Siti Suparti

Depart. Of. Pharmacology & Therapy

Faculty Of Medicine Padjadjaran University
NON STEROID ANTIINFLAMMATORY DRUGS
& DRUGS USE IN THE TREATMENT OF GOUT
What is NSAID ?
The antiinflamatory, analgesic, antipyretic
drugs are heterogenous group of
compounds, often chemically unrelated
(most of them are organic acids), which
nevertheless share certain therapeutic
actions and side effects
The prototype is aspirin, named: Aspirin
like drugs or NSAIDs
Chemical classification of
NSAIDs
Salicylic acid dervatives
Para-aminophenol derivatives
Indole and Indene acetic acids
Heteroaryl acetic acids
Anthranilic acids (fenamates)
Enolic acids
Alkanones
Therapeutic Activities
Analgesic - against pain of low to moderate
intensity
Chronic post operative pain or pain arising
from inflammation => (+)
Pain arising from the hollow viscera => (-)
Antipyretics - reduce the body temperature
in febrile states
Anti inflammatory agents - musculosceletal
disorder
Treatment of primary dysmenorrhea
Side Effects
Induce gastric or intestinal ulceration - erosions,
ulcers
GI side effects
Disturbances in platelet function
Prolongation of gestation
spontaneous labor
Changes in renal function
Prolongation of bleeding time
Intolerance => to Aspirin = to all NSAIDs
Choice of NSAIDs in varying
clinical situation
The choice among NSAIDs for the tretment of
arthritides is largely empirical.
Choice of the drug, given for a week or more.
If the drug is effective => treament should be
continued.
Mild arthropaties => together with rest and
physical therapy.
For children: aspirin, naproxen, tolmetin.
Precaution when patients given salicylates or
phenylbutazone together with warfarin,
sulfonylurea, hypoglycemic agents, methotrexate.
If patients can not tolerate NSAIDs => choice the
other form of therapy.
Gold, hydrochloroquine, penicillamine,
imunosuppressive agents and glucocorticoids are
another choice.
The selection of an NSAIDs for patient according
to cost of therapy, Aspirin is very inexpensive.
SALICYLATE
Pharmacological Properties
Effects: analgesia, antipyretic, on CNS,
respiration, acid base balance and
electrolyte pattern, CV, GI, hepatic and
renal, uricosuric, the blood, on rheumatic,
inflammatory and immunological process,
on connective tissue metabolism, on CH, N,
fat metabolism, on endocrine, salicylate and
pregnancy, local irritant effects.
Absorbtion: orally - absorbed rapidly
rectal - absorped slower than
orally.
Distribution: salicylates is distributed
throughout most body tissues and
most trancellular fluids.
Biotransformation: in many tissues,
particularly in the hepatic
endoplasmic reticulum and
mitochondria.
Excretion: renal (GF and proximal tubular
secretion)
THERAPEUTIC USE
Systemic uses: antipyresis, analgesia,
rheumatoid arthritis.
Other uses: in the treatment or prophylaxis
of diseases associated with
hyperaggregability.
Local uses; per rectal, local on skin.
TOXIC EFFECT OF SALICYLATES
=> May be fatal
Salicylate intoxication: 10 - 30 g (adult)
4,7 mg methyl salicylate
in children.
Simptoms and Signs (SALICYLISM)
Disturbances in acid balance
CNS disturbances
Fever
Dehydration
GI symptoms
Acidosis
Toxic encephalopathy.
In adult - toxic effects occured by therapeutic
dose:
Non cardiogenic pulmonary edem
Non focal neurologic abnormalities
Acid base abnormalities (ketosis)
Aspirin Hypersensitivity
Vasomotor rhinitis
Angioedema
Generalized urticaria
Bronchial asthma
Hypotension
Shock.
PARA AMINOPHENOL
DERIVATIES ACETAMMINOPHEN
An effective alternative to aspirin
Available without prescription
Acute overdosage causes fatal hepatic
damage
( hepetotoxicity )
For Analgesic antipyretic uses, a weak
antiinflammatory activity.
INDOMETHACIN
Congener of indomethacin : Sulindac
Used in rheumatoid arthritis and related
disorder as antiinflamatory drugs, including
acute gout.
Toxicity often limit its use
There is entherohepatic cycling of the
conjugate and probably indomethacin used
as an antipyretic in Hodgkins disease.

Precaution : In concurrent
administration with probenecid,
ancoagulant agents, furosemide,
thiazide diuretics, Beta adrenergic
blocking agents, inhibitor of
angiotensin converting enzyme.
Toxic effect of indomethacin
- Most adverse effect are close dependent :
GIT complaints
Occult blood loss
Acute pancreatitis
Hepatic abnormalities
Severe frontal headache ( CNS effect )
Hemopoietic reaction
Hypersensitivity
- Contraindication : renal disease, ulcus in
GIT
MEFENAMIC ACID
Have antiimflammatory, analgesic and
antipyretic properties
Inhibit cyclooxygenase
Meclofenamic acid may antagonize certain
effect of prostaglandis
Pharmacokinetic properties :
Meclofenamate reaches the peak concentration
faster than mefenamic acid
50 % of mefenamic acid excreted in urine 20
% is recovered in the feces
Toxic Effect and Precautions
GIT disorder
Hemolytic anemia of an autoimmune
type
Contraindicated on patients with a
history of gastrointestinal diseases
Diarrhea or skin rash : drug should be
stopped.
NAPROXEN
Fully absorbed. Influenced by food
Accelerated by sod.bicarbonate and reduce by
Mg oxide or Aluminium hydroxide.
Crosses the placenta , 1 % of the material
plasma concentration appears in milk of
lactating mother
GIT effect and CNS effect
Ototoxicity
Dermatological Problems
Other effect
PIROXICAM
Has antiinflammatory, analgesic and
antipyretic activity
For long term treatment of RA or OA
equivalent of aspirin indomethacin or
naproxen, be tolerated better
T
1
/ 2 is long single daily dose
For the treatment of AS, acute
musculoskeletal disorders, dysmenorrhea,
postop.pain and acute gout
PHENYLBUTAZONE
For the treatment of RA etc.
In long term therapy serious toxicity
Can cause agranulocytosis
Sulfinpyrazone much more effective
uricosuric agent for chronic gout
Can cause edema
Death especially caused aplastic anemia and
agranulositosis
Do not give drug more than 7 days.
Contraindicated in patient with
hypertension, cardiac, renal or hepatic
dysfuncion, a history of peptic ulcer, blood
dyscrasia, or hypersensitivity to the drug
Not advisable for elderly persons and not
recommended in children under the age of
14
GOLD
Can supress or prevent, but not cure
experimental arthritis and synovitis due to a
number of infectious and chemical agents
The best hypothesis related to the capacity
of gold compounds to inhibit maturation
and function of mononuclear phagocytes
and of T cell supressing immune
responsiviness
Aurothioglucose and gold sodium thiomalate :
Parenteral and oral
Interaction with dimercaprol, penicillamine
and N acethylcystein increase the
exretion of gold
Auranofin :
Per oral, par enteral
Predominantly exccreated in the feces.
Contraindication
Renal disease, hepatic dysfunction, a history
of infectious hapatitis, hematological
disorders.
Pregnancy, breast feeding
Concomitant use of antimalarials,
immunosupressants, phenylbutazone,
oxyphenbutazone
Urticaria, eczema, colitis
Poorly tolerated by elderly persons
Colchicine
Only againts gouty arthritis dramatic
relief of acute attack of gout
Effective prophylactic agent
An antimitotic agent
Inhibit the migration of granulocytes into
the inflammed area and a decreased
metabolic and phagosytic activity of
granulocytes
Allopurinol
Effective for the treatment of :
Primary hyperuricemia of gout
Secondary to hematological disorders
Antineoplastic therapy
Inhibit the terminal step in uric acid
biosyntesis
Well tolerated by most patients