NSAIDs/Pain Management

Question 1

NSAIDs only relate in the fact that they all

Answer 1

Inhibit the enzyme making prostaglandins- cyclooxygenase

Question 2

Mechanism of NSAIDs- two step process

Answer 2

COX breaks down arachidonic acid–> prostaglandin G2–>prostaglandin H2–> tissue specific prostaglandins.

Question 3

Two types of COX

Answer 3

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

Question 4

Prostaglandins and pain

Answer 4

Allodynia/hyperalgesia
Sensitize nerve endings- touch triggers them now
Enhance pain in CNS (amplifies pain by hyperalgesia) and PNS

Question 5

How do prostaglandins enhance pain in CNS

Answer 5

Increase SP and glutamate release
Increase sensitivity of 2nd order neurons
Decreased release of inhibitory transmitters descending

Question 6

NSAIDs and pain

Answer 6

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.

Question 7

Normal gastric protective mechanisms

Answer 7

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

Question 8

GI toxicity

Answer 8

Not often associated with dyspepsia- usually a silent ulceration in 70%

Question 9

NSAID renal concerns- 1st

Answer 9

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

Question 10

Renal concerns- 2nd

Answer 10

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

Question 11

NSAIDs and CV

Answer 11

They all have a CV risk but:
Naproxen is the lowest
Diclofenac is the highest

Question 12

PGs and hemostasis

Answer 12

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.

Question 13

NSAIDs and hemostasis

Answer 13

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.

Question 14

Hematologic toxicity- NSAIDs vs ASA

Answer 14

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

Question 15

COX-2 inhibitor

Answer 15

Have no platelet affects

*celecoxib

Question 16

NSAID side effects

Answer 16

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

Question 17

NSAID cautions

Answer 17

Wary of using in history of- ulcers, coagulopathy, renal disease, hepatic disease
CV disease: ASA okay on low dose

Question 18

Reye’s Syndrome

Answer 18

ASA (aspirin) given to children with a viral illness- causes hepatotoxicity, lactic acidosis, seizures, coma, death
Dose related risk increase

Question 19

NSAIDs to know

Answer 19

Ibuprofen (Motrin)
Naprosyn (naproxen, alleve)
Indomethacin
Diclofenac
Nabumetone
Ketorolac
Acetylsalicylic acid
Meloxicam
Celecoxib
Acetaminophen

Question 20

ASA and platelet inhibition is useful for

Answer 20

Cardioprotection and stroke protection

Question 21

Generic IV NSAID

Answer 21

Ketorolac- potent analgesic, hospital use, multimodal analgesia when IV opioids are not working, works on CNS

Question 22

An opioid resistant pain that NSAIDs are good for

Answer 22

Incident pain- pain only present when patient moves

Nerve pain- not C fiber mediated (which opioids primarily act on)

Question 23

What is neuropathic pain?

Answer 23

After a PNS/CNS injury- wiring damage
Opioid resistant- hard to treat
Shooting, burning with sensory changes.

Question 24

Acute pain medications

Answer 24

Non-opioid: NSAIDs/APAP, muscle relaxants, topical (lidocaine)
Opioid: tramadol, opioids

Question 25

IV benzodiazepines for muscle spasms warning

Answer 25

Warning with opioids*

Question 26

PCA continuous infusion option

Answer 26

For patients on chronic preop opioids ONLY

Tolerant to analgesia and hypovolent

Question 27

Muscle relaxants- antispasticity

Answer 27

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

Question 28

Muscle relaxants- MSK pain disorders

Answer 28

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

Question 29

Multimodal analgesia

Answer 29

Two work by DIFFERENT mechanisms

Synergy, reduced side effects

Question 30

Chronic pain management meds

Answer 30

Daily-Antidepressants, anticonvulsants, debatable are NSAIDs and opioids.
Acute on chronic- NSAIDs, muscle relaxants, opioids

Question 31

Antidepressants

Answer 31

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

Question 32

Antiepileptic drugs

Answer 32

Gabapentin- best for shooting, intermittent stabbing pain.