Mechanism of actionIt 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: 0.2-0.5mg IV to a maximum of 3mg)

DIAZEPAM MIDAZOLAM LORAZEPAM

Routes Oral, IM, IV IM, IV Oral, IM, IV

Onset of action IV: 30-60 secOral: 1-2 hrsIM: 30 min

IV: 30-60 secIM: 30 min

IV: 1-2 minOral: 1-2 hrsIM: 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

DiazepamIt 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.

IndicationsDiazepam 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 ADMINISTRATIONDosage should be individualized for maximum

beneficial effect. 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 WithdrawalThe 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 SpasmThe usual dose is 2mg to 10 mg----- 3 or 4 times daily.Convulsive DisordersThe usual dose is 2 mg to 10 mg------- 2 to 4 times daily

Systemic EffectsCNS: 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 SystemMinimal reduction in blood pressure , heart

rate and cardiac output.Hypotension is maximum with midazolam.

MetabolismMetabolized in Liver.The major active metabolite of diazepam is

des-methyl diazepam.Metabolites are excreted in Gut and Urine.

Side effectsFatigue and ataxia; venous thrombosis and

phlebitis at the site of injectionCNS: 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 PrecautionsValium 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.