NSAIDs and Acetaminophen Flashcards
(84 cards)
1
Q
Types of pain
A
- Nociceptive (somatic, visceral)
- Neuropathic
- Psychogenic
2
Q
What is the mechanism of pain and what are its mediators?
A
- Neural mechanism
- Chemical mediators
3
Q
Describe the stages of the neural pain pathway
A
- Stimulation
- Transmission
- Modulation
4
Q
What occurs in the stimulation phase of the neural pain pathway?
A
- Noxious stimuli activate receptors
- Release of bradykinins, H and K ions, PGs, histamine, ILs, TNF, serotonin and Sub P
5
Q
What occurs in the transmission phase of the neural pain pathway?
A
- A and C afferent nerve fibers stimulated
- Synapse along spinal cord dorsal horn releases NTs
- Impulses passed along ascending pathway to the brain
6
Q
What occurs in the modulation phase of the neural pain pathway?
A
- 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
7
Q
Describe inflammation
A
- Subset of nociceptive pain
- Natural shift from protection of damage to promotion of healing
8
Q
Describe maladaptive inflammation
A
- Action outlives function
- Chemical properties of neurons change which effects transmission of pain
- Often caused by disease
9
Q
What is the beginning component of the COX pathway normally?
A
Arachidonic acid (released upon trigger of natural inflammatory cascade)
10
Q
General function of COX?
A
Oxygenates arachidonic acid which forms PGs, prostacyclin, thromboxane
11
Q
What is misoprostol and what does it do?
A
- Synthetic PGE1
- Induces uterine contractions
- Protects GI mucosa
12
Q
What is alprostadil and what does it do?
A
- Synthetic PGE1
- Maintain patent ductus arteriosis
13
Q
What is latanoprost and what does it do?
A
- Synthetic PGF2a
- Treatment of open angle glaucoma
14
Q
What is prostacyclin and what does it do?
A
- Synthetic PGI2
- Treatment of pulmonary HTN
15
Q
Describe selective NSAIDs
A
Selectively blocks COX-2 (over COX-1)
16
Q
Describe COX-1
A
Physiological “housekeeping”
- Vascular homeostasis
- GI, renal blood flow
- Platelet function
17
Q
Describe COX-2
A
Activated only as needed
- Inflammation, fever, pain
- Ovulation
- Placental function
- Uterine contractions
18
Q
Major difference between aspirin and all other NSAIDs
A
Aspirin irreversibly (!) binds to COX-1 and COX-2
19
Q
MOA of Aspirin
A
Irreversibly binds to COX-1 and COX-2 (inhibiting PG synthesis and preventing formation of TXA2)
20
Q
Aspirin uses
A
- Anticoagulant (mainly)
- Antipyretic
- Analgesic (at high doses)
- Anti-inflamm (at high doses)
21
Q
Peak plasma levels of aspirin occurs when?
A
1-2 hours
22
Q
Is aspirin more selective to COX-1 or COX-2?
A
COX-1 as long as it is under 100 mg dosage
23
Q
Contraindications to aspirin
A
- Pregnancy C/D (avoid esp in 3rd trimester)
- Hemophiliacs
- Children under 16 yo w/viral illness (risk of Reye’s syndrome)
- Asthma, nasal polyps, recurrent sinusitis
24
Q
How does aspirin (or any salicylates) toxicity present?
A
Tinnitus
25
What is the MC used non-selective NSAID?
Ibuprofen
26
Ibuprofen MOA and use
- Reversibly blocks COX-1 and 2
| - Used in mild to moderate pain
27
What is the new formulation of ibuprofen and what does it do?
- Caldolor (IV)
- For moderate pain and used to decrease opioid dose required
- Very expensive
28
Pediatric use of ibuprofen?
- Commonly for fever and pain
| - 5 to 10 mg/kg/dose Q6-8h
29
Dosing of ibuprofen
It has both an OTC dose (200-400 mg Q6-8h) and a prescription dose (600-800 mg Q6-8h)
30
Toxicity of ibuprofen
- Similar to all non-selective NSAIDs
| - May be more prone to GI side effects due to increased use vs. other products
31
Until recently, what was the only NSAID available IV?
Ketorolac
| still most widely used
32
Ketorolac use
- Most widely used IV NSAID
- Used for moderate to severe pain (a level that would require opioid therapy)
- Never used pre-op!
33
Ketorolac toxicity
Believed to be more potent than other NSAIDs so higher risk for ADRs
34
Ketorolac contraindications
- All NSAID warnings
| - Any situation with increased bleeding risk
35
Naproxen key features
- Found in numerous OTC products in various strengths
| - Always dosed BID
36
Max dose of naproxen a day? With CVD risk?
- 660 mg/day
| - 440 mg/day w/CVD risk
37
What is the novel agent of naproxen?
- Vimovo = naproxen/esomeprazole
| - For patients w/GI bleed risks
38
Dosing of ketorolac
Total dose should NOT exceed 5 days or 20 doses
39
Nabumetone key features
- Nonselective NSAID
- 24+ hours half life (QD dosing)
- Monitor renal function!
- Preferred for chronic arthritis
- Increased photosensitivity
- Expensive
40
Piroxicam key features
- Nonselective NSAID
- 36-80 hrs half life (QD dosing)
- Much higher risk of ADRs
- Super high risk of GI ulceration
41
Oxaprozin key features
- Nonselective NSAID
| - 50 to 60 hrs half life (QD dosing)
42
Which nonselective NSAIDs can be dosed once a day? Why?
- Nabumetone
- Piroxicam
- Oxaprozin
* Long half life!
43
What is indomethacin and what population is it primarily used in?
- Nonselective NSAID
| - Neonates to close PDA when it is open
44
What are the increased risks of indomethacin?
- Pancreatitis
| - CNS (HA, dizzy, psychosis)
45
What is Sulindac and how is it dosed? What are the potential adverse effects?
- Nonselective NSAID
- Dosed BID
- Increased risk of SJS and liver damage
46
Diclofenac MOA
Somewhat selective for COX-2 (providing potentially less GI toxicity)
47
What is a novel agent of diclofenac?
- Arthrotec (diclofenac/misoprostol)
- Pregnancy X bc of misoprostol
- Increased diarrhea, cramping
48
Meloxicam MOA
More selective for COX-2 but not fully
49
Meloxicam dosing and half life
Can be dosed QD because half life is 15-20 hours
50
Celecoxib key features
- Only fully selective COX-2 still available in US
- Similar efficacy vs. non-selective NSAIDs
- Proposed decrease in GI toxicity
51
What is celecoxib MC used for?
- Osteoarthritis and RA
| - Decreases pain and swelling, increases function (no effect on disease itself)
52
Contraindications of celecoxib
- Same warnings as other NSAIDs
- Increased risk of MI/stroke (dose related)
- Sulfa allergy
- Preg Cat C prior to 30 wks gestation
- Preg Cat D 30 wks and beyond
53
General NSAID ADRs
- GI (dyspepsia, ulceration)
- Renal (decreased BF, interstitial nephritis)
- CV (MI/stroke)
- Pregnancy concerns
- Hematologic (d/t inhibition of TXA2)
54
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)
55
Which population is at greater risk for serious GI events with NSAIDs?
Elderly
56
What is the cause of GI toxicity with NSAIDs?
- Block of systemic PGE2/PGI2 synthesis
| - Loss of cytoprotection in gut
57
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)
58
What class is misoprostol, what is it used for, and what is important to know about it?
- Synthetic PGE
- Prevention of NSAID induced ulcers
- Preg Cat X
59
How do NSAIDs cause nephrotoxicity?
- PGs acts as vasodilators
- NSAIDs block PGs
- Afferent arteriole vasoconstricts which lowers GFR
60
Populations at risk for NSAID induced nephrotoxicity
- Volume depleted
- Kidney disease
- CHF
- 65 yo or older
- HTN
- DM
- Pts on methicillin abx
61
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
62
Patients at risk for CV events with NSAID use:
Have had or have risk factors for: CABG, UA, MI, ischemic events
63
What is the only NSAID studied to date that has NOT shown a risk of CV complications?
Naproxen
64
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
65
If a patient has known thrombotic risk and is using NSAIDs, what should be added to avoid CV concerns?
ASA 81 mg daily
OR
PPI
66
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)
67
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
68
If aspirin is taken with other NSAIDs, how should they be taken?
Space ASA by 2 hours and give it first
69
When is the only time you would recommend ASA with another NSAID in a patient?
Known thrombotic risk
70
Which NSAIDs should be avoided in hepatic dysfunction?
- Diclofenac
| - Sulindac
71
Which topical NSAIDs have shown effectiveness in reducing pain?
- Diclofenac (FDA approved)
- Ibuprofen
- Ketoprofen
- Piroxicam
* Benefit is likely only 2-4 wks
72
Describe topical diclofenac
- Patch (Flector), solution (Pennsaid), gel (Voltaren)
- Wash hands after use!
- Systemic warnings apply to topical diclofenac
73
What is topical diclofenac used for?
- Mild localized OA or RA
| - Penetration limits use on hip arthritis
74
What is methyl salicylate? MOA? How long should it be used?
- Salicylic acid (similar but different than aspirin)
- Bengay/Icy Hot
- Causes vasodilation of cutaneous vasculature
- Decreases PG synthesis (not believed to be through COX inhibition)
- No more than 1 week use!
75
Methyl salicylate ADRs
- Mostly topical irritation
| - Systemic toxicity can occur (tinnitus, increased HR, DOE)
76
Patient education on methyl salicylate
```
Avoid using with:
-Tight bandaging
-Heating pads
-Excessive exercise
(More absorption)
```
77
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
78
Peak plasma levels of acetaminophen? Half life?
- 30-60 mins peak levels
| - 2-3 hrs half life
79
Max dose of acetaminophen per day?
4 grams (4000 mg)
80
How is acetaminophen metabolized?
Hepatic (glucuronidation) primarily
81
Acetaminophen ADRs
- Increased AST/ALT
| - Liver failure in acute or chronic OD
82
When should acetaminophen be avoided?
Patients w/cirrhosis, liver failure, heavy drinking
83
How can acetaminophen overdose be treated?
N-acetylcysteine (NAC) available PO and IV
84
What is the new formulation of acetaminophen? What can it be used for?
- IV (Ofirmev)
| - May be used for inpatients to decrease opioid doses
