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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