Inflammatory Mediators Flashcards Preview

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Flashcards in Inflammatory Mediators Deck (71):
1

storage of histamine

-mast cells
-basophils

2

synthesis and release of histamine

-in epidermal cells
-gastric mucosa
-CNS
-regenerating or rapidly growing tissues

3

synthesis of histamine from

histidine

4

function of endogenous histamine

-allergic hypersensitivity response
-gastic acid secretion (by H2 receptors on gastric parietal cells)
-gastric carcinoid tumors (proliferation of mast cells and basophils)
-CNS neurotransmitter
-myenteric plexus

5

endogenous histamine inhibited by

-cromolyn sodium
-nedocromil
-moderated by beta-2 agonists

6

what non-immune compounds can release histamine

-organic bases
-venoms
-several drugs

7

metabolism of histamine

can occur by 2 different pathways:
1. N-methyltransferase
2. diamine oxidase

8

pharmacologic effect of H1 receptor

-vascular/extravascular smooth muscle
-nerves
-glands
-some CNS

9

pharmacologic effect of H2 receptor

-vascular/smooth muscle
-gastric parietal cell
-cardiac
-some CNS

10

pharmacologic effect of H3 receptor

-CNS
-dampening
-negative feedback

11

pharmacologic effect of H4 receptor

WBC

12

effects of histamine on the cardiovascular system

-vasodilation
-increased "capillary" permeability
-cardiac stimulation; arrhythmias

13

what is the "triple response" of Lewis (wheal and flare)

•Localized red spot
•Brighter red flush/flare
•Wheal that is noticeable in 1-2 mins that occupies the original red spot

14

extravascular effect of histamine

-bronchoconstriction
-intestinal smooth muscle contraction
-cause nerve ending pain or itch

15

Histamine Antagonists (ie. Antihistamines) are available as

drug block H1 and H2 receptors

16

how are H1 blockers divided

-older (1st) generation
-newer (2nd) generation agents

17

2nd generation H1 receptors

-penetrate CNS poorly
-are non sedating

18

H2 blockers (OTC) used to deccrease

gastric acid secretion

19

what are H1- Receptor Antagonists

-REVERSIBLE, competitive inhibitors of the H1 receptor (act like an inverse agonist)

20

1st generation H1 receptors are

-sedative
-anticholinergic

21

2nd generation H1 recptors are

-less or no sedation

22

what are the properties of H1 receptors

-sedation (varies)
-anticholinergic; some with alpha and 5-HT blocking action
-central antinausea and antiemetic effects (some agents irritate GI)
-mild antiparkinsonian effects (anticholinergic)
-local anesthetic effects (structural features of local anesthetics)
-drug allergy from topical administration

23

clinical uses of H1 Antagonists

-allergies
-allergic reactions
-pruritus
-itching
-motion sickness
-vestibular disturbances
-OTC sleep aid

24

function of H2 Receptor Antagonists

block histamine - induced gastric acid secretion

25

H2 receptor antagonists have a larger effect on

nocturnal acid secretion

26

all drugs in H2 receptor antagonists are available OTC to reduce

gastric acid secretion

27

name 4 H2 receptor antagonists

1. cimetidine
2. ranitidine
3. famotidine
4. nizatidine

28

function of cimetidine

inhibits p450 and may cause confusion in ELDERLY patient receiving larger doses

29

what are kinins

are peptide autocoids that act locally to produce pain, vasodilation, increased vascular permeability
-synthesize vasoactive substances (ie. prostaglandins)

30

kinins are activated by

-tissue damage
-allergic rxns
-viral infection
-inflammatory events

31

kinins are cleaved from

alpha 2 globulins (kininogens)

32

bradykinin and kallidin are cleaved by

plasma or tissue kallikrein

33

plasma killikrein activated by

factor XII

34

kinins are inactivated by

-ACE (kininase II)
-inactivated by conversion to active Des-Arg metabolites by other peptidases

35

bradykinin and kallidin are cleaved from

-HMW or LMW kininogens by plasma
-tissue kallikrein

36

B1 (kinin receptor) binds to

des-Arg metabolites

37

B1 (kinin receptors) are present in what cells

normal vascular smooth m.

38

B1 (kinin receptors) are unregulated during

inflammation by cytokines, GF and endotoxins

39

function B2 (kinin receptors)

-mediate the effects of bradykinin in the absence of inflammation
-activate proinflammatory transcription factors, NO synthesis, prostaglandin synthesis

40

pharmacological function of kinins

-pain
-inflammation - increase permeability
-respiratory disease - provokes bronchospasms
-kidney function - regulate urine volume and composition

41

drugs affecting kinins

-ACE inhibitors
-investigational bradykinin agonists and antagonisists
-kallikrein inhibitors

42

what are eicosanoids

-prostaglandins
-leukotrienes

43

eicosanoids are derived from

20-C essential F/A that contain 3,4 or 5 double bonds

44

where are eicosanoids found

in almost every tissue and body fluid

45

eicosanoid production increases in response to

diverse stimuli

46

what are the 2 routes of metabolism of arachidonic acid

1. lipoxygenase
2. cyclooxygenase

47

lipoxygenase pathway leads to

HPETEs
HETEs
leukotrienes

48

cyclooxygenase pahtway leads to

-cyclic endoperoxides (PGG and PGH)
-metabolic products

49

how many active sittes does cyclooxygenase have

2

50

expression of cyclooxygenase-1 (COX-1)

constitutively expressed

51

where is COX-2 expressed

-endothelial cells
-kidney
-brain

52

COX-2 induced by

-cytokines
-GF
-endotoxin
-an effect that is blocked by glucocorticoids
-laminar shear force

53

function of eicosanoids

-inflammation
-smooth muscle tone
-hemostasis/thrombosis
-paturation (labor delivery)
-gastrointestinal secretion
-renal function

54

what blocks Eicosanoids

NSAIDs

55

what drugs decrease the effect of leukotrienes

Leukotriene receptor antagonists
5-Lipoxygenase inhibitor

56

Name the Leukotriene receptor antagonists

1. Zafirlukast
2. Montelukast

57

name the 5-Lipoxygenase inhibitor

zileuton

58

what is zileuton used to treat

-asthma
-block leuoktriene derivatives

59

what are the effects of Eicosanoids on the Cardiovascular system

-vasodilate (PGI2, PGE2, PGD2)
-hypotension (LRC4, LTD4)
-vasoconstrict (TXAs, PGF2; endoperoxides)
-increase C.O (PGE2m PGF2)
-increase capillary permeability (LTC4, LTD4)

60

what are the effects of Eicosanoids on Blood Elements

-platelet aggregation (PGI2 inhibits; TXA2 promotes)
-chemotaxis (LTB4)
-inhibit lymphocyte function (PGE2)

61

postaglandins contract or relax what type of muscle

extravascular smooth muscle

62

leukotrines contract what kind of muscle

smooth muscle

63

broncoconstriciton caused by

LTC4
LTD4
PGF2
PGD2

64

uterine contraction caused by

PGE2
PGF2

65

gastrointestinal smooth muscle contraction caused by

LTC4
LTD4
PGE2
PGF2

66

effect of prostaglandins on GI

-decrease gastric secretion
-increase mucus
-promote local blood flow
-stimulate epithelial growth (PGE2 PGI2)

67

effect of prostaglandins on kidney and urine formation

-increase renal blood flow
-decrease chloride reabsorption
-increase renin secretion

68

affects of prostaglandins on afferent nerves

-direct pain producer
-hyperalgesia

69

effect of prostaglandins on CNS

-elevate body temp
-modulate NT

70

effect of prostaglandins on eye

PGF decrease intraocular pressure

71

what are the therapeutic uses of prostaglandins

-cervical ripening (PGE2)
-therapeutic abortion - stimulate uterine contraction)
-gastric cytoprotection (Misoprostol; PGE1 analog)
-maintenance of patent ductus arterioles
-primary pulmonary hypertension