NSAIDs part 2 Flashcards
GI prostaglandins’ impact:
- ↓ ______ secretions (protect stomach)
- ↑ __________
- ↑ secretion of ______
- ↑ secretion of ______
- ↓ gastric acid secretions (protect stomach)
- ↑ mucosal blood flow
- ↑ secretion of mucus
- ↑ secretion of bicarbonate
(Typical NSAIDs—renal adverse effects)
Inhibition of PGE2 production results in:
- ↑ Na+ reabsorption into the blood (Na retention)
- H2O retention
- peripheral oedema
- hypertension
(Typical NSAIDs—renal adverse effects)
Inhibition of PGI2 production results in:
- suppression of renin & aldosterone secretion
- hyperkalaemia
- acute renal failure
Risk factors for NSAID-induced AKI + effects:
a) ↑ ______/ ______→ narrowing of renal arterioles→ ↓ capacity for renal afferent dilatation
b) Pre-existing ______→ afferal dilation is required to maintain ______
c) ______ (water loss, blood loss)/effective vol dep (heart failure)–> ↓ ____________, ↑ secretion of ______
d) Use of ______→ prevent efferent arteriole ______
e) Use of ______→ diuretic cause vol depletion
a) ↑ age/ hypertension
b) Pre-existing glomerular disease→ …to maintain GFR
c) Volume depletion (water loss, blood loss)/effective vol dep (heart failure)–> ↓ afferent glomerular arteriolar pressure, ↑ secretion of Angiotensin II
d) Use of ACE inhibitor→ prevent efferent arteriole vasoconstriction
e) Use of triple whammy→ diuretic cause vol depletion
Other effects of NSAIDs
- Pseudo-allergic reaction (caused by hypersensitivity to COX inhibition)
Skin rashes, swelling, itching - Asthma
Trigger bronchospasm in susceptible asthmatics (from excess leukotrienes) - Bleeding
Failure of haemostasis, bruising (from strong antiplatelet effect)
Side effects are stronger in aspirin as it is an
irreversible COX inhibitor
Excess leukotrienes can lead to
bronchospasms
Examples of COX-2 selective inhibitors
(-coxib)
Celecoxib
Parecoxib
Etoricoxib
Adverse effects of COX-2 inhibition
- ______ → from constitutive expression of both COX-1 & COX-2 in kidney
- Delayed ______→ delayed ______
- Premature ______ of ductus arteriosus in late pregnancy
- Impairment of ______→ exacerbate ______
- ______ of fractures and bone repair
- ↑ risk of ______
- More COX-1 (TXA2,PGI2,PGE2) → ↑↑ TXA platelet aggregation → ↑ ______ - ______/______ → from renal effects causing hypertension/ risk of prothrombotic effects
- Renal toxicity → from constitutive expression of both COX-1 & COX-2 in kidney
- Delayed follicular rupture→ delayed ovulation
- Premature closure of ductus arteriosus in late pregnancy
- Impairment of wound healing→ exacerbate ulcers
- Non-union of fractures and bone repair
- ↑ risk of thrombosis
- More COX-1 (TXA2,PGI2,PGE2) → ↑↑ TXA platelet aggregation → ↑ thrombosis - Heart attack/ stroke → from renal effects causing hypertension/ risk of prothrombotic effects
Are ALL NSAIDs cox-2 inhibitors?
YES
cox-2 inhibitors contraindications + cautions
- 3rd tri pregnancy
- ppl w pre-existing GI ulcer
caution in: elderly, cerebrovascular/cardio pts
Contraindication in late pregnancy applies to:
1)
2)
1) ALL COX-2 inhibitors
2) non-selective NSAIDs
Eg of selective COX inhibitor
Paracetamol (acetaminophen)
Can ibuprofen exhibit some CNS selectivity?
Yes
Advs of Paracetamol (acetaminophen)
- good analgesic
- potent antipyretic
- spares GI tract- few SE
- few drug-drug interactions
