Chronic pain pharmaceuticals

Question 1

Common chronic pain syndromes

Answer 1

Headache - most common
Back pain - 2nd most common
Post herpetic neuralgia
Pain associated with diabetic neuropathy
Phantom limb pain
Myofascial pain
Posttraumatic neuropathic pain
Central pain
Complex regional pain syndrome (CRPS)
- type I: formerly reflex sympathetic dystrophy (RDS)
- type II: formerly causalgia (burning pain)

Question 2

Causalgia

Answer 2

Syndrome of sustained burning pain, allodynia, and hyperpathia after a traumatic nerve lesion, often combined with vasomotor and sudomotor dysfunction and later trophic changes

Question 3

1st line agents used in chronic neuropathic pain

Answer 3

TCAs

Anticonvulsants - gabapentin, pregabalin, carbamazepine

Question 4

2nd line agents used in chronic neuropathic pain

Answer 4

SSNRIs: venlafaxine

Topical lidocaine

Question 5

3rd/4th line agents used in chronic neuropathic pain

Answer 5

opioid analgesics
tramadol
SSRIs
other anticonvulsants
IV lidocaine, mexilitine
Topical capsaicin
Cannabinoids
NMDA receptor antagonists: ketamin, dextromethorphan

Question 6

TCA - secondary amines

Answer 6

Nortriptyline

Despiramine

Question 7

TCA - tertiary amines

Answer 7

Amitriptyline

Imipramine

Question 8

TCA effectiveness

Answer 8

avg treated patients have less pain than 74% of patients w/ placebo
most effective in diabetic neuropathy and postherpetic neuralgia
relief of concomitant symptoms: sleep disorder, anxiety disorder, depression

Question 9

TCA MOA (chronic pain)

Answer 9

unclear
serotonin/norepinephrine reuptake inhibition
increased endogenous inhibition by increasing descending pathway transmission

Question 10

TCA dose/onset

Answer 10

analgesic dose is lower than antidepressant dose

analgesic effect almost immediate

Question 11

TCA side effects

Answer 11

Anticholinergic
CVS:
- postural hypotension (due to alpha blockade - increased risk of falls in the elderly, particularly with amitryptiline)
- conduction delay/myocardial depression - typically in OD

2ndary amines are better tolerated than tertiary amines

Question 12

Calcium channel alpha-2-delta ligands

Answer 12

Gabapentin

Pregabalin

Question 13

Gabapentin

Answer 13

GABA analogue

anticonvulsant

Question 14

Pregabalin

Answer 14

Gabapentin analogue

anti-convulsant

Question 15

Gabapentin effectiveness/indications

Answer 15

antiallodynic
no effective on nociceptive threshold
used in chronic neuropathic pain
published evidence but true effectiveness questioned?

Question 16

Gabapentin MOA

Answer 16

does not act via GABA receptors
binds to alpha2delta-1 subunits of presynaptic CaV channels
Reduces release of glut, norepi, substance P, CGRP (excitatory nociceptive NTs

Question 17

Pregabalin effectiveness/indications

Answer 17

chronic neuropathic pain

anxiolytic

Question 18

Pregabalin MOA

Answer 18

similar to gabapentin
binds to alpha2delta-1 Ca channel subunits with higher affinity
Reduces release of glutamate, norepi, substance P, CGRP
More linear pharmacokinetics than gabapentin

Question 19

Gabapentin dose/onset

Answer 19

100-4800 mg/d
reduce in renal failure
oral bioavailability unpredictable

Question 20

Pregabalin dose/onest

Answer 20

75-600 mg/d

reduce in renal failure

Question 21

Gabapentin SEs

Answer 21

relatively well-tolerated with few SEs:

• dizziness, somnolence, confusion, ataxia
• peripheral edema

Question 22

Pregabalin SEs

Answer 22

generally well-tolerated with few SEs:

• dizziness, somnolence, confusion, ataxia
• peripheral edema

Question 23

Carbamazepine effectiveness (chronic pain)

Answer 23

anticonvulsant
drug of first choice for trigeminal neuralgia (tic doloreux)
otherwise limited evidence for analgesic effectiveness

Question 24

Carbamazepine MOA (chronic pain)

Answer 24

unclear

maybe? blockade of Na channels

Question 25

Carbamazepine dose/onset (chronic pain)

Answer 25

200-1200 mg/d divided in two doses | hepatic enzyme induction

Question 26

Carbamazepine major side effects

Answer 26

``` Dizziness Ataxia Nausea Hepatitis Aplastic anemia Stevens-Johnson syndrome ```

Question 27

Other anticonvulsants used for chronic pain

Answer 27

Lamotrigine, valproic acid, topiramate Few trials show effectiveness MOA unclear, Na blockade? Should be withheld until other interventions have been tried (other than trigeminal neuralgia)

Question 28

Tramadol effectiveness

Answer 28

postherpetic neuralgia diabetic neuropathy polyneuropathies/post-amputation pain Extended release formulation approved in Canada

Question 29

Tramadol MOA

Answer 29

synthetic opioid weak mu-agonist activity inhibits serotonin and norepinephrine reuptake peripheral local anesthetic properties

Question 30

Tramadol dose

Answer 30

100-300 mg once a day

Question 31

Tramadol side effects

Answer 31

Relative LACK of: - respiratory depression - major organ toxicity - depression of GI motility - reduced seizure threshold - relatively low abuse potential

Question 32

Topical capsaicin effectiveness

Answer 32

diabetic neuropathy postherpetic neuralgia anecdotal evidence for other types of neuropathic pain Transdermal application

Question 33

Capsaicin MOA

Answer 33

prototype agonist at transient receptor potential vanilloid 1 (TRPV1) receptors depetion of substance P in C-fibers Nociceptor desensitization

Question 34

Cannabinoid effectiveness

Answer 34

Delta-9-tetrahydrocannabinol-cannabidiol Buccal spray conditionally approved in Canada for neuropathic pain associated with MS effective in reducing central pain and painful spasms in MS

Question 35

Cannabinoid SEs

Answer 35

``` lack of long-term followup data dizziness, fatigue, nausea, mood changes potential for cognitive impairment precipitation of psychosis suicidal ideation Positive urine drug testing! ```

Question 36

Drugs NOT indicated in chronic pain

Answer 36

hypnotics/sedative-containing preparations example: FIORINAL, which contains: - butalbital (barbiturate, associated with high abuse potential) - caffeine - ASA

Question 37

Canadian Consensus Guideline: treatment algorithm (2007) for neuropathic pain

Answer 37

1) TCA/gabapentin or pregabalin 2) SNRI, topical lidocaine 3) Tramadol, CR opioid analgesic 4) cannabinoids, methadone, lamotrigine, topiramate, valproic acid - add sequentially if partial relief