Prof. Panditrao explains the whole new spectrum of pharmacological actions/ indications/ contra indications/ of Clonidine when used parenterally.

2. Clonidine
The ‘wonder drug’- most
misunderstood!

3. Dr. M. M. PANDITRAO
Consultant
Department of Anesthesiology
&
Intensive care
Public Hospital Authority’s Rand Memorial Hospital
Freeport, Grand Bahama
The Bahamas

4. Chemical Structure
2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride

5. α2 Adrenoceptor Agonist -
Clonidine
Agonist to postsynaptic α2 adrenoceptors
in brain, stimulation suppresses
sympathetic outflow.
High dose activates peripheral
presynaptic autoreceptors on adrenergic
nerve endings mediating negative
feedback suppression of noradrenaline
release.
Clonidine reduces blood pressure.

6. Overdose stimulates peripheral
postsynaptic α1 adrenoceptors &
cause hypertension by
vasoconstriction.
Abrupt or gradual withdrawal
causes rebound hypertension.

7. Treatment is to reinstitute
clonidine.
Never use Clonidine with
β- adrenoceptorblockers.

8. Mechanism of Analgesia
Clonidine attenuates the opioid
withdrawal syndrome.
“Indicating interaction with intrinsic Opioid
System”

9. Mechanism of Analgesia (Contd.)
Clonidine induced  α2 adrenoceptors
Analgesia is or
mediated by an  Imidazoline
agonist effect at: receptors
resulting in:

10. Mechanism of Analgesia (Contd.)
 Peripheral & central suppression of
sympathetic transmitter release
 Pre-synaptic inhibtion of nociceptive
afferents
 Post-synaptic inhibition of spinal cord
neurones
 Facilitating the Brain-stem pain
modulating system

11. Pharmacokinetics
Well absorbed orally
Nearly 100% bioavailable
The mean half life of the drug in plasma is about
12 hours
It is excreted in an unchanged form by the
kidney
Three or four days are required to achieve
steady state concentrations
Onset may be rapid (a few hours) or delayed for
as long as 2 days and subsides over 2-3 days

12. Pharmacokinetics (Contd.)
Epidurally:
 Absorbed into CSF, peak within 30-60 min.
excellent correlation between Analgesia &
CSF levels.
 Peak blood levels within 10 min.
 Poor correlation between Analgesia & blood
levels
 Metabolism-minimal: p-hydroxyclonidine
 Excretion- majority unchanged: Urine
I.V/ I.M./Intrathecally: mimics epidural
route

14. Adverse effects
Dry mouth
Sedation
Bradycardia
Sexual disfunction
20% of patients develop a contact
dermatitis to the transdermal delivery
system
Withdrawal syndrome and potentially life
threatening rebound hypertension

15. Precautions & Warnings
Withdrawal causes rebound hypertension
Caution needed in Cerebrovascular & coronary
insufficiency
Sedation is common with neuraxial route
Like other antihypertensives, in CHF pts. „high level
monitoring‟ needed
Very little amount of Clonidine removed by dialysis,
so „high level monitoring‟ needed in CRF patients

16. Drug Interactions
Non selective adrenergic blockers
Diuretics, Vasodilators & adrenergic
blockers
NSAIDs

17. Therapeutic uses
The major use of clonidine is in the treatment of
hypertension.
Clonidine is useful in the management of withdrawal
symptoms seen in addicts after withdrawal from
opiates, alcohol, and tobacco.
 due to its ability to suppress sympathomimetic
symptoms of withdrawal.
• Low dose Clonidine (50-100µg/dl) is used in
migraine prophylaxis and chorea.
• As an analgesic and adjuvant to LAAs / GA

18. Therapeutic uses (Contd.)
Has been successfully used to relieve the Myo-
spasms and hypertonia in spinal cord injury
patients
To improve the gastroparesis and ch. Diarrhea
secondary to Diabetes mellitus
To relieve “Hot Flushes” associated with
menopausal hormonal disturbances both in
males as well as females

19. Clonidine in Regional Anaesthesia
Published Reports of Pts. Receiving Clonidine for Regional Anaesthesia

20. Effect of route of administration on duration of analgesia from
a small dose of clonidine by Intra- Muscular, Epidural,
Placebo & Spinal Routes

21. Cholinergic interaction in spinal α 2 -
adrenergic analgesia
Descending noradrenergic pathways release norepinephrine (NE), to cause
analgesia directly and to stimulate acetylcholine (ACh) release, to produce
analgesia (left). This is consistent with an increase in cerebrospinal fluid
(CSF) acetylcholine after epidural clonidine injection (right, above) and with
neostigmine's potentiation of clonidine analgesia in humans (right, below).

22. Sites of hemodynamic actions of α 2 -
adrenergic agonists
α -Adrenergic agonists
produce sympatholysis and
reduced BP by actions in the
periphery, brainstem, and
spinal cord, effects opposed
by direct vasoconstriction
from α 2 -adrenergic agonists
in the periphery. As a result of
the spinal sympatholytic site
of action, epidural clonidine
reduces blood pressure more
when injected in the thoracic
than in the cervical or lumbar
space

23. Effect of Addition of Epidural Clonidine
to Bupivacaine for Labour Analgesia

24. Clonidine added to mepivacaine
for brachial plexus block
In 190 patients from 3
controlled studies
receiving 40 ml 1%
mepivacaine for
brachial plexus block,
clonidine produced
dose-dependent
increases in duration
of anesthesia (open
circles) and analgesia
(solid circles). Data
from each study are
connected by lines.

25. Summary of Clinical Experience with Clonidine for Regional Anesthesia

26. Conclusion
α -Adrenergic agonists
Parenteral Preparation
Unique Pharmacology
Multiple Indications
Good safety Profile
Adequate Clinical experience
“So It is going to stay & Prosper”