SUBJECT FORENSIC SCIENCE
Paper No. and Title PAPER No. 9: Drugs of Abuse
Module No. and Title MODULE No. 8: Common Depressants: Barbiturates
Module Tag FSC_P9_M8
FORENSIC SCIENCE PAPER No.9 : Drugs of Abuse MODULE No. 8: Common Depressants: Barbiturates
TABLE OF CONTENTS
1. Learning Outcomes 2. Introduction to Barbiturates 3. Classification of Barbiturates 4. Mechanism of Action of Barbiturates 5. Pharmacokinetics of Barbiturates 6. Effects of Barbiturates 7. Use of Barbiturates 8. Signs and Symptoms 9. Colour test for Barbiturates 10. Medico-Legal Aspect 11. Summary
FORENSIC SCIENCE PAPER No.9 : Drugs of Abuse MODULE No. 8: Common Depressants: Barbiturates
1. Learning Outcomes
After studying this module, you will be able to know about-
Barbiturates and their types Mode of action and pharmacokinetics of Barbiturates Forensic Examination of Barbiturates
2. Introduction to Barbiturates
Barbiturates are derivatives of Barbituric Acid. They can be used as hypnotics, sedatives, anticonvulsants and anesthetics, although they are probably most familiar as 'sleeping pills'. The different properties of the various barbiturates depend upon the side groups attached to the ring. Barbituric acid was first discovered by the German chemist Adolf von Baeyer in 1864 by combining Urea with Malonic Acid. The medical value of these substances was not realized, however, until 1903 when two other German chemists, Emil Fischer and Joseph von Mering, discovered that one of these compounds, diethylbarbituric acid, was very effective in putting dogs to sleep. It is said that Von Mering proposed that the new substance be called 'Veronal', because the most peaceful place he knew on Earth was the Italian city of Verona.
Barbituric Acid
FORENSIC SCIENCE PAPER No.9 : Drugs of Abuse MODULE No. 8: Common Depressants: Barbiturates
Different types of barbiturates: Barbiturates Common Name Allobarbital
Alphenal
Amobarbital Amytal Aprobarbital Alurate Brallobarbital Vesparax Butobarbital Soneryl, Butisol Butalbital Fiorinal, Fioricet Cyclobarbital Phanodorm Methylphenobarbital Prominal Mephobarbital Mebaral Methohexital Brevital Pentobarbital Nembutal Phenobarbital Luminal Secobarbital Seconal Talbutal Lotusate Thiamylal Surital Thiopental Pentothal
Slang names for barbiturates: Yellow Jackets, Reds, Blues, Amy’s and Rainbows.
Synthesis of Barbituric Acid:
Urea Malonic ester Barbituric acid Methanol
Barbiturates are white, crystalline, odorless powder with a faintly bitter taste. These compounds are used as sedative, hypnotics and when given intravenously as anesthetics. They are useful in psychiatric disorders, epilepsy and strychnine poisoning.
FORENSIC SCIENCE PAPER No.9 : Drugs of Abuse MODULE No. 8: Common Depressants: Barbiturates
3. Classification of Barbiturates
Barbiturates are classified into four groups as follows, depending on whether their action is long, intermediate, short or ultra-short.
a) Long action: It effects from 1 to 8 - 12hrs Fatal dose: 3 - 4gm These groups of barbiturates act for longer duration. E.g., Phenobarbitone, Mephobarbitone b) Intermediate action: It effects from half to 4 - 8 hrs. Fatal dose: 2 - 3gm These groups of barbiturates act for not long time or not to short. E.g., Pentobarbitone, Amylobarbitone. c) Short action: It effect from 15 min to 2 - 4 hrs Fatal dose: 1 - 2gm These drugs act for shorter duration of time. E.g., Butobarbitone, Serobarbitone, Pentobarbitone. d) Ultra short action: It effects for very shorter duration of time. Fatal dose: 1gm These barbiturates act as general anaesthetic. E.g., Thiopentone sodium
4. Mechanism of Action of Barbiturates
Barbiturates potentiate the effect of GABA at the GABA-A receptor. The GABA-A - receptor is a ligand gated ion channel membrane receptor that allows for the flow of Cl through the membrane in neurons. GABA is the principle neurotransmitter for this receptor which upon binding causes the channel to open and creates a negative change in the transmembrane potential. This makes it an Inhibitory neurotransmitter.
FORENSIC SCIENCE PAPER No.9 : Drugs of Abuse MODULE No. 8: Common Depressants: Barbiturates
Barbiturates potentiate the effect of GABA by binding to the GABA-A receptor at a nearby site and increasing the chloride flow through the channel. Barbiturates also block the AMPA receptor which is sensitive to glutamate, the excitatory neurotransmitter. Glutamate performs the opposite effect from GABA restricting ion flow and increasing the transmembrane action potential of the neuron. By blocking this action Barbiturates serve to increase the duration of the receptor response to GABA and extend the depressed condition of the cell.
The following are the actions of barbiturates on various systems of the body. Action of barbiturates on Central Nervous System Depending on the increasing dose barbiturates cause sedation, sleep, anesthesia and coma.
Action of barbiturates on Respiratory system Barbiturates cause the depression of respiratory system.
Action of barbiturates on Cardio-vascular system Barbiturates cause mild decrease in heart rate and blood pressure.
Action of barbiturates on skeletal muscles Barbiturates cause decreases the contractions of muscles.
Action of barbiturates on Smooth muscles Barbiturates decrease the tone and motility of smooth muscles in the intestines.
Action of barbiturates on Kidney Barbiturates can decrease the urine output.
FORENSIC SCIENCE PAPER No.9 : Drugs of Abuse MODULE No. 8: Common Depressants: Barbiturates
5. Pharmacokinetics of Barbiturates
Barbiturates rapidly absorbed from the GI tract including rectum and from subcutaneous tissues. They are concentrated in the liver for a short time and then evenly distributed in the body fluids. They are partly destroyed in liver and excreted in urine.
Most barbiturates which are used as sedative-hypnotics are administered orally. Intravenous route is usually reserved for management of status epilepticus or induction/maintenance of general anesthesia. Following absorption, barbiturates are distributed widely. The long acting barbiturates have a plasma half-life of about 80 hours. Metabolism of most of these drugs occurs by oxidation in the liver resulting in the formation of alcohols, ketones, phenols, or carboxylic acids which are excreted in the urine as such or in the form of glucuronic acid conjugates. Metabolism of barbiturates is more rapid in children and is slower in the elderly.
6. Effects of Barbiturates
Physical Effects Psychological Effects • Sleepiness • Mild Euphoria • Nausea • Disinhibition • Slurred Speech • Memory Impairment • Breathing Disorders • Increased Irritability • Reduced Sex Drive • Severe Paranoia • Coma • Suicidal Thoughts
7. Uses of barbiturates
Epilepsy/ convulsion, the drug of choice is phenobarbitone Anesthesia- thiopentane is used as an anesthetic drug Used as hypnotic Used as anxiolytic Used as sedative to induce sleep Used in treatment of psycho-somatic disorders
FORENSIC SCIENCE PAPER No.9 : Drugs of Abuse MODULE No. 8: Common Depressants: Barbiturates
8. Signs and Symptoms
First symptom is drowsiness. A short period of confusion, excitement, delirium and hallucination is common. A stupor progressing to deep coma, with inhibition or loss of response to painful, stimuli occurs. There is a fall in cardiac output and an increase in capillary permeability leading to an increase in the extracellular fluid. The pupils are usually slightly contracted but react to light; they may dilate during terminal asphyxia. Blisters (barbiturate blisters) on the skin, often on an area of erythematic, strongly suggest barbiturate poisoning.
9. Colour Test for Barbiturates
DILLE – KOPPAYANI TEST:
Preparation of Reagent: A. Cobalt Acetate Solution: 1 gm. of cobalt acetate (tetrahydrate) is dissolved in followed by addition of 0.2 ml. of Acetic Acid. B. Isopropyl amine Solution: 5 ml. of isopropylamine is mixed with 100 ml. of methanol.
Procedure No. 1: A small amount of extracted material is placed on a spot plate. 3-4 drops of cobalt acetate solution and 3-4 drops of isopropylamine solution are added. The appearance of a purple or blue violet colour indicates the presence of barbiturate.
Procedure No. 2: The residue of extract of sample is taken in 1 ml. of chloroform. To a portion of chloroform extract of the sample, 2 drops of freshly prepared 1% cobalt acetate in methanol is added followed by 1% lithium hydroxide in methanol drop by drop.
Result- A blue ring at the junction indicates the presence of barbiturates.
FORENSIC SCIENCE PAPER No.9 : Drugs of Abuse MODULE No. 8: Common Depressants: Barbiturates
ZWIKKER’S TEST:
The residue of extract is taken up in chloroform. To 1 ml. of chloroform extract, 2 - 3 drops of 0.5 ml. of 5% pyridine in chloroform is added and shaken. The colour of chloroform layer becomes purple. Then 1 drop of glacial acetic acid is added. If the colour of chloroform layer changes from purple to weak blue, the presence of non- Thiobarbiturates is indicated.
If chloroform layer becomes green after adding pyridine in chloroform, the presence of Thiobarbiturates is indicated.
Result -This green colour changes to light green on adding acetic acid.
10. Medico-legal Aspect
Most deaths from barbiturates are either suicidal or accidental. The popularity of barbiturates as soothers for the harrying pace and anxieties of modern life has resulted in a number of addicts who might poison themselves from an overdose taken accidently or through mental confusion from barbiturates automatism or simultaneous ingestion of alcohol.
11. Summary
Barbiturate is a sedative drug which is white, crystalline, odorless powder with little bitter taste. They are mostly used for psychiatric disorders, epilepsy and strychnine poisoning. They are rapidly absorbed from the GI Tract including rectum and from subcutaneous tissues. The mode of action of barbiturate is CNS Depressant. Barbiturates, particularly sodium pentothal, also have interesting applications in the field of psychology, since they can provide access to levels of consciousness not normally attainable except in dreams or trances. Dille- Koppanyi test and Zwikker’s test are the colour tests for barbiturate. Barbiturates present problems because patients develop tolerance for them and even higher doses are then required to produce the same effect. They are also habit forming, and the fatal dose is not much more than the normal therapeutic dose. Medico legal importance of barbiturate is that the most of the deaths from barbiturates are either suicidal or accidental, homicidal deaths are very rare.
FORENSIC SCIENCE PAPER No.9 : Drugs of Abuse MODULE No. 8: Common Depressants: Barbiturates