12.Sedatives and hypnotics

Barbiturates

• Definition: Barbiturates are white crystalline substances with a bitter taste. They are derivatives of barbituric acid.

Classification of Barbiturates

1. Long Acting (Duration: -24 hrs)

   • Examples: Barbitone, Phenobarbitone, Methyl phenobarbitone, Butobarbitone

2. Intermediate Acting (Duration: 3-6 hrs)

   • Examples: Amylobarbitone, Allobarbitone

3. Short Acting (Duration: <3 hrs)

   • Examples: Cyclobarbitone, Hexabarbitone, Pentobarbitone

4. Ultra Short Acting (Duration: 5-10 minutes)

   • Examples: Pentothal sodium (thiopentone sodium), Methohexobarbitone

Pharmacokinetics

• Absorption: Rapidly absorbed from the gastrointestinal tract; faster with alcohol.

• Administration: Immediate onset with intravenous (i.v.) or intramuscular (i.m.) administration.

• Distribution: Concentrated in the liver, brain, and kidneys. Metabolized in the liver to mostly inactive, water-soluble metabolites.

• Excretion: A small amount excreted unchanged in urine.

Mechanism of Action

• CNS Effects: Depresses central nervous system (CNS) activity.

• GABA Interaction: Acts at GABA receptors, increasing chloride ion channel duration, enhancing inhibitory effects.

• Nerve Transmission: At high concentrations, increases chloride conductance and inhibits neurotransmitter release.

• Cell Excitability: Decreases excitability of CNS cells; large doses can depress respiratory and vasomotor centers.

Physiological Effects

• Metabolism: Basal metabolism and intestinal mobility reduced; inhibits diuresis.

• Synergistic Action: Has enhanced effects when combined with alcohol.

Signs and Symptoms of Barbiturate Intoxication

• CNS:

  • Drowsiness, confusion, ataxia, slurred speech, headache, excitement.

  • May progress to stupor, deep coma, unresponsive to pain, and a positive Babinski's sign.

  • Pupil reaction alters from constricted to dilated and non-reactive.

• Respiratory System:

  • Respiratory depression leading to shallow, labored breathing; Cheyne-Stokes respiration may occur.

  • Risk of hypostatic pneumonia after prolonged survival.

• Cardiovascular System (CVS):

  • Decreased cardiac output, increased capillary permeability, potential for cardiovascular collapse; possible cyanosis and hypotension.

  • ECG may show slow waves during severe intoxication.

• Skin:

  • Blisters may appear due to toxic effects on the epidermis and tissue anoxia(anoxic bullae), especially at pressure points.

  • Affects areas like axilla, inter-digital clefts, inner aspects of knees and buttocks.

  • Associated Conditions:

    • Leucopenia and thrombocytopenia may occur.

    • Body temperature is reduced; peristaltic movements decreased.

    • Death primarily due to respiratory paralysis; faster with higher doses.

Dosage Information:

• Short Acting: Fatal Dose 1-2g; Treatment 2-3g

• Medium Acting: 3-5g; Blood level 7 mg%

• Long Acting: Fatal Dose 10g; Blood level 10 mg%

Fatal Period

• Generally: 1-2 days; massive doses can lead to death within hours.

Management & Treatment

1. Maintain airway and provide adequate respiratory support.

2. Administer artificial respiration and oxygen to prevent hypoxia.

3. Conduct stomach wash with 1:1000 KMnO4 if conscious; endotracheal intubation if unconscious.

4. Give activated charcoal.

5. Prophylactic antibiotics to prevent pneumonia.

6. Administer intravenous fluids for fluid and electrolyte balance.

   • The above 6 methods are called Scandinavian method

7. Implement Forced Alkaline Diuresis for drugs like phenobarbitone.

   • Alkalinisation of urine with sodium bicarbonate; maintain urinary pH 7.5-8.

8. Consider hemodialysis.

9. Exchange transfusion may be life-saving.

10. Provide symptomatic treatment as necessary.

Postmortem Findings

• Rapid Death: Generalized congestion of internal organs, edema of lungs and brain.

• Delayed Death: Bullous lesions, pneumonic consolidation, softening of corpus callosum, globus pallidus, and cerebral focal areas.

Circumstances of Poisoning

• Chronic Poisoning: Frequent in suicidal attempts; rare in homicide.

• Accidental Poisoning: Can arise from 'drug automatism'.

Chronic Barbiturate Poisoning

• Addiction Potential: Psychological and physical dependence with tolerance, which resolves within 2-3 days post-withdrawal.

• Resembles symptoms of chronic alcoholism:

  • Memory loss, dysarthria, ataxia, depression, Parkinsonian tremors, impaired intellectual function and behavior.

• Withdrawal Symptoms appear within a day and may persist for 2 weeks: anxiety, nausea, vomiting, tremors, restlessness, hypotension, potential convulsions.