Non-selective NSAIDs Flashcards
Therapeutic effects of NSAIDs
Reversible inhibitors of COX 1 and COX 2, with analgesic, antipyretic and anti-inflammatory action
effects of NSAIDs
1) Reduce the manifestations of inflammation:
- No effect on underlying tissue/damage.
- ↓ vasodilatation.
- ↓ edema.
* Vasodilatation facilitates the action of mediators that increase the permeability of post-capillary venules.
2) NSAIDs –> reduce fever
* Suppress PGs synthesis in the CNS that is stimulated by pyrogens;
3) *Analgesia – for mild to moderate pain
- ↓ production of PGs that sensitize nociceptors to inflammatory mediators.
–> decreased activation of peripheral pain sensors.
- ↓ vasodilator PGs acting on the cerebral vasculature
–> relieve headach
4) Reversibly inhibit both COX isoforms:
- ↓ PG and TX synthesis.
- ↓ inflammatory response.
- ↓ homeostatic function.
–> Aspirin (but not its metabolite salicylate) irreversibly inhibits COX
–> longer duration of its anti-platelet effect.
Aspirin overdose management
- Urine alkalization. (admin –> Sodium Bicarbonate)
- Gastric lavage (+/- activated charcoal)
- Ventilatory support
- Symptomatic management.
Category of Aspirin
NS-NSAID
Indication of Aspirin
1. Anti-inflammatory/antipyretic/analgesic
2. Acute coronary syndrome.
3. Primary and secondary prevention for patients at high risk of arterial thrombosis.
4. Ischemic stroke and transient ischemic heart attack.
5. RA, OA and spondyloarthropathy.
MoA of Aspirin
- Acetylation of COX -1 & 2 –> ↓ PG synthesis. (Irreversible inhibition of Cox – enzyme.)
PK/PD of Aspirin
–> 3 therapeutic dose ranges:
1) Low dose –>reducing platelet aggregation.
2) Intermediate dose –> anti-pyretic + analgesic effects.
3) High dose –> anti-inflammatory effect.
- Well absorbed.
- Crosses both BBB and PBB.
- Protein-binding varies.
- Metabolized via microsomal enzymes –> Salicylic acid – a reversible, non-selective inhibitor of COX.
- Elimination of Salicylic acid is first order at low doses (half-life of 3 – 5 h).
–> Becomes zero order at high doses (half-life of 15h). - Renal excretion. (rapid process).
Adverse effects of Aspirin
- Avoid use on patients with gout presentation or
patients taking probenecid.
Uric acid elimination;
1. Low to moderate doses –> ↓ tubular secretion –>
hyperuricemia.
2. High doses –> ↓ tubular reabsorptions –> uricosuria
–> Contraindicated in Gout.
Acid-base and electrolyte balance:
Dose-dependent actions.
Aspirin Toxicities
1) Gastrointestinal irritation –>Gastritis, ulcers, bleeding.
2) Salicylism –> Tinnitus, vertigo, ↓ hearing – often first signs of toxicity.
3) Bronchoconstriction –> Exacerbation of asthma.
4) Hypersensitivity –> Especially the “triad” of asthma, nasal polyp, rhinitis.
5) Increased of bleeding (antiplatelet effect).
6) Reye’s Syndrome –> Post-viral encephalitis in children.
7) Chronic use –> Associated with renal dysfunction.
8) Drug interactions –> Ethanol. (↑GI bleeding), Warfarin. (↑ effects), Uricosuric drugs ( ↓ effects)
Category of Paracetamol/Acetaminophen
NS-NSAID
Indication of Paracetamol/ Acetaminophen
- Analgesia.
- Antipyretic.
MoA of Paracetamol/ Acetaminophen
A very weak COX – 1 & 2 inhibitor in
peripheral tissues.
Effect of Paracetamol/Acetaminophen
–> Equivalent analgesic and antipyretic activity to ASA due to inhibition of COX in the CNS.
–> No antiplatelet action.
–> Not implicated in Reye’s
Syndrome.
–> No effects on uric acid.
–> Not bronchospastic (safe in NSAID hypersensitivity and asthmatics)
–> Gastrointestinal distress is minimal at low to moderate doses.
–> Useful in patients with aspirin allergies, peptic ulcer disease, and bleeding.
–> Well absorbed orally and metabolized in the liver.
AE of Paracetamol/ Acetaminophen
- Hepatotoxicity in overdose.
–> antidote – Acetylcysteine. - Hepatotoxicity > in chronic alcohol consumers –> induces CYP450 enzymes.
Category of Ibuprofen
NS-NSAID
