Clonidine

Milind Arolker

01.05.2013

Outline

Settings– Pain management– Other indications

Levels of evidence How it works (nice pictures)

Sources

PCF4 Interventional Pain Control in Cancer

Pain Management. Hester, Sykes, Peat (Eds). OUP (2012)

Other (blind-ish) alleys– search term on websites of major palliative

medicine related journals

…and the relevance with clonidine?

So…

RCT type evidence favouring intrathecal drug delivery over systemic drug delivery for cancer pain (opioid-induced side-effects; advantage of greater potency with intraspinal route)

WHO analgesic ladder changes: – Is there a point to weak opioids (step 2)?– “invasive procedures should be considered as an

adjuvant to common analgesic regimens at any stage and should not be regarded as ‘a last resort’” (Eisenberg, IASP clinical update, 2005, Vol XIII, No.5)

…and clonidine’s place?

…and clonidine’s place?

…the evidence base for IT clonidine is even more limited (case reports)…Farquhar-Smith (pg 76)

2-adrenergic receptor agonist

Licensed– Hypertension– Migraine prophylaxis– Menopausal flushing

• 50 µg po bd• up to 100 µg bd

Unlicensed– Pain poorly

responsive to ED/IT opioid +/- bupivacaine

– spasticity– sialorrhoea– diarrhoea, DM-

related autonomic gastroparesis

– Sweating

pre-synaptic inhibition!

Peripheral and/or central suppression of sympathetic tone

Pre-synaptic inhibition of nociceptive afferents

Post-synaptic inhibition of spinal cord neurons

pre-synaptic inhibition!

Peripheral and/or central suppression of sympathetic tone

Pre-synaptic inhibition of nociceptive afferents

Post-synaptic inhibition of spinal cord neurons

IT doses– 30 µg test dose– 150 µg / 24 hrs

CSCI route too: 1.5mg/24hrs (personal communication)

other effects & side-effects

muscle spasticity (adjunct to baclofen)

induces gut smooth muscle relaxation

2-receptors on enterocytesintestinal fluid and electrolyte reabsorption (improvement in diarrhoea)

Onset: 30-60mins. Half-life: 8-24hrs

Summary (pico?)

“What’s the evidence for clonidine in pain management (cancer)”– RCT for epidural (cases for IT route)– RCT for IT opioids (+clonidine, probably)

over CMM (pts on 200 mg OME) An adrenergic agonist whose beneficial

therapeutic effects arise from inhibition of sympathetic activity