# Dose adjustment of all of the following drugs will be required in patient with severe liver cirrhosis EXCEPT:

# Dose adjustment of all of the  following drugs will be required in a patient with severe liver cirrhosis EXCEPT:
a) Lorazepam
b) Theophylline
c) Paracetamol
d) Metronidazole

The correct answer is A. Lorazepam.

PHARMACOKINETICS

Most of the BZDS are metabolized in the liver to produce active products (thus long duration of action). Active metabolites may result in cumulative effects. After metabolism, these are conjugated

and are excreted via kidney. Estazolam, lorazepam, oxazepam, temazepam and triazolam are directly conjugated without metabolism to active products. These drugs are thus short-acting and do not

accumulate on repeated administration. Further these drugs can be safely administered in liver failure and in elderly because these are conjugated directly without undergoing metabolism in the liver.

(Mnemonics: @ TO-LET; Short-acting drugs are Triazolam, Oxazepam, Lorazepam, Estazolam and Temazepam,). Compounds with shorter half life are favored in patients with sleep-onset insomnia whereas longer acting BZDS are favored in patients with day time anxiety.

Adverse effects

Benzodiazepines are much safer than barbiturates (less chances of respiratory depression and coma) and also have less abuse potential. However, these drugs can also impair learning and memory

Flunitrazepam is a tasteless BZD and is implicated as a date rape drug due to its propensity to cause dose dependent amnesic effects.

Benzodiazepine Antagonist

Flumazenil is the substance that acts as competitive antagonist at BZD receptor. It blocks the depressant action of benzodiazepine, zolpidem and zaleplon as well as the convulsant action of inverse agonist (like B-carotene).  It is administered i.v. for the treatment of BZD poisoning (specitie antidote) and can also be used to reverse BZD anaesthesia.