Download NSAIDs - Virtual Medic

Problem Based Learning (PBL)
Group 8
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Drug
Acetylsalicylate Acid
(ASPIRIN)
Pharmacological Effects
1. Anti-inflammatory
2. ↓coagulation (the ONLY NSAIDs)
3. Anti-pyretic
4. Analgesia
Contraindication
1. Relative C/I
a. Bronchial asthma
i. Inhibit synthesis of PG
(bronchodilator)
2. Absolute C/I
a. Gouty arthritis
i. ↓dose (anti-platelete)
1. No effect on uric acid renal
secretion
ii. Usual OTC dose
(analgesia/antipyretic)
1. Inhibits uric acid renal
secretion
iii. ↑dose (Tx of RA)
1. Blocks reabsorption of uric
acid (uricosuric effect)
b. Children with influenza or cold
i. Reye’s syndrome
1. Potentially fatal
c. Pregnant ladies
i. Antiplatelet effects on 3rd
trimester
1. ↑risk of bleeding
ii. PG prolongs labour
Therapeutic Uses
1. Fever
2. Ischeamic heart disease
3. Arthritis
Prepared by Zaid Khalid
Non-Selective Cycloxygenase (COX) Inhibitor
Pharmacokinetic
Mechanism of Action
Absorption
1. Best absorp in acidic condition
a. It’s a weak acid in nature;
gastric environment is highly
acidic. Therefore aspirin will
remain unionized in the
stomach
b. Acidic drug tends to be lipid
soluble; readily being absorp
in through the GI mucosa
2. Most absorp at intestinal
mucosa due to high surface
area and low motility
Distribution
1. Hydrolyzes by esterases in tissue
and blood by
a. Acetic acid
b. Salicylate
2. Salicylate is highly plasma
protein bound (albumin)
Metabolism
1. Hepatic metabolism
(conjugation)
a. Conjugate with glycine =
salicyluric acid
b. Conjugate with glucuronic =
salicyl acyl + phenolic
glucuronide
Excretion
1. Renal excretion through
a. Glomerular filtration
b. Tubular secretion
2. Highly sensitive to pH changes
3. Interfere with uric acid
excretion*
1. Non-selective COX inhibitor, IRREVERSIBLY inhibits
both
a. COX 1 (constitutional enzyme) which coverts
arachidonic acid into
i. PGE2
1. Renal vasodilation
2. Bronchodilation
a. Inhibition of this will exarcebate asthmatic
pts (relative contraindication)
ii. TXA2
1. ↑platelete aggregation
a. Inhibition leads to anti-platelet activity
i. ↓risk for AMI
ii. ↓risk of CVA
iii. PGI2
1. ↑gastric mucus secretion
a. Inhibition of this will reduce mucus
secretion, exarcebate gastritis
b. COX 2 (inducible enzyme) which converts
arachidonic acid into
i. Prostaglandins which involved in
1. Inflammation
a. Vasodilation (hypereamia)
b. ↑capillary permeability (edema)
i. Inhibition will ↓inflammation
2. Pain sensation
a. Directly binds to pain receptor and elicit
pain sensation (not visceral pain)
i. Inhibition will lead to analgesia
3. Pyrexia (fever)
a. Prostaglandin together with IL-1b
stimulates thermostat at the OVLT to
increase temperature set point higher
than normal
i. Inhibition will return the temperature set
point to normal
Adverse Effects
1. Gastritis
a. Ion trapping inside the
gastric mucosa
b. Inhibition of PG12
synthesis ↓mucus
secretion
c. Prophylaxis tx with
Misosprostol (PGE1
analogue)
2. Hepatotoxicity
3. Allergic action
a. Periorbital edema
b. Rash
Drug-drug Interaction
1. Warfarin
a. Due to its higher
affinity towards
albumin compared
to warfarin, aspirin
may displace
warfarin and lead to
↑in warfarin toxicity
Problem Based Learning (PBL)
Drug
CELECOXIB
Compared to Aspirin, it is
1. Does not cause
a. Reye’s syndrome
b. Gastritis (less)
i. Except
INDOMETHACIN
c. Hyperuriceamia
2. Fewer DDI
3. Nephrotoxic if use in
long time
4. No anti-platelete
effects
Prepared by Zaid Khalid
Group 8
Selective Cycloxygenase (COX) Inhibitor
Mechanism of Action
Selectively inhibits COX2 enzyme
1. COX 2 (inducible enzyme) which converts arachidonic acid into
a. Prostaglandins which involved in
i.
Inflammation
1. Vasodilation (hypereamia)
2. ↑capillary permeability (edema)
a. Inhibition will ↓inflammation
ii.
Pain sensation
a. Directly binds to pain receptor and elicit pain sensation (not
visceral pain)
iii.
Pyrexia (fever)
a. Prostaglandin together with IL-1b stimulates thermostat at the
OVLT to increase temperature set point higher than normal
b. Inhibition will return the temperature set point to normal
Adverse Effects
1. ↑CVS adverse events
Why?
There are two mediators here, which
are:
a. Prostacyclin (PGI2) (synthesis by
COX2) on endothelial cells has
effect on
1. Anti-aggregating
2. Anti-proliferative
3. Vasodilatory effect
b. TxA2 (synthesis by COX1) on
platelets maintain homeostasis by
1. Irreversible platelet
aggregation
2. Vasconstriction
3. Smooth muscle proliferation
Celecoxib selectively inhibits COX2,
therefore, ↓PG12 level, ↑TxA2 level
leading to imbalance between
these two mediators
1. ↑in TxA2 will lead to
a. Formation of thrombosis
b. ↑BP due to vasoconstriction