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Submitted By :- M Abdelmotaal

Department of pharmacology

Rheumatoid arthritis & Gout

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(RA) is an autoimmune disease that causes chronic inflammation of the joints & can also cause inflammation of the tissue around the joints .

Inflammatory arthritis

Peak incidence in 3rd to 4th decades(عقود ) of life

3-5 times higher preponderance(( يكثر in females than males

Rheumatoid Arthritis

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Exact(الدقيقة) mechanism is not known 1) Autoantibody-Rheumatoid factor(R.F.) : R.f. is Anti-IgG

2)other autoantibodies:Antinuclear factor(ANF)Antibodies to Collagen type-2 classAntibodies to cytoskeleton

Etiopathogenesis

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3) Activation of cell-mediated immunity which is observed by numerous inflammatory cells

4)Trigger events :- Local/systemic infection It includes some infectius agents such as Epstein-Barr Virus(EBV) cytomegalovirus(CMV) rubella

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Longitudinal Course of RA

Reproduced with permission from McInnes IB, et al. Nat Rev Immunol. 2007;7(6):429-442.

CCP, cyclic citrullinated peptide; CTLA4, cytotoxic T-lymphocyte antigen 4; GP39, cartilage glycoprotein 39; PADI4, peptidyl arginine deiminase, type IV; PTPN22, protein tyrosine phosphatase, non-receptor type 22.

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Rheumatoid Arthritis

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Tender , warm , swollen joints

Joints inflammation often affect wrist & finger joints

Also affect other joints including neck ,shoulder ,elbow ,hips ,knees ,ankles ,feet

Fatigue ,occasional fever ,sense of not feeling well

Pain & stiffness after morning wake up or after a long rest

Signs & symptoms

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By imaging: X-ray MRI Ultra sound

By Blood tests:a)Inflammatory markers:

ESR(erythrocytes sedimentation rate) C reactive protein(CRP) ANA(anti-nuclear antibody)

b)Rheumatoid factor:c)Anti-ccp antibodies : it in 99% gives +ve resultd)Anti-MCV assay(anti-Mutated citrullinated Vimentin)

Diagnosis

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There is no cure for RA,there is some treatments which can modify the disease process.

GOAL for Treatments :1. Relieve pain2. Reduce inflammation 3. slow down or stop joint damage

TREATMENTS

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1)medication2)surgery3)lifestyle

1)medication: Classification:

1. Anti-inflammatory-analgesic drugs2. Anti-inflammatory drugs without direct analgesic action3. Disease Modifying Antirheumatic Drugs(DMRDs)4. immunosuppressants5. TNF-alpha blockers6. Interleukin-1 blockers

Current treatment approaches

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ANTIINFLAMMATORY-ANALGESIC DRUGSEg.aspirin,indomethacin,ibuprofen,naproxen, piroxicam,nabumetone,diclofenac,celecoxib M.O.A:It inhibit pg,& chemicals that are responsible for pain and swelling

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Ibuprofen-: Individuals should not use ibuprofen for more than 10 days for the treatment of pain or more than 3 days for the treatment of a fever unless directed by a physician

Celecoxib: The lowest effective dose should be used for each patient

GLUCOCORTICOIDS-:They are used when disease Is not responding NSAIDs. Have serious side effect incase of high doses Eg.prednisolone:-

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Eg. Methotrexate Hydroxychloroquine Sulfasalazine Gold salts

Remission inducing drugsDMARDs(metho,antiinf,3s sulf,ster,salts

gold)

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METHOTREXATE: It is antimetabolite drug

M.O.A:- It inhibit dihydro folate Reductase enzyme.

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It is antimalerial drug.OH-chloroquine

Sulfasalazine is used to treat rheumatoid arthritis in combination with anti- inflammatory medications. Sulfasalazine is generally well tolerated.

sulfasalazine

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Eg. Gold thioglucose(SOLGANAL) Gold thiomalate (MYOCHRYSINE) Auranofin (RIDAURA)

Gold salts

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Joint replacement

Hip replacement Knee replacement

SYNOVECTOMY

It is metabolic disorder characterized by hyperuricaemia

Normal plasma=1-5 mg/dl

Stages of gout:-1. asymptomatic hyperuricaemia2. acute gouty arthritis3. intercritical period4. chronic tophaceous stage

GOUT

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Types :- 1)metabolic-10% cases Over production of uric acid

2)renal- 90% cases Reduced renal excretion of uric acid

Causes:- 1)genetic(absence of hypoxanthine) 2)medication:- 3)lifestyle

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Drugs that causes hyperuricaemia : Alcohol Thiazide Cytotoxic drugs Amiloride Isoretinoin Ethambutol Cyclophosphamide

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Acute attack: Over hours frequently nocturnal Excruciating pain Swelling, redness and tenderness Podagra May effect knees, wrist, elbow, and rarely SI and hips

Chronic: Destructive tophacous Much greater chance if untreated nodules

Sign & symptoms

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DIAGNOSIS:-1. X-ray2. Synovial fluid test:-3. Blood test:-

Normal level:1-5mg/dl Above 7 in males Above 6 in females indicate hyperuricaemia. W.B.C.,ESR is increased in gout without infection.

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Uric acid is end product of purine metabolism Monosodium urate has low water solubility When conc. Of MSU is above 7mg/dl,their solubility is

decreased due to saturation and it form crystal.

Pathogenesis

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Goal of treatment:- Relieve pain Reduce inflammation Terminate acute attack Prevent recurrent attack Prevent complications associated with chronic

deposition of urate crysals in tissues.

Treatment

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Classification of drugs no cure alone) 1)NSAIDs 2)colchicine 3)corticosteroids 4)uricosuric drugs 5)xanthine oxidase inhibitor

NSAIDs:- Indomethacin Naproxen Piroxicam diclofenac

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COLCHICINE:- It is an alkaloid from

colchicum autumnale. It is antimitotic drug.

MOA- it inhibit release of

Glycoprotein & subsequent Events.

It inhibit granulocyte Migration into inflamed joints.

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CORTICOSTEROIDS:- Eg.prednisolone They are rarely used.they are used in case of patient which is

contraindicate to NSAIDs. they produce rapid response like colchicine.but it is

contraindicated to patients with renal failure.

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PROBENECID:- It is uricosuric drug. MOA- It is act by inhibiting reabsorption of uric acid.so,excretion

of uric acid is increased.

XANTHIN OXIDASE INHIBITOR:- Eg.allopurinol. It is hypoxanthine analogue. MOA:- It is act by inhibiting Xanthine oxidase which is required for

synthesis of uric acid.

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OA is a group of diseases and mechanical abnormalities entailing degradation of joints, including articular cartilage and the subchondral bone next to it

OA is derived from the Greek word ‘ostoe’, meaning ‘of the bone’, ‘arthro’, meaning ‘joint’, and ‘itis’, meaning inflammation

Osteoarthritis is the most common type of arthritis. The prevalence increases with age 80% of people over 60 years will have some radiological

evidence of it, although only 60% of those will show symptoms.

OsteoarthritisEtiology & Pathophysiology

Osteoarthritis-Xray

OsteoarthritisX-ray changes

Osteoarthritis Causes

Primary Osteoarthritis Most CommonThought to be result of AgingDecreased ability to withstand stressLigaments supporting joints weaken

Secondary Osteoarthritis

Obesity Trauma Surgery

Abnormal joints Gout Diabetes

Hormone disorders

Causes

Goals of Treatment

To Relieve painIncrease motionImprove strength

Osteoporosis means "porous bones," causes bones to become weak and brittle – so brittle that even mild stresses like bending over, lifting a vacuum cleaner or coughing can cause a fracture.

In most cases, bones weaken when low levels of calcium, phosphorus and other minerals in the bones and results as low bone density.

A common result of osteoporosis is fractures of the spine, hip or wrist.

Although it's often thought of as a women's disease, osteoporosis also affects many men.

SYMPTOMS

Back pain, which can be severe if fractured or collapsed vertebra

Loss of height over time, with an accompanying stooped posture

Fracture of the vertebrae, wrists, hips or other bones

Normal bone has the appearance of a honeycomb matrix (left). Under a microscope,

osteoporotic bone (right) looks more porous.

CAUSES

The strength of the bones depends on their size and density; bone density depends in part on the amount of calcium, phosphorus and other minerals bones contain.

When the bones contain fewer minerals than normal, they're less strong and eventually lose their internal supporting structure.

The process of bone remodeling

Scientists have yet to learn all the reasons why this occurs, but the process involves how bone is made. Bone is continuously changing — new bone is made and old bone is broken down — a process called remodeling, or bone turnover.

A full cycle of bone remodeling takes about 2-3 months.

In young – the body makes new bone faster than it breaks down old bone, and the bone mass increases.

Reaches the peak bone mass in mid-30s. After that, bone remodeling continues, but

loses slightly more than gain. At menopause, when estrogen levels drop,

bone loss increases dramatically. Many factors contribute to bone loss, the

leading cause in women is decreased estrogen production during menopause.

Risk of developing osteoporosis depends on how much bone mass attained between ages 25 and 35 (peak bone mass) and how rapidly loses it later. The higher peak bone mass, the more bones "in the bank" and less likely to develop osteoporosis as ages.

Not getting enough vitamin D and calcium in the diet may lead to a lower peak bone mass and accelerated bone loss later.

What keeps bones healthy

Regular exercise Adequate amounts of calcium Adequate amounts of vitamin D, which is

very essential for absorbing calcium

RISK FACTORS

Sex – Fractures from osteoporosis are about twice more in women than in men. Risk in women at menopause (45 yrs) that accelerates bone loss. Risk in men is greater than age 75.

Age. The older, the higher risk of osteoporosis. Bones become weaker as ages.

Race. Greatest risk – white or of Southeast Asian descent. Black and Hispanic men and women have a lower, but still significant, risk.

Family history. Frame size. Men and women who are

exceptionally thin or have small body frames tend to have higher risk because they may have less bone mass to draw from as they age.

Lifetime exposure to estrogen. The greater a woman's lifetime exposure to estrogen, the lower her risk of osteoporosis.

Excess soda consumption. Chronic alcoholism. Depression.

Eating disorders. Women and men with anorexia nervosa or bulimia are at higher risk of lower bone density in their lower backs and hips.

Corticosteroid medications. Long-term use like prednisone, cortisone, prednisolone and dexamethasone, is damaging to bone.

Thyroid hormone. Too much thyroid hormone can cause bone loss.

Other medications. Long-term use of the blood-thinning medication heparin, the cancer treatment drug methotrexate, some anti-seizure medications, diuretics and aluminum-containing antacids also can cause bone loss.

Breast cancer. Postmenopausal women who have had breast cancer are at increased risk of osteoporosis, especially if they were treated with chemotherapy or aromatase inhibitors such as anastrozole and letrozole, which suppress estrogen.

Low calcium intake. A lifelong lack of calcium plays a major role in the development of osteoporosis.

Medical conditions and procedures that decrease calcium absorption. Stomach surgery (gastrectomy) can affect the body's ability to absorb calcium.

Sedentary lifestyle. Bone health begins in childhood. Children who are physically active and consume adequate amounts of calcium-containing foods have the greatest bone density. Exercise throughout life is important, but can increase bone density at any age.

TREATMENTS AND DRUGS Hormone therapy (HT) Prescription medications – Bisphosphonates,

Raloxifene (Evista) / selective estrogen receptor modulators (SERMs), Calcitonin, Teriparatide (Forteo), Tamoxifen.

Emerging therapies – New physical therapy program combines the use of a device called a spinal weighted kypho-orthosis (WKO), a harness with a light weight attached and specific back extension exercises. The WKO is worn daily for 30 minutes in the morning and afternoon.

ESTROGEN AND BONE PROTECTION

Estrogen is essential for healthy bone, and that when the production of estrogen is reduced,

PREVENTION

Do exercise. Add soy in diet. Avoid smoking Avoid excessive alcohol. Avoid caffeine, which is very harmful. Consider hormone therapy. Maintain good posture – Prevent falls. Manage pain. Don't ignore chronic pain.