r. r rheumatoid arthritis (ra) chronic, generally progressive autoimmune disease that causes...
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Rheumatoid arthritis (RA)
chronic, generally progressive autoimmune disease that causes functional disability, significant pain
and joint destruction, and leads to premature mortality.
It is estimated to affect between 0.5 and 1.0% of the adult population worldwide, increases in prevalence with age
affects more women than men.
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Rheumatoid arthritis in Ugandan AfricansB. R. KANYEREZIDepartment of Medicine, Makerere University
College Medical School,H. BADDELEYDepartment of Radiology, Mulago Hospital and
Department of Radiodiagnosis, University of Bristol
D. KISUMBADepartment of Orthopaedics, Makerere
University
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1957 Until recently rheumatoid arthritis has been considered be rare in the tropics.
(1966)120 new patients attended the Arthritis Clinic, Mulago Hospital, Kampala, over a period of one year, and 65 of them were diagnosed as cases of rheumatoid arthritis.
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Overall sex incidencePopulation surveys indicate that RA manifests
itself
in women about three times as often as in men (male: female ratio 1: 3). This is true in Europe.
The figure previously reported for Ugandan patients was 1: 2
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For traditional and economic reasons Ugandan women may attend hospital clinics less often than men with similar complaints. Certainly several of the women patients who had symptoms for over
10
years had not attended a hospital clinic before.
Conclusion It is apparent that rheumatoid arthritis is
commoner in Ugandan Africans than was previously
recognized.
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UGANDA has only one specialist for rheumatic arthritis , Dr. Mark Kaddumukasa, 35. He also teaches and trains at Makerere University Faculty of Medicine.
We have only one clinic at Mulago. the clinic opens only on Fridays
http://www.newvision.co.ug/D/9/34/736702
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Kaddumukasa says out of Uganda population of about 30 million, 300,000 are affected by the disease.
He says the condition affects women more than men and normally begins at about 13 years, although it can also affect children.
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Kaddumukasa says there is no cure, but the disease is managed by pain killers and medication to prevent inflammation and strengthen the joints to prevent damage of the bones and cartilage.
The cheapest drug costs sh400,000 for a month dose, Kaddumukasa says. He says patients are also engaged to participate in physical exercises and sports to reduce pain, and relax the muscles and joints.
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1% or 2.5 million people in USA
Rheumatoid arthritis in Eastern Africa
Kenya 303,144 population 32,982,1092 Somalia 76,329 population 8,304,6012 Tanzania 331,533 population 36,070,7992
Uganda 242,557 population 26,390,2582
http://www.rightdiagnosis.com/r/rheumatoid_arthritis/stats-country.htm#extrapwarning
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1- Definition: is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints, producing an inflammatory synovitis that often progresses to destruction of the articular cartilage of the joints.
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• One or more joints are
affected (peripheral joints).
•It is an Autoimmune, Collagen disease.
Rheumatoid Arthritis
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2- Clinical features:
1- Arthritis.
2- Subcutaneous nodules.
3- Systemic features.
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1) Arthritis:
Pathology:
1- Synovitis: hyperemia, oedema, lymphocytes & plasma cell infiltration.2- Joint effusion.3- Proliferation of the synovial membrane.4- Erosion of the articular cartilage leading to characteristic pannus.5- Organization that results in fibrous or bony ankylosis (abnormal adhesion of the bones) leading to joint deformity.
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Symptoms & Signs:A) Distribution: - Symmetrical, peripheral, polyarthritis. - starts in the proximal inter phalangeal joints & the lateral four Metacarbophalangeal joints of the hands then wrists & ankles.
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B) Features:
-Morning stiffness for more than half an hour.
-Joints are swollen & painful at rest & on a movement .
-Fusiform appearance of the fingers .
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C) Deformity:
Lately, hands deformities appear & take 3 patterns
- Ulnar deviation.
- Swan-neck deformity.
- Button hole deformity.
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2) Subcutaneous nodules:
- In 30-40 % of patients.
- Commonly appear in pressure areas & in relation to tendon sheaths.
3) Systemic features:Arteritis, neuropathy,
myopathy, anemia, cardiac, pulmonary & ocular lesions.
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3- Investigation:A) Blood tests :
1. Erythrocyte Sedimentation Rate (ESR), 2. C-reactive protein, 3. Full blood count, 4. Renal function and 5. Liver enzymes
B) Immunological tests: 1. Rheumatoid factor: (RF, a specific antibody)
Positive in about 85% of cases.2. Lupus Erythematosis: specific antibody
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C) Imaging:
1. Magnetic resonance imaging ,
2. Ultrasound imaging
3. X-Ray findings:
A- Bone rarefaction (osteoporosis) of involved joints.
B- Joint space narrowing & bony cysts.
C- Joint deformity & subluxation (Incomplete or partial dislocation ).
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4- Management:There is no cure for RA. The goals of treatment are to:
Relieve pain Reduce inflammation Slow down joint damage Improve functional ability
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1) General Measures:
A- Rest.
B- Physiotherapy.
2) Drugs:
1st line drugs: NSAIDs
2nd line drugs: Gold, D-penicillamine.
3rd line drugs: Corticosteroids.
4th line drugs: Immunosuppressive drugs.
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Rheumatoid arthritis: Autoimmune, Collagen disease. Young age. Females more than males. Multiple joint affection. Small joints. Systemic manifestations. Synovitis lead to Pan-arthritis. Morning stiffness. Deformities.
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Properties of Oxicam groupProperties of Oxicam group
Potent anti-inflammatory Potent anti-inflammatory
Long half life Long half life
Less GIT side effects. Less GIT side effects.
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Drug 41(4) : 630 , 1991Drug 41(4) : 630 , 1991
PharmacokineticsPharmacokinetics Complete absorption after oral administration
(100% bioavailability). Complete absorption after oral administration
(100% bioavailability).
Rapid onset of action within 30 min. Rapid onset of action within 30 min.
Peak plasma level concentration within 1-2 hours. Peak plasma level concentration within 1-2 hours.
High plasma protein binding (99%). High plasma protein binding (99%).
Steady state conc. (10-15mcg/ml) not changed {no accumulation}
Steady state conc. (10-15mcg/ml) not changed {no accumulation}
Time to Steady state conc. is 10-15 days. Time to Steady state conc. is 10-15 days.
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Elimination is not significantly affected by age, gender, renal or hepatic diseases .
Elimination is not significantly affected by age, gender, renal or hepatic diseases .
Drug 41(4) : 630 , 1991Drug 41(4) : 630 , 1991
PharmacokineticsPharmacokinetics Long half life (72 hours) permitting once daily dose. Long half life (72 hours) permitting once daily dose.
Efficient penetration into the synovial fluid. Efficient penetration into the synovial fluid.
Complete metabolism into inactive metabolites. Complete metabolism into inactive metabolites.
Mainly excreted in the urine. Mainly excreted in the urine.
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PharmacologyPharmacology
Inflammation
Inhibition of migration of leucocytes
Inhibition of migration of leucocytes
Inhibition of leucocytes function including
phagocytosis
Inhibition of leucocytes function including
phagocytosis
Scavenging oxygen free
radicals
Scavenging oxygen free
radicals
Inhibition of prostaglandin synthesis
Inhibition of prostaglandin synthesis
Drug 41 (4): 629, 1991Drug 41 (4): 629, 1991
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Excellent TolerabiltyExcellent Tolerabilty
Higher GIT Tolerability
No enterohepatic circulation.
Worldwide clinically proved GIT better
tolerability.
Higher GIT Tolerability
No enterohepatic circulation.
Worldwide clinically proved GIT better
tolerability.
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Excellent TolerabiltyExcellent Tolerabilty Higher Hepatic Tolerability Higher Hepatic Tolerability
2.Least lipophilicity (affinity to fat cells) 2.Least lipophilicity (affinity to fat cells)
Poor diffusion into hepatic cells Poor diffusion into hepatic cells
Poor presentation to metabolizing enzymes Poor presentation to metabolizing enzymes
Least hepatic extraction ratio Least hepatic extraction ratio
&&
Scand J. Rheumatology 1987Scand J. Rheumatology 1987
1.Negligible first pass metabolism 1.Negligible first pass metabolism
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The first-pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the
concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of
absorption which is generally related to the liver and gut wall.
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Partition Coefficients of some NSAIDs
Partition Coefficients of some NSAIDs
Scand J. Rheumatology 1987Scand J. Rheumatology 1987
Increasing NSAID Partition Coefficient Lipophilia (Lipophilicity / hydrophilicity)Increasing NSAID Partition Coefficient Lipophilia (Lipophilicity / hydrophilicity)
TENOXICAM 0.3
Piroxicam 1.9
Flurbiprofen 8.0
Indomethacin 9.1
Diclofenac 15.6
TENOXICAM 0.3
Piroxicam 1.9
Flurbiprofen 8.0
Indomethacin 9.1
Diclofenac 15.6
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Excellent TolerabiltyExcellent Tolerabilty
Higher Renal Tolerability
Completely metabolized to inactive metabolites.
Higher Renal Tolerability
Completely metabolized to inactive metabolites.
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Dose & Administration Dose & Administration
Capsule: 2 capsules for 2 days
1 capsule as maintenance dose
Capsule: 2 capsules for 2 days
1 capsule as maintenance dose
Suppository: Once Daily DoseSuppository: Once Daily Dose
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Soral is available in two forms:
Capsule: Box of 10 capsules – 10 L.E.
Suppository: Box of 5 suppositories – 6 L.E.
Soral is available in two forms:
Capsule: Box of 10 capsules – 10 L.E.
Suppository: Box of 5 suppositories – 6 L.E.
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Compliable Once daily dose Two forms No Dose adjustment in
elderly, hepatic or renal patients
Capsule small Supp non irritant Economic
Compliable Once daily dose Two forms No Dose adjustment in
elderly, hepatic or renal patients
Capsule small Supp non irritant Economic
Tolerable
Safe on :
GIT
Liver
Kidney
Tolerable
Safe on :
GIT
Liver
Kidney
Effective
4 mechanisms of action
Efficient penetration into
the synovial fluid
Provides marked
analgesia within 30min
Effective
4 mechanisms of action
Efficient penetration into
the synovial fluid
Provides marked
analgesia within 30min
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Dr/Sameh BesharaGlobal NAPI Pharmaceuticals Egypt
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Fact Fact
In Osteoarthritic patients the increase
in proteoglycanase and collagenase activity
leads to increase in cartilage catabolism
In Osteoarthritic patients the increase
in proteoglycanase and collagenase activity
leads to increase in cartilage catabolism
Healthy knee joint Knee joint with Osteoarthritis
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In vitro study determining the effect of Soral
(Tenoxicam) on human Osteoarthritic cartilage
metallo-protease activity.
In vitro study determining the effect of Soral
(Tenoxicam) on human Osteoarthritic cartilage
metallo-protease activity.
Vignon- et al , Arthritis Rheum, (Vol. 34), 1332-5, Oct 1991 Vignon- et al , Arthritis Rheum, (Vol. 34), 1332-5, Oct 1991
Effect of Soral (Tenoxicam)
On human Osteoarthritic cartilage
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68.3%
36.8%
0
10
20
30
40
50
60
70
Suppressed proteoglycanase acitivity Suppressed collagenase acitivity
68.3%
36.8%
0
10
20
30
40
50
60
70
Suppressed proteoglycanase acitivity Suppressed collagenase acitivity
Soral helps to decrease cartilage catabolism in Osteoarthritic patients
Soral helps to decrease cartilage catabolism in Osteoarthritic patients
Vignon et al, Arthritis Rheum, (Vol. 34), 1332-5, Oct 1991Vignon et al, Arthritis Rheum, (Vol. 34), 1332-5, Oct 1991