Chronic pain pharmaceuticals Flashcards
Common chronic pain syndromes
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)
Causalgia
Syndrome of sustained burning pain, allodynia, and hyperpathia after a traumatic nerve lesion, often combined with vasomotor and sudomotor dysfunction and later trophic changes
1st line agents used in chronic neuropathic pain
TCAs
Anticonvulsants - gabapentin, pregabalin, carbamazepine
2nd line agents used in chronic neuropathic pain
SSNRIs: venlafaxine
Topical lidocaine
3rd/4th line agents used in chronic neuropathic pain
opioid analgesics tramadol SSRIs other anticonvulsants IV lidocaine, mexilitine Topical capsaicin Cannabinoids NMDA receptor antagonists: ketamin, dextromethorphan
TCA - secondary amines
Nortriptyline
Despiramine
TCA - tertiary amines
Amitriptyline
Imipramine
TCA effectiveness
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
TCA MOA (chronic pain)
unclear
serotonin/norepinephrine reuptake inhibition
increased endogenous inhibition by increasing descending pathway transmission
TCA dose/onset
analgesic dose is lower than antidepressant dose
analgesic effect almost immediate
TCA side effects
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
Calcium channel alpha-2-delta ligands
Gabapentin
Pregabalin
Gabapentin
GABA analogue
anticonvulsant
Pregabalin
Gabapentin analogue
anti-convulsant
Gabapentin effectiveness/indications
antiallodynic
no effective on nociceptive threshold
used in chronic neuropathic pain
published evidence but true effectiveness questioned?
Gabapentin MOA
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
Pregabalin effectiveness/indications
chronic neuropathic pain
anxiolytic
Pregabalin MOA
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
Gabapentin dose/onset
100-4800 mg/d
reduce in renal failure
oral bioavailability unpredictable
Pregabalin dose/onest
75-600 mg/d
reduce in renal failure
Gabapentin SEs
relatively well-tolerated with few SEs:
- dizziness, somnolence, confusion, ataxia
- peripheral edema
Pregabalin SEs
generally well-tolerated with few SEs:
- dizziness, somnolence, confusion, ataxia
- peripheral edema
Carbamazepine effectiveness (chronic pain)
anticonvulsant
drug of first choice for trigeminal neuralgia (tic doloreux)
otherwise limited evidence for analgesic effectiveness
Carbamazepine MOA (chronic pain)
unclear
maybe? blockade of Na channels
Carbamazepine dose/onset (chronic pain)
200-1200 mg/d divided in two doses
hepatic enzyme induction
Carbamazepine major side effects
Dizziness Ataxia Nausea Hepatitis Aplastic anemia Stevens-Johnson syndrome
Other anticonvulsants used for chronic pain
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)
Tramadol effectiveness
postherpetic neuralgia
diabetic neuropathy
polyneuropathies/post-amputation pain
Extended release formulation approved in Canada
Tramadol MOA
synthetic opioid
weak mu-agonist activity
inhibits serotonin and norepinephrine reuptake
peripheral local anesthetic properties
Tramadol dose
100-300 mg once a day
Tramadol side effects
Relative LACK of:
- respiratory depression
- major organ toxicity
- depression of GI motility
- reduced seizure threshold
- relatively low abuse potential
Topical capsaicin effectiveness
diabetic neuropathy
postherpetic neuralgia
anecdotal evidence for other types of neuropathic pain
Transdermal application
Capsaicin MOA
prototype agonist at transient receptor potential vanilloid 1 (TRPV1) receptors
depetion of substance P in C-fibers
Nociceptor desensitization
Cannabinoid effectiveness
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
Cannabinoid SEs
lack of long-term followup data dizziness, fatigue, nausea, mood changes potential for cognitive impairment precipitation of psychosis suicidal ideation Positive urine drug testing!
Drugs NOT indicated in chronic pain
hypnotics/sedative-containing preparations
example: FIORINAL, which contains:
- butalbital (barbiturate, associated with high abuse potential)
- caffeine
- ASA
Canadian Consensus Guideline: treatment algorithm (2007) for neuropathic pain
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
