Core pharmacology

Class Group

Central Antihypertensive

Legacy Cicm Level

-

Introduction

Central alpha2 agonist
exerts its antihypertensive action via an active metabolite.

Indications Uses

significant adverse effects currently limit its use
- used in treatment of hypertension in pregnancy, where it has a record for safety

Presentation

oral formulation in Australia in 250mg tablets

Mechanism of action

Its metabolite produces a clonidine like alpha2 agonist effect in cardiovascular
control centres that results in reduced sympathetic outflow. The metabolite also
acts as a false neurotransmitter reducing peripheral SNS effects by reducing
noradrenaline synthesis.

Physiological effects

It is primarily used to depress overall SNS activity (HR, BP and TPR) but can also cause sedation, psychosis and depression

Adverse Effects Toxicity

- Sedation, decreased mental acuity and depression may occur.
- Dry mouth is also a
problem.
- A small percentage of patients develop hepatotoxicity or a haemolytic anaemia.

Absorption

bioavailabilty absorded by an amino acid transporter (% ?)
routes of administration oral
onset of action 3-6 hours, duration 24 hours (this is becuase
of the prolonged process in substituting for noradrenaline in
peripheral sites)

Protein binding

<15%

Metabolism

mechanism Intestinal and hepatic

Excretion

Urine (85% as metabolites) within 24 hours

Half-life

75-80 minutes (extended in renal failure)

Route And Dose

PO
doses 125-250mg BD titrated