nsaid, dr. siti s

8/11/2019 NSAID, dr. Siti S.

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Siti Suparti

Depart. Of. Pharmacology & TherapyFaculty Of MedicinePadjadjaran University

NON STEROID ANTIINFLAMMATORY DRUGS& DRUGS USE IN THE TREATMENT OF GOUT


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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


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Chemical classification of

NSAIDs Salicylic acid dervatives

Para-aminophenol derivatives

Indole and Indene acetic acids

Heteroaryl acetic acids

Anthranilic acids (fenamates) Enolic acids

Alkanones


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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


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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


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Choice of NSAIDs in varying

clinical situationThe 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 andphysical therapy.

For children: aspirin, naproxen, tolmetin.


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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 accordingto cost of therapy, Aspirin is very inexpensive.


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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.


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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)


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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.


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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


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Dehydration

GI symptoms

Acidosis

Toxic encephalopathy.

In adult - toxic effects occured by therapeuticdose:

Non cardiogenic pulmonary edem

Non focal neurologic abnormalities Acid base abnormalities (ketosis)


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Aspirin Hypersensitivity

Vasomotor rhinitis

Angioedema

Generalized urticaria

Bronchial asthma

Hypotension Shock.


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PARAAMINOPHENOL

DERIVATIES ACETAMMINOPHEN

An effective alternative to aspirin

Available without prescription Acute overdosage causes fatal hepatic

damage

( hepetotoxicity )For Analgesicantipyretic uses, a weak

antiinflammatory activity.


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INDOMETHACIN

Congener of indomethacin : Sulindac

Used in rheumatoid arthritis and related

disorder as antiinflamatory drugs, includingacute gout.

Toxicity often limit its use

There is entherohepatic cycling of theconjugate and probably indomethacin usedas an antipyretic in Hodgkins disease.


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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


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MEFENAMIC ACID

Have antiimflammatory, analgesic andantipyretic properties

Inhibit cyclooxygenase

Meclofenamic acid may antagonize certaineffect of prostaglandis

Pharmacokinetic properties :

Meclofenamate reaches the peak concentrationfaster than mefenamic acid

50 % of mefenamic acid excreted in urine 20% is recovered in the feces


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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.


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NAPROXEN

Fully absorbed. Influenced by food

Accelerated by sod.bicarbonate and reduce byMg oxide or Aluminium hydroxide.

Crosses the placenta , 1 % of the materialplasma concentration appears in milk oflactating mother

GIT effect and CNS effect Ototoxicity

Dermatological Problems

Other effect


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PIROXICAM

Has antiinflammatory, analgesic andantipyretic activity

For long term treatment of RA or OAequivalent of aspirin indomethacin ornaproxen, be tolerated better

T 1/ 2 is longsingle daily dose

For the treatment of AS, acutemusculoskeletal disorders, dysmenorrhea,postop.pain and acute gout


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PHENYLBUTAZONE

For the treatment of RA etc.

In long term therapyserious toxicity

Can cause agranulocytosis Sulfinpyrazone much more effective

uricosuric agentfor chronic gout

Can cause edema

Death especially caused aplastic anemia andagranulositosis


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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


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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 phagocytesand of Tcellsupressing immune

responsiviness


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Aurothioglucose and gold sodium thiomalate :Parenteral and oral

Interaction with dimercaprol, penicillamine

and Nacethylcystein

increase theexretion of gold

Auranofin :

Per oral, par enteralPredominantly exccreated in the feces.


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Contraindication

Renal disease, hepatic dysfunction, a historyof infectious hapatitis, hematologicaldisorders.

Pregnancy, breast feeding Concomitant use of antimalarials,

immunosupressants, phenylbutazone,

oxyphenbutazone Urticaria, eczema, colitis

Poorly tolerated by elderly persons


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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

nsaid, dr. siti s

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