Inflammation And Anti-Inflammatory Drugs

Question 1

What is inflammation

Answer 1

Physiological response to injury

Question 2

2 processes at the level of microcirculation

What happens if not resolved?

Answer 2

Remove causative agent;
Repair/regenerate damaged tissue;

Becomes patho-physiological;

Question 3

3 phases

Answer 3

Late phase (4-21 days);
Proliferative or granulation phase (4-21 days);
Maturation phase (21 days to 2 years);

Question 4

Late phase (4-21 days)

Answer 4

Cytokines (IL-1 and TNF) are produced by activated neutrophils and macrophages -
Degradation of damaged tissue;
Preparation of site of injury for healing;

Leukocyte production of proteolytic enzymes and oxygen radicals leads to breakdown of tissue in preparation for repair;

Question 5

Systemic action of cytokines in response to injury/ inflammation

Answer 5

Acts centrally to elicit pyrogenic response;
Specific cytokine receptors in hypothalamus;
Elevates corticosteroids - stress response - promotes inflammatory in short term;
Increase hepatic protein (Heat shock or acute phase proteins);
Stimulate bone marrow;

Question 6

Proliferative or granulation phase (4-21 days)

Answer 6

Macrophages and platelets produce growth factors;

Proliferation of many cells leads to granulation of tissue -
Fibroblast produce collagen for structural purposes;
Proliferation of blood vessels ensures supply of nutrients and oxygen;
Metalloproteinases stimulate cell movement in would area;

Influenced by sex hormones;

Question 7

Failure to stop proliferative phase leads to?

Answer 7

Granulomatous condition - rheumatoid arthritis, scleroderma;

Cartilage calcification and ossification;

Question 8

What may inhibit angiogenesis?

Answer 8

Methotrexate

Question 9

Testosterone prolongs wound healing

Answer 9

Enhances cell infiltration and cytokine production;

Retards collagen production and re-epithelialization;

Question 10

Effects of estrogen

Answer 10

Reduces cell infiltration and cytokine production

Question 11

Maturation phase (21-2 years)

Answer 11

Cessation of proliferative phase;
Remodeling of tissue;
Involvement of macrophages;

Closure of wound not end-point of healing process -
Reduced vascularisation - reduced demand for nutrients due to reduced metabolic activity of tissue;
Collagen remodeling and reinnervaton of nerves - increases strength of tissue, return of sensation but lack of elastin produces scar tissue;

Question 12

Which systems does inflammation and wound healing involve?

Answer 12

Immune,nervous, endocrine, cardiovascular

Question 13

3 anti-inflammtory drugs

Answer 13

NSAIDS;
Glucocorticoids;
COX-2 inhibitors;

Question 14

NSAIDS

Answer 14

Cyclooxygenase inhibitors reduce inflammation by suppressing PG synthesis:
Reduced vasodilation and hyperaemia;
Reduced hydrostatic pressure in venules;
Reduced protein leakage to extracellular space;
Reduced pain;

Topical formulation to reduce gastrointestinal effects;

Question 15

Glucocorticoids

Answer 15

Long term anti-inflammatory treatment:
Prostanoid and leukotriene production - inflammatory synerg between cellular and human factors;
Reduces Cytokine production;
Potentiates vasoconstriction;
Chemotaxis of neutrophils;

Short term effects differ;
Expression of cell adhesion molecules;

Question 16

Selective COX-2 Inhibitors

Answer 16

Reduce effects on gastrointestinal tract, renal function;

Question 17

Side effects

Answer 17

Reduced healing of ulcers and wounds;
Effects on ovulation - COX;
Cardiac problems