Peripherally Acting Analgesics (non-steroidal anti inflammatory drugs : NSAID)
Drugs Therapeutic effects
Salicyclates a. Anti-inflammatory actions: Due to inhibition
(Aspirin, of CO activity and PG synthesis (neither arrest
Choline Mg progression nor induce remission of inflamm)
Salicyclates, b.Analgesic actions: PGE2 sensibilize nerve
Diflunisal) endings to the action of bradykinin and
histamine released during inflamm, thus
inhibit PG inhibit sensation of pain
c. Antipyretic action: inhibits PGE2 synthesis
and release by thermoregulatory centers of ant
hypothalamus, also increase heat dissipation
by vasodilation action
d.Respiratory actions: act on resp centers cause
hyperventilation and resp alkalosis
e. GI effects: PGI2 inhibits gastric secretion and
PGE2 and PGF2 stimulate synthesis of
protective mucus, thus inhibition of PG
increased acid secretion and diminished mucus f. Low dose aspirin: transient ischemic attack
protection leads to epigastric distress,
ulceration and hemorrhage
f. Effects on platelets:
g.Effects on kidney: PGE2 and PGI2 maintain
renal blood flow, thus inhibition of PG result
in water and Na retention leads to edema and
hyperkalemia. (interstitial nephritis may
occurs with all NSAIDs except aspirin)
Phenylbutazone a. Powerful anti-inflammatory effect
b.Weak analgesic and antipyretic effects
Indomethacin a. Anti-inflammatory effects (more potent than
aspirin)
b.Antipyretic effects
c. Analgesics effects
Sulindac a. Analgesic effects
b.Anti-inflammatory effects (but less potent
than indomethacin)
Therapeutics uses
a. Na salicyclate, choline salicyclate, choline Mg a. GI: epigastric distress, nausea, vomiting, microscopic GI bleeding
salicyclate and aspirin : anti-pyretics and
analgesics in treatment of gout, rheumaric
fever, rheumatoid arthritis and to inhibit
platelet aggregation (headache, arthralgia,
myalgia)
b.Salicyclic acid: treat corns, calluses and
epidermophytosis (eruption caused by fungi)
c. Salicylamide: analgesic and sedative
preparations
d.Methyl salicyclate: cutaneous counterirritant
in liniments
e. Diflunisal: 4x more potent than aspirin as
analgesic and anti-inflammatory agents (but
has no antipyretic effects and thus cannot relief
fever)
and unstable angina
a. Short-term therapy of acute gout and acute
rheumatoid arthritis when other NSAID agents
have failed
a. Control pain associated with uveitis and
postoperative ophthalmic pain
b.Antipyretic for Hodgkin disease
c. Effective anti-inflammatory agents in acute
gouty arthritis, ankylosing spondylitis and
osteoarthritis of the hip)
a. Treatment of rheumatoid arthritis, ankylosing
spondylitis, osteoarthritis, acute gout
Adverse effects
b.Blood: reduce level of platelet TXA2 leads to inhibition of platelet aggregation
(prolonged bleeding time, thus shouldn’t be taken 1 week before surgery)
c. Respiration: in toxic dose: respiratory depression with uncompensated respiratory
and metabolic acidosis
d.Metabolic processes: in toxic dose cause uncoupling of oxidative phosphorylation
leads to E wasting as heat (pyretic effects)
e. Hypersensitivity: urticaria, bronchoconstriction, angioneurotic edema
f. Reye’s syndrome (if given during viral infection): is an fatal fulminating hepatitis
with cerebral edema
g.Drug’s interaction: produce undesirable side effects
h.Salicylism (salicyclate intoxication) includes
i. Nausea
ii. Vomiting
iii. Marked hyperventilation
iv. Headache
v. Mental confusion
vi. Dizziness
vii. Tinnitus (ringing in ears)
i. In severe salicylism
i. All listed above (i-vii)
ii. Restlessness
iii. Delirium
iv. Hallucination
v. Convulsions
vi. Coma
vii. Resp and metabolic acidosis
viii. Death due to resp failures
a. Poorly tolerated (thus should be given for short period of time)
b.Nausea, vomiting, skin rashes and epigastric distress
c. Fluid and electrolyte retention with edema and increased urine volume
d.Diarrhea, vertigo, insomnia, blurred vision, euphoria, nervousness and hematuria
e. Reduce uptake of I2 by thyroid gland result in goiter and myxedema
f. Agranulocytosis and aplastic edema
a. GI: nausea, vomiting, anorexia, diarrhea, abdominal pain, ulceration of upper GI tract
with perforation and hemorrhage
b.CNS: frontal headache, dizziness, vertigo, light headache, mental confusion
c. Acute pancreatitis, hepatitis and jaundice
d.Hematopoietic reactions: neutropenia, thrombocytopenia, aplastic anemia
e. Hypersensitivity reactions: rashes, urticaria, itching, acute attack of asthma, 100%
cross reactivity with aspirin
Similar to other NSAIDs but less severe
Ibuprofen a. Analgesic effects Hypersensitivity reaction
(related drugs: b.Anti-inflammatory effects (same potency as GI disturbances (but better tolerated than aspirin)
naproxen, aspirin)
ketoprofen and c. Antipyretic effects
fenoprofen)

Piroxicam Treatment of rheumatoid arthritis, ankylosis GI disturbances

(t1/2 : 45hrs, spondylitis and osteoarthritis)
thus admin
once per day)

Ketorolac

Acetaminophen a. Antipyretic and analgesic effects (due to
Phenacetin inhibition of PG synthesis in CNS)
b.Weak anti-inflammatory effects (due to less
effect on cyclooxygenase in peripheral tissue)
c. Do not affect platelet fx, do not increase
blood clotting time
Non-Narcotic Analgesics
a. Substitute for analgesic and antipyretic effects
of aspirin in patients with gastric complaints,
prolongation of bleeding time or those do not
require anti-inflammatory effects of aspirin
b.Choice for children with viral infection or
chicken pox (coz aspirin enhance Reye
syndrome)
c. Can be used in patient with gout coz don’t
antagonize urisonic agent (e.g probenecid)
a. Do not cause physical dependent or tolerance
b.Skin rash and minor allergic reaction (rare)
c. Minor alteration in leukocyte counts
d.Transient renal tubular necrosis and hypoglycemic coma (in prolonged large-dose
therapy)
e. In overdose may cause hepatic necrosis (treatment: admin N-acetylcysteine which
toxic metabolite can bind) [in normal doses, toxic metabolites are bind to glutathione
forming non-toxic substances]