Pharmacology of Alcohol

Pharmacology of ethyl alcohol

1. Local action: Rubefacient, counterirritant, astringent. Injection s.c: pain, inflammation, necrosis, fibrosis. 70% alcohol is Antiseptic [100% <>

2. CNS Actions of alcohol

Neuronal depressant [¯doses à excitation]. Cortex & Reticular Activating System most sensitive. 30 mg – 100 mg/dL: excitation, euphoria, hesitation, caution, self criticism, restraint are lost and mood altered. 100-150 mg/dL: mental clouding, impaired memory, Disorganization of thought, alteration of perception and drowsiness. 150-200mg/dL: sloppy, ataxic, drunk. 200-300 mg/dL: stupor, unconsciousness, anesthesia of low safety margin, medullary paralysis, death. Effects increases when blood concentration is rising than falling.

Hypnotic: poor quality of sleep, early awakening, more sleep apnoea and altered sleep architecture.

Analgesic: raises pain threshold & reaction to pain

Anticonvulsant: initially ­ threshold & then lowers it May precipitate seizures in epileptics

3. CVS: Small doses: cutaneous vasodialation [flushing]. Moderate doses: mild tachycardia, increases BP. Chronic doses: cardiomyopathy, arrhythmia.

High doses: vasomotor centre depression

4. Blood: Regular intake in small doses: ­HDL & ¯LDL

5. Body Temp: Warmth; Combat cold, High doses: depress temp regulating

6. Respiration: Transient stimulant; High doses: medullary depression

7. GIT: Dilute alcohol (10%): decreases secretion; Increase Concentration: opposite

action

8. Liver: Increase, mobilises peripheral fat; lipid peroxidation, glutathione depletion,

Alcohol+ poor nutrition causes cirrhosis

9. Skeletal muscles: Chronic alcoholism: myopathy

10. Kidney: Inhibits ADH: diuresis; no effect on renal function

11. Sex: Aggressive, but impaired sexual act

12. Endocrine: Moderate: increases Adr release à increases blood sugar. Acute

intake: decreases hepatic glycogen à decreases blood sugar

13. Uterine contractions: Suppressed on moderate levels in blood

Mechanism of action of Alcohol [several theories proposed]

1. Alters membrane lipids

2. Operates on multi-receptor mediated ion channels

3. Promotes GABA-a receptor mediated synaptic inhibition through Cl- channel opening.

4. Inhibits NMDA excitatory amino acid receptors operating via cation channels

5. Decreases neurotransmitter release by inhibiting voltage sensitive neuronal Ca channels

6. Blocks adenosine uptake: synaptic depression

7. Enhanced turnover of NA in brain: causes pleasure and dependence

Kinetics of Alcohol;

Absorption varies with 1. Concentration, Presence of food 2. Gastric emptying

Fast absorption from intestines. High Volume of distribution = 0.7 L/Kg . Crosses placenta freely; 98% oxidised in liver

Zero order kinetics: Constant amount [8 – 12 ml] metabolised per hour irrespective of blood concentration. Eliminated via kidney & lungs [lung = 0.05% blood concentration]

Drug ineraction with alcohol

Synergy with tranquilisers, antidepressants, hypnotics, antihistaminics, opioids à CNS depression, accidents. Chlorpropamide, some cephalosporins, metronidzole à disulfiram reaction. Insulin + sulfonylureas à hypoglycemia. Aspirin à gastric bleeding. Increases paracetamol toxicity due to enhanced production of toxic metabolite

Contra indications for alcohol

1. Peptic ulcer, hyperacidity and reflux esophagitis

2. Epileptics

3. Liver disease

4. Pregnancy: Fetal Alcohol Syndrome: growth retardation, low IQ, and body weight

5. Unstable personality: susceptible to alcoholism

Empty Calories: 7 Cal /g; no body building nutrients, micronutrients & alcoholics suffer from malnutrition

Clinical uses of alcohol

1. Antiseptic

2. Rubefacient, Counterirritant

3. Rubbed on skin prevents bedsores

4. s.c injection for trigeminal neuralgia

5. Appetite stimulant

6. Methanol Antidote

7. Intranasal drops as stimulant for fainting

Chronic toxicity

Tolerance, physical dependence, malnutrition, cirrhosis, hypertension, CHF, Cardiomyopathy

Disulfiram

Inhibits aldehyde dehydrogenase leading to increase acetaldehyde level

Aldehyde syndrome: flushing, burning, throbbing headache, perspiration, uneasiness, tightness in chest, dizziness, vomiting, visual disturbances, mental confusion, postural fainting, circulatory collapse

Aversion technique

Category: Pharmacology Notes