Core pharmacology

Class Group

Mixed alpha and beta blocker

Legacy Cicm Level

Level 2

Introduction

an alpha 1 blocker and a non selective beta blocker.

Indications Uses

- Used in the setting of an acute hypertensive crisis
- Pregnancy related hypertension

Chemical Pharmaceutics

It is a racemic solution with four stereoisomers present in
equal proportions. The SR isomer is likely responsible for the alpha blocking
effects and the RR isomer for the betablockade

Presentation

available as a 50-400mg tablets and as a colourless solution containing 5mg/ml.

Mechanism of action

Beta blockage leads to ↓Gs activity in receptor associated organs and
associated ↓in adenylyl cyclase and intracellular Ca2+.

Alpha blockage leads to ↓ Gq activation and subsequent ↓in IP3 and intracellular Ca2+

Physiological effects

β: It produces
decreases in heart rate and cardiac output and myocardial oxygen consumption.

α: Peripheral vasodilation

Adverse Effects Toxicity

- Withdrawal.

- Care with: Opioids, Halo, OAD, CCB

- Due to its metabolism, it should be used in caution in liver failure patients and elderly

Absorption

bioavailabilty complete absorption but high first pass metabolism results in bioavailability 25%

Distribution

lipid solubility moderately lipid soluble, can enter CNS

Protein binding

50%

Volume of distribution

3-16 L/kg

Metabolism

Hepatic, primarily via glucuronide conjugation

Excretion

Urine (60% as glucuronide conjugates, <5% as unchanged drug)

Half-life

6-8 hours

Route And Dose

IV and oral
doses IV in 20mg pushes, oral for HTN 100-400mg BD