A Framework on the Anti-inflammatory Drugs for Pharmacy and Medical Students.

1. 04/22/1504/22/15 Dr. Medani A.B. , 2006Dr. Medani A.B. , 2006
Anti-inflammatory DrugsAnti-inflammatory Drugs
Non-steroidal anti-inflammatoryNon-steroidal anti-inflammatory
drugs(NSAIDSdrugs(NSAIDS))
INFLAMMMATIONINFLAMMMATION ::Is the mechanism by which theIs the mechanism by which the
body inactivate or destroy invading organisms , removebody inactivate or destroy invading organisms , remove
irritants and set the stage for tissue repair. It is triggeredirritants and set the stage for tissue repair. It is triggered
by the release of chemical mediators from injured tissuesby 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) , smallhydroxytryptamine) , lipids (prostaglndins) , small
peptides(bradykinins) and larger peptides(interleukin-1) .peptides(bradykinins) and larger peptides(interleukin-1) .

2. 04/22/15 Dr. Medani A.B. , 2006
ProstaglandinsProstaglandins
 Unsaturated fatty acids containing 20-C in aUnsaturated fatty acids containing 20-C in a
cyclic ring structure (eicosanoid) .cyclic ring structure (eicosanoid) .
 Many of the non-steroidal antinflammatoryMany of the non-steroidal antinflammatory
(NSAIDS) work by inhibiting(NSAIDS) work by inhibiting
prostaglandins(PGEprostaglandins(PGE22 or PGFor PGF22) ,the letter) ,the letter
referes to the sustituents of the cyclopentenereferes to the sustituents of the cyclopentene
ring and the subscript indicates the number ofring 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)

3. 04/22/15 Dr. Medani A.B. , 2006
Role of prostaglandins as localRole of prostaglandins as local
mediatorsmediators
 They are released in small amounts by allThey are released in small amounts by all
tissues , where they act locally and aretissues , where they act locally and are
metabolized there into the inactive product, sometabolized there into the inactive product, so
they do not circulate in blood .they do not circulate in blood .
 Thromboxanes , leukotriens ,Thromboxanes , leukotriens ,
hydroperoxyeicosatetraenoic acid andhydroperoxyeicosatetraenoic acid and
hydroxyeicosatetraenoic acid are related lipidshydroxyeicosatetraenoic acid are related lipids
produced by the same precursors and run theproduced by the same precursors and run the
same pathways as the prostaglandins .same pathways as the prostaglandins .

4. 04/22/15 Dr. Medani A.B. , 2006
Synthesis of prostaglandinsSynthesis of prostaglandins
 Arachidonic acid (20-C) is the primaryArachidonic acid (20-C) is the primary
percursor of prostaglandins and relatedpercursor of prostaglandins and related
compounds. It is a component of thecompounds. It is a component of the
phospholipids of cell membrane( likephospholipids of cell membrane( like
phosphatidyl inositol ). Free arachidonic acidphosphatidyl inositol ). Free arachidonic acid
is released from tissue phospholipids by theis released from tissue phospholipids by the
action of phospholipase Aaction of phospholipase A22 and otherand other
acylhydrolases.acylhydrolases.

5. 04/22/15 Dr. Medani A.B. , 2006
PathwaysPathways
PhospholipidsPhospholipids
PhospholipaseAPhospholipaseA22
Arachidonic acid cyclooxygenase
PGG2
5-Lipoxygenase
•5-HPETE leukotiens

6. 04/22/15 Dr. Medani A.B. , 2006
PathwaysPathways
Continues:Continues: PGG2
Hydroxyperoxidase
PGH2
PGI2
PGE2,PGF2α
Thromboxanes
Dipyridamole

7. 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 adenylcyclaseproteins that inhibit or activate adenylcyclase
or stimulate phospholipase- C which enhancesor 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 increasephosphatidyl inositol metabolism to increase
intracellular calcium ions.intracellular calcium ions.

8. 04/22/15 Dr. Medani A.B. , 2006
Functions in the bodyFunctions in the body
 Endogenous PGEndogenous PGSS act as local signals to tuneact as local signals to tune
the response of specific cell types dependingthe response of specific cell types depending
on the tissue ( TXAon the tissue ( TXA22 released from plateletsreleased from platelets
triggers the recruitment of new cells fortriggers the recruitment of new cells for
aggregation in clot formation , while in smoothaggregation in clot formation , while in smooth
muscles this compound induces contraction.muscles this compound induces contraction.
 PGPGSS are chemical mediators released duringare chemical mediators released during
allergic and inflammatory reactions.allergic and inflammatory reactions.

9. 04/22/15 Dr. Medani A.B. , 2006
Non-steroidal anti-inflammatoryNon-steroidal anti-inflammatory
drugsdrugs
 NSAIDS are a group of chemically dissimilarNSAIDS are a group of chemically dissimilar
compounds that differ in their anti-pyreticcompounds that differ in their anti-pyretic
,analgesic and anti-inflammatory activities .,analgesic and anti-inflammatory activities .
 They act by inhibiting the cyclooxygenasesThey act by inhibiting the cyclooxygenases
,but not the lipooxygenase enzymes .,but not the lipooxygenase enzymes .

10. 04/22/15 Dr. Medani A.B. , 2006
a/ Aspirin and other salicylatesa/ Aspirin and other salicylates
 It is the unique weak organic acid inIt is the unique weak organic acid in
irreversibly acetylation of cyclooxygenasesirreversibly 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 andIt acts as an anti-pyretic , anti-inflammtory and
analgesic effects .analgesic effects .

11. 04/22/15 Dr. Medani A.B. , 2006
Mode of action of salicylcylatesMode of action of salicylcylates
 Salicylates act by blocking the PGs synthesisSalicylates act by blocking the PGs synthesis
at the thermoregulatory centers in theat the thermoregulatory centers in the
hypothalamus , the peripheral target sites andhypothalamus , the peripheral target sites and
by decreasing prostaglandin synthesis , theyby decreasing prostaglandin synthesis , they
prevent the sensitization of pain receptors dueprevent the sensitization of pain receptors due
to chemical or mechanical stimuli even at theto chemical or mechanical stimuli even at the
subcortical sites( thalamus and hypothalamus )subcortical sites( thalamus and hypothalamus )

12. 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 :

13. 04/22/15 Dr. Medani A.B. , 2006

NSAIDSNSAIDS
STRONGSTRONG
ANITINFLAMMATORY ANTIPYRETICANITINFLAMMATORY ANTIPYRETIC
ANALGESICANALGESIC
STRONG WEAK STRONGSTRONG WEAK STRONG
ACETAMINOPHENACETAMINOPHEN

14. 04/22/15 Dr. Medani A.B. , 2006
1-Anti-inflammatory action1-Anti-inflammatory action
 They decrease PG synthesis which act asThey decrease PG synthesis which act as
mediators of inflammation.mediators of inflammation.
 Aspirin inhibits inflammation in inflammationAspirin inhibits inflammation in inflammation
in arthritis, but has no effect on diseasein arthritis, but has no effect on disease
progress or its remission .progress or its remission .

15. 04/22/15 Dr. Medani A.B. , 2006
2- Analgesic action2- Analgesic action
 PGEPGE22 is thought to sensitize the nerve endings to theis thought to sensitize the nerve endings to the
action of bradykinin , histamine and other chemicalaction of bradykinin , histamine and other chemical
mediators of the local inflammation and hencemediators of the local inflammation and hence
salicylates by decreasing its synthesis , they decreasesalicylates by decreasing its synthesis , they decrease
the sensation of pain of low to moderate intensitythe 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 inCombinations of NSAIDS and opiods are used in
malignancy.malignancy.

16. 04/22/15 Dr. Medani A.B. , 2006
3-Antipyretic action3-Antipyretic action
 Fever is the set-point of the anteriorFever is the set-point of the anterior
hypothalamus thermoregulatory center ishypothalamus thermoregulatory center is
elevated, may be by increasing PGEelevated, may be by increasing PGE22 synthesissynthesis
due to endogenous agent like pyogens anddue to endogenous agent like pyogens and
malignancy.malignancy.
 Salicylates decrease PGESalicylates decrease PGE22 synthesis andsynthesis and
aspirin increase heat dissipation due toaspirin increase heat dissipation due to
peripheral vasodilation and sweating , but noperipheral vasodilation and sweating , but no
effect on normal body temperature.effect on normal body temperature.

17. 04/22/15 Dr. Medani A.B. , 2006
4- Respiratory action4- Respiratory action
 Aspirin increases alveolar ventilation at EDAspirin increases alveolar ventilation at ED5050
and salicylates uncouple oxidativeand salicylates uncouple oxidative
phosphorylation leading to C0phosphorylation leading to C022 and respiration.and respiration.
 TDTD respiratorycentersof medullarespiratorycentersof medulla Hyperventilation+RespiratoryalkalosisHyperventilation+Respiratoryalkalosis
 TDTD continuedC02productioncontinuedC02production Centralrespiratory(paralysis+ acidosis)Centralrespiratory(paralysis+ acidosis)

18. 04/22/15 Dr. Medani A.B. , 2006
5- GIT Action5- GIT Action
 Prostacyclin PGIProstacyclin PGI22 inhibit gastric acidinhibit gastric acid
secretion .secretion .
 PGEPGE22 and PGFand PGF22αα stimulate the synthesis ofstimulate the synthesis of
protective mucus in the stomach and smallprotective mucus in the stomach and small
intestine.intestine.
 Aspirin decrease PG synthesis , increaseAspirin decrease PG synthesis , increase
gastric acid secretion and diminishes mucusgastric acid secretion and diminishes mucus
protection leading to gastric distress andprotection leading to gastric distress and
ulceration and/or haemorrhage.ulceration and/or haemorrhage.

19. 04/22/15 Dr. Medani A.B. , 2006
6-Effect on platelets6-Effect on platelets
 TXATXA22 increases platelet aggregation and henceincreases platelet aggregation and hence
the anticoagulant effect and bleeding timethe anticoagulant effect and bleeding time
,while PGI,while PGI22 decrease it.decrease it.
 Low aspirin dose inhibit thromboxaneLow aspirin dose inhibit thromboxane
production ,but not TXAproduction ,but not TXA22 in the blood vesselsin the blood vessels
endothelium( platelets lacking nuclei can notendothelium( platelets lacking nuclei can not
produce cyclooxygenases and hence itsproduce 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).

20. 04/22/15 Dr. Medani A.B. , 2006
7- Action on the kidney7- Action on the kidney
 PGEPGE22 and PGIand PGI22 maintain renal blood flowmaintain renal blood flow
especially if vasoconstritors are presentespecially if vasoconstritors are present
 Decreased PG synthesis may be due toDecreased PG synthesis may be due to
retention of sodium and water which enhancesretention of sodium and water which enhances
edema and hyperkalaemia .edema and hyperkalaemia .
 Interstitial nephritis occurs in all NSAIDSInterstitial nephritis occurs in all NSAIDS
except aspirin.except aspirin.

21. 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 forproduce antipyretic and analgesic effects for
the treatment of gout , rheumatic fever andthe treatment of gout , rheumatic fever and
rheumatoid arthritis.rheumatoid arthritis.
 They are analgesic for haedache ,arthralgiaThey are analgesic for haedache ,arthralgia
and myalgia.and myalgia.

22. 04/22/15 Dr. Medani A.B. , 2006
2-External applications2-External applications
 Salicylic acid is given topically in case cornSalicylic acid is given topically in case corn
calluses epidermatophytosis (fungal infection).calluses epidermatophytosis (fungal infection).
 Methyl salicylates (oil of wintergreen) worksMethyl salicylates (oil of wintergreen) works
as an external counter irritant in liniments.as an external counter irritant in liniments.

23. 04/22/15 Dr. Medani A.B. , 2006
3- Cardiovascular applications3- Cardiovascular applications
 Salicylates inhibit platelet aggregation leadingSalicylates inhibit platelet aggregation leading
to an anticoagulant effect ( prophylaxis into an anticoagulant effect ( prophylaxis in
transient ischaemic attacks ,unstable angina intransient ischaemic attacks ,unstable angina in
men and in coronary artery thrombosis.men and in coronary artery thrombosis.
 PGEPGE22 is responsible for keeeping the ductusis responsible for keeeping the ductus
arteriosus open , hence treatment is by usingarteriosus open , hence treatment is by using
aspirin .aspirin .

24. 04/22/15 Dr. Medani A.B. , 2006
4-Colon cancer4-Colon cancer
 Chronic use of aspirin decrease the incidenceChronic use of aspirin decrease the incidence
of colorectal cancer .of colorectal cancer .

25. 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 .

26. 04/22/15 Dr. Medani A.B. , 2006
Propionic acid derivativesPropionic acid derivatives
 Ibuprofen ,naproxen ,fenoprofen ,ketoprofenIbuprofen ,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 havethat is given once /day oxaprozin ,all have
antiinfalammatory , antipyretic and analgesicantiinfalammatory , antipyretic and analgesic
effects used in case of chronic rheumatoid andeffects used in case of chronic rheumatoid and
oesteoarthritis , but their GITeffects decreaseoesteoarthritis , but their GITeffects decrease
that of aspirin.that of aspirin.

27. 04/22/15 Dr. Medani A.B. , 2006
-Con.-Con.
 They are reversible inhibitors ofThey 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 oralThey are well absorped after oral
adminstration and totally bound to albumin .adminstration and totally bound to albumin .
After hepatic metabolism , renal excretion mayAfter hepatic metabolism , renal excretion may
occur .occur .

28. 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 likeSide effects are mostly CNS signs like
haedache,tinnitus and dizziness .haedache,tinnitus and dizziness .

29. 04/22/15 Dr. Medani A.B. , 2006
Indole acetic acidIndole acetic acid
 Indomethazine ,sulindac and etodolac haveIndomethazine ,sulindac and etodolac have
antiinflammatory ,analgesic and antipyretic effects byantiinflammatory ,analgesic and antipyretic effects by
reversibly inhibit cyclooxygenases , but not to lowerreversibly inhibit cyclooxygenases , but not to lower
fever :fever :
1/1/ IndomethazineIndomethazine toxicity limits its use as antoxicity limits its use as an
antiinflammatory.It is used in the postoperativeantiinflammatory.It is used in the postoperative
opthalmic conditions and as an antipyretic when theopthalmic conditions and as an antipyretic when the
condition is refractory to other agent. It can delaycondition is refractory to other agent. It can delay
labour by supressing uterine contractions and is alsolabour by supressing uterine contractions and is also
effective in patent ductus arteriosus.effective in patent ductus arteriosus.

30. 04/22/15 Dr. Medani A.B. , 2006
-Con.-Con.
 After oral dosing ,it is completely absorped from theAfter oral dosing ,it is completely absorped from the
upper GIT,under go hepatic metabolism and theupper GIT,under go hepatic metabolism and the
unchanged drug and its metabolites are then excretedunchanged 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 ofanorrehexia ,diarrhia ,abdominal pain ,ulceration of
upper GIT, frontalhaedache,vertigo andupper GIT, frontalhaedache,vertigo and
haemorrhages.There is 100% cross-reaction withhaemorrhages.There is 100% cross-reaction with
aspirin.aspirin.

31. 04/22/15 Dr. Medani A.B. , 2006
2-2-SulindacSulindac
 It is an inactive pro-drug closely related toIt is an inactive pro-drug closely related to
indomethazine which, after hepaticindomethazine which, after hepatic
metabolism, liberate the active sulfide with ametabolism, liberate the active sulfide with a
long active duration .long active duration .
 It is used less potently than the endomethazineIt is used less potently than the endomethazine
to treat reheumatoid arthritis ,ankylosingto treat reheumatoid arthritis ,ankylosing
spondylitis ,osteoarthritis and acute gout .spondylitis ,osteoarthritis and acute gout .
 Adverse reactions are similar to those ofAdverse reactions are similar to those of
NSAIDS .NSAIDS .

32. 04/22/15 Dr. Medani A.B. , 2006
3/3/ EtodolacEtodolac
 This has effects similar to the NSAIDs ,but hasThis has effects similar to the NSAIDs ,but has
less GIT problems .less GIT problems .
 Adverse effects include fluid retention andAdverse effects include fluid retention and
abnormal liver kidney function .abnormal liver kidney function .
 It may increase serum levels and increase theIt 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 thelithium , methotrexate ,and enhance the
nephrotoxicity of cyclosporin.nephrotoxicity of cyclosporin.

33. 04/22/15 Dr. Medani A.B. , 2006
Oxicam derivativesOxicam derivatives
 OnlyOnly piroxicampiroxicam is available to treat rhematoidis available to treat rhematoid
arthritis, ankylosing spodylitis andarthritis, ankylosing spodylitis and
oesteoarthritis .Its toesteoarthritis .Its t1/21/2 is 50 hours ,so itcan beis 50 hours ,so itcan be
given once /day.given once /day.
 GIT disturbances occur to 20% of the patientsGIT disturbances occur to 20% of the patients
before excretion with urine ,where it canbefore excretion with urine ,where it can
interfere with the excretion of lithium.interfere with the excretion of lithium.

34. 04/22/15 Dr. Medani A.B. , 2006
FenamatesFenamates
 Mefenamic acid and meclofenamates have sideMefenamic acid and meclofenamates have side
effects like diarrheoa ,bowel inflammtion andeffects like diarrheoa ,bowel inflammtion and
are reported in association with haemolyticare reported in association with haemolytic
anaemia.anaemia.

35. 04/22/15 Dr. Medani A.B. , 2006
PhenylbutazonePhenylbutazone
 It is a powerful antiinflammatory drug ,but aIt is a powerful antiinflammatory drug ,but a
weak analgesic and antipyretic drug .weak analgesic and antipyretic drug .
 It is rapidly and completely absorped after oralIt is rapidly and completely absorped after oral
or rectal dosing , metabolized intoor rectal dosing , metabolized into
oxyphenybutazone which is then bound tooxyphenybutazone which is then bound to
plasma proteins.plasma proteins.
 50% of patients show nausia , vomiting50% of patients show nausia , vomiting
,GITdisturbances ,skin rash, edema ,,GITdisturbances ,skin rash, edema ,
granulocytosis and aplastic anaemia.granulocytosis and aplastic anaemia.

36. 04/22/15 Dr. Medani A.B. , 2006
Non-narcotic analgesicsNon-narcotic analgesics
 Unlike the NSAIDs ,they have no or littleUnlike the NSAIDs ,they have no or little
antiinflammatory effects . They do not causeantiinflammatory 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 orperipheral tissues, do not affect platelets or
bleeding time .bleeding time .

37. 04/22/15 Dr. Medani A.B. , 2006
Con.Con.
 Acetaminophen produces analgesia andAcetaminophen produces analgesia and
antipyrexia instead of aspirin in case of gastricantipyrexia instead of aspirin in case of gastric
complaints ,prolonged bleeding time (lowcomplaints ,prolonged bleeding time (low
renal toxicity) ,kids with viral infections orrenal toxicity) ,kids with viral infections or
chicken pox ( aspirin increase the risk of Reychicken pox ( aspirin increase the risk of Rey,,
ss
syndrome) or with probencid for the fear ofsyndrome) or with probencid for the fear of
aspirin antagonism.aspirin antagonism.

38. 04/22/15 Dr. Medani A.B. , 2006
Con.Con.
 Acetaminophen and phenacetin are rapidlyAcetaminophen and phenacetin are rapidly
absorped ,undergo first-pass effect in th luminalabsorped ,undergo first-pass effect in th luminal
intestine and the hepatocytes, glucronated or sulfatedintestine 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 tubularProlonged acetaminophen can cause renal tubular
necrosis and hypoglycaemic coma.necrosis and hypoglycaemic coma.
 After glutathione depletion ,toxic doses may causeAfter glutathione depletion ,toxic doses may cause
hepatic necrosis and renal tubular necrosis due to thehepatic 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.

39. 04/22/15 Dr. Medani A.B. , 2006
Anti-rheumatic agentsAnti-rheumatic agents
 They are slowly acting and inhibitThey are slowly acting and inhibit
cyclooxygenases.cyclooxygenases.
 They are used in cases of inflammtion that doThey are used in cases of inflammtion that do
not respond to NSAIDs .not respond to NSAIDs .
 They are disease modifying antirheumaticThey are disease modifying antirheumatic
drugs (DMARDs) to slow the course of thedrugs (DMARDs) to slow the course of the
disease , induce remission and prevent furtherdisease , induce remission and prevent further
destruction of joints and involved tissues.destruction of joints and involved tissues.

40. 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 givenaurothioglucose given I/M and auranofin given
orally) can not repair the existing damage, butorally) can not repair the existing damage, but
can only prevent further injury .can only prevent further injury .
 They are taken by macrophages ,supressThey are taken by macrophages ,supress
phagocytosis and lyosomal enzymes activityphagocytosis and lyosomal enzymes activity
and hence retard the progression of bone andand hence retard the progression of bone and
articular destruction.articular destruction.

41. 04/22/15 Dr. Medani A.B. , 2006
Con.Con.
 They are water-soluble and are given orally and I/MThey are water-soluble and are given orally and I/M
to concentarte in macrophages (liver, kidney ,spleento concentarte in macrophages (liver, kidney ,spleen
and adrenal cortex) and then excreted in urine andand 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 mucusThey may cause dermatitis of skin or mucus
membranes , proteinurea and nephrosis.membranes , proteinurea and nephrosis.
 It should be avoided in patients with hepatic or renalIt should be avoided in patients with hepatic or renal
diseases ,pregnant or those with history of toxicity todiseases ,pregnant or those with history of toxicity to
these agents.these agents.

42. 04/22/15 Dr. Medani A.B. , 2006
Drugs embloyed in the treatment ofDrugs embloyed in the treatment of
goutgout
 Gout is a metabolic disorder characterized byGout is a metabolic disorder characterized by
increased uric acid in blood leading toincreased uric acid in blood leading to
hyperuricaemia and deposition of crystals ofhyperuricaemia and deposition of crystals of
sodium urates in tissue ( kidney and joints)sodium urates in tissue ( kidney and joints)
causing inflammation (infilteration ofcausing inflammation (infilteration of
granulocytes that phagocytose the urategranulocytes that phagocytose the urate
crystals, formation of oxygen-metabolitescrystals, formation of oxygen-metabolites
leading to tissue damage and production of anleading to tissue damage and production of an
inflammatory response by lyosomal enzymes).inflammatory response by lyosomal enzymes).

43. 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 isthe 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 orii/ Increase uric acid excretion with probencid or
sulfinpyrazone.sulfinpyrazone.
iii/Inhibit leukocyte entry into the affected joint byiii/Inhibit leukocyte entry into the affected joint by
cochicine .cochicine .
iv/ Adminster NSAIDs.iv/ Adminster NSAIDs.