ANALGESIC-ANTIPYRETIC

AGENTS;
PHARMACOTHERAPY OF
by:
GOUT
Edgar Allan A. Piatos,
M.D.
 NSAIDS
Non Steroidal Anti-Inflammatory Drugs
Mechanism of Action:
Inhibit cyclooxygenase enzyme
COX-1
COX-2
Therapeutic Effects:
b. Pain
- effective in pain of low to
moderate intensity
- do not change perception of
sensory modalities other than
pain
b. Fever
Other Clinical Uses:
Systemic Mastocytosis
Bartter’s Syndrome
Cancer Chemoprevention
Niacin Tolerability
Adverse Effects of NSAID Therapy:
Gastrointestinal
- Ulcers
Cardiovascular
- Myocardial Infarction; Stroke
Blood Pressure, Renal, Renovascular
Adverse Events
- Retention of salt and water
Analgesic Nephropathy
Pregnancy and lactation
- Prolongation of gestation
- Increase risk of
postpartum hemorrhage
Hypersensitivity
Aspirin Resistance
Drug Interactions
 Concomitant NSAIDS and Low Dose
Aspirin
- increase likelihood of
gastrointestinal adverse events
 ACE Inhibitors
- attenuate effectiveness of ACE
inhibitors
 Corticosteroids/Warfarin
- increase incidence of bleeding
 SALICYLATES
Pharmacological Properties
 Analgesia
 Antipyresis
 Respiration
 Acid-Base and Electrolyte Balance and
Renal Effects
 Cardiovascular Effects
 Gastrointestinal Effects
 Hepatic Effects
 Uricosuric Effects
 Effects on the Blood
 Metabolic Effects
* Oxidative phosphorylation
* Carbohydrate metabolism
 Endocrine Effects
 Salicylates and Pregnancy
 Local Irritant Effects
Therapeutic Effects:
Antipyresis
Analgesia
Rheumatoid Arthritis
Inflammatory Bowel Disease
Salicylate Intoxication
Coma; Convulsions
Cardiovascular Collapse
Salicylism:
Headache; dizziness; tinnitus; difficulty
of hearing
Treatment of Salicylate Poisoning:
Airway
Breathing
Circulation
Decontamination
 DIFLUNISAL
Difluorophenyl derivative of salicylic
acid
Devoid of antipyretic effects
Osteoarthritis, musculoskeletal strains
or sprains
No auditory side effects
Less gastrointestinal and platelet effects
 PARAAMINOPHENOL DERIVATIVES:
ACETAMINOPHEN
Active metabolite of phenacetin
Weak anti-inflammatory effects
No effect on CVS, respiratory systems,
on platelets and coagulation
No acid-base changes or uricosuric
effects
Does not produce gastric irritation
Associated with hepatic necrosis
 ACETIC ACID DERIVATIVES
b. INDOMETHACIN
* more potent inhibitor of COX than
aspirin
* does not interfere with uricosuric
effects of probenecid
* platelet inhibition; gastric irritation
* antagonizes the natriuretic and anti-
hypertensive effects of diuretics,
betablockers, ACE inhibitors, AT1
receptor antagonists
 * ankylosing spondylitis,
osteoarthritis, acute agout
* closusre of persistent PDA

Adverse Effects
Gastrointestinal
Frontal headache
b. SULINDAC
- related to indomethacin
- prodrug: sulfide metabolite
- rheumatoid arthritis,
osteoarthritis, ankylosing
spondylitis, acute gout
- prevent colon cancer in patients
with FAP
c. ETODOLAC
- COX-2 selective
- uricosuric
- osteoarthritis
-rheumatoid arthritis
 FENAMATES
(Mefenamic, Meclofenamic,
Flufenamic Acid)
Pain in soft tissue injuries
Dysmenorrhea
Rheumatoid arthritis
osteoarthritis
 TOLMETIN
Osteoarthritis; Rheumatoid Arthritis
Juvenile Rheumatoid Arthritis
Ankylosing Spondylitis
KETOROLAC
Parenteral administration
Greater analgesic than anti-
inflammatory activity
Short-term alternative to opoiods
Used widely in post-operative patients
 DICLOFENAC
Most commonly used NSAID in Europe
Potent against COX-2
Rheumatoid Arthritis; Osteoarthritis;
Ankylosing Spondylitis
Acute musculoskeletal pain
Post-operative pain
Dysmenorrhea
PROPIONIC ACID DERIVATIVES
IBUPROFEN NAPROXEN
FENOPROFEN KETOPROFEN
FLURBIPROFEN OXAPROZIN
- Rheumatoid Arthritis; Osteoarthritis
- Ankylosing Spondylitis; Bursitis
- Acute Tendinitis
- Acute Gouty Arthritis
- Primary Dysmenorrhea
 ENOLIC ACIDS (OXICAMS)
PIROXICAM
MELOXICAM
NABUMETONE
PYRAZOLON DERIVATIVES
PHENYBUTAZONE OXYPHENBUTAZONE
ANTIPYRINE AMINOPYRINE DIPYRONE
- associated with agranulocytosis
 CYCLOOXYGENASE 2
SELECTIVE NSAIDS
CELECOXIB VALDECOXIB
ROFECOXIB PARECOXIB
LUMIRACOXIB ETORICOXIB

OTHER NSAIDS
APARAZONE NIMESULIDE
 PHARMACOTHERAPY OF GOUT
COLCHICINE
Acute Gout
Familial Mediterranean Fever
ALLOPURINOL
Most commonly used antihyperuricemic
agent
Primary hyperuricemia of gout
Hyperuricemia secondary to
Polycythemia Vera, Myeloid
Metaplasia, Blood Dyscrasias
RASBURICASE
Recombinant urate-oxidase
Lowers urate levels more effectively
than allopurinol
Pediatric patients with leukemia,
lymphoma, solid tumor
malignancies
URICOSURIC AGENTS
PROBENECID
SULFINPYRAZONE
BENXBROMAZONE