Mechanism of action
 It interacts with specific receptors in the CNS,
particularly in the cerebral cortex.
 Benzodiazepine-receptor binding enhances the
inhibitory effects of various neurotransmitters. ( GABA
Facilitatory)
 Flumazenil (an imidazolebenzodiazepine) is a specific
benzodiazepine-receptor antagonist that reverses most
of the CNS effects of benzodiazepines. (Dose: 0.20.5mg IV to a maximum of 3mg)
DIAZEPAM
MIDAZOLAM
LORAZEPAM
Routes
Oral, IM, IV
IM, IV
Oral, IM, IV
Onset of action
IV: 30-60 sec
Oral: 1-2 hrs
IM: 30 min
IV: 30-60 sec
IM: 30 min
IV: 1-2 min
Oral: 1-2 hrs
IM: 30 min
Preparation (IV)
Oil based so
injection is
painful
Water based so
injection is not
painful
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Elimination Half
Life
30-60 hrs
2-3 hrs
15 hrs
Dose of Sedation
0.05-0.2mg/kg
0.01-0.1mg/kg
0.03-0.04mg/kg
Diazepam
 It is a colorless crystalline compound, insoluble in
water and has a molecular weight of 284.74.
 Each mL contains 5 mg diazepam compounded with
40% propylene glycol, 10% ethyl alcohol, 5% sodium
benzoate and benzoic acid as buffers, and 1.5% benzyl
alcohol as preservative.
Indications
 Diazepam is indicated for the management of anxiety
disorders or for the short-term relief of the symptoms
of anxiety.
 In acute alcohol withdrawal.
 Diazepam Injection is a useful adjunct in status
epilepticus and severe recurrent convulsive seizures.
 Diazepam is a useful premedication (the IM route is
preferred) for relief of anxiety and tension in patients
who are to undergo surgical procedures.
 To prevent hallucination caused by Ketmaine.
DOSAGE AND ADMINISTRATION
 Dosage should be individualized for maximum beneficial effect.
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The usual recommended dose in adults ranges from 2 mg to 20
mg IM or IV, depending on the indication and its severity.
Anxiety Disorders and Symptoms of Anxiety: 2 mg to 5 mg,
IM or IV
Acute Alcohol Withdrawal
The usual dose is 10 mg---- 3 or 4 times during the first 24 hours,
then 5 mg---- 3 or 4 times daily as needed.
Relief of Muscle Spasm
The usual dose is 2mg to 10 mg----- 3 or 4 times daily.
Convulsive Disorders
The usual dose is 2 mg to 10 mg------- 2 to 4 times daily
Systemic Effects
CNS: Mainly acts on RAS and amygdala ( limbic
system) producing sedation, anxiolysis and amnesia.
Also acts on medulla producing muscle relaxation and
on cerebellum producing ataxia.
 No any analgesic effects.
 Produce Muscle relaxation by acting on medullary and
spinal cord (central action) and not at neuromuscular
junction.
 Reduces cerebral metabolic rate, brain oxygen
consumption and Intracranial pressure.
Respiratory system:
 At higher dose cause respiratory depression and may
lead to death.
 It is maximum seen with midazolam.
Cardiovascular System
 Minimal reduction in blood pressure , heart rate and
cardiac output.
 Hypotension is maximum with midazolam.
Metabolism
 Metabolized in Liver.
 The major active metabolite of diazepam is des-methyl
diazepam.
 Metabolites are excreted in Gut and Urine.
Side effects
 Fatigue and ataxia; venous thrombosis and phlebitis at
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the site of injection
CNS: confusion, depression, dysarthria, headache,
slurred speech, syncope, tremor, vertigo.
GI: constipation, nausea.
GU: incontinence ,libido, urinary retention.
Cardiovascular: bradycardia, cardiovascular collapse,
hypotension.
OTHERS : blurred vision, diplopia,
nystagmus,urticaria, skin rash, jaundice.
Contraindications and Precautions
 Valium Injection is contraindicated in patients
with a known hypersensitivity to this drug.
 Valium Injection should not be administered to
patients in shock, coma.
 Should be used with precautions in patients with
pulmonary and cardiovascular diseases.
 Usage in Pregnancy: An increased risk of
congenital malformations associated with the use
of diazepam during the first trimester of
pregnancy has been suggested in several studies.