NSAIDs/Pain Management Flashcards
NSAIDs only relate in the fact that they all
Inhibit the enzyme making prostaglandins- cyclooxygenase
Mechanism of NSAIDs- two step process
COX breaks down arachidonic acid–> prostaglandin G2–>prostaglandin H2–> tissue specific prostaglandins.
Two types of COX
Both make PGs from AA
Each has its own gene
COX1 is the housekeeping one- present in most tissues all the time
COX2 is the inflammatory one- appears when injury/inflammation occurs, one causing pain, except in CNS, kidney, uterus
Prostaglandins and pain
Allodynia/hyperalgesia
Sensitize nerve endings- touch triggers them now
Enhance pain in CNS (amplifies pain by hyperalgesia) and PNS
How do prostaglandins enhance pain in CNS
Increase SP and glutamate release
Increase sensitivity of 2nd order neurons
Decreased release of inhibitory transmitters descending
NSAIDs and pain
They simply blunt PNS/CNS sensitization, so they are anti-hyperalgesics, not anti-inflammatories.
They can act without inflammation: CNS action, hangover, headache, postop pain, molar extractions, sunburn
Need an upregulation of PGs to have benefit
‘Afterward’ pain is blunted, not initial pain.
Normal gastric protective mechanisms
PG-dependent protective factors that increase mucous layer thickness, pH gradient, bicarbonate secretion, and mucosal blood flow. Mostly COX-1
Why NSAIDs are an indirect cause of stomach ulcers
GI toxicity
Not often associated with dyspepsia- usually a silent ulceration in 70%
NSAID renal concerns- 1st
BP elevation/diuretic interaction- because they are highly protein bound, they cannot be dialyzed. NSAIDs enhance the ability to absorb sodium concentrate, so we hold onto more water. Edema, stroke, heart attacks. Caution of those who are HTN/renal issues
Renal concerns- 2nd
Decreases perfusion states, PGs normally dilate afferent blood vessels. NSAIDs choke off blood supply- ischemia, renal failure
Caution in patients with: Dehydration, blood loss, reduced cardiac output (CHF), and low blood pressure
NSAIDs and CV
They all have a CV risk but:
Naproxen is the lowest
Diclofenac is the highest
PGs and hemostasis
Prostacyclin (PGI2) made by COX2- made in endothelium which have nuclei, platelet inhibitor and vasodilator.
Thromboxane A2 made by COX1- made in platelets which do not have nuclei. Platelet activator and vasoconstrictor.
The platelet side is usually very inactive, endothelial side is minimally active.
NSAIDs and hemostasis
Blocks formation of COX1 making TXA2 more so, since this one is more active during bleeding/injury in platelets. Inhibiting it= decreasing clotting (bad if undergoing surgery)
Since the endothelial COX2 and PGI2 are minimally active, no big change is seen from blocking it.
Hematologic toxicity- NSAIDs vs ASA
NSAIDs reversibly bind COX, so coagulation normalizes after a couple half lives
ASA irreversibly acetylates COX, so since platelets do not have nuclei, have to make completely new platelets before coagulation can recover: 7-10 days. Endothelium has nuclei and can recover
COX-2 inhibitor
Have no platelet affects
*celecoxib
NSAID side effects
Stomach/duodenal ulceration Decrease platelet clotting function Decrease blood flow in kidneys Edema and HTN- in at risk patients only, it will increase CV risk (high BP and CAD) Reports of hepatic dysfunction
NSAID cautions
Wary of using in history of- ulcers, coagulopathy, renal disease, hepatic disease
CV disease: ASA okay on low dose
Reye’s Syndrome
ASA (aspirin) given to children with a viral illness- causes hepatotoxicity, lactic acidosis, seizures, coma, death
Dose related risk increase
NSAIDs to know
Ibuprofen (Motrin) Naprosyn (naproxen, alleve) Indomethacin Diclofenac Nabumetone Ketorolac Acetylsalicylic acid Meloxicam Celecoxib Acetaminophen
ASA and platelet inhibition is useful for
Cardioprotection and stroke protection
Generic IV NSAID
Ketorolac- potent analgesic, hospital use, multimodal analgesia when IV opioids are not working, works on CNS
An opioid resistant pain that NSAIDs are good for
Incident pain- pain only present when patient moves
Nerve pain- not C fiber mediated (which opioids primarily act on)
What is neuropathic pain?
After a PNS/CNS injury- wiring damage
Opioid resistant- hard to treat
Shooting, burning with sensory changes.
Acute pain medications
Non-opioid: NSAIDs/APAP, muscle relaxants, topical (lidocaine)
Opioid: tramadol, opioids
IV benzodiazepines for muscle spasms warning
Warning with opioids*
PCA continuous infusion option
For patients on chronic preop opioids ONLY
Tolerant to analgesia and hypovolent
Muscle relaxants- antispasticity
Baclofen- GABA pre and post receptor for muscle pain and neuropathic pain
Tizanidine- alpha-2 receptor agonist to blunt sympathetic outflow, sedation and hypotension possible
Muscle relaxants- MSK pain disorders
Cyclobenzaprine- only one that can be used daily, TCA like action
Carisoprodol- aka soma, metabolized to meprobamate, withdrawal from this can kill you, sedative and habituative, barbiturate metabolite, DO NOT USE
Multimodal analgesia
Two work by DIFFERENT mechanisms
Synergy, reduced side effects
Chronic pain management meds
Daily-Antidepressants, anticonvulsants, debatable are NSAIDs and opioids.
Acute on chronic- NSAIDs, muscle relaxants, opioids
Antidepressants
TCAs and SNRIs are analgesic- block reuptake of both 5-HT and NE Enhance descending inhibitory system NOT via Rx of depression Need 2-4 weeks to see effects NO TOLERANCE
Antiepileptic drugs
Gabapentin- best for shooting, intermittent stabbing pain.
