Block 2 Bolded Terms Flashcards
Histamine
Inflammatory Mediator - Biogenic amine
Cellular source: Mast cells, basophils
Physiological response: Vasodilation, increased vascular permeability, pain
Mechanism: GPCRs
Pharmacology: Antihistamines (H1 antagonists)
Bradykinin
Inflammatory Mediator - Peptide
Cellular source: Endothelial cells
Physiological reponse: Vasodilation, microvessel permeability, pain
Mechanism: GPCRs
Pharmacology: BK receptor antagonists being tested
Complement System
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
C-reactive protein
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
Cytokines
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
Adenosine
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
Cell adhesion molecules
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
Prostaglandins
Lipid mediator Cellular source: Virtually all cells Physiological response: Vasodilation/vasoconstriction, pain, fever, platelet aggregation Mechanism: Activation of specific GPCRs Pharmacology: NSAIDS
Leukotrienes
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)
Glucocorticoid
Lipid mediator
Cellular source: Adrenal cortex
Physiological response: Inhibition of cytokines, PLA2, COX-2, CAMs
Mechanism: Activation of nuclear receptors
Pharmacology: Steroids
Eicosanoids
Family of prostaglandins, leukotrienes, and epoxide compounds
Derived from 20-C fatty acids
Arachidonic Acid
Common precursor to eicosanoids in humans
Cycloxygenases (COX1/2)
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
COX-1
Constitutive cycloxygenase expressed in all tissues
COX-2
Inducible cycloxygenase often linked with inflammation
Bigger more accessible binding site
Lipoxygenase
Cytosolic enzymes that oxygenate FAs
5-Lipoxygenase responsible for leukotriene synthesis
PGE2
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
PGE1
Bronchodilator
TXA2
Thrombotic
Vasoconstrictor
Bronchoconstrictor
PGI2
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
PGF2a
Mediate uterine contractility during labor
Contribute to symptoms of primary dysmenorrhea
Bronchocontrictor
LTB4
BLT1/2 GPCR
Chemotaxis
LTC4 and LTD4
cysLT1/2 GPCR
Bronchoconstriction
Increase vascular permeability
Thromboxane
An eicosanoid, along with prostoglandins and leukotrienes
Angiotensin II
Actions:
Pharmacology:
Actions: Vasoconstrictor (AT1 receptor)
- Increases epinephrine/norepinephrine release
- Increases aldosterone synthesis
Pharmacology: ACE inhibitors - hypertension and congestive heart failure
- Angiotensin II antagonists - hypertension
Bradykinin
Actions:
Limited Pharmacology:
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
Vasopressin (ADH)
Release inititated by signals from osmoreceptors and baroreceptors
Action: Anti-diuresis - V2 receptors in collecting duct stimulate water reabsorption
- Contract vasculature (V1 receptors)
