Arthritis drugs Flashcards
Explain the inflammatory response leading to arthritis
The breakdown of arachidonic acid leads to the activation of COX enzymes.
COX stimulates the secretion of prostaglandins.
List examples of NSAIDS
Aspirin
Ibuprofen
Didofenac
Meloxicam
What are the actions of NSAIDs?
Antipyretic- inhibit actions of PG on the hypothalamus
Analgesic- reduce sensitivity of neurons in bradykinin.
Anti-inflammatroy- reduce vasodilation and decrease permeability of venules.
Uses up oxygen radicals, decreasing tissue damage.
How are NSAIDs limited?
Only suppress signs and symptoms. Do not reduce damage.
What are the problems with NSAIDs?
Many inhibit COX1 (good) and COX2 (bad). Prostaglandins produced by COX1 are involved in the production of GI mucus and inhibit platelet aggregation in cardiovascular system.
NSAIDs may therefore causes gastric ulcers, impair coagulation, induce asthma attack, angioedema and rhinitis.
What are examples of drugs with COX2 selectivity?
Meloxicam
Give two examples of COX2 inhibitors.
Celecoxib and Etoricoxib.
Mainly used in patients with high risk of GI side effects.
Causes headache, rash, oedema.
Name a drug that can eliminate the problems of NSIADs
Misoprostol- a synthetic prostaglandin that reduces stomach acid production and stimulates mucous production.
Side effects include diarrhoea, vaginal bleeding, proton pump inhibitor.
Why is paracetamol not strictly a NSAID?
No anti-inflammatory response.
What are the 5 main treatment options for rheumatoid arthritis?
NSAIDs, Glucocorticoids, Immunosuppressants, DMARDS and anticytokines.
How do glucocorticoids help prevent inflammatory response?
Inhibit the production of macrophages- substance responsible for secreting cytokines.
List examples of steroids that prevent inflammation.
Short acting- Cortisone/hydrocortisone- 1-12 hours.
Intermediate- Predinsolone and predinisone- 12-36 hours.
Longer- Dexamethasone and betamethasone- 36-55 hours.
Explain the actions of glucocorticoids on RA
Lipid soluble so cross membrane and alter DNA.
Decrease cytokines IL2, increase synthesis of anti-inflammatory proteins and inhibit phospholipase A2 therefore decreasing secretion of arachidonic acid.
What are the unwanted effects of oral corticosetroids?
Buffalo hump, moon face, hypertension, increased abdominal fat, thinning of the skin, increased risk of infection, poor wound healing, muscle wasting, osteoporosis
How do you reduce the unwanted side effects of oral corticosteroids?
Lower plasma concentration reducing bioavailability.
Change route of administration e.g topically.
What is sulfasalazine?
DMARD that is made up of NSAID and antibiotic.
Uses up free radicals to prevent tissue damage.
Causes remission of active RA.
Administed in enteric tablet.
Causes GI upset, headache, skin rashes, leukopenia.
What is penicillimine
DMARD produced by the hydrolysis of penicillin.
Lowers IL-1 gene transcription.
Administered orally.
Side effects include rashes, stomatitis, anorexia, taste disturbance, fever.
Should not be used with gold compounds.
Explain gold compounds.
DMARD.
Auranofin- given orally.
Sodium auranofin- administered in deep injection.
Side effects include rashes, flu, ulcers, blood disorders, encephalopathy, peripheral neuropathy and hepatitis.
Explain antimalarials.
DMARD.
Increase pH of intracellular vacuoles which slows down antigen presenting.
Last line treatment.
E.g Chloroquine and hydroxychloroquine.
What are anticytokine drugs?
Engerneered antibodies- very expensive. Used if DMARDs don't work. Administered as an injection. Adalimumab, enterept. Drugs that end in imab and ept. Side effects- develop latent disease (TB or opportunistic infections).
What is ciclosporin
Potent immunosupressant however has no affect on acute inflammation.
Inhibits IL-2
Side effects- nephrotoxicity, hepatoxicity, hypertension.
What is azathioprine?
Cytotoxic immunosupressant.
Blocks purine metabolism.
Suppresses bone marrow production -thus preventing the production of RBC and WBC.
What is methotrexate?
Immunosupressant. Folic acid antagonist. Inhibits T cell activation. Causes liver cirrhosis and folate deficiency (not to be used when pregnant). Antimetabolite
What is leflunomide?
Immunosupressant.
Inhibits T cells.
Causes diarrhoea, alopecia and hepatoxicity.
What is cyclophosphamide?
Immunosuppressant use when all else has failed.
Pro drug
Causes acrolein- can lead to hemorrhagic cystitis.
Nitrogen mustard
