Clonidine

Chemical

An aniline derivative

Use

  1. Hypertension
  2. Sedation
  3. Analgesia
  4. Chronic pain
  5. Withdrawal

Presentation

Tablets, syrup

Clear, colourless solution 150mcg/mL

Dose

Up to 100mg/day

(IV) 15 – 300mcg → acts in 10 mins, lasts 3 – 7hrs

(EPIDURAL) 150mcg

(PO) 50 – 600mcg TDS

Route

PO/IV/Epidural

Onset

Acts within 10 mins

DoA

Lasts 3 – 7 hours (IV)

MoA

Partial α agonist →α2 : α1 affinity 200 : 1

  1. α2 agonism at PRE-SYNAPTIC SYMP PERIPHERAL NERVES → ↓NA production
  2. α2 agonism at CNS/SC

→ Decreased symp outflow

→ Augments endogenous opiate release

→ Sedation/anxiolysis

3. α1 agonism of vessels → some VC

PD

CVS

  • ↑BP initially due to α2 agonism in peripheral vasculature
  • Then sustained ↓BP due to centrally mediated ↓ symp tone & ↑ Vagal tone
  • longer lasting ↓HR & ↓VR
  • ↓SVR with chronic use → ↓response vessels to vasoactive substances & symp stimulation
  • No effect on inotropy
  • Reduction in coronary and systemic vascular resistance

CNS

  • Dose reated sedation, analgesia & anxiolysis
  • Depresses sympathetic outflow and afferent A elta & C fibre mediated somatosympathetic reflexes
  • ↓ICP & ↓IOP by ↓CBF & ↓CMRO2

GI

  • ↓gastric & SB motility
  • Antisialagogue
  • ↑BGL due to α-adrenoreceptor stimulation

Renal – ↓ renal vascular resistance = diuresis

PK

A

OBA 85%

D

V. lipid soluble

Penetrates CNS

20% PPB

VD 2.5L/kg

M

<half dose metabolized in liver to inactive metabolite

E

65% excreted unchanged

t ½ B 6 – 24hrs

Adverse Effects

  • Drowsy
  • Dry mouth
  • Fluid retention
  • Impotence
  • Constipation
  • Rebound hypertension & ↑HR