Pharmacology Block 2 > 01 Inflammation > Flashcards

01 Inflammation Flashcards

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1
Q

Protective response to rid the body of the cause of cell injury and the resultant necrotic cells that cell injury produces

A

Inflammation

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2
Q

Restores homeostatic balance, fights disease, and drives wound-healing responses

A

“Little” Inflammation

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3
Q

Results in pathologic conditions such as asthma, rheumatoid arthritis, inflammatory bowel diseases, gout, atherosclerosis, and possibly cancer.

A

“Lot of” Inflammation

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4
Q

Cardinal Signs of Acute Inflammation

A
  • Rubor (red discoloration)
  • Calor (heat)
  • Dolor (pain)
  • Tumor (mass effect)
  • Loss of function
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5
Q

Physiological Effects of Acute Inflammation

A
  • Vasodilation
  • Increased vascular permeability
  • Recruitment of neutrophils

EDEMA

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6
Q

What causes these physiological effects?

  • Vasodilation
  • Increased vascular permeability
  • Recruitment of neutrophils
  • Edema
A

Acute Inflammation

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7
Q

What causes acute inflammation

A

microbial infection, physical agent, irritants/corrosive chemicals, tissue necrosis

Action via PMNs

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8
Q

What is the cause of chronic inflammation?

A

persistence of irritant, endogenous antigen or “factor”

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9
Q

Persistence of irritant endogenous antigen or “factor” can lead to what?

A

Chronic Inflammation

Leads to upregulation of damage/apoptosis and auto-amplification of the inflammatory response

Fibrosis

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10
Q

What are the harmful effects of inflammation?

A
  • Release of lysosomal enzymes (collagenases and proteases) may digest normal tissue
  • Inflammatory swelling may result in death from obstructing airways or swelling within the cranial cavity
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11
Q

Mediator Theory

A

signs and symptoms of inflammation are caused by the release of chemicals (mediators) from inflammatory and structural cells

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12
Q

Histamine

A

Inflammatory Mediator

Biogenic amine

Source: Mast cells, basophils

Phys:

  • vasodilation
  • increased vascular permeability
  • pain

Mech: GPCR activation

Tx: Antihistamines (H1 antagonists)

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13
Q

What inflammatory mediator is released specifically from mast cells and basophils?

A

Histamine

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14
Q

What inflammatory mediators causes:

  • vasodilation
  • increased vascular/microvessel permeability
  • pain
A

Histamine and Bradykinin

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15
Q

Bradykinin

A

Inflammatory mediator

Peptide

Source: Endothelial cells
- activated by tissue injury, allergic reactions, viral infections

Phys:

  • vasodilation
  • increased microvessel permeability
  • pain

Mech: GPCR activation

Tx: BK receptor antagonist

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16
Q

What causes increased microvessel permeability?

A

Bradykinin

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17
Q

Complement System (Inflammatory Mediator)

A

Plasma proteins

Source: Synthesized by liver, circulates in blood

Phys:

  1. Chemotaxis
  2. Promote release of mediators from neutrophils
  3. Increase vascular permeability
  4. Excessive activation leads to tissue injury

Mech:

  • Aggregate to cell surface and cause osmotic lysis
  • GPCR activation

Tx:

  • Eculizumab inhibits C5 cleavage
  • APT070 is a truncated CR1 which regulates overproduction of completment
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18
Q

What inflammatory mediators increase vascular permeability?

A

Histamine and Complement System

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19
Q

What inflammatory mediator causes chemotaxis?

A

Complement System

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20
Q

What inflammatory mediator promotes the release of mediators from neutrophils?

A

Complement System

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21
Q

What inflammatory mediator with excessive activation can contribute to tissue injury?

A

Complement System

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22
Q

C-Reactive Protein

A

Inflammatory Mediator

Plasma Protein

Source: Synthesized in liver and adipocytes in response to cytokines

Phys:

  1. Acute phase reactant
  2. Activates complement cascade
  3. Mediates phagocytosis
  4. Marker of inflammation

Mech: bind to phospholipids in bacteria and damaged cells (Ca2+ dependent)

Tx: Elevated CRP associated with inc risk of DM, HTN, CV disease. Statins may be effective.

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23
Q

What inflammatory mediator is produced in the liver in response to cytokines as well as in adipocytes?

A

C-Reactive Protein

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24
Q

What inflammatory mediators are an acute phase reactant?

A

C-Reactive Protein and cytokines TNF−α and IL−1

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25
What inflammatory mediator activates complement cascade?
C-Reactive Protein
26
What inflammatory mediator mediates phagocytosis?
C-Reactive Protein
27
What inflammatory mediator is a marker of inflammation?
C-Reactive Protein
28
What inflammatory mediator binds to phospholipids in bacteria and damaged cells?
C-Reactive Protein
29
An elevated level of what inflammatory mediator is associated with an inc risk of DM, HTN, and CV disease?
C-Reactive Protein
30
Cytokines
Inflammatory Mediator Proinflammatory cytokines: Interleukin-1 (IL-α and IL-β) and Tumor Necrosis Factor-α (TNF−α) Source: nearly all inflammatory cells Phys: 1. TNF−α: acute phase reaction, fever, sepsis 2. IL−1: acute phase reaction, fibroblast and lymphocyte proliferation, fever Mech: Induce gene expression of many proteins via NFkB and AP-1 - increase cyclooxygenase (fever) and lipoxygenase - increase adhesion molecule expression - induce collagenase (fibrosis) Tx: - Entanercept - Infliximab
31
What are the proinflammatory cytokines?
Interleukin-1 (IL-α and IL-β) and Tumor Necrosis Factor-α (TNF−α)
32
What inflammatory mediator causes acute phase reaction, fever, and sepsis?
TNF−α
33
What inflammatory mediator causes acute phase reaction, fibroblast and lymphocyte proliferation, and fever?
Interleukin-1
34
What inflammatory mediator causes the activation of NFkB and AP-1?
Proinflammatory cytokines: Interleukin-1 (IL-α and IL-β) and Tumor Necrosis Factor-α (TNF−α)
35
What is the result of activating NFkB and AP-1 by Interleukin-1 TNF−α?
Increase cyclooxygenase (fever) and lipoxygenase Increase adhesion molecule expression Induce collagenase
36
What is treated with Etanercept or Infliximab?
Pro-inflammatory cytokines Interleukin-1 (IL-α and IL-β) and Tumor Necrosis Factor-α (TNF−α)
37
What causes an increase in cyclooxygenases (fever) and lipoxygenases?
Activation of NFkB and AP-1 by pro-inflammatory cytokines Interleukin-1 (IL-α and IL-β) and Tumor Necrosis Factor-α (TNF−α)
38
What inflammatory mediators induce collagenase (fibrosis)?
Activation of NFkB and AP-1 by pro-inflammatory cytokines Interleukin-1 (IL-α and IL-β) and Tumor Necrosis Factor-α (TNF−α)
39
Adenosine
Inflammatory Mediator Purine nucleoside formed from ATP breakdown Source: all cells Phys: 1. Anti-inflammatory: Increased extracellulary during injury 2. Inhibits cytokine action Mech: GPCR activation Tx: Adenosine A2 agonists
40
What inflammatory mediator is increases extracellularly during injury?
Adenosine (anti-inflammatory)
41
What inflammatory mediator inhibits cytokine action?
Adenosine (anti-inflammatory) and glucocorticoids
42
Cell Adhesion Molecules (CAMs)
Inflammatory Mediator Family of Proteins Source: endothelial cells, platelets, leukocytes Phys: 1. Leukocyte adhesion to endothelium is a pivotal event in host defense and tissue repair 2. Endothelial adhesion molecules contribute to recruitment of activated platelets Mech: "contact molecules" calcium dependent Tx: Abciximab or Natalizumab
42
What inflammatory mediator causes leukocyte adhesion to endothelium?
Cell Adhesion Molecules
42
What inflammatory mediator contributes to recruitment of activated platelets?
Endothelial (Cell) adhesion molecules
42
Oxygen-Derived Free Radicals
Superoxide, hydroxy radicals Source: all cells Phys: Intracellular killing of bacterial by neutrophils Mech: - protein oxidation - lipid peroxidation - DNA mutations Tx: anti-oxidants Vit C and E
42
What inflammatory mediator causes intracellular killing of bacteria by neutrophils?
Oxygen-derived free radicals
42
What inflammatory mediator works via protein oxidation, lipid peroxidation, and DNA mutations?
Oxygen-Derived Free radicals
42
What are the lipid inflammatory mediators?
Prostaglandins, Leukotrienes, and Glucocorticoids
42
Prostaglandin
Lipid Inflammatory Mediator Eicosanoids, Steroids Source: virtually all cells Phys: 1. Vasodilation/vasoconstriction 2. Pain 3. Fever 4. Platelet aggregation (via thromboxane) Mech: GPCR activation Tx: NSAIDs
42
What inflammatory mediator causes: 1. Vasodilation/vasoconstriction 2. Pain 3. Fever 4. Platelet aggregation (via thromboxane)
Prostaglandin (Lipid mediator)
42
What inflammatory mediator is treatment for chronic inflammatory diseases?
Glucocorticoids
43
What inflammatory mediator is treated with NSAIDs?
Prostaglandins (Lipid mediator)
43
Leukotriene
Lipid inflammatory mediator Source: macrophages, neutrophils Phys: 1. Inc vascular permeability 2. Bronchoconstriction Mech: GPCR activation Tx: - Zileuton (5-lipoxygenase inhibitor) - Zafirlukast (cys-leukotriene receptor antagonist)
43
What inflammatory mediator causes: 1. Inc vasc permeability 2. Bronchoconstriction
Leukotrienes (lipid mediator)
43
5-lipoxygenase inhibitor
Zileuton (Tx of leukotriene)
43
Cys-leukotriene receptor antagonist
Zafirlukast (Tx of leukotriene)
43
Glucocorticoids
Lipid inflammatory mediator Source: Adrenal cortex Phys: 1. Inhibition of cytokines 2. inhibition of phospholipase A2 3. inhibition of cyclooxygenase-2 4. inhibition of cell adhesion molecules Mech: nuclear receptor activation Tx: Steroids (controlling chronic inflammatory diseases)
44
What inflammatory mediator inhibits cyclooxygenase-2?
Glucocorticoids (lipid mediator)
45
What inflammatory mediator inhibits cell adhesion molecules?
Glucocorticoids (lipid mediator)
60
What inflammatory mediator is used to treat chronic inflammatory diseases?
Glucocorticoids
61
What is the mechanism of steroids (glucocorticoids)?
Bind to cytoplasmic receptors activated receptor-steroid complex localizes to nucleus/binds DNA (glucocorticoid response elements) resulting transcription of certain target genes (induction or repression) Inhibits cytokines, protaglandins, leukotrienes, cell adhesion molecules
62
What is the mechanism of action of non-steroidal anti-inflammatory drugs?
Inhibition of cyclooxygenase
63
Leukotriene Antagonists
Zafirlukast | Zileuton
64
Zafirlukast
competitive antagonist of leukotriene receptors
65
Zileuton
Inhibits the synthesis of leukotrienes
66
Inflammatory Cytokine Inhibitors
Etanercept | Infliximab
67
What is the Acute Phase Reaction?
In response to injury, local inflammatory cells secrete cytokines that cause the liver to increase or decrease production of various proteins
68
What mediator contributes to signs and symptoms of inflammations (pain, fever, vasoactive effects)?
Prostaglandins
69
What mediator directly increases blood flow and indirectly enhances edema formation and leukocyte infiltration?
Prostaglandins
70
What mediator releases slow reacting substance of anaphylaxis (SRS-A) from mast cells?
Leukotrienes
71
What mediator is increased in allergies/asthma?
Leukotrienes
72
What mediator causes vasodilation?
Prostaglandins
73
What mediator causes increased vascular permeability?
Vasoactive amines Complement Proteins Bradykinin Leukotriene
74
What mediator causes chemotaxis?
Complement Protein | Leukotrienes
75
What mediator causes fever?
Cytokines IL-1 and TNF-alpha | Prostaglandins
76
What mediator causes pain?
Prostaglandins and Bradykinin
77
What mediator causes tissues damage?
Neutrophil and macrophage lysosomal enzymes | Oxygen metabolites
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