrogenase to acetaldehyde, then by aldehyde dehydrogenase to acetate. About 25% of the acetaldehyde is metabolised extrahepatically (Fig. 11.1.2).
Metabolism of alcohol follows zero order kinetics : a constant amount is metabolized per unit time, i. e. about 10 ml absolute alcohol is metabolized per hour. It is excreted through kidneys and lungs.
- Small amounts of ethanol are excreted in urine and expired air. Hepatic metabolism shows saturation kinetics, mainly because of limited availability of NAD+. Maximal rate ethanol metabolism is about 10 ml/hour.Thus, plasma concentration falls linearly rather than exponentially.
- Acetaldehyde may produce toxic effects. Inhibition of aldehyde dehyrogenase by disulifram accentuates nausea discomfort, etc. caused by acetaldehyde, and can be used in aversion therapy.
- Methanol is similarly metabolized to formic acid, which is toxic, especially to retina.
- Asian races show a high rate of genetic polymorphism of alcohol and aldehyde dehydrogenase, associated with alcoholism and alcohol intolerance, respectively.
Mechanism of Action
- Alcohol is amphophilic, i.e. both hydrophilic and lipophilic, and therefore can dissolved in neural plasma membrane. The mechanism is equivalent to many volatile anesthetic agent, i.e. produces membrane fluidizing effect. Therefore,
- It hampers the movements of Na+ and Ca++, while movement of Cl−, specifically stimulation by GABA is increased.
Actions
- Local: On topical application, ethanol evaporates quickly and has a cooling effect. It is an astringent, i.e. precipitates surface proteins and hardens the skin. 40–50% alcohol is rubefacient and counter irritant. Alcohol is also an antiseptic. At 70% it has maximum antiseptic properties (kills > 90% surface bacteria) which decrease above that. It is not effective against spores. Isopropyl alcohol is 60–70% more effective)Injection around nerve causes neuritis followed by nerve degeneration.
- CNS: Alcohol is a CNS depressant. Small doses cause euphoria, relief of anxiety and loss of social inhibitions. Moderate doses impair muscular coordination and visual acuity making driving dangerous. (Fig. 11.1.1) With higher doses mental clouding, impaired judgment, drowsiness and loss of self control result. High doses cause stupor and coma. Death is due to respiratory depression. Alcohol may precipitate convulsions in epileptics. Tolerance develops on long-term use. Chronic ingestion results into neurological disorders, i.e.
- Wernick's encephalopathy (vit. B1 deficiency, mental confusion, ataxia, polyneuropathy, etc)
- Korsakoffs Psychosis (learning and memory disability)
- Sleep disorders.
- If CNS there occur increase in GABA mediated inhibition, similar to the action of BDZ.
- Inhibition of Ca++ entery through voltage gated calcium channels.
- Inhibition of NMDA receptor functions.
- Therefore flumazenil reverse the central depressant action of ethanol.
- CVS: The actions are dose dependent. Small doses cause Cutaneous vasodilatation resulting in flushing and feeling of warmth. Large (moderate) doses cause rise in HDL (High density Lipoprotein) level, depression of myocardium (fall in contractility). Intake in higher (chronic) dose causes development of CCF [congestive cardiac failure] or other Cardiomyopathy, Hypertension and Arrhythmia (death).
- GIT and liver: Alcohol is an irritant (produces Gastritis); increase gastric acid secretion and produces vasodilatation and warmth.
- It causes deficiency of water soluble vitamins and may induces pancreatitis. It is an appetizer in small amount.
- Chronic consumption of moderate amount of alcohol results in peptic ulcer, hepatitis.
- Accumulation of fat in the liver, liver enlargement, followed by fatty degeneration and cirrhosis. Alcohol also induces microsomal enzymes. It may causes alcoholic cirrhosis.
- Endocrine: Though alcohol is called an aphrodisiac (Increases aggressive sex behavior) this effect could be due to loss of inhibition, i.e. (inhibition of control) but ultimately it causes:
- Testicular atrophy
- Gynecomastia and
- Impotence/sterility on long-term consumption.
- Musculoskeletal: It impairs psychomotor performance and blunt the Reflex motor activity (muscle relaxation). Even previously used as an Uterine relaxant (in premature labor).
- In pregnant females: It crosses placenta easily. It produces teratogenic effect called as Fetal Alcohol Syndrome, which is characterized by microcephaly, deficient growth (IUGR) short palpebral fissure, wide eyes, small cheek bone, mental retardation ← hyperactivity + presence of anatomical abnormality.
Other effects
Low doses taken over a long time increases HDL and lowers LDL cholesterol. Alcohol is a diuretic (↓ ADH secretion). It interferes with folate metabolism and may cause megaloblastic anemia. Though it causes a feeling of warmth, heat loss is increased due to vasodilatation and should not be used for ‘warming up’ in cold surroundings. Food value is 7 calories/gram. It may stimulate respiration.
Uses
- Sponging on body surface for decreasing body temperature.
- It acts as an Antiseptic/disinfectant, if 70% alcohol is applied topically.
- Bed sores (decubitus ulcer): when rubbed onto the skin, alcohol hardens the skin and prevents bed sores.
- As anhydrotic lotion: to reduce sweating.
- Appetite stimulant: About 50 ml of 6–10% alcohol given before meals is an appetite stimulant.
- Neuralgias: In sever neuralgias like trigeminal neuralgia, injection of alcohol around the nerve cause permanent loss of transmission and relieves pain.
- As an solvent or vehicle for injecting medicinal mixture.
- Bramptons mixture: It is the mixture of alcohol, opioid and or phenothiazine used sometimes to relieve pain of terminal illness.
- In methanol or ethyl glycol poisoning.
- Rarely used to treat premature labor: Its 10% solution suppresses the uterine contraction by reducing the release of oxytocin.
Drug interactions
- Alcohol potentates other CNS depressants including hypnotics, opioids and anti-psychotics.
- Sulfonylureas, (chlorpropamide) metronidazole, griseofulvin and certain cephalosporins have disulfiram like effects on alcohol consumption.
- Alcohol is an enzyme inducers.
- Alcohol with NSAIDS ® more GIT bleeding.
- Alcohol + Insulin or sulfonylurea ® - hypoglycemia
Acute alcoholic intoxication: It causes severe gastritis, hypotension, hypoglycemia, hypothermia, disturbed sensorial, hypostatic pneumonia, increased intracranial pressure, respiratory depression, coma and death.
Treatment
- Measures include gastric lavage, airway maintenance, positive pressure ventilation and maintenance of fluid and electrolyte balance.
- Maintenance of BP, Temperature and Hemodialysis is needed in severe intoxication.
- Administration of hypertonic mannitol IV.
- Phenothiazine/butryphenon is administered to control psychotic behavior.
- Analeptics are not recommended (produces convulsions).
Chronic alcoholism causes
- Both tolerance and dependence are due to increased metabolism and neuronal receptor adaptation.
- Withdrawl symptoms:
- – Stage I: Nausea, vomiting, sweating, tremors and hyperactivity
- – Stage II: Auditory and visual hallucination.
- – Stage III: Delirium, tremors, confusion, disorientation, autonomic hyperactivity and other systemic toxicity and later on.
- Wernicke's encephalopathy, Korsakoff's psychosis, tremors, cirrhosis of liver, hypertension and cardiomyopathy can occur.
- In addition, nutritional deficiencies such as polyneuritis, anemia and pellagra can occur. In pregnant women, alcohol is teratogenic. Even moderate drinking during pregnancy can produce fetal alcohol syndrome with manifestations like low IQ, microcephaly, growth retardation and facial anomalies. It can also cause stillbirths and abortions.
Treatment
- Multivitamin tablet/capsule (specially vitamin B6).
- Treatment of acidosis
- Benzodiazapine (DOC) for supporting withdrawal symptoms.
- Using Disulfiram (Tetraethyl thiuram disulfide): discussed below.
- Using Naltrexone (opioid antagonists): It reduces alcohol consumption and craving probably by inhibiting dopaminergic pathway in the brain which is critical for reward phenomenon.
- Daidzine: It is a Chinese herbal medicine and is a specific inhibitor of ALDH-1
- Nalmefene: It has better oral bioavailability, less hepatotoxic and longer duration of action as compared to naltrexone.
- Using Acamproste: It GABA analog and NMDA antagonist. It reduces neuronal hyper-excitability and inhibit alcohol craving.
- Using Fluoxetine
- Psychiatric counseling: for complete abstinence from alcohol.
- Supportive management.
- Including symptomatic treatment, i.e T/t with β-blockers, clonidine, etc.
Disulfiram
- Disulfiram inhibits the enzyme aldehyde dehydrogenase. (Fig. 11.1.2) If alcohol is consumed after taking disulfiram, acetaldehyde accumulates and within few minutes it can produce flushing, throbbing headache, nausea, vomiting, sweating, hypo →← tension and confusion called the ant abuse reaction, due to accumulation of acetaldehyde. The effect lasts for 7–14 days after stopping disulfiram. The reaction can sometimes be very severe and therefore treatment should be given in a hospital.
- Other drugs that cause ant-abuse reaction are metronidazole, chlorpropamide, tolbutamide, griseofulvin, cephalosporins and phenyl-butazone.
- Contraindications: Patients with liver disease, patients physically dependant on alcohol.
METHYL ALCOHOL (Methanol, wood Alcohol). Methanol is used to denature ethyl alcohol, Ingestion results in methanol poisoning.
Toxic effects are due to formic acid. Manifestations are vomiting, headache, vertigo, severe abdominal pain, hypotension, delirium, acidosis and coma. Formic acid has affinity for optic nerve and causes retinal damage resulting in blindness. Death is due to respiratory failure.
Treatment
Correction of acidosis: As acidosis hastens retinal damage, immediate correction of acidosis with IV sodium bicarbonate infusion helps in preventing blindness, i.e. NaHCO3 infusion (3 gm/hr) until pH riches up to 7.5
- Patient should be kept in a dark room to protect the eyes from light.
- Induction of vomiting.
- Gastric lavage should be given.
- Multivitamins tablets specially Vitamin B should started.
- Ethyl alcohol (Ethanol): Ethyl alcohol is given as infusion or 25 ml 50%, 3 hourly till the acidosis is controlled. It competes with methanol for alcohol dehydrogenase, slows the metabolism of methanol and thus prevents the formation of toxic metabolites.
- Fomepizole: 4 methyl pyrazole, is the specific antidote. It also inhibits alcohol dehydrogenase so as to prevent formation of toxic metabolite.
- Folinic acid: It may protect ocular toxicity by increasing format metabolism.
- BP and ventilation should be maintained (Positive pressure ventilation).
- Diuretics/Dialysis
- Supportive management.