The Use Of Adjuvants In Pain Management - PowerPoint PPT Presentation

Loading...

PPT – The Use Of Adjuvants In Pain Management PowerPoint presentation | free to download - id: 3ecd06-ZDQ4Z



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

The Use Of Adjuvants In Pain Management

Description:

The Use Of Adjuvants In Pain Management Stewart W. Stein, M.D. Medical Director, Good Shepherd Hospice Lamotrigine Dosing: Start at 25-50mg po daily Increase by 50mg ... – PowerPoint PPT presentation

Number of Views:90
Avg rating:3.0/5.0
Slides: 62
Provided by: KimR83
Learn more at: http://enp-network.s3.amazonaws.com
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: The Use Of Adjuvants In Pain Management


1
The Use Of Adjuvants In Pain Management
Stewart W. Stein, M.D. Medical Director, Good
Shepherd Hospice
2
Objectives
  • Understand basic principles of pain transmission
  • Understand the role of adjuvants in the
    management of pain
  • Understand advantages and disadvantages of
    various agents in the management of chronic pain
  • Understand the use of other modalities in pain
    management.

3
Ascending Pathways
  • A-delta fibers are myelinated (insulated with a
    myelin sheath). The pain is fast and well
    localized, like the initial prick or stinging
    sensation following an injury.
  • C fibers are nonmyelinated and smaller than
    A-delta fibers. They transmit pain much slower.
    The pain is more lasting, generalized and
    described as a dull ache.

4
Ascending Pathways
  • After afferent A-delta (myelinated and fast) and
    C-fibers (unmyelinated and slow) synapse with the
    interneurons.
  • These cross over to the contralateral side and
    ascend primarily via the spinothalamic tracts to
    the thalmus and cortex.

5
Ascending Pathways
6
Pathophysiology
  • Nociceptor activation / Types of receptors
  • Mechanical
  • Thermal
  • Chemical
  • Respond to stimuli that approach or exceed
    harmful intensity by undergoing conformational,
    electrical and biochemical changes

7
WHO Pain Ladder
8
  • Adjuvant Analgesics

9
Adjuvant Analgesics
  • Non-opioids with analgesic efficacy
  • Primarily used to treat neuropathic pain
    syndromes although also effective in management
    of nociceptive pain when used as adjuvants to
    other medications

10
Adjuvant AnalgesicsStep 1 Agents on the WHO
ladder
  • Non-steroidal anti-inflammatories (NSAIDS)
  • Antidepressants (TCAs)
  • Anticonvulsants / Antiepileptics (AEDs)
  • Cortisteroids
  • Bisphosphonates
  • Anesthetics
  • N-Methyl D-aspartate antagonists (NMDA)

11
Acetaminophen / Paracetamol
  • Mechanism of action unclear but may inhibit
    cyclooxygenase in the CNS
  • Acetaminophen can cause liver damage if dose
    exceeds 4 grams a day
  • Risk of hepatic injury is increased in patients
    having pre-existing liver damage (alcoholism,
    hepatitis)
  • Acetaminophen has also been shown to cause renal
    damage.

12
NSAIDS
  • Mechanism of action is the inhibition of
    cyclooxygenase to decrease prostaglandin
    synthesis
  • May have central action at the spinal cord level
  • They do have a ceiling effect
  • Tolerance and physical dependence is NOT seen!
  • Can be associated with end-organ toxicity

13
Neuropathic Pain Syndromes
  • Trigeminal neuralgia
  • Post-herpetic neuralgia
  • Diabetic neuropathy
  • Chemotherapy-induced neuropathy
  • Plexopathies
  • Phantom limb pain
  • Complex regional pain syndrome
  • Central post-stroke (damage to thalamus, cortical
    or subcortical structures)
  • Syringomyelia
  • Sympathetically maintained pain syndrome (RSD)

14
Adjuvant Analgesics
  • Tricyclic Anti-depressants
  • Inhibit reuptake of norepinephrine and serotonin
    in nerve endings in the spinal cord and in the
    brain
  • NMDA antagonism

15
Antidepressants
  • Tricyclic Antidepressants
  • Tertiary amines
  • amitriptyline
  • doxepin
  • imipramine
  • clomipramine
  • Secondary amines
  • desipramine
  • nortriptyline

16
Antidepressants
  • Serotoninergic agents
  • Fluoxetine
  • Paroxetine
  • Sertraline
  • Citalopram
  • Escitalopram

17
Antidepressants
  • SNRIs (serotonin / norepinephrine reuptake
    inhibitors)
  • Venlafaxine
  • Desvenlafaxine
  • Duloxetine

18
Antidepressants
  • Used for
  • Analgesia
  • Depression
  • Insomnia
  • (even pruritis)

19
Antidepressants
  • Mechanism of action is inhibition of reuptake of
    neurotransmitters (serotonin, norepinephrine and
    dopamine)
  • Only tricyclic antidepressants have analgesic
    properties independent of their antidepressant
    activity

20
AntidepressantsSide Effects
  • Nausea
  • Sedation
  • Confusion
  • Xerostomia
  • Tachycardia
  • Drug interactions
  • (Anticholinergic )

21
Side Effects of TCAs
  • ?MI
  • Long term use of TCAs is associated with a 2.2
    relative risk of myocardial infarction and a
    1.7fold increase in mortality vs. placebo or
    SSRIs. (screen elderly with EKG?)
  • American Journal of Medicine (2000)
    Jan108(1)2-8
  • European Heart Journal (2004) 25 (1) 3-9

22
  • AEDs
  • (Antiepileptic Drugs)

23
Mechanism of action of AEDs
  • Slow recovery of voltage gated Na channels from
    depolarization (carbamazepine, phenytoin)
  • Indirect or direct enhancement of inhibitory
    Gama-aminobutyric acid neurotransmission
    (Valproic acid, Tiagabine)
  • Inhibition of excitatory glutamatergic
    neurotransmission (lamotrigine)

24
Mechanism of action of AEDs
  • Block voltage dependent Ca channel (Gabapentin
    and Pregabalin)
  • Carbonic anhydrase inhibition (Topiramate,
    Zonisamide)

25
Mechanism of action of AEDs
26
New AEDs (Anti-Epileptic Drugs)
  • Gabapentin
  • Topiramate
  • Levitiracetam
  • Tiagabine
  • Oxcarbazepine
  • Lamotrigine
  • Felbamate
  • Pregabalin

27
Use of AEDs
  • Start with a low evening dose
  • Increase GRADUALLY over 4-6 weeks depending on
    response. (Typically effective at higher doses)

28
New AEDsSide Effects
  • Drowsiness
  • Unsteadiness
  • Aplastic anemia (CB)
  • Dizziness
  • Confusion
  • Rash (VPA)
  • Ataxia
  • Nausea and vomiting

29
Gabapentin
  • Established efficacy in treatment of post
    herpetic neuralgia
  • Most common mistake is failure to titrate to
    effective doses (900mg ineffective in managing
    PDN in one series)

30
Gabapentin
  • Titration Schedule
  • Day 1 300mg po at HS
  • Day 2 300mg po bid
  • Day 3 300mg po tid
  • Titrate 100-300mg per day over next 2 weeks to
    target dose of 1800mg. Continue titration over 2
    more weeks to 3600mg if indicated for effect.
    Higher doses have also been successfully used.

31
Pregabalin
  • Advantages include predictable absorption across
    the GI tract. Not metabolized or protein-bound.
    Minimal drug-drug interactions.
  • Multiple studies demonstrate effective pain
    relief and decreased sleep interference in PHN
    and PDN

32
Pregabalin
  • Dosing schedule
  • Days 1-3 50mg po tid
  • Days 4-7 100mg po tid
  • Thereafter 200mg po tid.
  • Taper dose over 7 days to discontinue

33
Lamotrigine
  • Demonstrated efficacy in trigeminal neuralgia.
  • Utility in vascular HAs and PDN suggested by
    open label studies

34
Lamotrigine
  • Dosing
  • Start at 25-50mg po daily
  • Increase by 50mg per day per week until effective
    or an arbitrary maximum is reached (usually
    around 900mg daily in 2-3 divided doses)

35
Topiramate
  • Studies demonstrate utility in management of
    cluster headache and diabetic neuropathy
  • Effective dose range is 200-400mg daily in
    divided (2) doses
  • Associated with weight loss
  • Side effects may include abnormal thinking,
    delusional and psychotic thinking, kidney stones.

36
Carbamazepine
  • Used in trigeminal neuralgia since the 1960s!
  • Starting dose is 200mg po bid. Effective dose is
    usually 400-1000mg per day.
  • Induces P450 system so potential for drug-drug
    interactions.
  • Aplastic anemia occurs in 1200,000. More
    commonly, a reversible leukopenia or
    thrombocytopenia may occur.

37
Oxcarbezapine
  • An analog of carbamazepine that retains many
    therapeutic properties of the drug while avoiding
    toxicities. (No bone marrow suppression or
    induction of P450 system)
  • Start with 300mg at HS. Increase weekly by
    300-600mg until effective up to a maximum of
    1200-2400mg per day.

38
Phenytoin
  • Mixed results in trials (1970s) for PDN.
  • Usual dose 200-400mg po daily
  • Side effects include nausea, diplopia, dizziness,
    confusion, gingival hyperplasia and rarely
    Stevens-Johnson syndrome.
  • Induces P450 cytochrome system

39
Valproic acid
  • Demonstrated efficacy in migraine HAs.
  • Side effects include nausea, vomiting, sedation,
    rash, ataxia and appetite stimulation
  • 40 develop increased transaminases.
  • 150,000 will develop HEPATIC FAILURE

40
Also part of the equation .
  • NNT The number of patients that need to be
    treated with a particular drug in order for one
    patient to experience a 50 reduction in pain
  • NNH The number of patients that need to be
    treated with a particular drug in order for one
    patient to drop out due to adverse effects

41
TCA (amitriptyline)
  • NNT 2-3
  • NNH 14.7

42
AED (gabapentin)
  • NNT 5.1 (Includes all doses, high and low)
  • NNH 26.1

43
Opioids
  • Morphine NNT 2.5
  • Oxycodone NNT 2.6
  • Tramadol NNT 3.9
  • NNH for tramadol 9.0
  • NNH morphine and oxycodone not significant

44
Bisphosphonates
  • Pamidronate and Zolendronic acid
  • Localize to bone and inhibit osteoclastic
    activity
  • Widely studied in treatment of metastatic bone
    pain
  • Risk of osteonecrosis of the mandible.

45
Corticosteroids
  • Inhibit arachodonic acid (prostaglandin
    synthesis) resulting in anti-infalmmatory action
  • Also a membrane stabilizer (blocking c-fiber
    transmission)

46
NMDA Receptors
  • Located mostly in the dorsal horn of the spinal
    cord
  • Activated by chronic, painful stimulus leading to
    allodynia, hyperalgesia, and neuropathic pain.
  • Also responsible for opioid tolerance.

47
Therefore
  • Blocking NMDA results not only in improved pain
    control but also reverses opioid tolerance to
    varying degrees.

48
NMDA receptor antagonists
  • Methadone
  • Ketamine
  • Dextromethorphan

49
Ketamine
  • Useful in refractory neuropathic pain states
  • Useful to reset opioid sensitivity in an
    opioid-tolerant patient
  • Also very useful for procedures such as painful
    wound care

50
Neuropathic painHow do we proceed?
  • If we were to look only at pain relief, the order
    would be
  • TCA
  • opioids
  • tramadol
  • gabapentin / pregabalin (recall NNT)

51
BUT.
  • If criteria are to be both relief of pain AND
    quality of life, the order would be
  • Gabapentin / pregabalin
  • Tramadol
  • Opioids
  • TCAs

52
Nerve BlocksCeliac Plexus Block
  • Used with upper abdominal malignancies
  • Variable benefit
  • (alcohol neurolysis most common)

53
Nerve BlocksMandibular / Maxillary / Gasserian
ganglion block
  • Used in head and neck cancer pain. Phenol /
    alcohol used for neurolysis
  • Radiofrequency ablation also used
  • Post neurolytic dysesthesia can occur

54
Axial therapy
  • Both presynaptic and post synaptic opioid
    receptors within the dorsal horns of the spinal
    matter inhibit synaptic transmission from the
    peripheral afferent nociceptor to the second
    order spinal neuron.

55
Axial Therapy
  • Intrathecal
  • subarachnoid
  • Epidural
  • requires 10 times the intrathecal volume to
    spread medication over several dermatomal segments

56
Axial Therapy
  • Advantages
  • Effective
  • Markedly reduced side effects.
  • Disadvantages
  • Surgical procedure
  • Infection
  • CSF leak

57
Axial vs. Oral Opiate Dosing
  • Oral morphine 300mg
  • IV morphine 100mg
  • Epidural 10mg morphine
  • Intrathecal 1mg morphine

58
Other Modalities
  • Vertebroplasty
  • Cement (polymethyl methacrylate) is injected into
    the damaged vertebra and acts as an internal
    splint. Useful in osteoporosis and
    cancer-associated fractures

59
Other Modalities
  • TENS
  • Stimulates large A fibers that then close the
    gate for pain coming in from C fibers. Used in
    acute and chronic pain syndromes.
  • Low intensity not reversed by naloxone
  • High intensity reversed by naloxone

60
Other Modalities
  • Acupuncture Possibly acts on reward center
    (dopamine and serotonin)
  • May increase muscle blood flow
  • May reduce gastric acid and correct gastric
    arrhythmia, thereby reducing nausea and vomiting.

61
Questions Comments
About PowerShow.com