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.

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.

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

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

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

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)

lipid solubility highly lipid soluble in order to cross the BBB

20% to 40%

<15%

2.1 L/kg

Extensively hepatic to inactive metabolites

mechanism Intestinal and hepatic

Urine (40% to 60% as unchanged drug)

Urine (85% as metabolites) within 24 hours

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

75-80 minutes (extended in renal failure)

- 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- If withdrawn suddenly it may cause a rebound hypertension

- 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.

Central Antihypertensive

Central Antihypertensive

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

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

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

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

Level 3

-

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

oral formulation in Australia in 250mg tablets

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

PO
doses 125-250mg BD titrated