04/22/1504/22/15 Dr. Medani A.B. , 2006Dr. Medani A.B. , 2006

Anti-inflammatory DrugsAnti-inflammatory DrugsNon-steroidal anti-inflammatory Non-steroidal anti-inflammatory

drugs(NSAIDSdrugs(NSAIDS))

INFLAMMMATION INFLAMMMATION ::Is the mechanism by which the Is the mechanism by which the body inactivate or destroy invading organisms , remove body inactivate or destroy invading organisms , remove irritants and set the stage for tissue repair. It is triggered irritants and set the stage for tissue repair. It is triggered by the release of chemical mediators from injured tissues by the release of chemical mediators from injured tissues

and migrating cells like amines(histamine and 5-and migrating cells like amines(histamine and 5-hydroxytryptamine) , lipids (prostaglndins) , small hydroxytryptamine) , lipids (prostaglndins) , small

peptides(bradykinins) and larger peptides(interleukin-1) . peptides(bradykinins) and larger peptides(interleukin-1) .

04/22/15 Dr. Medani A.B. , 2006

ProstaglandinsProstaglandins

Unsaturated fatty acids containing 20-C in a Unsaturated fatty acids containing 20-C in a cyclic ring structure (eicosanoid) .cyclic ring structure (eicosanoid) .

Many of the non-steroidal antinflammatory Many of the non-steroidal antinflammatory (NSAIDS) work by inhibiting (NSAIDS) work by inhibiting prostaglandins(PGEprostaglandins(PGE2 2 or PGFor PGF22) ,the letter ) ,the letter

referes to the sustituents of the cyclopentene referes to the sustituents of the cyclopentene ring and the subscript indicates the number of ring and the subscript indicates the number of double bonds in the side chain ( 2 in humans) double bonds in the side chain ( 2 in humans)

04/22/15 Dr. Medani A.B. , 2006

Role of prostaglandins as local Role of prostaglandins as local mediatorsmediators

They are released in small amounts by all They are released in small amounts by all tissues , where they act locally and are tissues , where they act locally and are metabolized there into the inactive product, so metabolized there into the inactive product, so they do not circulate in blood .they do not circulate in blood .

Thromboxanes , leukotriens , Thromboxanes , leukotriens , hydroperoxyeicosatetraenoic acid and hydroperoxyeicosatetraenoic acid and hydroxyeicosatetraenoic acid are related lipids hydroxyeicosatetraenoic acid are related lipids produced by the same precursors and run the produced by the same precursors and run the same pathways as the prostaglandins .same pathways as the prostaglandins .

04/22/15 Dr. Medani A.B. , 2006

Synthesis of prostaglandinsSynthesis of prostaglandins

Arachidonic acid (20-C) is the primary Arachidonic acid (20-C) is the primary percursor of prostaglandins and related percursor of prostaglandins and related compounds. It is a component of the compounds. It is a component of the phospholipids of cell membrane( like phospholipids of cell membrane( like phosphatidyl inositol ). Free arachidonic acid phosphatidyl inositol ). Free arachidonic acid is released from tissue phospholipids by the is released from tissue phospholipids by the action of phospholipase Aaction of phospholipase A2 2 and other and other acylhydrolases. acylhydrolases.

04/22/15 Dr. Medani A.B. , 2006

PathwaysPathways PhospholipidsPhospholipids

PhospholipaseAPhospholipaseA22

Arachidonic acid cyclooxygenase

PGG2

5-Lipoxygenase

•5-HPETE leukotiens

04/22/15 Dr. Medani A.B. , 2006

PathwaysPathways

Continues:Continues: PGG2

Hydroxyperoxidase

PGH2

PGI2

PGE2,PGF2α

Thromboxanes

Dipyridamole

04/22/15 Dr. Medani A.B. , 2006

Action of prostaglandinsAction of prostaglandins

They bind to receptors that operate via G-They bind to receptors that operate via G-proteins that inhibit or activate adenylcyclase proteins that inhibit or activate adenylcyclase or stimulate phospholipase- C which enhances or stimulate phospholipase- C which enhances the formation of diacylglycerol and inositol-the formation of diacylglycerol and inositol-1,4,5-triphosphate (IP).1,4,5-triphosphate (IP).

PGFPGF22αα ,leukotienes and thromboxane ,leukotienes and thromboxane AA22(TXA(TXA22)mediate certain actions activating )mediate certain actions activating phosphatidyl inositol metabolism to increase phosphatidyl inositol metabolism to increase intracellular calcium ions.intracellular calcium ions.

04/22/15 Dr. Medani A.B. , 2006

Functions in the bodyFunctions in the body

Endogenous PGEndogenous PGSS act as local signals to tune act as local signals to tune

the response of specific cell types depending the response of specific cell types depending on the tissue ( TXAon the tissue ( TXA2 2 released from platelets released from platelets

triggers the recruitment of new cells for triggers the recruitment of new cells for aggregation in clot formation , while in smooth aggregation in clot formation , while in smooth muscles this compound induces contraction.muscles this compound induces contraction.

PGPGSS are chemical mediators released during are chemical mediators released during

allergic and inflammatory reactions.allergic and inflammatory reactions.

04/22/15 Dr. Medani A.B. , 2006

Non-steroidal anti-inflammatory Non-steroidal anti-inflammatory drugsdrugs

NSAIDS are a group of chemically dissimilar NSAIDS are a group of chemically dissimilar compounds that differ in their anti-pyretic compounds that differ in their anti-pyretic ,analgesic and anti-inflammatory activities .,analgesic and anti-inflammatory activities .

They act by inhibiting the cyclooxygenases They act by inhibiting the cyclooxygenases ,but not the lipooxygenase enzymes .,but not the lipooxygenase enzymes .

04/22/15 Dr. Medani A.B. , 2006

a/ Aspirin and other salicylatesa/ Aspirin and other salicylates

It is the unique weak organic acid in It is the unique weak organic acid in irreversibly acetylation of cyclooxygenases irreversibly acetylation of cyclooxygenases leading to inactivation.leading to inactivation.

It is rapidly metabolized by esterases .It is rapidly metabolized by esterases . It acts as an anti-pyretic , anti-inflammtory and It acts as an anti-pyretic , anti-inflammtory and

analgesic effects . analgesic effects .

04/22/15 Dr. Medani A.B. , 2006

Mode of action of salicylcylatesMode of action of salicylcylates

Salicylates act by blocking the PGs synthesis Salicylates act by blocking the PGs synthesis at the thermoregulatory centers in the at the thermoregulatory centers in the hypothalamus , the peripheral target sites and hypothalamus , the peripheral target sites and by decreasing prostaglandin synthesis , they by decreasing prostaglandin synthesis , they prevent the sensitization of pain receptors due prevent the sensitization of pain receptors due to chemical or mechanical stimuli even at the to chemical or mechanical stimuli even at the subcortical sites( thalamus and hypothalamus )subcortical sites( thalamus and hypothalamus )

04/22/15 Dr. Medani A.B. , 2006

Action of salicylatesAction of salicylates

NSAIDS unequally work as antiinfalmmatory , NSAIDS unequally work as antiinfalmmatory , antipyretic and analgesic compounds :antipyretic and analgesic compounds :

04/22/15 Dr. Medani A.B. , 2006

NSAIDSNSAIDS

STRONGSTRONG

ANITINFLAMMATORY ANTIPYRETICANITINFLAMMATORY ANTIPYRETICANALGESICANALGESIC

STRONG WEAK STRONGSTRONG WEAK STRONG

ACETAMINOPHENACETAMINOPHEN

04/22/15 Dr. Medani A.B. , 2006

1-Anti-inflammatory action1-Anti-inflammatory action

They decrease PG synthesis which act as They decrease PG synthesis which act as mediators of inflammation.mediators of inflammation.

Aspirin inhibits inflammation in inflammation Aspirin inhibits inflammation in inflammation in arthritis, but has no effect on disease in arthritis, but has no effect on disease progress or its remission .progress or its remission .

04/22/15 Dr. Medani A.B. , 2006

2- Analgesic action2- Analgesic action

PGEPGE22 is thought to sensitize the nerve endings to the is thought to sensitize the nerve endings to the

action of bradykinin , histamine and other chemical action of bradykinin , histamine and other chemical mediators of the local inflammation and hence mediators of the local inflammation and hence salicylates by decreasing its synthesis , they decrease salicylates by decreasing its synthesis , they decrease the sensation of pain of low to moderate intensity the sensation of pain of low to moderate intensity arising from integument rather than the viscera .arising from integument rather than the viscera .

Combinations of NSAIDS and opiods are used in Combinations of NSAIDS and opiods are used in malignancy.malignancy.

04/22/15 Dr. Medani A.B. , 2006

3-Antipyretic action3-Antipyretic action

Fever is the set-point of the anterior Fever is the set-point of the anterior hypothalamus thermoregulatory center is hypothalamus thermoregulatory center is elevated, may be by increasing PGEelevated, may be by increasing PGE 22 synthesis synthesis due to endogenous agent like pyogens and due to endogenous agent like pyogens and malignancy.malignancy.

Salicylates decrease PGESalicylates decrease PGE22 synthesis and synthesis and aspirin increase heat dissipation due to aspirin increase heat dissipation due to peripheral vasodilation and sweating , but no peripheral vasodilation and sweating , but no effect on normal body temperature.effect on normal body temperature.

04/22/15 Dr. Medani A.B. , 2006

4- Respiratory action4- Respiratory action

Aspirin increases alveolar ventilation at EDAspirin increases alveolar ventilation at ED 5050

and salicylates uncouple oxidative and salicylates uncouple oxidative phosphorylation leading to C0phosphorylation leading to C022 and respiration. and respiration.

TD TD respiratory centers of medulla respiratory centers of medulla Hyperventilation + Respiratory alkalosisHyperventilation + Respiratory alkalosis

TD TD continued C02 production continued C02 production Central respiratory (paralysis + acidosis)Central respiratory (paralysis + acidosis)

04/22/15 Dr. Medani A.B. , 2006

5- GIT Action5- GIT Action

Prostacyclin PGIProstacyclin PGI22 inhibit gastric acid inhibit gastric acid secretion .secretion .

PGEPGE22 and PGF and PGF22αα stimulate the synthesis of stimulate the synthesis of protective mucus in the stomach and small protective mucus in the stomach and small intestine.intestine.

Aspirin decrease PG synthesis , increase Aspirin decrease PG synthesis , increase gastric acid secretion and diminishes mucus gastric acid secretion and diminishes mucus protection leading to gastric distress and protection leading to gastric distress and ulceration and/or haemorrhage. ulceration and/or haemorrhage.

04/22/15 Dr. Medani A.B. , 2006

6-Effect on platelets6-Effect on platelets

TXATXA22 increases platelet aggregation and hence increases platelet aggregation and hence the anticoagulant effect and bleeding time the anticoagulant effect and bleeding time ,while PGI,while PGI22 decrease it. decrease it.

Low aspirin dose inhibit thromboxane Low aspirin dose inhibit thromboxane production ,but not TXAproduction ,but not TXA22 in the blood vessels in the blood vessels endothelium( platelets lacking nuclei can not endothelium( platelets lacking nuclei can not produce cyclooxygenases and hence its produce cyclooxygenases and hence its acetylation is irreversible for their life-time {3-acetylation is irreversible for their life-time {3-7ays} ,while enothelial cells can produce it).7ays} ,while enothelial cells can produce it).

04/22/15 Dr. Medani A.B. , 2006

7- Action on the kidney7- Action on the kidney

PGEPGE22 and PGI and PGI22 maintain renal blood flow maintain renal blood flow

especially if vasoconstritors are presentespecially if vasoconstritors are present Decreased PG synthesis may be due to Decreased PG synthesis may be due to

retention of sodium and water which enhances retention of sodium and water which enhances edema and hyperkalaemia .edema and hyperkalaemia .

Interstitial nephritis occurs in all NSAIDS Interstitial nephritis occurs in all NSAIDS except aspirin. except aspirin.

04/22/15 Dr. Medani A.B. , 2006

Therapeutic Uses:- Therapeutic Uses:- 1-Antipyretic and analgesic1-Antipyretic and analgesic

Na salicylates, choline salicylates(liquid) Na salicylates, choline salicylates(liquid) ,choline magnesium salicylate and aspirin ,choline magnesium salicylate and aspirin produce antipyretic and analgesic effects for produce antipyretic and analgesic effects for the treatment of gout , rheumatic fever and the treatment of gout , rheumatic fever and rheumatoid arthritis.rheumatoid arthritis.

They are analgesic for haedache ,arthralgia They are analgesic for haedache ,arthralgia and myalgia. and myalgia.

04/22/15 Dr. Medani A.B. , 2006

2-External applications2-External applications

Salicylic acid is given topically in case corn Salicylic acid is given topically in case corn calluses epidermatophytosis (fungal infection).calluses epidermatophytosis (fungal infection).

Methyl salicylates (oil of wintergreen) works Methyl salicylates (oil of wintergreen) works as an external counter irritant in liniments. as an external counter irritant in liniments.

04/22/15 Dr. Medani A.B. , 2006

3- Cardiovascular applications3- Cardiovascular applications

Salicylates inhibit platelet aggregation leading Salicylates inhibit platelet aggregation leading to an anticoagulant effect ( prophylaxis in to an anticoagulant effect ( prophylaxis in transient ischaemic attacks ,unstable angina in transient ischaemic attacks ,unstable angina in men and in coronary artery thrombosis.men and in coronary artery thrombosis.

PGEPGE22 is responsible for keeeping the ductus is responsible for keeeping the ductus

arteriosus open , hence treatment is by using arteriosus open , hence treatment is by using aspirin . aspirin .

04/22/15 Dr. Medani A.B. , 2006

4-Colon cancer4-Colon cancer

Chronic use of aspirin decrease the incidence Chronic use of aspirin decrease the incidence of colorectal cancer .of colorectal cancer .

04/22/15 Dr. Medani A.B. , 2006

Home workHome work

Write an assignment on :-Write an assignment on :-

* Pharmacokinetics .* Pharmacokinetics .

* Dose .* Dose .

* Fate .* Fate .

* Toxicity .* Toxicity .

of aspirin .of aspirin .

04/22/15 Dr. Medani A.B. , 2006

Propionic acid derivatives Propionic acid derivatives

Ibuprofen ,naproxen ,fenoprofen ,ketoprofen Ibuprofen ,naproxen ,fenoprofen ,ketoprofen ,flurbiprofen and the drug with long half-time ,flurbiprofen and the drug with long half-time that is given once /day oxaprozin ,all have that is given once /day oxaprozin ,all have antiinfalammatory , antipyretic and analgesic antiinfalammatory , antipyretic and analgesic effects used in case of chronic rheumatoid and effects used in case of chronic rheumatoid and oesteoarthritis , but their GITeffects decrease oesteoarthritis , but their GITeffects decrease that of aspirin.that of aspirin.

04/22/15 Dr. Medani A.B. , 2006

-Con.-Con. They are reversible inhibitors of They are reversible inhibitors of

cyclooxygenases that decrease PG synthesis , cyclooxygenases that decrease PG synthesis , but not that of leukotriens.but not that of leukotriens.

They are well absorped after oral They are well absorped after oral adminstration and totally bound to albumin . adminstration and totally bound to albumin . After hepatic metabolism , renal excretion may After hepatic metabolism , renal excretion may occur .occur .

04/22/15 Dr. Medani A.B. , 2006

-Con.-Con.

Adverse effects are dyspepsia and bleeding .Adverse effects are dyspepsia and bleeding . Side effects are mostly CNS signs like Side effects are mostly CNS signs like

haedache,tinnitus and dizziness .haedache,tinnitus and dizziness .

04/22/15 Dr. Medani A.B. , 2006

Indole acetic acidIndole acetic acid

Indomethazine ,sulindac and etodolac have Indomethazine ,sulindac and etodolac have antiinflammatory ,analgesic and antipyretic effects by antiinflammatory ,analgesic and antipyretic effects by reversibly inhibit cyclooxygenases , but not to lower reversibly inhibit cyclooxygenases , but not to lower fever :fever :

1/ 1/ IndomethazineIndomethazine toxicity limits its use as an toxicity limits its use as an antiinflammatory.It is used in the postoperative antiinflammatory.It is used in the postoperative opthalmic conditions and as an antipyretic when the opthalmic conditions and as an antipyretic when the condition is refractory to other agent. It can delay condition is refractory to other agent. It can delay labour by supressing uterine contractions and is also labour by supressing uterine contractions and is also effective in patent ductus arteriosus. effective in patent ductus arteriosus.

04/22/15 Dr. Medani A.B. , 2006

-Con.-Con.

After oral dosing ,it is completely absorped from the After oral dosing ,it is completely absorped from the upper GIT,under go hepatic metabolism and the upper GIT,under go hepatic metabolism and the unchanged drug and its metabolites are then excreted unchanged drug and its metabolites are then excreted with urine .with urine .

50% of patients suffer from nausea , vomitting , 50% of patients suffer from nausea , vomitting , anorrehexia ,diarrhia ,abdominal pain ,ulceration of anorrehexia ,diarrhia ,abdominal pain ,ulceration of upper GIT, frontalhaedache,vertigo and upper GIT, frontalhaedache,vertigo and haemorrhages.There is 100% cross-reaction with haemorrhages.There is 100% cross-reaction with aspirin.aspirin.

04/22/15 Dr. Medani A.B. , 2006

2-2-SulindacSulindac

It is an inactive pro-drug closely related to It is an inactive pro-drug closely related to indomethazine which, after hepatic indomethazine which, after hepatic metabolism, liberate the active sulfide with a metabolism, liberate the active sulfide with a long active duration .long active duration .

It is used less potently than the endomethazine It is used less potently than the endomethazine to treat reheumatoid arthritis ,ankylosing to treat reheumatoid arthritis ,ankylosing spondylitis ,osteoarthritis and acute gout .spondylitis ,osteoarthritis and acute gout .

Adverse reactions are similar to those of Adverse reactions are similar to those of NSAIDS .NSAIDS .

04/22/15 Dr. Medani A.B. , 2006

3/ 3/ EtodolacEtodolac

This has effects similar to the NSAIDs ,but has This has effects similar to the NSAIDs ,but has less GIT problems .less GIT problems .

Adverse effects include fluid retention and Adverse effects include fluid retention and abnormal liver kidney function .abnormal liver kidney function .

It may increase serum levels and increase the It may increase serum levels and increase the risk of adverse reactions due to digoxin , risk of adverse reactions due to digoxin , lithium , methotrexate ,and enhance the lithium , methotrexate ,and enhance the nephrotoxicity of cyclosporin. nephrotoxicity of cyclosporin.

04/22/15 Dr. Medani A.B. , 2006

Oxicam derivativesOxicam derivatives

Only Only piroxicampiroxicam is available to treat rhematoid is available to treat rhematoid arthritis, ankylosing spodylitis and arthritis, ankylosing spodylitis and oesteoarthritis .Its toesteoarthritis .Its t1/21/2 is 50 hours ,so itcan be is 50 hours ,so itcan be

given once /day.given once /day. GIT disturbances occur to 20% of the patients GIT disturbances occur to 20% of the patients

before excretion with urine ,where it can before excretion with urine ,where it can interfere with the excretion of lithium.interfere with the excretion of lithium.

04/22/15 Dr. Medani A.B. , 2006

FenamatesFenamates

Mefenamic acid and meclofenamates have side Mefenamic acid and meclofenamates have side effects like diarrheoa ,bowel inflammtion and effects like diarrheoa ,bowel inflammtion and are reported in association with haemolytic are reported in association with haemolytic anaemia.anaemia.

04/22/15 Dr. Medani A.B. , 2006

PhenylbutazonePhenylbutazone

It is a powerful antiinflammatory drug ,but a It is a powerful antiinflammatory drug ,but a weak analgesic and antipyretic drug .weak analgesic and antipyretic drug .

It is rapidly and completely absorped after oral It is rapidly and completely absorped after oral or rectal dosing , metabolized into or rectal dosing , metabolized into oxyphenybutazone which is then bound to oxyphenybutazone which is then bound to plasma proteins.plasma proteins.

50% of patients show nausia , vomiting 50% of patients show nausia , vomiting ,GITdisturbances ,skin rash, edema , ,GITdisturbances ,skin rash, edema , granulocytosis and aplastic anaemia.granulocytosis and aplastic anaemia.

04/22/15 Dr. Medani A.B. , 2006

Non-narcotic analgesicsNon-narcotic analgesics

Unlike the NSAIDs ,they have no or little Unlike the NSAIDs ,they have no or little antiinflammatory effects . They do not cause antiinflammatory effects . They do not cause physical dependance or tolerance :-physical dependance or tolerance :-

Acetaminophen andphenacetin:-Acetaminophen andphenacetin:--They inhibit PGs synthesis in the CNS to give -They inhibit PGs synthesis in the CNS to give

analgesic and antipyretic effects.analgesic and antipyretic effects.-They have less effect on cyclooxygens in the -They have less effect on cyclooxygens in the

peripheral tissues, do not affect platelets or peripheral tissues, do not affect platelets or bleeding time .bleeding time .

04/22/15 Dr. Medani A.B. , 2006

Con.Con.

Acetaminophen produces analgesia and Acetaminophen produces analgesia and antipyrexia instead of aspirin in case of gastric antipyrexia instead of aspirin in case of gastric complaints ,prolonged bleeding time (low complaints ,prolonged bleeding time (low renal toxicity) ,kids with viral infections or renal toxicity) ,kids with viral infections or chicken pox ( aspirin increase the risk of Reychicken pox ( aspirin increase the risk of Rey ,,s s syndrome) or with probencid for the fear of syndrome) or with probencid for the fear of aspirin antagonism.aspirin antagonism.

04/22/15 Dr. Medani A.B. , 2006

Con.Con.

Acetaminophen and phenacetin are rapidly Acetaminophen and phenacetin are rapidly absorped ,undergo first-pass effect in th luminal absorped ,undergo first-pass effect in th luminal intestine and the hepatocytes, glucronated or sulfated intestine and the hepatocytes, glucronated or sulfated in an inactive metabolite (N-acetl-benzo-in an inactive metabolite (N-acetl-benzo-quinoneimine ),which is excreted in urine.quinoneimine ),which is excreted in urine.

Prolonged acetaminophen can cause renal tubular Prolonged acetaminophen can cause renal tubular necrosis and hypoglycaemic coma.necrosis and hypoglycaemic coma.

After glutathione depletion ,toxic doses may cause After glutathione depletion ,toxic doses may cause hepatic necrosis and renal tubular necrosis due to the hepatic necrosis and renal tubular necrosis due to the binding of N-acetyl cystein with the toxic metabolite. binding of N-acetyl cystein with the toxic metabolite.

04/22/15 Dr. Medani A.B. , 2006

Anti-rheumatic agentsAnti-rheumatic agents

They are slowly acting and inhibit They are slowly acting and inhibit cyclooxygenases.cyclooxygenases.

They are used in cases of inflammtion that do They are used in cases of inflammtion that do not respond to NSAIDs .not respond to NSAIDs .

They are disease modifying antirheumatic They are disease modifying antirheumatic drugs (DMARDs) to slow the course of the drugs (DMARDs) to slow the course of the disease , induce remission and prevent further disease , induce remission and prevent further destruction of joints and involved tissues. destruction of joints and involved tissues.

04/22/15 Dr. Medani A.B. , 2006

Gold saltsGold salts

These (gold sodium thiomalate given I/M , These (gold sodium thiomalate given I/M , aurothioglucose given I/M and auranofin given aurothioglucose given I/M and auranofin given orally) can not repair the existing damage, but orally) can not repair the existing damage, but can only prevent further injury .can only prevent further injury .

They are taken by macrophages ,supress They are taken by macrophages ,supress phagocytosis and lyosomal enzymes activity phagocytosis and lyosomal enzymes activity and hence retard the progression of bone and and hence retard the progression of bone and articular destruction.articular destruction.

04/22/15 Dr. Medani A.B. , 2006

Con.Con.

They are water-soluble and are given orally and I/M They are water-soluble and are given orally and I/M to concentarte in macrophages (liver, kidney ,spleen to concentarte in macrophages (liver, kidney ,spleen and adrenal cortex) and then excreted in urine and and adrenal cortex) and then excreted in urine and feaces ( hastened by dimercaprol, penicellamine or N-feaces ( hastened by dimercaprol, penicellamine or N-acetylcystein.acetylcystein.

They may cause dermatitis of skin or mucus They may cause dermatitis of skin or mucus membranes , proteinurea and nephrosis.membranes , proteinurea and nephrosis.

It should be avoided in patients with hepatic or renal It should be avoided in patients with hepatic or renal diseases ,pregnant or those with history of toxicity to diseases ,pregnant or those with history of toxicity to these agents.these agents.

04/22/15 Dr. Medani A.B. , 2006

Drugs embloyed in the treatment of Drugs embloyed in the treatment of goutgout

Gout is a metabolic disorder characterized by Gout is a metabolic disorder characterized by increased uric acid in blood leading to increased uric acid in blood leading to hyperuricaemia and deposition of crystals of hyperuricaemia and deposition of crystals of sodium urates in tissue ( kidney and joints) sodium urates in tissue ( kidney and joints) causing inflammation (infilteration of causing inflammation (infilteration of granulocytes that phagocytose the urate granulocytes that phagocytose the urate crystals, formation of oxygen-metabolites crystals, formation of oxygen-metabolites leading to tissue damage and production of an leading to tissue damage and production of an inflammatory response by lyosomal enzymes).inflammatory response by lyosomal enzymes).

04/22/15 Dr. Medani A.B. , 2006

Con.Con.

Due to the lactate production in the synovial tissue, Due to the lactate production in the synovial tissue, the pH is lowered and further urate production is the pH is lowered and further urate production is enhanced.enhanced.

For treatment :-For treatment :- i/ Interfere with uric acid synthesis by allopuinol.i/ Interfere with uric acid synthesis by allopuinol. ii/ Increase uric acid excretion with probencid or ii/ Increase uric acid excretion with probencid or

sulfinpyrazone.sulfinpyrazone. iii/Inhibit leukocyte entry into the affected joint by iii/Inhibit leukocyte entry into the affected joint by

cochicine .cochicine . iv/ Adminster NSAIDs. iv/ Adminster NSAIDs.