Core pharmacology

Class Group

Central Antihypertensive

Legacy Cicm Level

Level 3

Introduction

partial alpha agonist with an affinity for alpha2 receptors 200 times that for alpha1 receptors

Indications Uses

- refractory hypertension
- adjunct in pain management and during anaesthesia
- in patients withdrawing from opiods
- diagnosis of phaechromocytoma

Presentation

both in oral form as a white tablet in dosages of 100-150mcg and
IV/IM forms as a colourless solution with 150mcg/ml

Mechanism of action

useful effects of clonidine rest on its ability to stimulate alpha2 receptors in
the lateral reticular nucleus resulting in decreased central sympathetic outflow by
a positive feedback mechanism, and in the spinal cord where it augments
endogenous opiate release and modulates descending noradrenergic pathways.

Physiological effects

CVS
- transient increase in BP due to alpha2 agonism peripherally but this is followed by a more prolonged fall in BP.
- CO is usually maintained despite bradycardia.

CNS
- sedation and anxiolysis at low doses but anxigenic at higher doses.
- Provides analgesia without respiratory centre depression and is synergistic with opiods.

Renal
- inhibition of ADH may be the cause of diuresis. Endocrine
- stress response to surgery inhibited. Insulin release in reduced, usually BSL ok

Adverse Effects Toxicity

- multiple effects of this drug make it intolerable to many patients, with
somnolence and dry mouth being a frequent concern.
- It may cause profound bradycardia if used with beta blockers.
- If withdrawn suddenly it may cause a rebound hypertension

Absorption

bioavailabilty Immediate release: 75% to 85%
routes of administration Oral, IV and IM

Distribution

lipid solubility highly lipid soluble in order to cross the BBB

Protein binding

20% to 40%

Volume of distribution

2.1 L/kg

Metabolism

Extensively hepatic to inactive metabolites

Excretion

Urine (40% to 60% as unchanged drug)

Half-life

12-16 hours (increased in pts with renal disease)

Route And Dose

PO/IV/IM
doses usually 150-300mcg twice daily