Barbiturates

Nature

Barbiturates are hypnotics and sedatives. The number of these substances has increased tremendously in recent years. They are derivatives of barbituric acid. They are white, odourless and slightly bitter in taste. Fatal poisoning occurs due to excessive doses. They are frequently met with in suicides cases but may also occur in homicidal cases. They are given when the victim is drunk. Accidental poisoning is rare.

Classification

The barbiturates are classified according to the time they take to act on the body. They are-

1. Long – Acting Barbiturates– The action of these barbiturates usually commences after an hour or more and lasts for 6 to 10 hours.

Examples are- Barbitone, Pheno-barbitone, Methyl Phenobarbitone etc. Commercially, the products are known as medinal, veronal, Gardenal, Luminol, Somonal, Prominal etc.

2. Intermediate Acting Barbiturates– The action of these barbiturates starts in about 30 minutes and their effect lasts for 5 to 6 hours. They are less likely to leave the patient sleepy the next day than the long-acting barbiturates. Therefore, they are widely used against insomnia.

Examples are- Allobarbitore, Butobarbitone and Amylobarbitone. Their commercial names are Dial, Amytal and Soneryl.

3. Short Acting Barbiturate– They are effective within 15 minutes and their action lasts for 2 to 3 hours only. They are specially suited for people who have difficulty in going to sleep.

Examples are- Cyclobarbitone and pentobarbitone. Commercial names are Phenedran, Cyclonal, Nembutal, Seconal.

4. Ultra Short Acting Barbiturate– These type of barbiturates are used as rapidly acting anaesthetics. They are given alone or in combination with inhalation anaesthetics.

Fatal Dose

• For Short-acting – 1 to 2 g.
• For Medium-acting- 2 to 3 g.
• For Long-acting – 3 to 5 g.
• For phenobarbitone it is 6–10 gm

The lethal blood levels are-

• For Long-acting – 10 mg. per 100 ml.
• For Medium-acting: 7mg. per 100 ml.
• For Short-acting: 3 mg. per 100 ml.

Fatal Period

• One to two days.

Absorption, Metabolism and Elimination

► Barbiturates are rapidly absorbed through the gastrointestinal tract including the rectum or from the intravenous route. They are concentrated in the liver for a short time, and then evenly distributed widely in the body fluids and tissues.

► Metabolism occurs in liver by oxidation resulting in formation of alcohols, ketones, phenols and carboxylic acid.

► These are excreted in urine as such or in the form of glucuronic acid conjugates.

► Some percentage of long-acting barbiturates like phenobarbitone is excreted in the urine as such.

Sign and Symptoms

For Acute Poisoning symptoms are-

• Drowsiness
• A short period of confusion
• Excitement
• Delirium
• Hallucinations
• Ataxia
• Vertigo
• slurred speech
• Headache
• Paraesthesias
• Subjective visual disturbances
• A stupor progressing to deep coma.
• Loss of superficial and deep reflexes.
• Gradual loss of response to painful stimuli.
• The Babinski toe sign may occur.
• Rapid and shallow Respirations.
• Fall in cardiac output
• Increase in capillary permeability leading to an increase in the extracellular fluid.
• Cardiovascular collapse
• Cyanosis,
• Hypotension
• Weak rapid pulse
• Cold clammy skin
• Dialtated pupil
• Decreased peristalsis may occur in deeply comatose patient and tends to be a bad prognostic sign.
• The urine may be scanty or suppressed and may contain sugar, albumen and haematoporphyrin.
• Incontinence of urine and faeces.
• The body temperature is usually reduced
• Fever indicates bronchopneumonia.
• Respirations become irregular.
• Blisters on the skin and also on an area of erythema which is strongly suggest barbiturate poisoning. (Blisters contain transparent serous fluid. Rupture of a blister initially shows a red, raw surface which later dries to a brown parchment-like area. They are commonly found in the sites where pressure has been exerted between two skin surfaces, such as the interdigital clefts and inner aspects of the knees, buttocks, backs of thighs, calves and forearms.)
• An entire side of a forearm or a thigh is blistered. Blisters occur in about 6% of cases, and are believed to be due to a direct toxic action on the epidermis.
• The coma may continue for a few hours to a few days and the patient then makes a gradual recovery. During recovery symptoms are as follows- Nystagmus, Diplopia.
• Temporary failure of accommodation.
• Death may occur due to respiratory failure or ventricular fibrillation in early stages.
• In the later stage Bronchopneumonia or irreversible anoxia with pulmonary oedemamay occur.
• The combination of alcohol and barbiturates causes rapid death.
• Phenytoin causes gingival hyperplasia in chronic therapy.
• Patients who have taken an overdose of phenobarbitone may remain unconscious for a prolonged period of time, but they tend to remain at a somewhat safer level of unconsciousness than patients who have taken a large overdosage of shortacting barbiturate.
• severe shock or respiratory failure are more common and more serious with medium and short -acting barbiturates.

For Chronic Poisoning symptoms are as follows-

• Poor judgement
• Loss of memory
• Skin eruption (cutaneous bullae)
• Constipation
• Irritability
• Ataxic gait
• Stammering
• Cramps and orthostatic hypotension.

Clinical Features

According to toxicologist Sunshine and Hackett, there are five stages in barbiturate poisoning. They are as follows-

• Awake, competent and normally sedated.
• Sedated, reflex present, prefers sleep, answer questions when aroused, does not cerebrate properly.
• Comatose and reflexes present.
• Comatose and areflexia.
• Comatose with respiratory and circulatory difficulty.

The symptoms of barbiturate poisoning depend on mainly these factors-

• Dose- Higher the dose of barbiturates, severe are the symptoms.
• Short acting barbiturates are more toxic than others classified barbiturates.

Forensic Examination and Detection Test

Colour Test

Dillie-koppanyi Test– Firstly, 1 % mixture of cobalt acetate and methanol is added to the suspected material followed by 5% of isopropylamine in methanol. Then this reagents shows violet-blue in colour which indicate barbiturates

A few drops of Million’s reagent give white precipitate which indicates barbiturates.

Others Test

• Fusion with caustic soda gives ammonia.
• Melting points are characteristics.
• Thin Layer Chromatography gives characteristics R_f value.
• UV and IR Spectrophotometry.
• Gas chromatography.
• High Pressure Liquid Chromatography.

Treatments

● The treatment of barbiturate poisoning is conservative and involves supporting of respiration and circulation. The control of hypothermia is a must. Treatment can be done in following ways:

● Gastric lavage – It should be carried out by with warm water mixed with potassium permanganate within 4 hours of ingestion and may be attempted even up to 8 hours of ingestion.

● Suspension of activated charcoal or tannic acid is very effective.

● Doxapram should be infused.

●Forced alkaline dieresis: It is very useful only in long-acting barbiturates but not in short- and intermediate-acting barbiturates.

● Peritoneal dialysis is also given.

● Hemodialysis is nine times more effective in long-acting barbiturates and six times more effective in short-acting barbiturates.

● Artificial respiration and oxygen is given.

● Scandinavian method’ may be administered.

● Normal saline with 5% glucose should be given in 24 hours.

● Bowels should be evacuated by enema.

● Charcoal haemoperfusion.

● Forced alkaline diuresis is most useful in poisoning by barbiturates which are not protein-bound like phenobarbitone, allobarbitone and barbitone.

● For deep-vein thrombosis and thromboembolism in patients with prolonged coma, mini-heparinisation, elastic stockings, and inflable cuffs are useful.

● Antibiotics to minimise risk of pneumonia.

● Symptomatic treatment.

Postmortem Appearance

• Peripheral cyanosis is seen.
• Barbiturate blisters is present on dependent parts of body.
• Froth may be seen at mouth and nose.
• Erosion or congestion may be seen in stomach and intestine.
• Lungs are intensely congested.
• The fundus may be thickened, granular and haemorrhagic.
• The cardiac and lower oesophagus may be eroded from regurgitation.
• Haemorrhagic blistering and haemorrhagic necrosis of the gastric mucosa may be seen.
• The lungs are congested, oedematous and appear black.
• Petechial haemorrhages may be present in the lungs and on the pleura and pericardium.
• The kidneys show degeneration of the convoluted tubules.

Medicolegal Appearances

►Many cases are reported where doctors or paramedical workers have committed suicide by using short-acting barbiturates along with muscle relaxants.

►Thiopental is used as truth serum to extract confession or secrets during interrogation by inducing a state of hypnosis. The person may tell the truth or reveal crucial links to help investigation. This technique is called Narcoanalysis and is now allowed by courts in India to investigate hardened criminals.

►Accidental poisoning is common in persons using barbiturates as medicines because of tolerance.

►Automatism is reported in chronic barbiturate use as the person may keep on taking medicine by thinking that he has not taken medicine.

►Homicidal poisoning is also reported.

Toxicological Materials

• Stomach contents
• Urine and blood
• Kidney
• Brain
• Liver

References

1. Dr. K.S. Narayan Reddy. The essential of forensic medicine and toxicology.34^th edition.
2. VV Pillay.Modern medical toxicology.4th edition.
3. Richard Saferstein. Criminalistics-An introduction to forensic science. 11^th Edition.