Drugs used in Treatment of Gout and Rheumatoid Arthritis

Question 1

Recurrent acute inflammatory arthritis with red, tender, hot and swollen
joints
?

Answer 1

Gout

Question 2

Uric acid, a product of purine metabolism, has low water solubility, especially at low pH. When blood levels are high, it precipitates and deposits in joints, especially the big toe, kidney and subcutaneous tissue called?

Answer 2

tophy

Question 3

Types of gout ?

Answer 3

1. Primary or hereditary gout :
   - to genetic error in purine metabolism
2. Secondary gout:
   due to drugs that
   - Inhibit uric acid excretion
   - Increase urate production by increasing rate of cell death (cancer chemotherapy)

Question 4

Stages of Gout?

Answer 4

• Asymptomatic hyper-uricemia (serum uric acid higher than 6 mg/dl)
• Acute intermittent gout (attacks of gout or flares)
• Inter-critical stage (in between attacks)
• Chronic gout (deformities)

Question 5

Non-pharmacological treatment of gout: ?

Answer 5

 Try to lose weight and do physical exercises
 Drink a lot of water (2-3 liters/day)
 Avoid alcohol and smoking
 Avoid drugs as salicylate and diuretics
 Low purine diet (avoid red meat, sea products, dried fruits, beans,…)

Question 6

Pharmacological treatment of gout ?

Answer 6

1. Uricostatics (drugs that interfere with uric acid synthesis):
   - Allopurinol
   - Febuxostat
2. Uricosurics (drugs that increase uric acid excretion)
   - Probenecid
3. Uricases (enzyme that breakdown uric acid):
   - Pegloticase
4. Tubulin inhibitors
   - Colchicine
5. Anti-inflammatory drugs
   - Non-steroidal anti-inflammatory drugs (NSAIDs) except salicylate
   - Corticosteroids

Question 7

Interfere with uric acid synthesis by inhibiting xanthine oxidase enzyme.
xanthine and hypoxanthine are more soluble, have a higher renal clearance
than that of uric acid

Type of drug?

Answer 7

Uricostatic drugs: Allopurinol

Question 8

Uricostatic drugs: Allopurinol

Pharmacokinetics?

Answer 8

Converted by the liver to active metabolite alloxanthine (oxypurine)

Question 9

Uricostatic drugs: Allopurinol

Uses?

Answer 9

1. first choice drug in chronic gout:
   (With long-term allopurinol therapy, tophi gradually disappear and nephropathy is halted, even reversed.)
2. Secondary hyperuricaemia : due to cancer chemotherapy/
   radiation/thiazides or other drugs

Question 10

Adverse effects of Uricostatic drugs: Allopurinol

Answer 10

uncommon.

- May induce acute attack of gout, Fever, rash, toxic epidermal necrolysis

Question 11

Interfere with uric acid synthesis by inhibiting xanthine oxidase
enzyme.

Drug?

Answer 11

Uricostatic drugs: Febuxostat

Question 12

Uricostatic drugs: Febuxostat

Uses?

Answer 12

1. alternative drug for treating symptomatic gout only in patients intolerant to allopurinol, or in those with some contraindications.

Question 13

Adverse effects Of Uricostatic drugs Febuxostat?

Answer 13

Liver damage: liver function needs to be monitored during
febuxostat therapy.

Like other drugs used to treat hyperuricaemia, NSAID/colchicine
cover should be provided for 1–2 months while initiating febuxostat therapy.

Question 14

Inhibit Urate Transporters (URAT1) of renal proximal tubule,
preventing urate reabsorption

Drug?

Answer 14

Uricosurics: Probenecid

Question 15

Uses of Uricosurics: Probenecid

Answer 15

1. Chronic gout and hyperuricaemia: Probenecid is a second line/adjuvant drug to allopurinol.
2. prolong penicillin or ampicillin action by
   enhancing and sustaining their blood levels, e.g. in gonorrhoea.

Question 16

Adverse effects of Uricosurics: Probenecid?

Answer 16

• May induce acute attack of gout
• Uric acid kidney stones
• Gastric irritation

Question 17

Contraindications of Uricosurics: Probenecid?

Answer 17

• Acute gout
• Previous kidney stones or existing renal disease
• Elderly patients Caution in peptic ulcer disease

Question 18

Recombinant mammalian uricase enzyme that convert urate to allantoin,
which is more soluble and easily excreted in urine

Drug?

Answer 18

Uricase enzyme: Pegloticase

Question 19

Uricase enzyme: Pegloticase

Uses?

Answer 19

Chronic gout in patients refractory to conventional therapy, given by I.V.
infusion given every 2 weeks

Question 20

Adverse effects of Uricase enzyme: Pegloticase?

Answer 20

 May induce acute attack of gout
 Kidney stones
 I.V. Infusion reactions and anaphylaxis- due to presence of
antipegloticase antibodies

Question 21

Inhibition of microtubule assembly decreases macrophage migration into the inflamed joint and phagocytosis of urate crystals.

Drug?

Answer 21

Tubulin inhibitor: Colchicine

Question 22

Treatment of acute attacks of gout

Drug?

Answer 22

Tubulin inhibitor: Colchicine

Question 23

Tubulin inhibitor: Colchicine

Adverse effects?

Answer 23

Severe diarrhea, nausea, vomiting, abdominal cramps
 Bone marrow depression
 Cardiac toxicity, arrhythmia
 Hepatotoxicity
 Alopecia (hair loss)
Because of higher toxicity, it is used only when NSAIDs are ineffective or
cannot be used

Question 24

First line of treatment of acute attack of gout- in high and quickly repeated
doses.
?

Answer 24

Anti-inflammatory drugs

 Non-steroidal anti-inflammatory drugs: naproxen, piroxicam, diclofenac

Question 25

Anti-inflammatory drugs | Avoided in case of?

Answer 25

 Gastric ulcer  Renal insufficiency  Heart failure

Question 26

contraindicated in gout ?

Answer 26

Salicylate

Question 27

Used in acute gout attacks only in cases resistant to NSAIDs and colchicine, ?

Answer 27

Corticosteroids

Question 28

Preferred route of administration is intra-articularly | ?

Answer 28

Corticosteroids

Question 29

Chronic autoimmune disorder in which the normal immune response is directed against an individual's own tissue, especially joints ?

Answer 29

Rheumatoid Arthritis

Question 30

Rheumatoid Arthritis lead to?

Answer 30

- Damage in joints: = Synovial inflammation and hyperplasia = Cartilage and bone destruction (“deformity”) - Systemic effects as: = Anemia, weight loss, osteoporosis = Cardiovascular, renal and central nervous system problems

Question 31

Pharmacological treatment of rheumatoid arthritis | ?

Answer 31

1. Non-steroidal anti-inflammatory drugs (NSAIDs) 2. Disease modifying anti-rheumatic drugs (DMARDs) - DMARDs are chemically diverse drugs aiming at slowing tissue-damaging process - Has no effect on relieving pain, but slow deformity after months of starting treatment

Question 32

DMARD | Onset? Stop progress of disease ? Prevent formation of new deformities ? Uses?

Answer 32

- slow - yes - yes - moderate to serve chronic cases to arrest the disease

Question 33

NSAID | Onset? Stop progress of disease ? Prevent formation of new deformities ? Uses?

Answer 33

- rapid - no - no - mild/early cases : afford symptomatic relief in pain, swelling , morning stiffness , immobility

Question 34

Disease modifying antirheumatic drugs (DMARDs)?

Answer 34

A. Nonbiological drugs : 1. Immunosuppressants: Methotrexate 2. Sulfasalazine 3. Chloroquine or Hydroxychloroquine 4. Leflunomide B. Biological agents 1. TNFα inhibitors: Etanercept, Infliximab 2. IL-1 antagonist: Anakinra

Question 35

Inhibits dihydrofolate reductase, thus inhibit production of inflammatory cytokines, as TNF-α, chemotaxis and cell-mediated immune reaction Drug ?

Answer 35

Methotrexate

Question 36

Methotrexate Adverse effects ?

Answer 36

 At low-dose: nausea, diarrhea, rash, headache |  Severe toxicity: hepatotoxicity, bone marrow depression (treated by folic acid)

Question 37

Onset of symptom relief is relatively rapid (4–6 weeks), therefore preferred for initial treatment. Oral low-dose weekly Mtx regimen has improved acceptability ?

Answer 37

Methotrexate

Question 38

is now the DMARD of first choice and the standard treatment for most patients. Combination regimens of 2 or 3 DMARDs include Mtx. ?

Answer 38

Methotrexate

Question 39

Anti-malarial drug, Reduce monocyte IL–I, consequently inhibiting B lymphocytes, and inhibit them to produce inflammatory cytokines. Drug?

Answer 39

Hydroxychloroquine

Question 40

Induce remission in upto 50% patients of RA, but take 3–6 months ?

Answer 40

Hydroxychloroquine

Question 41

1. Fastest onset of action (4 weeks) 2. Inhibits T-cell proliferation by blocking pyrimidine synthesis Drug?

Answer 41

Leflunomide

Question 42

TNF-α blocking agents (Infliximab) | ?

Answer 42

Biologic disease modifier

Question 43

monoclonal antibody?

Answer 43

Biologic disease modifier | Example: TNF-α blocking agents (Infliximab)

Question 44

Binds TNF-α preventing its interaction with cell surface receptors decreasing macrophage and T-cell function ?

Answer 44

TNF-α blocking agents (Infliximab)

Question 45

Quicker response than nonbiologic DMARDs . | ?

Answer 45

Biologic disease modifier

Question 46

Though effective as monotherapy, they are generally added to Mtx when response to the latter is not adequate or in rapidly progressing cases, ?

Answer 46

Biologic disease modifier | Example: TNF-α blocking agents (Infliximab)

Question 47

Adverse effects: Of Biologic disease modifier Example: TNF-α blocking agents (Infliximab) ?

Answer 47

Infections, especially upper respiratory tract infections, cough