Core pharmacology

Class Group

Alpha Blocker

Legacy Cicm Level

Level 3

Introduction

highly selective alpha1 blocker

Indications Uses

- essential hypertension
- congestive heart failure
- raynaud’s
- benign prostatic hypertrophy

Presentation

presented as 0.5 - 2mg tablets

Mechanism of action

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

Physiological effects

CVS: peripheral arterial and venous vasodilation and subsequent decrease in TPR but little or no reflex tachycardia (diastole decreases the most).

GU: bladder trigone and sphincter muscle relaxation which is useful in BPH (Tamulosin is also an alpha1 blocker).

CNS:
- syncope and headaches may occur due to rapid BP decrease.

Adverse Effects Toxicity

- May ppt orthostatic hypotension, syncope or vertigo.
- It blunts the compensatory vasoconstriction in spinal and epidural anaesthesia and may cause profound hypotension.
- Dryness of mouth is also a side-effect

Absorption

bioavailabilty 43% to 82% due to first pass metabolism

Protein binding

92% to 97%

Volume of distribution

0.5 L/kg

Metabolism

Extensively hepatic by demethylation and
conjugation with some active metabolites

Excretion

Mostly faeces, (6% to 10% as unchanged drug)

Half-life

2-3 hours

Route And Dose

oral
doses commenced at 0.5mg TDS then uptitrated