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Pharmacologic agents used in treatment of persistent pain

Pharmacologic Agents Used in the Treatment of
Persistent Pain

Indications and Common Uses

Class/Agent Indication Common
(Off-Label) Use
Level of Evidence
Acetaminophen
Multiple randomized controlled clinical trials for headache and non-neuropathic pain conditions Lidocaine patch 5%
postherpetic neuralgia Moderate- Randomized trial for osteoarthritis; open-label trials for diabetic neuropathy, low back pain Carbamazepine:
Carbamazepine:
Carbamazepine
Gabapentin
Gabapentin:
Gabapentin: Diabetic
gabapentin and pregabalin.
Lamotrigine
Lamotrigine: Diabetic neuropathy
Phenytoin
Pregabalin:
Pregabalin
Lamotrigine, phenytoin:
Duloxetine: Diabetic
Duloxetine: Some evidence for
Venlafaxine: No
Duloxetine
Venlafaxine
Venlafaxine: Equivocal findings for
neuropathy and neuralgia (very
limited published data)
Amitriptyline
Amoxapine
Desipramine
Nortriptyline
Protriptyline
Capsaicin
Celecoxib
Rofecoxib
Valdecoxib
Baclofen
Ketamine
as yet unproven. Some use for breakthrough pain in chronic pain Diclofenac
Ibuprofen
Naproxen
Ibuprofen: Acute
Salsalate
Diclofenac, naproxen:
Ankylosing spondylitis
Tramadol
Oxycodone and
Hydromorphone
Levorphanol
Levorphanol specifically for
Morphine
levorphanol and
neuropathic pain, oxycodone for
Oxycodone
morphine: Chronic
Fentanyl
Transdermal System§
Sites/Modes of Action and Safety

Class/Agent
Site/Mode of Action
Side Effects/Tolerability
Inhibits synthesis of prostaglandins in the central Acetaminophen
nervous system. Peripherally blocks pain impulse Safety concerns: Renal and/or hepatic dysfunction (may be irreversible) with chronic use Peripherally blocks neuronal permeability to Lidocaine patch 5%
sodium ions preventing depolarization and Work centrally. Gabapentin and pregabalin have
Carbamazepine
specific GABA binding sites; also produce calcium Gabapentin
channel blockade. Carbamazepine may limit
Lamotrigine
influx of sodium ions across cell membranes, Phenytoin
depressing synaptic transmission or decreasing Pregabalin
summation of temporal stimulation. Lamotrigine
Gabapentin: Concerns only in
and phenytoin produce sodium channel
blockade. Lamotrigine inhibits release of
Carbamazepine: Bone marrow
suppression/blood dyscrasias,
hypersensitivity/anaphylaxis, hepatic
dysfunction, SIADH
Lamotrigine: Stevens-Johnson
syndrome
Centrally inhibit serotonin-norepinephrine reuptake inhibition. Possible calcium channel Duloxetine
Venlafaxine
Work centrally and possibly peripherally. Sodium Amitriptyline
channel blockade. Inhibition of norepinephrine Amoxapine
and serotonin reuptake. Possible calcium channel Desipramine
blockade and central and peripheral alpha- Nortriptyline
Protriptyline
changes, orthostatic hypotension, serotonin syndrome (with other serotonergic agents) Vanilloid receptor antagonist suppresses spinal cord pain signaling; depletes the neuron of Capsaicin
Safety concerns: Few, but may cause burning of mucous membranes if applied inadvertently Work peripherally by inhibiting COX-2 enzyme, Celecoxib
reducing inflammation and pain. Possible central Rofecoxib
Valdecoxib
Work centrally. GABA-B agonism inhibits pain signaling. Inhibits transmission of reflexes at Baclofen
spinal cord level, possibly by hyperpolarization of Safety concerns: Respiratory depression with unintentional overdose Direct action on the cortex and limbic system of Ketamine
hallucinations Safety concerns: Hypersensitivity Work peripherally on inflammation and pain by Diclofenac
Ibuprofen
Naproxen
Salsalate
lower extremity edema Safety concerns: Gastrointestinal ulceration, bleeding/impaired coagulation, renal impairment Work centrally by weak mu opioid receptor agonism and serotonin-norepinephrine reuptake Tramadol
inhibition. Possible sodium, calcium, and/or Safety concerns: Seizures (usually with overdosage), serotonin syndrome with antidepressants Central: Binds to opioid receptors in CNS to inhibit Side effects: Sedation, drowsiness, Hydromorphone
ascending transmission of nociceptive signals; Morphine
activates midbrain descending pain controls. Oxycodone
Peripheral: Binds to opioid receptors on peripheral sexual dysfunction due to decreased nerves, decreasing pain signaling sex hormone levels Safety concerns: Respiratory depression (rare in ambulatory settings), immune dysfunction via lymphocyte depletion Fentanyl
Transdermal System§

*FDA requested labeling for COX-2 agents to include boxed warning highlighting potential increased risk of
cardiovascular (CV) events; FDA requested revised labeling for NSAIDs to provide more specific information about
potential CV and GI risks.
†Removed from market in 2005 at FDA request because of safety issues. ‡Removed from market in 2004 at FDA request because of safety issues. §Public health advisory issued July 2005 by FDA regarding the safe use of transdermal fentanyl patches for pain control.

Source: http://www.painedu.org/Downloads/NIPC/Pharmacologic_Agents.pdf

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