Flashcards in NSAIDs and Acetaminophen Deck (84):
Types of pain
-Nociceptive (somatic, visceral)
What is the mechanism of pain and what are its mediators?
Describe the stages of the neural pain pathway
What occurs in the stimulation phase of the neural pain pathway?
-Noxious stimuli activate receptors
-Release of bradykinins, H and K ions, PGs, histamine, ILs, TNF, serotonin and Sub P
What occurs in the transmission phase of the neural pain pathway?
-A and C afferent nerve fibers stimulated
-Synapse along spinal cord dorsal horn releases NTs
-Impulses passed along ascending pathway to the brain
What occurs in the modulation phase of the neural pain pathway?
-Pain becomes a conscious experience via limbic system
-Endogenous opiate system in CNS modulates pain impulses
-Descending system of nerves may inhibit synaptic pain transmission
-Subset of nociceptive pain
-Natural shift from protection of damage to promotion of healing
Describe maladaptive inflammation
-Action outlives function
-Chemical properties of neurons change which effects transmission of pain
-Often caused by disease
What is the beginning component of the COX pathway normally?
(released upon trigger of natural inflammatory cascade)
General function of COX?
Oxygenates arachidonic acid which forms PGs, prostacyclin, thromboxane
What is misoprostol and what does it do?
-Induces uterine contractions
-Protects GI mucosa
What is alprostadil and what does it do?
-Maintain patent ductus arteriosis
What is latanoprost and what does it do?
-Treatment of open angle glaucoma
What is prostacyclin and what does it do?
-Treatment of pulmonary HTN
Describe selective NSAIDs
Selectively blocks COX-2 (over COX-1)
-GI, renal blood flow
Activated only as needed
-Inflammation, fever, pain
Major difference between aspirin and all other NSAIDs
Aspirin irreversibly (!) binds to COX-1 and COX-2
MOA of Aspirin
Irreversibly binds to COX-1 and COX-2 (inhibiting PG synthesis and preventing formation of TXA2)
-Analgesic (at high doses)
-Anti-inflamm (at high doses)
Peak plasma levels of aspirin occurs when?
Is aspirin more selective to COX-1 or COX-2?
COX-1 as long as it is under 100 mg dosage
Contraindications to aspirin
-Pregnancy C/D (avoid esp in 3rd trimester)
-Children under 16 yo w/viral illness (risk of Reye's syndrome)
-Asthma, nasal polyps, recurrent sinusitis
How does aspirin (or any salicylates) toxicity present?
What is the MC used non-selective NSAID?
Ibuprofen MOA and use
-Reversibly blocks COX-1 and 2
-Used in mild to moderate pain
What is the new formulation of ibuprofen and what does it do?
-For moderate pain and used to decrease opioid dose required
Pediatric use of ibuprofen?
-Commonly for fever and pain
-5 to 10 mg/kg/dose Q6-8h
Dosing of ibuprofen
It has both an OTC dose (200-400 mg Q6-8h) and a prescription dose (600-800 mg Q6-8h)
Toxicity of ibuprofen
-Similar to all non-selective NSAIDs
-May be more prone to GI side effects due to increased use vs. other products
Until recently, what was the only NSAID available IV?
(still most widely used)
-Most widely used IV NSAID
-Used for moderate to severe pain (a level that would require opioid therapy)
-Never used pre-op!
Believed to be more potent than other NSAIDs so higher risk for ADRs
-All NSAID warnings
-Any situation with increased bleeding risk
Naproxen key features
-Found in numerous OTC products in various strengths
-Always dosed BID
Max dose of naproxen a day? With CVD risk?
-440 mg/day w/CVD risk
What is the novel agent of naproxen?
-Vimovo = naproxen/esomeprazole
-For patients w/GI bleed risks
Dosing of ketorolac
Total dose should NOT exceed 5 days or 20 doses
Nabumetone key features
-24+ hours half life (QD dosing)
-Monitor renal function!
-Preferred for chronic arthritis
Piroxicam key features
-36-80 hrs half life (QD dosing)
-Much higher risk of ADRs
-Super high risk of GI ulceration
Oxaprozin key features
-50 to 60 hrs half life (QD dosing)
Which nonselective NSAIDs can be dosed once a day? Why?
*Long half life!
What is indomethacin and what population is it primarily used in?
-Neonates to close PDA when it is open
What are the increased risks of indomethacin?
-CNS (HA, dizzy, psychosis)
What is Sulindac and how is it dosed? What are the potential adverse effects?
-Increased risk of SJS and liver damage
Somewhat selective for COX-2 (providing potentially less GI toxicity)
What is a novel agent of diclofenac?
-Pregnancy X bc of misoprostol
-Increased diarrhea, cramping
More selective for COX-2 but not fully
Meloxicam dosing and half life
Can be dosed QD because half life is 15-20 hours
Celecoxib key features
-Only fully selective COX-2 still available in US
-Similar efficacy vs. non-selective NSAIDs
-Proposed decrease in GI toxicity
What is celecoxib MC used for?
-Osteoarthritis and RA
-Decreases pain and swelling, increases function (no effect on disease itself)
Contraindications of celecoxib
-Same warnings as other NSAIDs
-Increased risk of MI/stroke (dose related)
-Preg Cat C prior to 30 wks gestation
-Preg Cat D 30 wks and beyond
General NSAID ADRs
-GI (dyspepsia, ulceration)
-Renal (decreased BF, interstitial nephritis)
-Hematologic (d/t inhibition of TXA2)
Black box warnings of NSAIDS
1. CV (esp post MI and stroke)
2. GI (including bleeding, ulcers)
3. CABG (contraindicated for peri-op pain during CABG)
Which population is at greater risk for serious GI events with NSAIDs?
What is the cause of GI toxicity with NSAIDs?
-Block of systemic PGE2/PGI2 synthesis
-Loss of cytoprotection in gut
Which agents are proven to prevent NSAID induced gastric AND duodenal ulcers?
-Misoprostol (not used by itself often though)
-H2 blockers (can be used interchangeably 1st line with PPI)
-PPIs (MC used)
What class is misoprostol, what is it used for, and what is important to know about it?
-Prevention of NSAID induced ulcers
-Preg Cat X
How do NSAIDs cause nephrotoxicity?
-PGs acts as vasodilators
-NSAIDs block PGs
-Afferent arteriole vasoconstricts which lowers GFR
Populations at risk for NSAID induced nephrotoxicity
-65 yo or older
-Pts on methicillin abx
What are the CV concerns with NSAID use?
COX2 selective NSAIDs!
-Block COX2 (blocking PG synthesis) resulting in vasoconstriction
-Lack of COX1 blockage results in platelet aggregation
-Vasoconstriction and platelet aggregation increases risk of cardiac events
Patients at risk for CV events with NSAID use:
Have had or have risk factors for: CABG, UA, MI, ischemic events
What is the only NSAID studied to date that has NOT shown a risk of CV complications?
If you have to use a COX-inhibitor, avoid CV concerns by:
-Choosing NON-selective first (Naproxen)
-Use COX2 selective agents LAST
-Use lowest dose possible and titrate while monitoring closely
-Add ASA 81 mg daily or a PPI if pt has a known thrombotic risk
If a patient has known thrombotic risk and is using NSAIDs, what should be added to avoid CV concerns?
ASA 81 mg daily
Pregnancy concerns of NSAID use?
-May be a/w miscarriage (weak evidence)
-Closure of ductus arteriosus and development of pulm HTN (a/w 3rd trimester use)
NSAID drug-drug interactions
1. Warfarin and anticoag (increased bleeding risk)
2. ACE-I (renal toxicity and may decrease effectiveness of anti-HTN)
3. Aspirin w/other NSAIDs
If aspirin is taken with other NSAIDs, how should they be taken?
Space ASA by 2 hours and give it first
When is the only time you would recommend ASA with another NSAID in a patient?
Known thrombotic risk
Which NSAIDs should be avoided in hepatic dysfunction?
Which topical NSAIDs have shown effectiveness in reducing pain?
-Diclofenac (FDA approved)
*Benefit is likely only 2-4 wks
Describe topical diclofenac
-Patch (Flector), solution (Pennsaid), gel (Voltaren)
-Wash hands after use!
-Systemic warnings apply to topical diclofenac
What is topical diclofenac used for?
-Mild localized OA or RA
-Penetration limits use on hip arthritis
What is methyl salicylate? MOA? How long should it be used?
-Salicylic acid (similar but different than aspirin)
-Causes vasodilation of cutaneous vasculature
-Decreases PG synthesis (not believed to be through COX inhibition)
-No more than 1 week use!
Methyl salicylate ADRs
-Mostly topical irritation
-Systemic toxicity can occur (tinnitus, increased HR, DOE)
Patient education on methyl salicylate
Avoid using with:
What is acetaminophen? MOA? Use?
-Used for mild-mod pain (antipyretic, analgesic)
-NOT an NSAID, NO effect on inflammation
-Blocks PG synthesis in CNS, prohibits peripheral pain impulses
-May act on COX-3
Peak plasma levels of acetaminophen? Half life?
-30-60 mins peak levels
-2-3 hrs half life
Max dose of acetaminophen per day?
4 grams (4000 mg)
How is acetaminophen metabolized?
Hepatic (glucuronidation) primarily
-Liver failure in acute or chronic OD
When should acetaminophen be avoided?
Patients w/cirrhosis, liver failure, heavy drinking
How can acetaminophen overdose be treated?
N-acetylcysteine (NAC) available PO and IV