36. Anti-inflammatory, Antipyretic and Analgesic Agents INCOMPLETE

Question 1

Briefly explain the concept of autoimmune disease.

Answer 1

WBCs see the self as nonself and initiate an inflammatory attack. The WBC activation leads to T lymphocyte stimulation, which recruit and activate monocytes and macrophages. These cells secrete proinflammatory cytokines, including tumour necrosis factor-a and interleukin-1.This leads to increased cellular infiltration, increased production of CRP by hepatocytes, and increased production and release of proteolytic enzymes.

Question 2

What is the result of autoimmune disease in RA?

Answer 2

Progressive tissue injury, leading to joint damage and erosions, functional disability, significant pain, and reduction in quality of life.

Question 3

What is the pharmacotherapy used in RA management?

Answer 3

Anti-inflammatory and/or immunosuppressive agents that modulate/reduce inflammatory processes.

Question 4

What is the goal in RA pharmacotherapy?

Answer 4

Reduce inflammatory processes to reduce inflammation and pain, halt and slow disease progression.

Question 5

Name an NSAID.

Answer 5

Aspirin, ibuprofen, naproxen, diclofenac, celecoxib.

Question 6

Name an RA drug.

Answer 6

Methotrexate, Sulfasalazine, Infliximab,

Rituximab, Adalimumab.

Question 7

Name a drug used for gout.

Answer 7

Allopurinol, colchicine, febuxostat.

Question 8

What are prostaglandins?

Answer 8

Unsaturated fatty acid derivatives containing 20 carbons with a cyclic ring structure.

Question 9

What is the primary precursor of prostaglandins?

Answer 9

Arachidonic acid.

Question 10

What are the roles of COX-1 and COX-2?

Answer 10

COX-1 is responsible for production of prostanoids (physiological), COX-2 causes elevated production of prostanoids in sites of chronic disease and inflammation.

Question 11

Why can antileukotriene drugs be used in asthma?

Answer 11

Lipoxygenases can act on arachidonic acid to form leukotrienes to synthesise prostaglandins.

Question 12

What are the therapeutic potential uses of prostaglandins?

Answer 12

Modulation of pain, inflammation and fever; control of acid secretion and mucus production in GI tract, uterine contractions, renal blood flow; released in allergic and inflammatory processes.

Question 13

What is the main action of NSAIDs?

Answer 13

Inhibit cyclooxygenase enzymes that catalyse the first step in prostanoid biosynthesis so reduced prostaglandin synthesis.

Question 14

How is aspirin different from other NSAIDs?

Answer 14

It irreversibly inhibits COX activity.

Question 15

What is the mechanism of action of NSAIDs?

Answer 15

They irreversibly inhibits COX enzymes. This reduces inflammation, pain, and fever.

Question 16

How do NSAIDs help with pain?

Answer 16

PGE2 sensitises nerve endings to the action of bradykinin, histamine, and other inflammatory mediators. COX-2 is expressed in inflammation and is inhibited by NSAIDs so reduces nerve ending sensitivity.

Question 17

How do NSAIDs help with fever?

Answer 17

Fever is due to the set point of anterior hypothalamic thermoregulatory centre being elevated due to PGE2 synthesis. NSAIDs impend PGE2 synthesis and release so reset the set point of the thermoregulatory centre back to normal.

Question 18

What is the cardiovascular application of aspirin?

Answer 18

It inhibits platelet aggregation. It inhibits COX-1 mediated production of TXA2 so stops TXA2 mediated vasoconstriction and platelet aggregation.

Question 19

Why is aspirin avoided in patients with gout?

Answer 19

At low doses it reduces uric acid secretion but at high doses it can increase uric acid secretion.

Question 20

What are the ADRs of NSAIDs?

Answer 20

GI, increased bleeding risk, risk of AKI, asthma contraindication (promoted leukotriene production so increases exacerbations), headache, tinnitus, dizziness.

Question 21

What are the GI ADRs of NSAIDs?

Answer 21

Dyspepsia, bleeding.

Question 22

How can GI effects of NSAIDs be prevented?

Answer 22

Use a PPI with the NSAID.

Question 23

How do kidney ADRs result from NSAIDs?

Answer 23

NSAIDs prevent synthesis of PGE2 and PGI2 prostaglandins that are responsible for maintaining renal blood flow so without these, sodium and water are retained.

Question 24

GOT TO PART B/

Answer 24

Pg/ 455