Core pharmacology

Class Group

Mixed alpha and beta blocker

Legacy Cicm Level

Level 3

Introduction

third generation non selective beta blocker with alpha 1 antagonist
properties.

Indications Uses

- used to reduce the excessive adrenergic activity that occurs in
response to heart failure.
- hypertension

Presentation

oral form in both immediate and sustained release formulations

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 rapid and extenisve absorption but high fi-rst pass metabolism leading to bioavailability of 25-35%

Distribution

lipid solubility moderate

Protein binding

98% to albumin

Volume of distribution

105 L/kg

Metabolism

Extensively hepatic, via CYP2C9, 2D6, 3A4, three
active metabolites

Excretion

faeces

Half-life

7-8 hours

Route And Dose

oral
doses start at 6.25 BD and doubled 1/52 until not tolerated