Allopurinol

Lecture on GOUT

1. 11
AllopurinolAllopurinol
Prof. Dr. Shah MuradProf. Dr. Shah Murad
[email protected]@yahoo.com

2. 22
ZYLOPRIM (allopurinol)ZYLOPRIM (allopurinol)

3. 33
ZYLOPRIM is known chemically as 1,5-ZYLOPRIM is known chemically as 1,5-
dihydro-4dihydro-4HH-pyrazolo [3,4--pyrazolo [3,4-dd]pyrimidin-4-]pyrimidin-4-
one. one.
It is a It is a xanthinexanthine oxidase inhibitor which is oxidase inhibitor which is
administered orally. administered orally.

4. 44
Xanthine oxidaseXanthine oxidase is an is an enzymeenzyme that that
catalyzes the catalyzes the oxidationoxidation of of hypoxanthinehypoxanthine to to
xanthinexanthine and can further catalyze the and can further catalyze the
oxidation of xanthine to oxidation of xanthine to uric aciduric acid. .
This enzyme plays an important role in the This enzyme plays an important role in the
catabolism of purines in some species, catabolism of purines in some species,
including humanincluding human

5. 55
Xanthine oxidase can be converted to Xanthine oxidase can be converted to
xanthinexanthine dehydrogenasedehydrogenase by reversible by reversible
sulfhydryl oxidation sulfhydryl oxidation

6. 66
ReactionReaction
The following chemical reactions are catalyzed by The following chemical reactions are catalyzed by
xanthine oxidase:xanthine oxidase:
hypoxanthine + H2O + O2>>>>xanthine+ hypoxanthine + H2O + O2>>>>xanthine+
H2O2 H2O2
xanthine + H2O + O2 >>>> uric acid + H2O2 xanthine + H2O + O2 >>>> uric acid + H2O2

7. 77
Hypoxanthine XanthineHypoxanthine Xanthine

8. 88
Protein structureProtein structure
The protein is large, having a The protein is large, having a molecular weightmolecular weight
of 270,000, and has 2 of 270,000, and has 2 flavinflavin molecules (bound molecules (bound
as FAD), 2 as FAD), 2 molybdenummolybdenum atoms, and 8 atoms, and 8 ironiron
atoms bound per enzymatic unit. atoms bound per enzymatic unit.
The molybdenum atoms are contained as The molybdenum atoms are contained as
molybdopterinmolybdopterin cofactors and are the active cofactors and are the active
sites of the enzyme. sites of the enzyme.
The iron atoms are part of [2Fe-2S] The iron atoms are part of [2Fe-2S] ferredoxinferredoxin
iron-sulfur clustersiron-sulfur clusters and participate in electron transfer and participate in electron transfer
reactionsreactions

9. 99
Catalytic mechanismCatalytic mechanism
The active site of XO is composed of a molybdopterin The active site of XO is composed of a molybdopterin
unit with the molybdenum atom also coordinated by unit with the molybdenum atom also coordinated by
terminal oxygen (terminal oxygen (oxooxo), sulfur atoms and a terminal ), sulfur atoms and a terminal
hydroxidehydroxide. .
In the reaction with xanthine to form uric acid, an In the reaction with xanthine to form uric acid, an
oxygen atom is transferred from molybdenum to oxygen atom is transferred from molybdenum to
xanthine. xanthine.
The reformation of the active molybdenum center The reformation of the active molybdenum center
occurs by the addition of water.occurs by the addition of water.
Like other known molybdenum-containing Like other known molybdenum-containing
oxidoreductases, the oxygen atom introduced to the oxidoreductases, the oxygen atom introduced to the
substratesubstrate by XO originates from water rather than by XO originates from water rather than
from from dioxygendioxygen (O2) (O2)

10. 1010
Clinical significanceClinical significance
In humans, xanthine oxidase is normally found In humans, xanthine oxidase is normally found
in the in the liverliver and not free in the blood. and not free in the blood.
During severe liver damage, xanthine oxidase is During severe liver damage, xanthine oxidase is
released into the blood, so a blood assay for XO released into the blood, so a blood assay for XO
is a way to determine if is a way to determine if liverliver damage has damage has
happenedhappened

11. 1111
As well, because xanthine oxidase is a As well, because xanthine oxidase is a
metabolic pathwaymetabolic pathway for for uric aciduric acid formation, the formation, the
xanthine oxidase inhibitor xanthine oxidase inhibitor allopurinolallopurinol is used in is used in
the treatment of the treatment of goutgout. .
Since xanthine oxidase is involved in the Since xanthine oxidase is involved in the
metabolism of metabolism of 6-mercaptopurine6-mercaptopurine, caution , caution
should be taken before administering should be taken before administering
allopurinol and 6-mercaptopurine, or its allopurinol and 6-mercaptopurine, or its
prodrug prodrug azathioprineazathioprine, in conjunction., in conjunction.

12. 1212
XanthinuriaXanthinuria is a rare is a rare genetic disordergenetic disorder where the where the
lack of xanthine oxidase leads to high lack of xanthine oxidase leads to high
concentration of xanthine in blood and can concentration of xanthine in blood and can
cause health problems such as cause health problems such as renal failurerenal failure. .
There is no specific treatment, sufferers are There is no specific treatment, sufferers are
advised by doctors to avoid foods high in advised by doctors to avoid foods high in
purinepurine and to maintain a high fluid intake. and to maintain a high fluid intake.

13. 1313
InhibitorsInhibitors
XanthineXanthine oxidaseoxidase inhibitor inhibitor
Inhibitors of XO include Inhibitors of XO include allopurinolallopurinol, ,
oxypurinoloxypurinol,and ,and phyticphytic acid acid

14. 1414
Allopurinol is taken in tablet form (oral). Allopurinol is taken in tablet form (oral).
It is taken in low dosages at first. It is taken in low dosages at first.
The dosage is gradually increased to control The dosage is gradually increased to control
uric acid levels.uric acid levels.

15. 1515
MOAMOA
Allopurinol prevents the release of a Allopurinol prevents the release of a
substance called xanthine oxidase, which substance called xanthine oxidase, which
helps in the formation of uric acid. helps in the formation of uric acid.
In treatment for In treatment for goutgout, allopurinol blocks , allopurinol blocks
the production of the production of uric aciduric acid in the body. in the body.

16. 1616
Allopurinol may be prescribed to prevent gout attacks. Allopurinol may be prescribed to prevent gout attacks.
It also may be used because of:It also may be used because of:
Overproduction of uric acid. Overproduction of uric acid.
Frequent gout attacks. Frequent gout attacks.
Presence of gritty, chalklike clumps of uric acid Presence of gritty, chalklike clumps of uric acid
crystals (crystals (tophitophi). ).
Failure of other medicines to adequately reduce uric Failure of other medicines to adequately reduce uric
acid levels. acid levels.
Allergy to uricosuric medications, which increase the Allergy to uricosuric medications, which increase the
elimination of uric acid, or serious side effects from elimination of uric acid, or serious side effects from
these medicines. Uricosuric medications include these medicines. Uricosuric medications include
probenecid (Probalan) and sulfinpyrazone (Anturane). probenecid (Probalan) and sulfinpyrazone (Anturane).
Poor kidney function. Poor kidney function.
History of uric acid kidney stones. History of uric acid kidney stones.

17. 1717
Allopurinol may also be used for the prevention Allopurinol may also be used for the prevention
of kidney disease in people going through of kidney disease in people going through
treatment for cancer.treatment for cancer.
The dose of allopurinol may need to be lower The dose of allopurinol may need to be lower
for people who have chronic kidney disease or for people who have chronic kidney disease or
are taking azathioprine.are taking azathioprine.

18. 1818
Allopurinol is not Allopurinol is not
recommended for people whorecommended for people who
Have a known sensitivity to allopurinol. Have a known sensitivity to allopurinol.
Have a condition in which there is too much Have a condition in which there is too much
iron in the body (iron in the body (hemochromatosishemochromatosis). ).
Allopurinol should not be started for the first Allopurinol should not be started for the first
time by people who are still having symptoms time by people who are still having symptoms
caused by a gout attack.caused by a gout attack.

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Allopurinol lowers the amount of uric acid in the body. Allopurinol lowers the amount of uric acid in the body.
After the proper dose is reached, the uric acid levels After the proper dose is reached, the uric acid levels
should return to normal. should return to normal.
 doctor will monitor uric acid level within one month doctor will monitor uric acid level within one month
of starting or changing a dose of allopurinol.of starting or changing a dose of allopurinol.
Treatment with allopurinol can reduce the size of Treatment with allopurinol can reduce the size of tophitophi
. .

20. 2020
Side EffectsSide Effects
Skin rash is a common side effect. Skin rash is a common side effect.
Because a skin rash may be a symptom of an Because a skin rash may be a symptom of an
allergic reaction to allopurinol, have your doctor allergic reaction to allopurinol, have your doctor
evaluate any skin rash that develops while you evaluate any skin rash that develops while you
are taking this medicine.are taking this medicine.

21. 2121
Rare, serious side effects includeRare, serious side effects include
Inflammation of the liver (Inflammation of the liver (hepatitishepatitis). ).
Failure of bone marrow to produce Failure of bone marrow to produce
blood cells (blood cells (aplasticaplastic anemia anemia). ).
Inflammation of blood vessels (Inflammation of blood vessels (
vasculitisvasculitis). ).
Allopurinol hypersensitivity syndrome Allopurinol hypersensitivity syndrome
(a widespread rash, fever, mouth (a widespread rash, fever, mouth
sores, poor kidney function, liver sores, poor kidney function, liver
inflammation, and other inflammation, and other
complications), which can be life-complications), which can be life-
threateningthreatening. .

22. 2222
Allopurinol interferes with many other Allopurinol interferes with many other
medicines. medicines.
It may increase or decrease the levels of It may increase or decrease the levels of
other medicines, which may increase the other medicines, which may increase the
toxicity of these medicines or reduce their toxicity of these medicines or reduce their
effectiveness.effectiveness.

23. 2323
Allopurinol should not be used until the symptoms of a Allopurinol should not be used until the symptoms of a
gout attack are gone. But if you are already taking gout attack are gone. But if you are already taking
allopurinol, continue to take it (even during an attack). allopurinol, continue to take it (even during an attack).
Gout attacks may increase at first for some people Gout attacks may increase at first for some people
taking allopurinol. taking allopurinol.
To avoid this, doctors may prescribe either colchicine, To avoid this, doctors may prescribe either colchicine,
which blocks the inflammation caused by uric acid which blocks the inflammation caused by uric acid
crystals, or low-dose nonsteroidal anti-inflammatory crystals, or low-dose nonsteroidal anti-inflammatory
drugs (drugs (NSAIDsNSAIDs) to be taken at the same time. ) to be taken at the same time.
After normal uric acid levels have been maintained for After normal uric acid levels have been maintained for
6 to 12 months and no further attacks occur, 6 to 12 months and no further attacks occur,
colchicine or NSAIDs do not need to be taken. colchicine or NSAIDs do not need to be taken.
Because of the rare risk of serious side effects, many Because of the rare risk of serious side effects, many
doctors may prefer uricosuric medications to doctors may prefer uricosuric medications to
allopurinol. allopurinol.

24. 2424
Laboratory studies, including a Laboratory studies, including a
complete blood countcomplete blood count (CBC) and liver and (CBC) and liver and
kidney function studies, may be done after kidney function studies, may be done after
a few months of using allopurinol. a few months of using allopurinol.

25. 2525
NSAIDsNSAIDs
INDOCIN is a non-steroidal anti-INDOCIN is a non-steroidal anti-
inflammatory drug (NSAID) that exhibits inflammatory drug (NSAID) that exhibits
antipyreticantipyretic and and analgesicanalgesic properties. properties.

26. 2626
MOAMOA
INDOCIN is a potent inhibitor of INDOCIN is a potent inhibitor of prostaglandinprostaglandin
synthesissynthesis. .
Prostaglandins sensitize Prostaglandins sensitize afferentafferent nerves and nerves and
potentiate the action of bradykinin in inducing potentiate the action of bradykinin in inducing
pain in animal models.pain in animal models.
 prostaglandins are known to be among the prostaglandins are known to be among the
mediators of inflammation. mediators of inflammation.
Since indomethacin is an inhibitor of Since indomethacin is an inhibitor of
prostaglandin synthesis, its mode of action may prostaglandin synthesis, its mode of action may
be due to a decrease of prostaglandins in be due to a decrease of prostaglandins in
peripheral tissues.peripheral tissues.

27. 2727
Other usesOther uses
INDOCIN has been shown to be an effective INDOCIN has been shown to be an effective
anti-inflammatory agent, appropriate for long-anti-inflammatory agent, appropriate for long-
term use in term use in rheumatoid arthritisrheumatoid arthritis, ,
ankylosing spondylitisankylosing spondylitis, and , and osteoarthritisosteoarthritis..
INDOCIN affords relief of symptoms; it does INDOCIN affords relief of symptoms; it does
not alter the progressive course of the not alter the progressive course of the
underlying disease.underlying disease.

28. 2828
INDOCIN suppresses inflammation in rheumatoid INDOCIN suppresses inflammation in rheumatoid
arthritis as demonstrated by relief of pain, and arthritis as demonstrated by relief of pain, and
reduction of fever, swelling and tenderness. reduction of fever, swelling and tenderness.
Improvement in patients treated with INDOCIN for Improvement in patients treated with INDOCIN for
rheumatoid arthritis has been demonstrated by a rheumatoid arthritis has been demonstrated by a
reduction in joint swelling, average number of joints reduction in joint swelling, average number of joints
involved, and morning stiffness; by increased mobility involved, and morning stiffness; by increased mobility
as demonstrated by a decrease in walking time; and as demonstrated by a decrease in walking time; and
by improved functional capability as demonstrated by by improved functional capability as demonstrated by
an increase in grip strength. an increase in grip strength.
INDOCIN may enable the reduction of steroid dosage in INDOCIN may enable the reduction of steroid dosage in
patients receiving steroids for the more severe forms of patients receiving steroids for the more severe forms of
rheumatoid arthritis. rheumatoid arthritis.
In such instances the steroid dosage should be reduced In such instances the steroid dosage should be reduced
slowly and the patients followed very closely for any slowly and the patients followed very closely for any
possible adverse effects.possible adverse effects.

29. 2929
Capsules INDOCIN have been found Capsules INDOCIN have been found
effective in relieving the pain, reducing the effective in relieving the pain, reducing the
fever, swelling, redness, and tenderness fever, swelling, redness, and tenderness
of acute of acute gouty arthritisgouty arthritis

30. 3030
PKPK
Following single oral doses of Capsules Following single oral doses of Capsules
INDOCIN 25 mg or 50 mg, indomethacin is INDOCIN 25 mg or 50 mg, indomethacin is
readily absorbed, attaining peak readily absorbed, attaining peak plasmaplasma
concentrations of about 1 and 2 mcg/mL, concentrations of about 1 and 2 mcg/mL,
respectively, at about 2 hours. respectively, at about 2 hours.
Orally administered Capsules INDOCIN are Orally administered Capsules INDOCIN are
virtually 100% bioavailable, with 90% of the virtually 100% bioavailable, with 90% of the
dose absorbeddose absorbed within 4 hours. within 4 hours.
A single 50 mg dose of Oral Suspension A single 50 mg dose of Oral Suspension
INDOCIN was found to be bioequivalent to a 50 INDOCIN was found to be bioequivalent to a 50
mg INDOCIN capsule when each was mg INDOCIN capsule when each was
administered with foodadministered with food

31. 3131
Indomethacin is eliminated via Indomethacin is eliminated via renalrenal excretion, excretion,
metabolismmetabolism, and , and biliarybiliary excretion. excretion.
Indomethacin undergoes appreciable enterohepatic Indomethacin undergoes appreciable enterohepatic
circulationcirculation. .
The mean half-life of indomethacin is estimated to The mean half-life of indomethacin is estimated to
be about 4.5 hours. be about 4.5 hours.
With a typical therapeutic With a typical therapeutic regimenregimen of 25 or 50 mg of 25 or 50 mg
t.i.d.t.i.d., the steady-state plasma concentrations of , the steady-state plasma concentrations of
indomethacin are an average 1.4 times those indomethacin are an average 1.4 times those
following the first dosefollowing the first dose

32. 3232
The rate of The rate of absorptionabsorption is more rapid from the is more rapid from the
rectalrectal suppository than from Capsules suppository than from Capsules
INDOCIN. INDOCIN.
Ordinarily, therefore, the total amount Ordinarily, therefore, the total amount
absorbed from the suppository would be absorbed from the suppository would be
expected to be at least equivalent to the expected to be at least equivalent to the
capsule. capsule.

33. 3333
Indomethacin exists in the plasma as the Indomethacin exists in the plasma as the
parent drug and its desmethyl, desbenzoyl, and parent drug and its desmethyl, desbenzoyl, and
desmethyl-desbenzoyl metabolites, all in the desmethyl-desbenzoyl metabolites, all in the
unconjugated form. unconjugated form.
About 60 percent of an oral dosage is About 60 percent of an oral dosage is
recovered in recovered in urineurine as drug and metabolites (26 as drug and metabolites (26
percent as indomethacin and its glucuronide), percent as indomethacin and its glucuronide),
and 33 percent is recovered in and 33 percent is recovered in fecesfeces (1.5 (1.5
percent as indomethacin).percent as indomethacin).

34. 3434
About 99% of indomethacin is bound to About 99% of indomethacin is bound to
proteinprotein in plasma over the expected range in plasma over the expected range
of therapeutic plasma concentrations. of therapeutic plasma concentrations.
Indomethacin has been found to cross the Indomethacin has been found to cross the
blood-brain barrierblood-brain barrier and the and the placentaplacenta..

35. 3535
ProbenecidProbenecid (Benuryl) (Benuryl)
is a is a uricosuricuricosuric drug that increases drug that increases uric aciduric acid
excretion in the excretion in the urineurine. .
It is primarily used in treating It is primarily used in treating goutgout and and
hyperuricemiahyperuricemia..
Probenecid competitively inhibits the renal Probenecid competitively inhibits the renal
excretion of some drugs, thereby increasing excretion of some drugs, thereby increasing
their plasma concentration and prolonging their their plasma concentration and prolonging their
effects.effects.

36. 3636
In the In the kidneyskidneys probenecid is filtered at the probenecid is filtered at the
glomerulusglomerulus, secreted in the , secreted in the proximal tubuleproximal tubule and and
reabsorbed in the reabsorbed in the distal tubuledistal tubule..
Probenecid's exact mechanism is explained as follows. Probenecid's exact mechanism is explained as follows.
The kidney's The kidney's organic anion transporterorganic anion transporter (OAT) reclaims (OAT) reclaims
uric acid from the urine and returns it to the plasma. uric acid from the urine and returns it to the plasma.
Probenecid interferes with these systems.Probenecid interferes with these systems.
 If probenecid (an organic acid) is administered If probenecid (an organic acid) is administered
to a patient, the OAT binds to probenecid to a patient, the OAT binds to probenecid
instead of to uric acid, preventing the instead of to uric acid, preventing the
reabsorption of uric acid. reabsorption of uric acid.
As a result, more uric acid leaves the body in the As a result, more uric acid leaves the body in the
urine, lowering the uric acid concentration in the urine, lowering the uric acid concentration in the
plasmaplasma..

37. 3737
UsesUses
probenecid was shown to more than double blood probenecid was shown to more than double blood
concentrations of concentrations of oseltamiviroseltamivir (trade name Tamiflu), an (trade name Tamiflu), an
antiviral drugantiviral drug used to combat used to combat influenzainfluenza..
This is significant because nations are currently This is significant because nations are currently
stockpiling oseltamivir in anticipation of an stockpiling oseltamivir in anticipation of an
influenza pandemicinfluenza pandemic, and there could be supply , and there could be supply
shortages.shortages.
During World War II, probenecid was used to extend During World War II, probenecid was used to extend
limited supplies of limited supplies of penicillinpenicillin, and is still currently used , and is still currently used
to increase antibiotic concentrations in serious to increase antibiotic concentrations in serious
infections.infections.
It has also found use as a It has also found use as a masking agentmasking agent

38. 3838
CORTICOSTEROIDSCORTICOSTEROIDS
corticosteroids are naturally produced by corticosteroids are naturally produced by
your own body and may help reduce your own body and may help reduce
swelling, redness and pain in joints. swelling, redness and pain in joints.
Systemic corticosteroids come in a pill Systemic corticosteroids come in a pill
form or as an injection form or as an injection

39. 3939
There is inconclusive evidence for the There is inconclusive evidence for the
efficacy and effectiveness of systemic efficacy and effectiveness of systemic
corticosteroids in the treatment of acute corticosteroids in the treatment of acute
gout. gout.
Patients with gout did not report serious Patients with gout did not report serious
adverse effects from systemic adverse effects from systemic
corticosteroids, when used for short term. corticosteroids, when used for short term.

40. 4040
USES of corticosteroidsUSES of corticosteroids
Gout attacks that are limited to a single joint. Gout attacks that are limited to a single joint.
Gout attacks that do not respond to Gout attacks that do not respond to
nonsteroidal anti-inflammatory drugs (nonsteroidal anti-inflammatory drugs (NSAIDsNSAIDs) )
or colchicine. or colchicine.
People who cannot take NSAIDs or colchicine, People who cannot take NSAIDs or colchicine,
such as those with kidney disease or a history of such as those with kidney disease or a history of
serious serious ulcerulcer disease and gastrointestinal disease and gastrointestinal
bleeding. bleeding.
Corticosteroids may also be used by people Corticosteroids may also be used by people
who have congestive heart failure or take who have congestive heart failure or take
the blood-thinner warfarin, or who are the blood-thinner warfarin, or who are
allergic to aspirin.allergic to aspirin.

41. 4141
Side EffectsSide Effects
Mood swings. Mood swings.
Nervousness. Nervousness.
InsomniaInsomnia. .
Weight gain. Weight gain.
Fluid retention. Fluid retention.
Very rounded (moon) face. Very rounded (moon) face.
Poor wound healing. Poor wound healing.
Increased risk of infection. Increased risk of infection.
High blood pressureHigh blood pressure. .
DiabetesDiabetes. .

42. 4242
Uncommon short-term side Uncommon short-term side
effects effects
Muscle weakness. Muscle weakness.
GlaucomaGlaucoma. .
Stomach ulcersStomach ulcers. .
AcneAcne. .
Long-term side effects includeLong-term side effects include
OsteoporosisOsteoporosis. .
CataractsCataracts (uncommon). (uncommon).
Damage to the hip, shoulder, or knee Damage to the hip, shoulder, or knee
joints (uncommon). joints (uncommon).

43. 4343
ACTHACTH
Corticotropin alone or in combination with Corticotropin alone or in combination with
colchicine is more rapidly effective and colchicine is more rapidly effective and
associated with fewer adverse effects than associated with fewer adverse effects than
indomethacin.indomethacin.
 This regimen may be considered an This regimen may be considered an
alternative, especially for patients with medical alternative, especially for patients with medical
problems in which other regimens are problems in which other regimens are
contraindicated. contraindicated.

44. 4444
adrenocorticotropic hormone (ACTH) possess adrenocorticotropic hormone (ACTH) possess
potent antirheumatic properties. potent antirheumatic properties.
rheumatoid arthritis, rheumatoid arthritis,
rheumatoid (ankylosing) spondylitis, rheumatoid (ankylosing) spondylitis,
acute rheumatic fever, acute rheumatic fever,
disseminated lupus erythematosus, disseminated lupus erythematosus,
periarteritis nodosa, periarteritis nodosa,
psoriatic arthritis, psoriatic arthritis,
dermatomyositis, and dermatomyositis, and
gout gout

45. 4545
In general the effects of ACTH/Cortisone are In general the effects of ACTH/Cortisone are
temporary and they cause suppression rather temporary and they cause suppression rather
than cure of the disease processes. than cure of the disease processes.
Improvement is maintained usually only by Improvement is maintained usually only by
continuing administration, and on hormonal continuing administration, and on hormonal
withdrawal prompt or fairly prompt relapse of withdrawal prompt or fairly prompt relapse of
the disease manifestations ensues the disease manifestations ensues

46. 4646
ACTHACTH
Its chief function is to stimulate the cortex of Its chief function is to stimulate the cortex of
the the adrenal glandadrenal gland to secrete adrenocortical to secrete adrenocortical
steroids, chief among them steroids, chief among them cortisonecortisone. .
The release of adrenocorticotropic hormone The release of adrenocorticotropic hormone
(ACTH), also known as corticotropin, is (ACTH), also known as corticotropin, is
stimulated by corticotropin-releasing factor stimulated by corticotropin-releasing factor
(CRF), a secretion of the hypothalamus. (CRF), a secretion of the hypothalamus.

47. 4747
ACTH secretion is an excellent example of ACTH secretion is an excellent example of
the regulation of a biological system by a the regulation of a biological system by a
negative-feedback mechanism; high levels negative-feedback mechanism; high levels
of adrenocortical steroids in the blood of adrenocortical steroids in the blood
tend to decrease ACTH release, whereas tend to decrease ACTH release, whereas
low steroid levels have the opposite effect. low steroid levels have the opposite effect.

48. 4848
ACTH has the same pharmacologic and ACTH has the same pharmacologic and
clinical effects as cortisone when given clinical effects as cortisone when given
intravenously or intramuscularly;intravenously or intramuscularly;
however, it has no value when applied however, it has no value when applied
externally and cannot be taken orally since externally and cannot be taken orally since
it is deactivated by digestive enzymes it is deactivated by digestive enzymes

49. 4949
ARTHRITISARTHRITIS

50. 5050
Arthritis literally means joint inflammation. Arthritis literally means joint inflammation.
Arthritis is not a single Arthritis is not a single
diseasedisease. .
Arthritis refers to a group of more than Arthritis refers to a group of more than
100 rheumatic diseases and other conditions100 rheumatic diseases and other conditions
that can cause pain, stiffness and swelling that can cause pain, stiffness and swelling
in the in the joints.joints.

51. 5151
The most common form, The most common form, osteoarthritisosteoarthritis
(degenerative joint disease) is a result of (degenerative joint disease) is a result of
trauma to the joint, infection of the joint, or trauma to the joint, infection of the joint, or
age. Other arthritis forms are age. Other arthritis forms are
rheumatoid arthritisrheumatoid arthritis and and psoriatic arthritispsoriatic arthritis, ,
autoimmune diseasesautoimmune diseases in which the body attacks in which the body attacks
itself. itself.
Septic arthritisSeptic arthritis is caused by joint is caused by joint infectioninfection. .
Gouty arthritisGouty arthritis is caused by deposition of is caused by deposition of
uric aciduric acid crystals in the joint, causing crystals in the joint, causing
inflammation. inflammation.

52. 5252
Any part of your body can become Any part of your body can become
inflamed or painful from arthritis. Some inflamed or painful from arthritis. Some
rheumatic conditions can result in rheumatic conditions can result in
debilitating, even life-threatening debilitating, even life-threatening
complications or may affect other parts of complications or may affect other parts of
the body including the body including the musclesthe muscles, , bonesbones, ,
and internal organs.and internal organs.

53. 5353
OsteoarthritisOsteoarthritis
Rheumatoid Arthritis

54. 5454
Psoriatic Arthritis Psoriatic Arthritis
Fibromyalgia Fibromyalgia
Scleroderma Scleroderma
Lupus / SLE Lupus / SLE

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Extra-articular features of joint diseaseExtra-articular features of joint disease
CutaneousCutaneous nodulesnodules
CutaneousCutaneous vasculitis vasculitislesionslesions
LymphadenopathyLymphadenopathy
OedemaOedema
OcularOcular inflammationinflammation
UrethritisUrethritis
TenosynovitisTenosynovitis ( (tendontendon sheathsheath effusionseffusions))
BursitisBursitis (swollen (swollen bursabursa))
DiarrheaDiarrhea
ulcerationulceration

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Treatment options vary depending on the type Treatment options vary depending on the type
of arthritis and include of arthritis and include Physical therapyPhysical therapy, lifestyle , lifestyle
changes (including exercise and weight control), changes (including exercise and weight control),
medications and dietary supplements medications and dietary supplements
(symptomatic or targeted at the disease process (symptomatic or targeted at the disease process
causing the arthritis). causing the arthritis).
ArthroplastyArthroplasty (joint replacement surgery) may be (joint replacement surgery) may be
required in eroding forms of arthritis.required in eroding forms of arthritis.

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In general, studies have shown that In general, studies have shown that
physical exercising of the affected joint physical exercising of the affected joint
can have noticeable improvement in terms can have noticeable improvement in terms
of long-term pain relief. of long-term pain relief.
Furthermore, exercising of the arthritic Furthermore, exercising of the arthritic
joint is encouraged to maintain the health joint is encouraged to maintain the health
of the particular joint and the overall body of the particular joint and the overall body
of the personof the person