Arthritis Drugs Flashcards
Whtat is arthritis?
Inflammation of the joints causing pain and affecting mobility.
What are the causes of osteoarthritis?
Wear and tear related to aging.
Trauma, disease or obesity
Where is most affected by rheumatoid arthritis?
The small joints, e.g. hands and feet.
Why does rheumatoid arthritis occur?
Because antibodies are targeted towards normal proteins in the connective tissue of joints and this results in the release of pro-inflammatory cytokines.
What do pro-inflammatory cytokines do?
They promote systemic inflammation
Which joints are most affected by osteoarthritis?
The synovial joints
What is osteoarthritis?
Loss of cartilage and bone from articulating surfaces. It alters the repair process after a trauma and insufficient repair takes place.
Give an example of a synovial joint
Wrist, elbow, shoulder, knee, fingers, feet and spine
Why is cartilage degraded?
- Upregulation of cytokines
- Interleukin 1B inhibits type II collagen synthesis of hyaline cartilage
- An increase in matrix metalloproteins cause a breakdown of collage and cartilage degradation
Where is type I collagen found and what is it’s function?
Found in the bones. Its function is osteoblast differentiation from bone marrow.
Where is type II collagen found and what is its function?
Found in the cartilage and its function is to maintain the integrity of the cartilage
Where is aggrecan found and what is its function?
found in the synovial membrane and it degrades ECM proteins to enable growth.
What are the risk factors for arthritis?
Obesity, gender, age, previous joint injury/disease, metabolic disorders and genetics.
Why is arthritis more common in women?
Due to an decrease in oestrogen after menopause. Oestrogen inhibits osteoclasts which breakdown bone during remodelling and increase blood calcium.
What is arachidonic acid?
Aconstituent of the cell membrane derived fromn linoleic acid.
What does the COX1 enzyme do?
Protects the GI mucosa, controls renal blood flow and helps in the initiation of labour.
Where are COX2 enzymes found and when are they produced?
Produced when needed in inflammatory cells induced by injury, infection or cytokines.
What does the COX2 enzyme do?
Produces inflammatory mediators
Where is the COX3 enzyme found?
In the CNS of some species
All COX enzymes catalyse which reaction?
Arachidonic acid into prostaglandins and thromboxanes
What is the classification for the most widely prescribed drugs for arthritis?
NSAIDS (non steroidal anti inflammatory drugs)
Aspirin, ibuprofen, diclofenac, meloxicam and indomthacin are examples of…
NSAIDS
What are the actions of NSAIDS?
Antipyretics by inhibiting actions of prostaglandins on the hypothalamus, analgesics by reducing the sensitivity of the neurons to bradykinin and anti inflammatory by reducing vasodilation and decreasing the permeability of venules
What are the risks with NSAIDS?
Can cause gastric ulcers, impair coagulation, GI bleeding in elderly, risk of CV events in those with cardiac disease/hypertension and can induce asthma attack, angioedema, urticaria or rhinitis
What is angioedema?
Rapid swelling of dermis, subcutaneous tissues.
What is urticaria?
Skin rash (hives)
What causes the problems with NSAIDS?
They inhibit both the COX1 and COX2 enzymes and COX1 produces prostaglandins that are beneficial.
Name an NSAID drug that is a selective COX2 inhibitor
Meloxicam, celecoxib, etoricoxib and etodolac
Common side effects of COX2 inhibitors
Headaches, dizziness, rash and peripheral oedema.
What is misoprostol?
A synthetic prostaglandin given alongside NSAIDs that preserves the mucous lining of the gi tract, protects against ulcerations.
Why is paracetamol not considered an NSAID?
Because it has no anti inflammatory effect.
Chronic use of large doses of paracetamol causes…
Kidney damage
Toxic doses of paracetamol causes…
Fatal liver damage 24-48 hours after overdosing
Treatment options for osteoarthritis
Exercise, weight loss, thermotherapy/TENS devices, joint supports or braces and suitable footwear.
What drugs will be used to treat osteoarthritis?
Paracetamol
Topical NSAID or capsaicin.
Opioid analgesic
Intra articular corticosteroid injections
What does strontium ranelate do?
It promotes osteoblast differentiation and inhibits osteoclast activity and reduces pain.
Where is aspirin absorbed?
In the small intestine and the stomach
Why does aspirin damage the lining of the stomach?
Because it inhibits COX1 which is responsible for the production of the prostaglandins that protect the mucosa from the stomach acid.
When is rheumatoid arthritis most commonly diagnosed?
Between ages 40 and 60
What are the treatment options for rheumatoid arthritis?
NSAIDS/ opioid analgesics for pain Glucocorticoids Immunosuppressants Disease modifying antirheumatic drugs (DMARDS) Anticytokines
How are T cells activated?
By an abnormal interaction with B cells
Activated T cells cause macrophages to secrete what?
Cytokines like TNF and interleukin 1 to stimulate fibroclasts and osteoclasts,
How do immunosuppressant drugs work?
By reducing the production and activation of T cells.
How do glucocorticoids work?
By suppressing the function of macrophages and therefore reducing the secretion of inflammatory cytokines.
How do anticytokine drugs work?
By suppressing the activation of osteoclasts and fibroblasts.
How do DMARDS work?
By acting directly on the joint to block the inflammatory processes.
Glucocorticoids are naturally produced where in the body?
Adrenal cortex
Example of a short acting steroid
Cortisone, hydrocortisone
Example of a intermediate acting steroid
Prednisolone
Example of a long acting steroid
Dexamethasone
Drugs used to treat both asthma and arthritis
Becolometasone, budesonide and prednisolone due to the decrease in histame release
Side effects of oral corticosteroids (cushingoid features)
Buffalo hump, Moon face, Increased abdo fat, hypertension, thinning skin, Inc risk of infection, poor wound healing, muscle wasting and osteoporosis
Methotrexate is an example of a…
DMARD
How does methotrexate work?
It is a folic acid antagonist and inhibits DNA synthesis. It also blocks growth and differentiation of rapidly dividing cells. And inhibits T cell activation.
Which is the most common choice of DMARD in the UK?
Sulfasalazine
Sulfasalazine is a complex of…
An NSAID (salicylate) and an antibiotic (sulphonamide)
Why is sulfasalazine given as enteric coated tablets?
Because it is poorly absorbed orally.
Ciclosporin, azothioprine and methotrexate are examples of…
Immunosuppressants
Lefunomide and cyclophosphamide are examples of …
Immunosuppressants
How do immunosupprassants work?
By inhibiting DNA synthesis or T cell activation
Prednisolone, dexamethasone and fludrocortisone are examples of…
Corticosteroids
How do corticsteroids work?
By blocking gene transcription and synthesis of inflammatory proteins .
Sulfasalazine, pencillamine, gold compounds and anti-malarials are examples of…
DMARDS
How do DMARDs work
A variety of mechanisms including free radical scavenging and decreasing interleukin1
Etenercept, infliximab, rituximab and abatacept are examples of…
Anticytokines.
