What are benzodiazepines? |A quick review | Mr medico blogs

 

Benzodiazepines

·       Oral midazolam remains the mainstay of anxiolytic premedication in children despite occasional unpredictable effects.

·       Elders are more sensitive to the midazolam probably because of the  increased receptor binding affinity, impaired hemostatic mechanism and higher sensitivity of the aged CNS

Mechanism of action

·       As we know that benzodiazepines are anxiolytics and anxiety is caused by the over stimulation of excitatory neurotransmitters

·       In order to reduce anxiety, seizures and epilepsy we do  use these class of drugs as to increase the inhibitory activity

·       Antidote for the overdose of the BZD is flumazenil

·       BZD also binds to the gaba receptors A but it bind to another site as do by gaba so they both enhances the inhibitory effect and hence increase the influx of cl ions to inside the cell

·       The imidazole provide its water solubility at low pH

·       As you can see in below picture 

 

 Overview of  benzodiazepines

·       Diazepam and lorazepam are well absorbed from GIT with peak plasma concentration usually achieve in 1-2 hours

·       IV midazolam dose is 0.05-0.1mg/kg

·       Oral midozlam 0.25-1mg/kg 

·       All  BZD are highly protein bound about 90-98%

·       Lorazepam and diazepam is used as antiepileptic agents

·       BZD used for acute insomnia

·       It’s not recommended in chronic insomnia because of dependence and tolerance effect of BZD

·       In dose dependent fashion BZD decreases the CMRo2 and CBF and hence decrease ICP

·       It causes mild muscle relaxation which may be good one but due to its muscle relaxation it can causes the airway obstruction too so in premedication dose should be reduced

·       It also cause the dose related respiratory depression and ventilator response to co2 is impaired and hypoxic ventilator responses are markedly depressed it’s because it don’t depress the oblongata

·       That’s why patient with hypoventilation syndromes and type 2 respiratory failure are more prone to the depression

·       They have modest effect on the hemodynamic effects though a decreases in SVR and hence arterial bp may occur and so significant hypotension can occur in hypovolemic patients

·       After intravenous bolus administration, termination of action occurs largely by redistribution and hepatic metabolism.

·       Elimination takes place by hepatic metabolism followed by renal excretion of the metabolites.

·       Some of the benzodiazepines, including diazepam, have active metabolites which greatly prolong their clinical effects. Renal dysfunction results in the accumulation of these metabolites, and this is an important factor in delayed recovery from prolonged sedation in the ICU.

·       The half-life of diazepam is 20-70h but its active metabolites like desmethyl diazepam have half-life of 36-200h and also nor diazepam>100h

·       Temazepam is the only orally available drug its widely used as premedication because of its anxiolytic properties

·       Oral absorption can take up to 2h for peak concentration

·       Elimination half-life is shorter  than diazepam and is 8-15h and onset of action more rapid and is 45-60min

·       Tolerance and dependence less likely occur that’s why advised as hypnotic agent

·       Premedication dose is 10-20mg orally 60-120 min prep

·       Lorazepam is drug of choice for status epilepticus

·       Also panic attacks

·       Amnesia is marked feature of this drug

Drug	Features
Temazepam	Anxiolytic agent and only oral drug
Lorazepam	Status epileptics, panic attacks  and marked one is amnesia
Diazepam	First BZD available
Midazolam	1.5-2 times more potent than diazepam and use short term IV sedative