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Sedative & Hypnotic Drugs

 Sedative: Drugs that reduce anxiety, excitement, and exert a calming effect without affecting mental functions are called sedative

Hypnotics: Drugs that produce hypnosis is called hypnotics.

Hypnosis: It is a sub conscious condition in which the objective manifestations of the mind are more or less inactive, accompanied by abnormal sensitivity.

Classifications of hypnotics: Hypnotics are mainly two types.

1. Barbiturate hypnotics

2. Non- barbiturate hypnotics

 

Barbiturate hypnotics: They are sub divided into four classes:

a) Long acting barbiturates (8-12 hours)

 

For example: Barbitone, Phenobarbitone

b) Intermediate acting barbiturates (6-8 hours)

 

For example: Allo- barbitone, Amilo barbitone

c) Short acting barbiturates (3-6 hours)

 

For example: Pento barbitone, Seco- barbitone

d) Ultra short acting barbiturates (0.5-3 hours)

 

For example: Thiopental sodium

Non barbiturate hypnotics: They are sub divided into two classes:

a) Organic group: Benzodiazepines (Diazepam, Oxazepam, Nitrazepam)

 

Aldehyde derivatives (Paraldehyde)

Alcohol (Chloral hydrate)

Carbamate derivatives (Ethinamate)

Miscellaneous (Anti- histamines, scopolamine)

b) Inorganic group: Sodium Bromide (NaBr), Potassium Bromide (KBr), Ammonium Bromide (NH4Br)

 

Clinical use of sedatives and hypnotics:

 To relief anxiety and depression

 For hypnosis

 Sedation and amnesia before and after surgical procedure

 In the treatment of epilepsy and seizure

 Pre medication prior to anaesthesia

 For muscle relaxation

 Diagnosis aids or for the treatment in psychiatry

 As a component of balanced anaesthesia

 

BARBITURATES

Barbiturates: Barbiturates are the derivatives of barbituric acid.

Mechanism of action of barbiturates: Mechanism of action of barbiturates is schematically shown below:

Barbiturates + GABA
          
Activation of GABA Receptor
          
Opening of Cl- channel
          
Hypotension of cells
          
CNS depression 

Pharmacological action of barbiturates:

1) On CNS: Mild degree of sedation to general anesthesia, anti- convulsant effect, respiratory depression

2) On CVS: Hypotension, decrease heart rate

3) On kidney: Increase ADH secretion, Depress GFR.

4) On GIT: Constipation may occur in prolonged use.

5) On liver: Stimulate glucoronyl transferase enzyme secretion

6) On eye: Toxic dose causes myosis.

 

Therapeutic use of barbiturates:

1) Used as sedative & hypnotics

2) In narco-analysis and narcolepsy.

3) As anti-convulsant: Tetanus, Epilepsy.

4) During surgical anesthesia

5) Sometimes used to antagonize unwanted CNS stimulant drug.

6) Cholestasis

7) Help in diagnosis & therapeutic use for psychiatric patient.

 

Adverse effect of barbiturates:

1) At hypnotic dose, drowsiness may contain for long time

2) Nausea, vomiting, diarrhea

3) Paradoxical excitement: In some persons, barbiturates repeatedly produce excitement rather than depression

4) Hypersensitivity: Rash, localized swelling at eye, leaps etc.

5) Respiration: In hypnotic dose, the effect of respiratory system is minor. But serious respiratory depression may occur sometimes.

6) Tolerance & dependence: Cellular and pharmacokinetic dependence may occur.

 

Barbiturate poisoning: 20%-70% of poisoning occurs due to barbiturates. It occurs due to suicidal or accidental.

Fatal dose is ten times of clinically used dose.

Symptoms of barbiturate poisoning:

1) On CNS: Drowsiness, respiratory depression, slow breathing, coma.

2) On CVS: Hypotension, dehydration, shock.

3) Lungs: Pulmonary edema, bronchopneumonia

4) Kidney: Cerebral depression, renal failure.

5) Eye: Miosis

6) Skin: Lesion

7) Death from: Respiratory depression

 

Treatment of barbiturate poisoning:

1) Removal of unabsorbed drug by stomach wash.

2) Artificial respiration and oxygen inhalation

3) Use activated charcoal as specific antidote

4) Hemodialysis

5) Forced alkaline diuresis

6) Use cardio tonic agent: for example, dopamine

7) Use antibiotic to prevent pulmonary infection

 

Benzodiazepines

Benzodiazepines are the drugs which have sedative, hypnotic, anti- anxiety, anti-convulsant and muscle relaxant properties. They are more popular than barbiturates.

Classification of benzodiazepines:

Based on duration of action, benzodiazepines are three types:

a) Short acting ( Half life is less than 5 hours)

 

For example: Triazolam, Midazolam

b) Intermediate acting (Half life is within 8-15 hours)

 

For example: Lorazepam , Oxazepam

c) Long acting (Half life is upto 200 hours)

 

For example: Diazepam, Nitrazepam, Clonazepam, Flurazepam

Mechanism of action of Benzodiazepines:

Mechanism of action of Benzodiazepines is schematically shown below:

Benzodiazepines

Binds with GABA receptor in brain

Enhance GABA activity

Opening Cl- channels

Hyperpolarization of cells

CNS depression

Pharmacological action of benzodiazepines:

1) Show anxiolytic and tensiolytic effect.

2) Sedative and hypnotic effect

3) Anti- convulsant effect

4) Skeletal muscle relaxant effect

5) Neuromuscular blockage

6) Coronary vasodilation

 

Therapeutic use of Benzodiazepines:

1) Treatment of anxiety

2) As sedative and hypnotic

3) Used as skeletal muscle relaxant

4) Used as pre anesthetic medication

5) Used as anticonvulsant

6) For general anesthesia

7) Management of alcohol withdrawal syndrome

8) In case of endoscopy and cardioversion

 

Antidote of Diazepam: ‘Flumazenil’ is very active antagonist of Benzodiazepine

Adverse effect of Benzodiazepine:

1) Dry mouth

2) Light headache

3) Lassitude

4) Ataxia

5) Drowsiness

6) Ataxia

7) Confusion

8) Acute overdose causes prolong sleep

9) Tolerance and dependency

 Advantage of Benzodiazepine over Barbiturates: 

Barbiturates

Benzodiazepines

1. It has more pronounced CNS depressant action.

It has less pronounced CNS depressant action.

2. Barbiturates depress general neurons also.

Benzodiazepines not depress general neurons.

3. It has less therapeutic index

High therapeutic index.

4. Not so safe

More safer than benzodiazepines

5. Acute overdose causes serious cardio respiratory depression, coma & death

Relatively safer in overdose in comparison with barbiturates.

6. Marked hangover

Less hangover

7. Rapid developing tolerance

Slowly developing tolerance

8. Addiction liability is greater

Less addiction liability

 

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