Inflammatory Overview- Mediators And Drugs

Question 1

Bradykinin

Answer 1

Cellular Source: endothelial cells and activated by tissue injury, allergic reaction, viral infection
Response: vasodilation, increased vascular permeability, pain
Mechanism: activation of GPCR and B2 receptor
Pharmacology: BK2 receptor antagonist, treatment of acute attacks of hereditary angioedema

Question 2

Complement System

Answer 2

Plasma proteins
Cell source: synthesized by liver and circulate in blood
Physiological response: chemotaxis (recruit inflammatory cells to site of injury), promote release of mediators from PMN, increase vascular permeability, too much tissue injury
Mechanism: complex of complement proteins aggregate to cell surface membrane and cause osmotic lysis and receptors for complement can cause mast cell degranulation

Question 3

C-Reactive Protein

Answer 3

Plasma protein
Cellular source: synthesized by liver and fat cells
Protein binds to C polysaccharide of bacterial cell wall
Response: acute phase reactant, activate complement cascade, mediate phagocytosis, inflammation marker
Mechanism: binds to phosphatidlycholine containing substances in bacteria and damaged cells (calcium depends binding)
Pharmacology: Too much CRP leads to diabetes, hypertension and CV diseases
No CRP inhibitors (statins reduce levels)

Question 4

Cytokines

Answer 4

Secreted proteins (TNF and IL)
Source: nearly all cells
Physiological response : stimulate acute phase reactants
TNF alpha- fever and sepsis
IL-1- fibroblast and lymphocyte proliferation, fever
Mechanism: Interaction with specific receptors to induce gene expression of a number of proteins through activation of TF NFKb AP-1–> increase COX (fever) and lip oxygenate and increase adhesion molecule expression
Induce collagenase (fibrosis)

Question 5

Infliximab and Entanercept

Answer 5

TNF alpha inhibitor

Question 6

Adenosine

Answer 6

Purine nucleoside formed from breakdown of ATP
Cell source: all cells
Physiological response: increased EC during injury and anti-inflammatory because also inhibit cytokine action
Mechanism: activation of GPCR
Pharmacology: adenosine A2 antagonist
Methotrexate (rheumatoid arthritis, folic acid antagonist)

Question 7

Cell Adhesion Molecules

Answer 7

Family of proteins
Cell source: endothelial cells, platelets, leukocytes
Physiological response:
Leukocytes adhesion to endothelium for defense and tissue repair
Endothelial adhesion for recruitment of platelets
Mechanism: contact molecules and Ca dependent
Pharmacology: Abciximab and Natalizumab inhibit this

Question 8

Prostaglandins

Answer 8

Lipid mediator and is anti inflammatory
Cell source: all cells 
Physiological response: vasodilation, pain, fever, platelet aggregation (thromboxane)
Mechanism: activation of specific GPCR
Pharmacology: NSAIDs

Question 9

Leukotrienes

Answer 9

Cell source: macrophage and neutrophils
Physiological response: increase vascular permeability, bronchoconstriction
Mechanism: activation of GPCR
Pharmacology: zileuton (5-lipoxygenate inhibitor) and Zafirlukast(cys-leukotriene receptor antagonist)

Question 10

Glucocorticoids

Answer 10

Cell source: adrenal cortex
Physiological response: inhibit cytokines, inhibit phospholipase A2, inhibit COX-2, inhibit cell adhesion molecules
Mechanism: activation of nuclear receptors
Pharmacology: steroids (most potent and effective for controlling chronic inflammatory diseases)

Question 11

NSAIDS

Answer 11

Inhibit cyclooxygenase for prostaglandins

Aspirin

Question 12

Leukotrien antagonists

Answer 12

Zafirlukast –> antagonist of receptor

Zileuton–> inhibit synthesis of the leukotrienes

Question 13

Cytokine Inhibitors

Answer 13

Etanercept

Infliximab

Question 14

Histamine

Answer 14

Biogenic Amine
Cell Source: stored in mast cells and basophils (non- mast cells source is neurons and cell in stomach)
Response: vasodilation, increase vascular permeability, pain
Mechanism: activate GPCR to activate signaling pathway
Antihistamine to block at H1 receptor antagonist