Block 2 Bolded Terms

Question 1

Histamine

Answer 1

Inflammatory Mediator - Biogenic amine
Cellular source: Mast cells, basophils
Physiological response: Vasodilation, increased vascular permeability, pain
Mechanism: GPCRs
Pharmacology: Antihistamines (H1 antagonists)

Question 2

Bradykinin

Answer 2

Inflammatory Mediator - Peptide
Cellular source: Endothelial cells
Physiological reponse: Vasodilation, microvessel permeability, pain
Mechanism: GPCRs
Pharmacology: BK receptor antagonists being tested

Question 3

Complement System

Answer 3

Inflammatory Mediator - Plasma proteins
Cellular source: Synthesized by liver, circulate in blood
Physiological response: Chemotaxis, promote release of mediators from neutrophil, increase vascular permeability
Mechanism: Complement protein complexes cause osmotic lysis; activation of GPCRs

Question 4

C-reactive protein

Answer 4

Inflammatory Mediator - Plasma protein
Cellular source: Produced in liver in response to cytokines, produced in adipocytes
Physiological response: Acute-phase reactant, activates complement cascade, Mediates phagocytosis, Marker of inflammation
Mechanism: Bind to phospholipids in bacteria and damaged cells; specific receptors in macrophages
Elevated CRP associated with increase risk of diabetes, HTN, CVD; can be treated with statins

Question 5

Cytokines

Answer 5

Inflammatory Mediator - Secreted proteins (IL-1, TNF-a)
Cellular source: Neraly all inflammatory cells
Physiological response: TNF-a : Acute phase reaction, fever, sepsis; IL-1: acute phase reaction, fibroblast and lymphocyte proliferation, fever
Mechanism: Bind to specific receptor proteins to induce expression via NFkB and AP-1; Increase COX (fever), lipoxygenase, adhesion molecule expression, collagenase (fibrosis)
Pharmacology: Etanercept, infliximab

Question 6

Adenosine

Answer 6

Inflammatory Mediator - Purine nucleoside
Cellular source: All cells
Physiological response: Increased extracellularly during injury anti-inflammatory, inhibit cytokine action
Mechanism: Activation of GPCRs
Pharmacology: Adenosine A2 agonists, Methotrexate, Adenosine A3

Question 7

Cell adhesion molecules

Answer 7

Inflammatory Mediator - Family of proteins
Cellular source: Endothelial cells, platelets, leukocytes
Physiological response: Leukyocyte adhesion to endothelium is pivotal event in host defense and tissue repair; Recruitment of activated platelets
Mechanism: Contact molecules, calcium dependent

Question 8

Prostaglandins

Answer 8

Lipid mediator
Cellular source: Virtually all cells
Physiological  response: Vasodilation/vasoconstriction, pain, fever, platelet aggregation
Mechanism: Activation of specific GPCRs
Pharmacology: NSAIDS

Question 9

Leukotrienes

Answer 9

Lipid mediator
Cellular source: Macrophages, neutrophils
Physiological response: increase vascular permeability, bronchoconstriction
Mechanism: Activation of GPCRs
Pharmacology: 5-lipoxygenase inhib (Zileuton), cys-LT receptor antagonists (Zafirkulast)

Question 10

Glucocorticoid

Answer 10

Lipid mediator
Cellular source: Adrenal cortex
Physiological response: Inhibition of cytokines, PLA2, COX-2, CAMs
Mechanism: Activation of nuclear receptors
Pharmacology: Steroids

Question 11

Eicosanoids

Answer 11

Family of prostaglandins, leukotrienes, and epoxide compounds
Derived from 20-C fatty acids

Question 12

Arachidonic Acid

Answer 12

Common precursor to eicosanoids in humans

Question 13

Cycloxygenases (COX1/2)

Answer 13

Membrane bound heme proteins responsible for synthesis of prostaglandins and thromboxanes
1st activity: Oxygenates and cyclizes precursor to make PGG2
2nd activity: Peroxidase that converts PGG2 to PGH2

Question 14

COX-1

Answer 14

Constitutive cycloxygenase expressed in all tissues

Question 15

COX-2

Answer 15

Inducible cycloxygenase often linked with inflammation

Bigger more accessible binding site

Question 16

Lipoxygenase

Answer 16

Cytosolic enzymes that oxygenate FAs

5-Lipoxygenase responsible for leukotriene synthesis

Question 17

PGE2

Answer 17

Vasodilator,
Hyperalgesic
Fever,
Induce uterine contractility
Major maintenance of patent ductus arteriosus
Bronchodilator
Increase renal blood flow, diuresis, naturesis
Inhibit gastric acid secretion
Increase gastric mucosal blood flow, release of viscous mucus, bicarbonate secretion, smooth GI contractility

Question 18

PGE1

Answer 18

Bronchodilator

Question 19

TXA2

Answer 19

Thrombotic
Vasoconstrictor
Bronchoconstrictor

Question 20

PGI2

Answer 20

Vasodilator
Hyperalgesic
Stop platelet aggregation
Keep uterus in quiescent state
Bronchodilator
Increase renal blood flow, diuresis, naturesis
Inhibit gastric acid secretion
Increase gastric mucosal blood flow

Question 21

PGF2a

Answer 21

Mediate uterine contractility during labor
Contribute to symptoms of primary dysmenorrhea
Bronchocontrictor

Question 22

LTB4

Answer 22

BLT1/2 GPCR

Chemotaxis

Question 23

LTC4 and LTD4

Answer 23

cysLT1/2 GPCR
Bronchoconstriction
Increase vascular permeability

Question 24

Thromboxane

Answer 24

An eicosanoid, along with prostoglandins and leukotrienes

Question 25

Angiotensin II
Actions:
Pharmacology:

Answer 25

Actions: Vasoconstrictor (AT1 receptor)
- Increases epinephrine/norepinephrine release
- Increases aldosterone synthesis
Pharmacology: ACE inhibitors - hypertension and congestive heart failure
- Angiotensin II antagonists - hypertension

Question 26

Bradykinin
Actions:
Limited Pharmacology:

Answer 26

Actions: Stimulate production of prostoglandins, leukotrienes, cytokine - mediate pain, inflammation, edema
- Implicated in athsma, allergic rhinitis, cough, and bronchial spasms
- Vasodilation of arteries and vasoconstriction of veins
- Pancreatitis
Limited Pharmacology: Ace Inhibitors

Question 27

Vasopressin (ADH)

Answer 27

Release inititated by signals from osmoreceptors and baroreceptors
Action: Anti-diuresis - V2 receptors in collecting duct stimulate water reabsorption
- Contract vasculature (V1 receptors)