Rheumatology

P. Potměšil, K. Němeček

Programme

• Gout

• RA

• SLE

• Fibromylagia

purine nucleotides

hypoxantin

xantin

uric acid

xantin oxidase

alimentary excretion

uric excretion tissue depozition

crystals of uric. acid Chalk stones

phagocytosis and acute inflamm. arthritis

uricosurics

colchicin NSA

allopurinol

febuxostat

Treatment of hyperuricaemia and gout

xantinoxidáza

purine nucleotides

hypoxantin

NHN

NN

OH

HO

xantin

N

N

NH

OH

N

OH

Uric acid

N

N

NH

OH

HO

N

xantinoxidáza

Elimination by esp. tubularsecretion

Hyperuricaemia

Increasedsynthesis(metab. deviation or decay of N. Ac.)

decreased excretion(inhibition of tubul. secretion,reduced ren. function)

Hyper-uricemia

Allopurinol and febuxostate

- inhibitors of xanthinoxidase

- febuxostat is during chronic hyperuricemia prescribed to patients, in whom allopurinol is contraindicated, not tolerated or if treatment with allopurinol doesnt result in uric acid level 360 mikromol/l.

- Symbol „P“ = temporary reimboursement

Uricosurics - probenecid, sulfinpyrazon, benzbromaron

• inhibit reabsorption of uric acid by

blockade of transport syst. URAT-1 in

proxim. renal tubulus

• risk of urolithiasis is increased by

upregulation of concentration of uric

acid

• condition of treatment by uricosurics –

good ren. function and sufficient diuresis

• Not registered in Cz. Rep.

capillary proximal tubulus

Rheumatoid arthritis pharmacology, physiotherapy, (surgery) • autoimmune inflamm. disorder, that most prominently

affects synovial joints = attack against joint tissue• cartilage destruction leads to deformities (joint

ossification), accumulation of synovial fluid leads to pain• women more often (30-50 yrs), tends to occur bilaterally• Rheumatoid factor from B lymfocytes = anti Ig-G,M antib.

+ Increase of inflamm. cytokines (IL-1, IL-6 + TNF-alpha)• Stadiums of RA; morning stifness indicates RA + ↑ CRP

I. Damage of soft tissues (joint membranes)

II. Osteoporosis

III. Deformities + muscular atrophy

IV. Ancylosis

Rheumatoid arthritis: anti TNF + methotrexate• Pharmacol. biol. ther. possibilities:

A/ anti TNF-α1/ MAb: adalimumab, golimumab, infliximab,

certozulimab pegol

2/ recept. for TNF: etanercept

B/ abatacept = selective immunosuppressant - inhibits signal transduction (costimulation

molecules for T-lymphocytes) - indicated after failure of anti TNF-α (e.g. because of production of neutralising

antibodies)

C/ anti IL-6: tocilizumab

D/ anti IL-1: anakinrum

• „Classic“ possibilities

1/ methotrexate

2/ corticosteroidsPrednison 10 mg daily

3/ azatioprin

4/ sulfasalazin,penicilamin

5/ aurum salts (inj.)

6/ antimalarics (chlorochin)

7/ (cyclosporin A, cyklofosfamide,

rituximab)

Biological drugs used for therapy of rheumatoid/psoriatic arthritis

Inhibitors of TNF – alpha, monoclonal antibodies: cannot be combined with anti IL-1 or with abatacept!, if combined risk for infection is increased

1/ Infliximab: contraindicated in pregnancy + breastfeeding,

severe infection (sepsis, TBC), heart failure, hypersensitivity

- rheumatoid artritis

- psoriatic artritis and psoriasis, ancylosing spondylitis

2/ Adalimumab: contraindicated in pregnancy + breastfeeding,

severe infection (sepsis, TBC), heart failure, hypersensitivity

- rheumatoid artritis, polyarticular juvenile idiopathic artritis

- psoriatic artritis and psoriasis, ancylosing spondylitis

Rheumatology

• Glucocorticoids

antiinflammatory + immunosuppressive

rheumatology: inh. of cox-2, inh. of TNF-alpha etc.

(astma – inhal. systems, if severe p.o., dermatology – eczema,

ophthalmology)

• Immunosuppressive drugs

1) azathioprin - transplantation, severe RA, SLE - autoimmune hemolytic anemia - polyarteritis nodosa - autoimmune chronic act. hepatitis

2) methotrexate: cytostat. + immunosuppr.

a) oncology ac. lymfobl. leucaemia,

osteosarcomab) rheumatology severe active rheumat. + psoriat.

artritis

Glucocorticoids (corticosteroids)

A) Anti-inflammatory effect:

1) inhibition of enzymes phospholipase A2, COX

2) reduction of expression of inflammatory:

a/ cytokines: IL-1, TNF-alpha

b/ chemokines = chemoattractant cytokines: MIP-1α, MCP-1

B) Effect on cells: suppress function of T-lymfocytes,

monocytes/macrophages

C) Reduction of permeability of capillars + suppression

of fibroproduction in organs

Glucocorticoids /corticosteroids/

• standard part of treatment of autoimmunne

disorders - usually in combination with

immunosupressants

• treatment and prevention of rejection and reaction

of graft versus host in transplantation esp. bone

marrow transpl.: in comb. with imunosupressants,

anti-lymfocyte immunoglobulins and cytotoxic

drugs (cytostatics)

Rheumatoid artritis

• A/ Analgetics:

1/ coxibs = selective (celecoxib, etoricoxib)

2/ meloxicam = preferential COX-2

3/ not nimesulide!!! (hepatotoxicity, approved only for ac. pain treatment)

• B/ Surgery

1/ synovectomy

2/ endoprothesis, if indicated

• C/ REHABILITATION

Celecoxib, etoricoxib: selective COX-2 inhibitors (p.o.) (valdecoxib for parenteral use: ac. postoperat. pain )

Celecoxibe (Celebrex)

• Pharm. Form and dosage

cps. 100/200 mg: once/twice daily• Indications

- osteoarthritis

- rheumatoid arthritis

- pain in dysmenorrhea• Contraindications

- CAD, heart failure NYHA III or IV,

not controlled hypertension

Etoricoxibe (Arcoxia)

• Pharm. Form and dosage

Tbl. 30/60/90/120 mg: once daily• Indications

- osteoarthritis

- rheumatoid arthritis

- ac. gout attack• Contraindications

- CAD, heart failure NYHA III or IV,

not controlled hypertension

SLE: corticosteroids + immunosuppressants

• Chronic autoimmune disorder: immuno-complex vasculitis primarily with renal localization:

glomerulonephritis that can lead to renal failure

• Joint syndrome = not destructive inflammation

• Other manifestations:

- dermatol.: facial butterfly exantema

- pneumol.: pleuritis + pneumonia

- cardiol.: pericarditis + endocarditis

- hepatomegalia

- splenomegalia + lymphadenopathy

- hematol.: anemia + leucopenia

• Labor. + immunol.: ↑CRP, LE cells, antinuclear factor

Fibromyalgia• A/ FDA approved

specific therapy:

1. Pregabalin (AED)- Calcium channel inhib. + inh. of

subst. P effect

(also for epilepsy + GAD)

1. Duloxetine (SNRI)

2. Milnacipran (SNRI)

• B/ Pain alleviation

1. Tramadol

2. NSAIDs

• C/ Myorelaxant drugs

• What is not recommended?

• A/ corticosteroids• B/ strong opioids• C/ long term use of NSAIDs

• Non pharmacological therapy

• Balneotherapy• Physiotherapy• Cognitive behavioral type of

psychotherapy