Arthritis drugs

Question 1

Explain the inflammatory response leading to arthritis

Answer 1

The breakdown of arachidonic acid leads to the activation of COX enzymes.
COX stimulates the secretion of prostaglandins.

Question 2

List examples of NSAIDS

Answer 2

Aspirin
Ibuprofen
Didofenac
Meloxicam

Question 3

What are the actions of NSAIDs?

Answer 3

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.

Question 4

How are NSAIDs limited?

Answer 4

Only suppress signs and symptoms. Do not reduce damage.

Question 5

What are the problems with NSAIDs?

Answer 5

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.

Question 6

What are examples of drugs with COX2 selectivity?

Answer 6

Meloxicam

Question 7

Give two examples of COX2 inhibitors.

Answer 7

Celecoxib and Etoricoxib.
Mainly used in patients with high risk of GI side effects.
Causes headache, rash, oedema.

Question 8

Name a drug that can eliminate the problems of NSIADs

Answer 8

Misoprostol- a synthetic prostaglandin that reduces stomach acid production and stimulates mucous production.
Side effects include diarrhoea, vaginal bleeding, proton pump inhibitor.

Question 9

Why is paracetamol not strictly a NSAID?

Answer 9

No anti-inflammatory response.

Question 10

What are the 5 main treatment options for rheumatoid arthritis?

Answer 10

NSAIDs, Glucocorticoids, Immunosuppressants, DMARDS and anticytokines.

Question 11

How do glucocorticoids help prevent inflammatory response?

Answer 11

Inhibit the production of macrophages- substance responsible for secreting cytokines.

Question 12

List examples of steroids that prevent inflammation.

Answer 12

Short acting- Cortisone/hydrocortisone- 1-12 hours.
Intermediate- Predinsolone and predinisone- 12-36 hours.
Longer- Dexamethasone and betamethasone- 36-55 hours.

Question 13

Explain the actions of glucocorticoids on RA

Answer 13

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.

Question 14

What are the unwanted effects of oral corticosetroids?

Answer 14

Buffalo hump, moon face, hypertension, increased abdominal fat, thinning of the skin, increased risk of infection, poor wound healing, muscle wasting, osteoporosis

Question 15

How do you reduce the unwanted side effects of oral corticosteroids?

Answer 15

Lower plasma concentration reducing bioavailability.

Change route of administration e.g topically.

Question 16

What is sulfasalazine?

Answer 16

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.

Question 17

What is penicillimine

Answer 17

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.

Question 18

Explain gold compounds.

Answer 18

DMARD.
Auranofin- given orally.
Sodium auranofin- administered in deep injection.
Side effects include rashes, flu, ulcers, blood disorders, encephalopathy, peripheral neuropathy and hepatitis.

Question 19

Explain antimalarials.

Answer 19

DMARD.
Increase pH of intracellular vacuoles which slows down antigen presenting.
Last line treatment.
E.g Chloroquine and hydroxychloroquine.

Question 20

What are anticytokine drugs?

Answer 20

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).

Question 21

What is ciclosporin

Answer 21

Potent immunosupressant however has no affect on acute inflammation.
Inhibits IL-2
Side effects- nephrotoxicity, hepatoxicity, hypertension.

Question 22

What is azathioprine?

Answer 22

Cytotoxic immunosupressant.
Blocks purine metabolism.
Suppresses bone marrow production -thus preventing the production of RBC and WBC.

Question 23

What is methotrexate?

Answer 23

Immunosupressant. 
Folic acid antagonist. 
Inhibits T cell activation. 
Causes liver cirrhosis and folate deficiency (not to be used when pregnant). 
Antimetabolite

Question 24

What is leflunomide?

Answer 24

Immunosupressant.
Inhibits T cells.
Causes diarrhoea, alopecia and hepatoxicity.

Question 25

What is cyclophosphamide?

Answer 25

Immunosuppressant use when all else has failed.
Pro drug
Causes acrolein- can lead to hemorrhagic cystitis.
Nitrogen mustard