Rheumatoid Arthritis

Question 1

NSAIDs
- Effect

Answer 1

Anti-inflammatory Action
- Decrease Prostaglandin E2
- Prostacyclin reduces vasodilation
- Reduction of mediators, number of inflammatory cells are not reduced

Analgesic Effect
- Decrease Prostaglandin generation
–> Less inflammatory mediators to activate nociceptive nerve ending
- Decreased Prostaglandin mediated vasodilation
–> Headache relief

Antipyretic Effect
- Prevent interleukin-1 from releasing prostaglandins in the CNS
–> Prevent elevation of hypothalamic set point for temperature control
–> Prevent fever

Question 2

NSAIDs
- MOA

Answer 2

Inhibit Cyclooxygenase Enzyme (COX-1/COX2)
- Inhibiting conversion of arachidonic acid to prostaglandin

Question 3

NSAIDs
- COX-1 vs COX-2

Answer 3

COX-1: Constitutive Enzyme
- Protective role
–> Responsible for producing cytoprotective mucus in stomach
–> Responsible for platelet aggregation

COX-1: Inducible Enzyme
- Have to be stimulated by inflammatory mediators
–> Associated with inflammation
(COX-2 has no effect on stomach)

Question 4

NSAIDs
- Indication

Answer 4

• Pain
• Inflammation
  -Fever

Question 5

NSAIDs
- Adverse Effects

Answer 5

Contraindicated with Active Peptic Ulcer
Aspirin must be taken with food

Question 6

NSAIDs
- Nonselective Adverse Effects

Answer 6

Gastrointestinal Effects
- Inhibition of COX-1 affects production of cytoprotective mucus)

Edema
- PG inhibits Water and Salt retention

Acute Renal Failure
- Renal PGs protect high-risk patients by countering the effect of angiotensin 2 and vasopressin

Question 7

NSAIDs
- COX-2 Adverse Effects

Answer 7

Cardiovascular
- Caused by the disruption in the balance between platelet-activating effects of COX-1 and platelet inhibiting effects of COX-2

Question 8

NSAIDs
- All Adverse Effects

Answer 8

CNS (Confusion, Dizziness, Depression, Hallucination)
- Likely caused by COX-2 which is abundant in the CNS
- Could also be caused by COX-3

Question 9

Methotrexate
- Indication

Answer 9

Rheumatoid Arthritis
- Anti-inflammatory Action in small doses

Cancer
- Cytotoxic in large doses

Psoriasis Arthritis

Ankylosing Spndylitis

Polymyositis and Vaculitis

Question 10

Methotrexate
- MOA

Answer 10

Disease-Modifying Antirheumatoid Drug (DMARD)

Folate Antagonist (Oral)
- Interferes with thymidylate synthesis (Essential in DNA synthesis)
–> Suppresses immune system

Question 11

Methotrexate
- Adverse Effects

Answer 11

Gastrointestinal Disturbance

Dose-related Liver Toxicity

Bone Marrow Depression

Question 12

Sulfasalazine
- Indication

Answer 12

• Rheumatoid Arthritis
• Juvenile Arthritis
• Inflammatory Bowel Disease

Question 13

Sulfasalazine
- MOA

Answer 13

Disease-Modifying Antirheumatoid Drug (DMARD)
- Acts in the colon to release salicylic acid
–> Anti-inflammatory action

Question 14

Leflunomide
- Indication

Answer 14

Rheumatoid Arthritis

Question 15

Leflunomide
- MOA

Answer 15

Disease-Modifying Antirheumatoid Drug (DMARD) - (Oral)
- Increases amount of metabolite that inhibits dihydroorotate dehydrogenase
–> Inhibition of T-Cell Proliferation
–> Decreased production of autoantibodies by B cells

Question 16

Leflunomide
- Adverse Effects

Answer 16

• 25% of patients get diarrhoea
• Increased BP
• Weight Gain

Question 17

Targeted Synthetic DMARD
- MOA

Answer 17

Tofacitinib
- Inhibits Janus Kinase (JAK)
–> Reduces inflammation

Question 18

Biological DMARD
- MOA

Answer 18

Infliximab (IV)
- Monoclonal antibody against TNF-alpha that prevents it from interacting with receptors on inflammatory cells

Question 19

Biological DMARD
- Indication

Answer 19

Active Rheumatoid Arthritis
- Combined with methotrexate if DMARDs have yet to work

Ankylosing Spondylitis (If other therapy has not worked)

Psoriatic Arthritis (If other therapy has not worked)

Question 20

Biological DMARd
- Adverse Effects

Answer 20

• Nausea
• Vomiting
• Headache
• Upper Respiratory Tract Infections with Cough

Question 21

Colchicine
- MOA

Answer 21

Crystal Associated Arthritis (Gout)
- Inhibits microtubule polymerization
–> Binds protein and tubulin needed for mitosis

• Inhibits Neutrophil
  –> Prevents activation and migration
• Blocks inflammasome complex in neutrophils and monocyte
  –> Prevent inflammation
• Inhibits superoxide anion production in response to Urate Crystals
• Interrupts mast cell degranulation

Result: Inhibits Inflammation

Question 22

Colchicine
- Indications

Answer 22

• Gout
• Acute Attack (Joint pain caused by gout)
• Prevent recurrent attacks (Uric Acid Lowering Therapy)

Question 23

Colchicine
- Adverse Effects

Answer 23

Contraindicated in Renal Failure
- Increased Risk of Toxicity

Narrow Therapeutic Index

Gastrointestinal
- Diarrhea (Very Common)

Bone Marrow Suppression
- Antimitotic target rapidly dividing cells such as bone marrow

Myopathy may occur
Neuropathy may occur

Question 24

Uricosurics
- MOA

Answer 24

Treats Gout
- Enhance Uric acid excretion
- Prevent Uric acid reabsorption (Probenecid)
–> Lower Uric Acid level

Question 25

Uricosurics
- Indications

Answer 25

Gout

Question 26

Uricosurics
- Adverse Effects

Answer 26

Do not give with Salicylates (Sulfasalazine)
- They will inhibit each other

Contraindicated in:
- Renal Insufficiency
- Urolithiases (Renal Stone)
- Peptic Ulcer

Mild Gastrointestinal Irritation

Mild Allergies (Rate)

Question 27

Xanthine Oxidase Inhibitors
- MOA

Answer 27

Allopurinol
- Purine Analogue of Hypoxanthine
- Inhibits Enzyme Xanthine Oxidase
–> Can not convert Hypoxanthine to Xanthine to Uric Acid

Febuxostat
- Nonpurine Inhibitor of Xanthine Oxidase
- Does not inhibit purine / pyrimidine synthesis

Result: Reduces production of Uric Acid

Question 28

Xanthine Oxidase Inhibitors
- Indications

Answer 28

Gout

Renal Stones made up of Uric Acid

Complicated Hyperuricemia

Question 29

Xanthine Oxidase Inhibitors
- Considerations

Answer 29

Contraindicated in those Hypersensitive to allopurinol

Allopurinol increases half-life of probenecid
- Enhances its Uricosuric effect

Question 30

Allopurinol
- Adverse Effect

Answer 30

Skin Reactions
- Mild to Severe

Stevens-Johnson Syndrome
- Toxic Epidermal Necrolysis (Rare & Fatal)

Liver Reactions
- Elevated liver enzymes, fever, eosinophilia, rash

Renal Insufficiency

Be careful of hypersensitivity to allopurinol

Question 31

Febuxostat
- Adverse Effect

Answer 31

No hypersensitivity

Cardiovascular
- Increased risk of myocardial infarction, stroke, cardiovascular death