52. Common Adverse Effects
Platelet Dysfunction
Gastritis and peptic ulceration with bleeding (inhibition of PG +
other effects)
Acute Renal Failure in susceptible
Sodium+ water retention and edema
Analgesic nephropathy
Prolongation of gestation and inhibition of labor.
Hypersenstivity (not immunologic but due to PG inhibition)
54. COX-1 is expressed in all tissues and serves a variety of
homeostatic physiologic functions.
COX-1 is responsible for the production of protective prostaglandins in
the kidney and stomach, as well as the functional thromboxane of
platelets.
COX-2, Not normally found in most tissues, expressed under
conditions of tissue damage and plays an active role in the
inflammatory response.
55. NSAID’S
Injury causes cells to increase prostaglandin synthesis, which
results in the clinical symptoms:
redness (dilation of blood vessels),
pain (sensitization of pain receptors),
swelling (leakage of fluid from capillaries),
fever (hypothalamus thermometer)
56. NSAIDs find their chief clinical application as anti-
inflammatory agents in the treatment of musculoskeletal
disorders, such as rheumatoid arthritis, osteoarthritis, and
ankylosing spondylitis.
In general, NSAIDs provide only symptomatic relief from the
pain and inflammation associated with the disease and do
not arrest the progression of pathological injury to tissue
during severe episodes
57. Relief of Pain and Inflammation
NSAID’s can relieve pain equally, but some patients respond
better to one drug than another
Aspirin should not be used in children because of an
association with Reye’s syndrome, which is potentially fatal
None has demonstrated superiority over others for pain relief
However, some patients respond to one agent and not to
another
60. Acetic Acids Products
Indomethacin
One of the strongest COX inhibitors
Typically fully excreted w/in 48 hours
Patient intolerance generally limits its use to short-term
dosing
Is not used as analgesic because of side effects
Used for rheumatoid arthritis, osteoarthritis, and ankylosing
spondylitis
Uricosoric
61. Diclofenac
Absorbed rapidly, short half-life
Its potency against COX-2 is substantially greater than that
of indomethacin, naproxen, or several other tNSAlDs
The selectivity of diclofenac for COX-2 resembles that of
celecoxib.
Used in osteoarthritis, rheumatoid arthritis, dysmenorrhea,
ankylosing spondylitis
Acetic Acids Products
62. …. Diclofenac
food will affect the rate, but not the amount of drug absorbed
from the GI tract
fasting condition……. completely absorbed
is not recommended for use during late pregnancy or during
breastfeeding
63. Fenamic Acid Derivatives
Mefenamic acid
Rapid absorption
Peak effect of drug w/in 0.5-2 hours
Is used mostly in the short-term treatment of pain
in soft-tissue injuries, dysmenorrhea, and in rheumatoid and
osteoarthritis
64. …. Mefenamic acid
Is not recommended for use in:
Children (under 14 years old)
Elderly (> 65 years old)
pregnant women
Patients with history of convulsion
Blood disorders
65. Propionic Acids
Ibuprofen
Used more often for analgesic effect than for anti-inflammatory
effect
Analgesic effects in 2-4 hours
Anti-inflammatory effects require days to weeks
Absorption slowed when taking w/ food, however total absorption
is unaffected
Maximum dose = 3200 mg/day
Self-medication is common
66. …. Ibuprofen
Is not recommended for use by pregnant
Does not enter breast milk
Patients with ocular disturbances should not use
ibuprofen
Uses: Fever, mild to moderate pain, rheumatoid
arthritis, Osteoarthritis, Primary Dysmenorrhea, Gout,
dental pain, musculoskeletal disorder
67. …. Ibuprofen
Ibuprofen and aspirin should not be administered
together as there is no therapeutic advantage and it
increases the gastro intestinal side effects significantly.
68. Propionic Acids
Naproxen
Better patient tolerance than aspirin and indomethacin
Half-life of 10-20 hr
Is ~ 20 times more potent than aspirin
Is fully absorbed when administered orally
Absorption is reduced by aluminum hydroxide
69. …. Naproxen
Crosses the placenta and appears in the
milk at approximately 1% of the maternal
plasma conc.
The free form of naproxen in females is more than males
70. Carboxylic Acids
Aspirin
1st NSAID introduced
Prodrug – inactive until metabolized into constituent parts
by liver
Permanently binds to platelets ~ producing anticoagulant
effect up to 10 days
72. Selective COX-II Inhibitors
Celecoxib
It is the first of a new class of NSAIDs
Is highly selective for COX-2 (375X more than
COX-1)
Relieves the pain and inflammation of
osteoarthritis and rheumatoid arthritis
It does not affect platelet aggregation.