Benzodiazepine equivalence

Among benzodiazepine equivalence , differences in the onset and duration of action are due to their potency, lipid solubility and pharmacokinetics.

Benzodiazepine equivalence is used to understand the relative differences in the action and effects of the different types of benzodiazepines.

All benzodiazepines are highly lipid soluble and are highly bound to plasma proteins, especially albumin. Following oral administration, benzodiazepines are highly absorbed from the gastrointestinal tract and after IV injection they rapidly enter the CNS and other highly perfused organs.

Therefore, any condition producing hypoalbuminaemia may result in increase of the unbound fraction of benzodiazepine equivalence , resulting in enhanced clinical effects produced by these drugs.

Miller’s anesthesia says the following about benzodiazepine equivalence –

The binding of benzodiazepines to their respective receptors is of high affinity and is stereospecific and saturable; the order of receptor affinity (potency) of the three agonists is lorazepam > midazolam > diazepam. Midazolam is approximately 3 to 6 times, and lorazepam 5 to 10 times, as potent as diazepam.

The three benzodiazepines used in anesthesia are classified as short-lasting (midazolam), intermediate-lasting (lorazepam), and long-lasting (diazepam), according to their metabolism and plasma clearance. The plasma disappearance curves of all the benzodiazepines can be fitted to a two-compartment or three-compartment model.

Protein binding and volumes of distribution are not much different among these three benzodiazepines, but the clearance is significantly different.

The clearance rate of midazolam ranges from 6 to 11 mL/kg/min, whereas the clearance of lorazepam is 0.8 to 1.8 mL/kg/min, and the clearance of diazepam is 0.2 to 0.5 mL/kg/min. Because of these differences in clearance, the drugs have predictably different plasma disappearance curves

Leave a Reply