Transcript soral and rheumatoid arthritis for Ugandan medical accossiation

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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 Africans
 B. R. KANYEREZI
Department of Medicine, Makerere University
College Medical School,
 H. BADDELEY
Department of Radiology, Mulago Hospital and
Department of Radiodiagnosis, University of
Bristol
 D. KISUMBA
Department 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 incidence
 Population 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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Rheumatoid Arthritis
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.
One or more joints are affected •
(peripheral joints).
It is an Autoimmune, Collagen •
disease.
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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.
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:
1.
2.
3.
4.
5.
1.
2.
A) Blood tests :
Erythrocyte Sedimentation Rate (ESR),
C-reactive protein,
Full blood count,
Renal function and
Liver enzymes
B) Immunological tests:
Rheumatoid factor: (RF, a specific antibody)
85% of cases.
Lupus Erythematosis: specific antibody
Positive in about
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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 group
Potent anti-inflammatory
Long half life
Less GIT side effects.
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Pharmacokinetics
Complete absorption after oral administration
(100% bioavailability).
Rapid onset of action within 30 min.
Peak plasma level concentration within 1-2 hours.
High plasma protein binding (99%).
Steady state conc. (10-15mcg/ml) not changed
{no accumulation}
Time to Steady state conc. is 10-15 days.
Drug 41(4) : 630 , 1991
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Pharmacokinetics
Long half life (72 hours) permitting once daily dose.
Efficient penetration into the synovial fluid.
Complete metabolism into inactive metabolites.
Mainly excreted in the urine.
Elimination is not significantly affected by age, gender,
renal or hepatic diseases .
Drug 41(4) : 630 , 1991
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Pharmacology
Inhibition of leucocytes
function including
Inhibition of migration
phagocytosis
of leucocytes
Scavenging
oxygen free
radicals
Inhibition of
prostaglandin synthesis
Inflammation
Drug 41 (4): 629, 1991
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Excellent Tolerabilty
Higher GIT Tolerability
 No
enterohepatic circulation.
 Worldwide
tolerability.
clinically proved GIT better
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Excellent Tolerabilty
Higher Hepatic Tolerability
1.Negligible first pass metabolism
2.Least lipophilicity (affinity to fat cells)
Poor diffusion into hepatic cells
&
Poor presentation to metabolizing enzymes
Least hepatic extraction ratio
Scand J. Rheumatology 1987
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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
Increasing
Lipophilia
NSAID
 TENOXICAM
Partition Coefficient
(Lipophilicity / hydrophilicity)
0.3
 Piroxicam
1.9
 Flurbiprofen
8.0
 Indomethacin
9.1
 Diclofenac
15.6
Scand J. Rheumatology 1987
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Excellent Tolerabilty
Higher Renal Tolerability
 Completely
metabolized to inactive metabolites.
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Dose & Administration
Capsule:
2 capsules for 2 days
1 capsule as maintenance dose
Suppository:
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.
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Effective
Tolerable

4 mechanisms of action
Safe on :

Efficient penetration into
GIT
the synovial fluid

Provides marked
analgesia within 30min
Liver
Kidney
Compliable
Once daily dose
 Two forms
 No Dose adjustment in
elderly, hepatic or
renal patients
 Capsule small
 Supp non irritant
 Economic

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Dr/Sameh Beshara
Global NAPI Pharmaceuticals Egypt
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Fact
Healthy knee joint
Knee joint with
Osteoarthritis
In Osteoarthritic patients the increase
in proteoglycanase and collagenase activity
leads to increase in cartilage catabolism
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Effect of Soral (Tenoxicam)
On human Osteoarthritic cartilage
 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
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Soral helps to decrease cartilage catabolism in
Osteoarthritic patients
70
60
50
40
68.3%
30
20
36.8%
10
0
Suppressed proteoglycanase acitivity
Suppressed collagenase acitivity
Vignon et al, Arthritis Rheum, (Vol. 34), 1332-5, Oct 1991