NSAIDS are indicated for
Fever <3 days
Pain <5 days
What is the difference between COX-1 and COX-2
COX-1 is constitutive (always there), COX-2 is inducible
COX-1 for: GI mucosa, Platelet aggregation, Renal function
COX-2 for: inflammation, renal function
What renal damage occurs with NSAIDS
• Pre-renal (dehydration, volume depletion etc) • Intra-renal (injury) – Acute interstitial nephritis – Nephrotic syndrome – Chronic renal failure
Who is at risk for kidney damage
>65 CHF Hypertension Renal Disease ACE/ARB (ace inhibitors/angiotensin blockers) Diuretics Dehydration
How to reduce risk of kidney damage
- Stop NSAIDs if can’t eat/drink
- Avoid ACE/ARB + diuretic + NSAID
- Start low. Go slow.
- Use the lowest effective dose
How do NSAIDs affect GI tract
- Disrupt mucous layer
- Inhibit bicarbonate secretion (neutralize acid)
- Cause epithelial necrosis
Should you take COX-1 or COX-2 to avoid stomach injury
COX-2 (celebrex, diclofenac)
Who is at risk for dyspepsia and heartburn
if prior intolerance, female, prior ulcer, ASA
What to do if you have dyspepsia or heartburn
- May help to take with food
- D/C if dyspepsia >7d
- Treat heartburn with antacids, H2RAs, switch NSAID (ie. take tums)
what are the 3 main injuries caused by NSAID
- perforated ulcers
- hemorrhage (dark, tarry stool due to stomach bleed)
- obstruction (swelling, painful)
What happens when you increase the dose of NSAID
increases duration of action
Alarm symptoms (for stomach)
- New onset anemia (fatigue, dizziness, shortness of breath)
- New dysphagia (difficulty swallowing)
- Hematemesis (vomiting blood)
- Melena (blood in stomach leads to smelly stool)
- Persistent vomiting
Who is at higher risk for stomach damage
>65 Prior PUD/UGIB (peptic ulcer disease/upper GI bleed) Rheum Arthritis NSAIDs + ASA Anticoagulants (warfarin, apixaban) Glucocorticoids (prednisone) H. Pylori
dextamethasone
- inhibits immune system
- impairs wound healing
How to reduce risk of stomach injuries
- Avoid drug interactions
- Choose coxibs
- Add misoprostol/PPI (gastroprotection - prevents GI bleed)
- Celecoxib/PPI if prior bleed
- Start low. Go slow.
- Use the lowest effective dose
Impact of NSAIDS on BP
- increase BP (in Normotensive and hypertensive)
• Also antagonize ACE-I, ARBs (beta blockers) - (medications that reduce BP)
• increases SBP 3-7 mmHg, DBP 1-3 mmHg
• Monitor BP 1-3 wks after starting NSAID
How long to wait if taking both ASA and ibuprofen
Take ASA 30 min before or 8 hours after ibuprofen
Who is at higher risk for heart damage
>65 CHF Vascular disease Diabetes Hypertension Rheum Arthritis
How to reduce risk of heart injuries
- Avoid in high risk patients.
- Choose non-selective NSAIDs.
- Monitor BP.
- Start low. Go slow.
- Use the lowest effective dose
How to reduce risk OVERALL
- Identify high risk patients.
- Minimize drug interactions: ACE, ARB, diuretic, steroids, ASA, blood thinners
- Weigh risks/benefits of COX-2 selectivity
- Gastroprotect: PPI, misoprostol
- Monitor: peeing, bleeding, BP
- Start low. Go slow.
- Use the lowest effective dose
COX-1 vs. COX-2 risk graph
slide 65
- COX-2 increases risk of CV, decreases GI risk (ex. etoricoxib, rofecoxib)
- COX-1 increases risk of GI, decreases risk of CV (ex. naproxen)
- in the middle: celecoxib, diclofenac (more CV risk), ibuprofen (more GI risk)
