Treatment of Neuropathic Pain Flashcards

1
Q

Nociceptive pain

def

A

Nociceptive pain- Nociception is the transmission of “noxious” stimuli from the sight of injury to the CNS. Nociceptive pain usually the result of damage to normal tissue

 Pain is usually “aching” or “throbbing
 Responds well to opioids, NSAIDS

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2
Q

Neuropathic pain

def

A

Neuropathic pain- Results from direct neuronal injury which causes a pathological change in the nerve to promote pain.

 Pain is described as burning, “shooting” or “electric-like”
 Positive vs. negative symptoms
 Therapy often unsuccessful
 Pain often effects quality of life (worsened sleep, energy, mood)
 Diagnosis based heavily on clinical presentation, history, and exclusion of other causes

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3
Q

Pathophysiology of neuropathic pain

A

 Is characterized as central or peripheral depending upon where the lesion occurs.
 Many types of neuropathic pain have BOTH peripheral and central components
 Neuropathic pain results from hyper-excitability of either peripheral or central neurons or BOTH

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4
Q

Neuropathic pain

Peripheral vs central

etiology

A
Peripheral:
Diabetic neuropathy
Post-herpetic neuralgia
Trigeminal neuralgia
Chemo-induced
HIV induced sensory neuropathy
Tumor infiltration neuropathy
Phantom limb pain
Central:
Post-Stroke Pain
Multiple Sclerosis induced pain
PD
SC injury
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5
Q

Normal pain propagation (pain processing loop)

A

Painful stimuli carried by nociceptors in the periphery to a collection of cell bodies in the spinal cord known as the dorsal root ganglion
The impulse is carried to the spinalthalamic tract to the cortex for higher processing
The cortex then initiates a complex set of reactions that will ultimately inhibit excitatory impulses Release of NE, 5HT and GABA facilitates inhibition of excitatory impulses.
Overall, the pain processing loop is composed of ascending pain signals and then antinociceptive inhibitory signals

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6
Q

Peripheral sensitization

chars

A

 Inflammatory “soup” causes damage or destruction of peripheral neurons
 Neurons become sensitized (lowered threshold)
 As regeneration of the nerve occurs, an excess of sodium channels and adrenergic receptors occurs
 Peripheral neurons fire impulses spontaneously leading to pain

Sprouting of NEW sodium channels: ENHANCED EXCITATION

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7
Q

Central sensitization

chars

A

Direct injury to central or peripheral structures may permanently alter sensory processing and lead to pain
Damage can cause a LOSS of inhibition (GABA) producing exaggerated pain response
May be the result of an upregulation of excitatory pathways or a loss of inhibitory pathways leading to excitation
Enhanced transmission via NMDA (N-methyl-D-aspartate) receptor
Glutamate is major excitatory amino acid which activates NMDA receptor
Glutamate binds to the NMDA receptor which causes depolarization and calcium influx into cells

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8
Q

Peripheral Diabetic Neuropathy

Gen chars

A

 5-50% of diabetics experience
 Burning, tingling sensations in extremities (usually bilateral)
 More than half of all lower extremity amputations due to DN
Loss of sensation
Loss of proprioception
 May be due to accumulation of sorbitol into peripheral nerves

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9
Q

Drug induced Neuropathic pain

Anti-retrovirals

A

Didanosine

Zalcitabine

Stavudine

Up to 30%

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10
Q

Drug-induced neuropathic pain

Cancer chemo

A

Cisplatin
Vincristine
Paclitaxel
Thalidomide

Up to 80%

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11
Q

Drug-induced neuropathic pain

antibiotics

A

Metronidazole

INH

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12
Q

Post-herpetic neuralgia

chars

A

 A complication of herpes zoster reactivation (shingles)
 Shingles results from reactivation of chickenpox virus
 Most commonly occurs in elderly persons
 Early antivirals + steroids may decrease severity
 Post-herpetic neuralgia is the most common chronic complication of herpes zoster
 Defined as pain persisting longer than 1-3months after healing of shingles lesions
 Usually pain is self-limiting

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13
Q

Post-herpetic neuralgia

prevention

A

Vaccine significantly reduced the incidence of shingles by 51%, PHN by 66.5%, and also reduced the severity of pain by 61%.

Most common AE was injection site rash

Contraindicated in patients immunocomprimised (AIDS/cancer chemotherapy) or in patients with allergy to neomycin or gelatin

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14
Q

Trigeminal Neuralgia

chars

A

 Tic douloureux
 Multiple sclerosis at increased risk
 May be due to compression/demyelinization of 5th cranial nerve
 95% of cases are unilateral
 Episodes can last for months and then spontaneously go into remission

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15
Q

Trigeminal Neuralgia

Tx options

A

1st line: Carbamazepine

2nd line: gabapentin, pregabalin, tramadol, opioids (all +/- CBZ)

3rd line: antiepileptic alone or in combination

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16
Q

Approach to pharmacotherapy

A

 Drug regimen is based upon available evidence and safety information
 Choice is patient specific- consider co-morbidities, drug interactions
 Adequate drug trail needed before considering treatment failure
 Initiate at the lowest possible dose
 Slowly titrate dose (usually every week)
 Titrate one drug at a time
 Try combinations for non-responders or partial responders
 Re-evaluate therapy after several month

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17
Q

Gabapentin

MOA/adverse events/DDI

A

MOA:
Binds to alpha 2 delta subunit of Ca channels to decrease excitation

Adverse Events:
Dizziness
Drowsiness
Peripheral Edema
Cognitive dysfunction
Weight gain

DDI:
Not metabolized thus no DDI
Antacids decrease absorption by 20%

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18
Q

Pregabalin

MOA/adverse events/DDI

A

MOA:
Binds to alpha 2 delta subunit of Ca channels to decrease excitation

Adverse Events:
Dizziness
Drowsiness
Dry Mouth
Cognitive dysfunction
Weight gain

DDI:

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19
Q

Carbamazepine (CBZ)

MOA/adverse events/DDI

A

MOA:
Sodium channel blockade

Metabolized to 10-11 epoxide intermediate; may be resp for many SE

Adverse Events:
Dizziness
Drowsiness
Cognitive dysfunction
Aplastic anemia
Hepatotoxicity
Leukopenia
SJS
SIADH

DDI:
Inducer of P450

Substrate of CYP3A4

CBZ reduces conc of antiepileptics, antidepressants, antipsychs, steroids, warfarin, oral contraceptives

20
Q

Oxcarbazepine

MOA/adverse events/DDI

A

MOA:
Sodium channel blockade

NOT metabolized to 10-11 epoxide intermediate (vs CBZ)

Adverse Events:
Dizziness
Drowsiness
Cognitive dysfunction
Weight gain
Vomiting

Rash
SJS
Hyponatremia

DDI:
Inducer of P450

Substrate of CYP3A4

CBZ reduces conc of antiepileptics, antidepressants, antipsychs, steroids, warfarin, oral contraceptives

21
Q

Lamotrigine

MOA/adverse events/DDI

A

MOA:
Sodium channel blockade

Adverse Events:
Dizziness
Drowsiness
Incoordination

Rash
Hepatotoxicity
SJS (esp with valproic acid)

DDI:
Enzyme inducing AEDs (CBZ) will reduce conc; inhibitors (valproic acid) will increase conc)

22
Q

Topiramate

MOA/adverse events/DDI

A

MOA:
Sodium channel blockade

Adverse Events:
Cognitive dysfunction
Weight loss
Fatigue
Kidney stones
parasthesias

DDI:
Topiramate conc decreased by CBZ

23
Q

Valproic Acid

MOA/adverse events/DDI

A

MOA:
Unknown; may increase GABA; may block sodium channels

Adverse Events:
GI disturbances
Drowsiness
Incoordination
Hair loss
Weight gain

Aplastic anemia
Thrombocytopenia
Hepatotoxicity

DDI:
Inhibits metabolism of other drugs

24
Q

Gabapentin

Indication

A

PHN

1st line for many types of NP pain

25
Q

Pregabalin

indication

A

PHN

PDN

26
Q

Carbamazepine

indication

A

1st line for TN;

useful in many other types of NP pain but side effects limit use to 3rd line agent

27
Q

Oxcarbazepine

indication

A

Alternative for tx of TN

May consider for other types of NP pain (3rd line)

28
Q

Lamotrigine

indication

A

2nd or 3rd line for NP pain

29
Q

Topiramate

indication

A

2nd or 3rd line for PDN

30
Q

Valproic acid

indication

A

3rd line for NP pain

31
Q

TCA

MOA/adverse events/DDI

A

MOA:
Blocks re-uptake of NE and 5HT

Adverse Events:
Anticholinergic SE: weight gain, sedation, orthostatic hypotension

Cardiac arrhythmias

DDI:
Do not use with MAO-Inhibitor

Duloxetine may increase levels

Do not use in patients with acute MI

Do not use in patients with glaucoma or BPH

32
Q

SSRI

MOA/adverse events/DDI

A

MOA: SSRI

Adverse Events:
Insomnia
Dizziness
n/d
dry mouth
sexual dysfunction

DDI:
Concomitant use with NSAIDs may increase risk of bleeding

Inhibits metabolism of TCAs

Do not use with MAO-inhibitors

33
Q

Duloxetine

MOA/adverse events/DDI

A

MOA: Inhibits re-uptake of NE and 5HT

Adverse Events:
Dizziness
Drowsiness
Sexual dysfunction
Diarrhea
Dry mouth
Weight loss

DDI:
Inhibitor of P450 2D6 may incr conc of TCAs

Do not use with MAO-inhibitor

34
Q

Venlafaxine

MOA/adverse events/DDI

A

MOA: Inhibits re-uptake of NE and 5HT

Adverse Events:
Nausea
Constipation
Sexual dysfunction
Dizziness
Orthostasis
Insomnia
HTN
Somnolence
Ventricular arrhythmias

DDI:
Concmittant use with NSAIDS may incr risk of bleeding

Caution with TCAs and SSRIs

35
Q

Tramadol

MOA/adverse events/DDI

A

MOA: Inhibits re-uptake of NE and 5HT

Adverse Events:
Dizziness
Drowsiness
Orthostatic Hypotension

Incr risk of seizures in patients w/ hx of seizures

DDI:
CBZ increases metabolism

Both tramadol and TCAs lower seizure threshold

SSRIs can decrease metabolism and cause serotonin syndrome and seizures

36
Q

Opioid analgesics (morphine, oxycodone)

MOA/adverse events/DDI

A

MOA: Bind to opioid recs in the CNSq

Adverse Events:
Constipation
Nausea
Sedation
Cognitive impairment
Dependence

Serious: respiratory depression

DDI:
Additive effects of sedation and respiratory depression when used with other opioids

37
Q

Lidocaine patch

MOA/adverse events/DDI

A

MOA: Sodium channel blockade

Adverse Events:
Skin erythema, pain

Little systemic absorption

Do not apply to open lesions

DDI:
none

38
Q

Capsaicin cream/patch

MOA/adverse events/DDI

A

MOA: Stimulation of nerve fibers to release substance P

Adverse Events:
Local irritation and burning

Coughing

DDI:
None

Do not apply to open lesions

39
Q

TCA

indication

A

1st line for most types of NP pain

40
Q

SSRI

indication

A

3rd line agent for NP

41
Q

Duloxetine

Indication

A

1st line for PDN

42
Q

Venlafaxine

indication

A

1st line for PDN

43
Q

Tramadol

indication

A

1st line for most types of NP pain

44
Q

Opioid analgesics

indication

A

1st line for most types of NP pain

45
Q

lidocaine patch

indication

A

PHN

46
Q

Capsaicin

indication

A

PHN

PDN

47
Q

Look at chart on pg. 398 about what to give with which pain

A

Do it