Introduction
Sleeping pills are a drug that helps to treat insomnia by making you feel drowsy and relaxed. These drugs have a depressant effect on the body and make it insensitive to pain and also affectsaffect the central nervous system. Names of some sleeping pills are:
► Paraldehyde,
► Zolpidem,
► Zopiclone,
► Methaqualone,
► Buspirone.
Others Name
- Hypnotics,
- Sedatives,
- Sleep aids,
- Sleep medicines,
- Tranquilizer,
What happens if you take too many sleeping pills?
Sleeping pills are used to help a person have a sound sleep and overcome insomnia. But sometimes people take it in an excessive amount due to various reasons, such as: committing Suicide. Overdosing on sleeping pills might result in death. Sleeping pill overdose symptoms include excessive sleepiness, stomach discomfort, difficulty breathing, clumsiness, etc.
Common Symptoms
- Constipation
- Dry mouth
- Headache
- Diarrhea
- Muscle weakness
- Heart burn
- Nausea
- Death
Some Sleeping Pills are described below–
Paraldehyde
Introduction
- Paraldehyde is a polymer of acetaldehyde.
- It is colourless liquid with a pungent odour and disagreeable taste.
- It is a popular hypnotics.
Fatal Dose
- Deaths have been reported with ingestion of as little as 25 ml of paraldehyde.
- Ingestion of 31 to 120 ml
- Rectal administration of 12 to 31 ml.
- Intravenous paraldehyde has been fatal at doses of 35 ml.
Metabolism
● 80% of paraldehyde is converted to acetaldehyde in the liver which is then converted to acetic acid.
● Acetic acid is to be further metabolized via the Krebs cycle to carbon dioxide and water.
● Approximately 28% is excreted by way of the lungs, and 3% is excreted unchanged in the urine.
Sign and Symptoms
- Bleeding gastritis
- Muscular irritability
- Vertigo
- Hypotension
- Tachycardia
- Miosis (or mydriasis)
- Pulmonary haemorrhages
- Oedema
- Dilatation of the right heart
- Oliguria
- Albuminuria
- Fatty changes in the liver and kidney.
- Nephrosis
- Azotaemia
- Coma.
Treatment
- Supportive measures with particular emphasis on maintenance of airway, breathing, and circulation.
- Therapeutic levels of paraldehyde vary considerably due to individual susceptibility, but the estimated concentration to prevent convulsions is 100 to 200 mg/L.
- Check for possible acidosis.
- Correction of metabolic acidosis is imperative.
Zolpidem
Introduction
● Zolpidem is an imidazopyridine derivative which is a sedative as well as hypnotic.
● It binds selectively to the benzodiazepine w-1 receptor subtype in the central nervous system.
Fatal dose
The fatal dose of Zolpidem is about a single 10 mg dose.
Fatal Period
The fatal period of Zolpidem starts within 30 minutes.
Sign and Symptoms
- Dizziness or light-headedness
- Somnolence
- Headache
- Gastrointestinal upset.
- Visual and tactile hallucinations
- Confusion
- Nightmares
- Delirium
- Agitation
- Coma and pinpoint pupils
- Preceded by vertigo
- Vomiting
- Tremor, myoclonic jerks, and diplopia
- Pulmonary oedema has been reported.
- Slurred speech
- Confusion, loss of co-ordination, and sleepiness after ingesting an unknown amount of zaleplon (a related drug). He was amnestic for the events after recovering from the overdose.
- Chronic use of zolpidem can cause tremors, sweats, chills, and headache.
- Sudden withdrawal has been reported to cause convulsions.
Treatment
- Stomach wash with activated charcoal should be effective.
- Supportive measures.
- Flumazenil (repeated doses) is said to be effective in reversing the coma.
Zopiclone
● Zopiclone is a member of cyclopyrrolones, and is a new generation sedative-hypnotic with anticonvulsant and muscle relaxant properties.
● Zopiclone and related drugs such as eszopiclone and suriclone are non-benzodiazepine hypnotic/ anxiolytic agents.
● Even though these drugs are chemically unrelated to benzodiazepines, they nevertheless potentiate gamma-aminobutyric acid (A)-mediated neuronal inhibition.
● Overdose leads to rapid loss of consciousness.
● Chronic use is associated with metallic or bitter taste, dry mouth or sialorrhoea, GI distress, drowsiness, rebound insomnia, and confusion.
● Other common adverse effects include asthenia, dizziness, memory impairment, feeling of drunkenness, euphoria, anxiety, depression, impaired co-ordination, hypotonia, and speech disorder.
● Severe overdoses may result in hypoxia, pulmonary oedema, and respiratory failure.
● The potential for physical dependence has been reported.
● Abrupt withdrawal of zopiclone, particularly following higher dosages and longer usage, may result in convulsions, tremor, abdominal and muscle cramps, vomiting, sweating, dysphoria, perceptual disturbances, and insomnia.
● Treatment of overdose includes; Provide general supportive therapy as indicated, including administering intravenous fluids and maintaining adequate airway. Monitor respiratory, cardiac, and haemodynamic status of all patients following significant overdose. Flumazenil may be also beneficial.
Methaqualone
Introduction
● Methaqualone is a non-barbiturate sedative-hypnotic with anticonvulsant, anaesthetic, antihistaminic and antispasmodic properties.
● Combination of methaqualone with wine (“luding out”) is said to produce powerful euphoria with feelings of invincibility.
● Methaqualone is highly lipid soluble.
Fatal Dose
- Usual fatal dose is around 8 grams.
- Acute ingestion of greater than 800 mg in an adult is usually considered toxic.
- Ingestion of 1 tablet in a child can cause toxicity.
Metabolism
● Absorption of this drug after oral administration is rapid and metabolism occurs in the liver leading to the formation of numerous hydroxy metabolites.
● Methaqualone is completely metabolised by the hepatic microsomal enzyme system, primarily by hydroxylation.
Sign and Symptoms
Mild intoxication
- Dizziness
- Ataxia
- Slurred speech
- Drowsiness
Overdose is characterised by: Ataxia, lethargy, coma (sometimes preceded by delirium), hyperreflexia, and respiratory arrest.
In severe poisoning
● Pyramidal signs such as hypertonicity, limb hyperreflexia, clonus, flailing limb motions, myoclonia and upgoing Babinski responses are common.
● Hypotension, absence of EEG activity, muscular hyperactivity, and respiratory depression are also common phenomena.
● Tachycardia, hypotension, and myocardial infarction have been reported.
● Reversible ECG changes may occur.
● Pupils may be mydriatic and sluggishly responsive, or may be miotic.
Treatment
● Patients monitor CBC, liver and renal function tests, platelets, coagulation tests, electrolytes, arterial blood gases, and ECG.
● Prehospital administration of activated charcoal as an aqueous slurry in patients with potentially toxic ingestion who are awake and able to protect their airway.
● Activated charcoal is most effective when administered within one hour of ingestion.
● Gastric lavage is also beneficial.
● Haemodialysis and haemoperfusion are effective in removing methaqualone, they should be reserved for life-threatening situations.
● Forced diuresis is contraindicated because of the possibility of precipitating pulmonary oedema.
Withdrawal symptoms
- Nausea
- Vomiting
- Abdominal cramp
- Weakness
- Anxiety
- Restlessness
- Tachycardia
- Hyperreflexia
- Agitation, convulsions, and delirium.
- Death may occur if severe withdrawal is not treated.
Buspirone
● Buspirone is an azaspirodecanedione agent (azapirone) which is mainly employed as an anxiolytic agent.
● It is chemically and pharmacologically unrelated to benzodiazepines, barbiturates, and other sedative/anxiolytic drugs.
● Buspirone has a high affinity for serotonin (5-HT1a) receptors with no significant affinity for benzodiazepine receptors, and does not affect gamma-aminobutyric acid (GABA) binding.
Metabolism
● Buspirone is rapidly absorbed, highly protein-bound and metabolised in the liver.
● The presence of food in the stomach decreases the rate of absorption and increases the amount of unchanged (unmetabolised) drug in the system.
● 20 to 40% of the drug is excreted in faeces.
Mode of Action
● The heteroarylpiperazine moiety of buspirone may be responsible for its anxiolytic and serotonergic activity.
● Buspirone suppresses serotonergic activity while enhancing dopaminergic and noradrenergic cell firing.
● It also acts on the dopaminergic system in the CNS.
Sign and Symptoms
- Dizziness
- Headache
- Nervousness
- Lightheadedness, and excitement. Dysphoria
- Motor impairment
- Paraesthesias, and toxic psychosis
- Dysuria, enuresis, nocturia, and priapism have been also reported.
Sleeping Aid
It is H1 Receptor Antagonists.
Absorption, Metabolism and Excretion
● They are generally well-absorbed after ingestion.
● Following oral administration, effects start within 15 to 30 minutes and are fully developed within one hour.
● Oral bioavailability is incomplete, ranging from 25 to 50%.
● Antihistamines are widely distributed throughout the body including the CNS, and are metabolised in the liver.
● Unchanged drug and metabolites are excreted in the urine.
Adverse Effects
- Drowsiness
- Tachycardia
- Dilated pupils
- Decreased bowel sounds, and urinary retention .
- Nausea and vomiting
- Dystonic reactions and hepatotoxicity.
- Pneumonitis
- chest tightness, and wheezing have also been reported.
- Anticholinergic effects such as mydriasis visual disturbances, diplopia, nasal dryness and stuffiness.
- Mouth and throat dryness, can occur with overdose or therapeutic use.
Symptoms
- Somnolence
- Lethargy
- Mydriasis
- Blurred vision
- Convulsions
- Hallucinations
- Extra-pyramidal movement disorders
- Psychosis.
- Nystagmus and catatonic stupor have been reported.
- Sinus tachycardia with hypo- or hypertension
- Dryness of skin and mucous membranes
- Cutaneous flushing, anhydrosis
- Hyperthermia, urinary retention, vomiting and diarrhoea/constipation.
- Skin is usually flushed, warm and dry after overdose.
- Hypertension is more commonly reported than hypotension.
- Tachycardia is also very common.
- Rhabdomyolysis can occur.
- Acute renal failure has been reported in patients who developed rhabdomyolysis after overdose.
- Terfenadine and astemizole are known to cause ventricular dysrhythmias and cardiac conduction defects. Several cases of prolonged QTc and QRS intervals and non-specific ST and T-wave changes were reported following antihistamine overdoses.
- Children are more likely to suffer from CNS stimulation, convulsions, and ARDS.
- Hallucinations, anxiety, restlessness, and agitation have been reported following overdoses of carbinoxamine, cetirizine, dexchlorpheniramine, diphenhydramine, doxylamine, pheniramine, and tripelennamine.
- Cetirizine, loratidine, terfenadine, and astemizole cause much less CNS depression and anticholinergic effects
References
- Dr. K.S. Narayan Reddy. The essential of forensic medicine and toxicology.34th edition.
- VV Pillay.Modern medical toxicology.4th edition.
