1 / 21

KETAMINE

KETAMINE. Nicola Holtom Palliative Medicine Consultant NNUH 2007. ADJUVANT ANALGESICS IN CANCER PAIN. WHO ladder controls 80% of pains Adjuvant analgesia is required for 20% pains Nerve injury: 59% require adjuvants Nerve compression: 32% require adjuvants

thao
Download Presentation

KETAMINE

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. KETAMINE Nicola Holtom Palliative Medicine Consultant NNUH 2007

  2. ADJUVANT ANALGESICS IN CANCER PAIN • WHO ladder controls 80% of pains • Adjuvant analgesia is required for 20% pains • Nerve injury: 59% require adjuvants • Nerve compression: 32% require adjuvants • Stute et al 2003 Journal of Pain+ Symptom management 26(6) 1123-1131

  3. NERVE INJURY PAIN Spinal NMDA receptor analgesia blocker / class 1 Step 4 antiarrhythmic TCA + Step 3 TCA or anticonvulsant anticonvulsant Step 2 +steroid Step 1

  4. NEUROPHYSIOLOGY OF PAIN PATHWAYS • C fibres (slow myelinated 0.5 m/s) • Polymodal : heat, mechanical, chemical • Silent population - woken by inflammation • A fibres (moderate myelination) • Responsible for static allodynia • A fibres • Responsible for dynamic allodynia (pain on brushing movements) • Nociceptors • Complex: up to 20 different receptors on C fibres responsible for transmitting pain • Na+ channels are particularly found on C fibres

  5. NEUROPHYSIOLOGY OF PAIN PATHWAYS • Inflammation  prostanoids, bradykinin, 5HT • These chemical mediators  peripheral sensitisation of C fibre  wakes up silent receptors • Vasodilatation + plasma extravasation  increased transmission along C fibre  central sensitisation and allodynia • Ectopic action potentials accumulate at point of damage in C fibres  allodynia and hyperalgesia • NB NSAID’s + Aspirin inhibit prostanoids via COX • There are no drugs that target bradykinin or triptans

  6. FOLLOWING NERVE INJURY • Major changes in sodium channel • Entirely new sodium channels appear • Sodium 1.7 and 1.8 are only found on C-fibres • Currently no drugs which specifically target these sodium channels • In chronic pain there is also an increase in calcium channels in spinal cord

  7. Mechanisms of neuropathic pain • Increased activity in primary sensory neurones • Central hypersensitivity (NMDA) • Activation of calcium channels

  8. MECHANISMS OF NEUROPATHIC PAIN • 1.Increased activity in primary sensory neurones • Sensory neurone specific voltage-gated sodium channels (SNS) • SNS1 + SNS2 are expressed in sensory neurones, particularly nociceptors • Ectopic action potentials accumulate at point of nerve injury ( SNS1 + SNS2 ) • Patients with chronic local hyperalgesia + allodynia have  SNS1 but little or no SNS2 • This suggests SNS1 is responsible for persistent hypersensitive state

  9. MECHANISMS OF NEUROPATHIC PAIN • 2. Central hypersensitivity • The AMPA receptor sets the baseline response of the spinal neurones • Kainate receptors may also be important • Release of peptides and glutamate allow the NMDA receptor to be activated • NMDA activation underlies wind-up

  10. MECHANISMS OF NEUROPATHIC PAIN • 3. Ca 2+ channel activity • Following nerve damage there are more activated Ca2+ channels (N type) • No changes in P or T type • Influx of Ca2+ into cells  release of neurotransmitters

  11. a2d K+ K+ OP2 CB1 OP1 OP3 a2 Ca2+ Primary afferent 5HT3 Ca2+ a2 Mg2+ NMDA GABAB CB1 GLU OP2 OP1 OP3 GLU Na+ AMPA Na+ Postsynaptic neurone SP SP 5HT2 NK1 Ca2+ Gs Mg2+ NMDA NK1 Inhibitory receptor GABAA 5HT1B GABAB Excitatory receptor ADN Cl- K+

  12. NMDA receptors • Receptors require glutamate or system does not operate • Normally Mg2+ prevents influx of ions • Accumulated activation of neurones depletes Mg2+ so system can operate • Once Mg2+ is depleted there is influx of Ca2+ • Ketamine sits in the NMDA channel and blocks it

  13. NMDA RECEPTOR • Blocking the NMDA receptor with ketamine blocks the hyperalgesic response preventing wind-up • NR2 ABCD subgroups of NMDA receptor exist • Drugs targeted towards subgroups might be better tolerated

  14. INTERPERSONAL VARIATIONS • Three factors which dictate interpersonal variations in pain : • Ca2+ channel receptor • Opiate receptor • 5HT genes

  15. Mechanism of action of anti-neuropathic drugs • Block peripheral sensitisation (sodium channels : Valproate) • Block central sensitisation (Ketamine) • Restore inhibitory control (TCA,SNRI) • Modulate release of neurotransmitters (Gabapentin / Pregabalin)

  16. OPIOIDS • Opioids work on C fibres and fibres with NMDA receptors • If wind-up has occurred higher doses of opiates are required to ‘chase’ neuropathic pain • Consensus is that opioids are useful in neuropathic pain MORPHEUS : GOD OF DREAMS SON OF HYPNOS : GOD OF SLEEP

  17. KETAMINE • Pharmacology • NMDA receptor blocker • Reduces post-synaptic excitation • Interactions with Ca and Na channels • NA + 5HT reuptake inhibition • μ + К opioid like actions • Indications • Neuropathic • Inflammatory • Ischaemic • Contra-indications • Epilepsy, raised intracranial pressure

  18. FORMULATIONS BNF 4.7.3 / 15.1.1 Oral ketamine solution 50mg / 5mls Injection 10mg/ml : 20ml vial Injection 50mg/ml : 10ml vial Injection 100mg/ml : 10ml vial

  19. PHARMACOKINETICS • Extensive first- pass hepatic metabolism to nor-ketamine • <10% excreted unchanged by kidneys and in faeces • Hepatic enzyme induction with long term use of ketamine • Plasma concentration increased by diazepam • Adverse effects • Dysphoria, vivid dreams, hallucinations, altered body image • Hypertension • Tachycardia • Delirium • Diplopia,nystagmus

  20. KETAMINE AUDIT NNUH 2005-2006 • 29 patients • 9 outpatients ( 9% new referrals with pain) • 20 inpatients (14% new inpatient pain) referrals) • 27/29 excellent response • 1/29 dysphoria • 1/29 disliked taste

  21. PAIN AUTONOMY HETERONOMY X NO PAIN

More Related