Anti-inflammatory- Regal Flashcards Preview

IHO WEEK 5 > Anti-inflammatory- Regal > Flashcards

Flashcards in Anti-inflammatory- Regal Deck (67):
1

Describe the process of acute inflammation

-Changes in blood vessel caliber and flow
-Increased vascular permeability
-Leukocytic infiltration

2

Histamine

Redness, heat, swelling, and airway constriction

*NOT chemotaxis

3

PGE2

Vasodilate, increase vascularpermeability, cause pain

4

PGD2 and thromboxane

Bronchoconstriction

5

TXA2

Causes platelet aggregation (and vasoconstriction)

6

PGI2

Vasodilates, increases vascular permeability, causes pain, opposes platelet aggregation

7

Leuktorienes (LTB4)

Chemotactic (PMNs) and reduces pain threshold

8

Kinins

Everything!
STRONG vasodilator = hypotension

*Not major chemotactic agent

9

Diphenhydramine

First gen. antihistamine
Blocks H1, muscarinic, alpha adrenergic, and serotonin receptors

**SEDATION!!!

10

Chlorpeiramine

First gen. antihistamine
Blocks H1, muscarinic, alpha adrenergic, and serotonin receptors

**DAY TIME USE! (Non-drowsy)

11

Certirizine

Second gen. antihistamine → blocks H1

Minimal anticholinergic properties

Do not cause sedation and drying of secretions (less penetration into CNS)

Not cardiotoxic

12

Fexofenadine

Second gen. antihistamine → blocks H1

Minimal anticholinergic properties

Do not cause sedation and drying of secretions (less penetration into CNS)

Not cardiotoxic

13

Loratadine

Second gen. antihistamine → blocks H1

Minimal anticholinergic properties

Do not cause sedation and drying of secretions (less penetration into CNS)

Not cardiotoxic

14

What enzyme makes histamine?

L-histidine decarboxylase converts histidine to histamine in basophils and mast cells

15

What is the triple response to histamine?

Vasodilation
Flare
Wheal

16

Which histamine receptor is primarily responsible for bronchoconstriction, increased capillary permeability, pruritis and pain?

H1

17

After an allergic reaction, why do you give epinephrine rather than norepinephrine for difficulty breathing?

You want to stimulate the Beta 2 receptor: responsible for bronchodilation, mostly found in the lungs

This receptor has a higher affinity for Epi

Note** bronchoconstriction to an allergen is mostly caused by LTC4 -- so Epi is physiological antagonist (not competing for same receptor but competing for what smooth muscle is going to do)

18

Why don't you use antihistamines to prevent bronchoconstriction during anaphlaxis?

Too slow and leukotrienes are mostly responsible for bronchoconstriction in response to an allergen

19

What are the aspect of anaphalaxis that cause death?

Bronchoconstriction
Hypotension

B2 (bronchodilator)
Alpha receptor (increase bp)

20

What would be the effect on the dose response curve of chlorpheniramine in response to allergen induced bronchoconstriction?

Nothing really for bronchoconstriction due to allergen

No shift

21

What would be the effect on the dose response curve of Loratadine in response to allergen induced bronchoconstriction?

Nothing really for bronchoconstriction due to allergen

No shift

22

Why doesn’t loratadine cause sedation or drying of the mouth in over the counter doses?

No anticholinergic properties → no drying of the mouth

No sedation → affinity for p-glycoprotein in the CNS

23

What prostaglandin in the most potent fever inducer?

PGE2

On EP1-EP4 receptors

24

What prostaglandin is the most potent bronchoconstrictor?

PGD2

25

What enzyme releases arachadonic acid from the membrane?

Phopholipase A2

26

What is the main role of LTB4?

attracts and activates neutrophils (CHEMOTAXIS)

also reduces pain threshold

27

What do peptido leukotrienes causes?

Bronchoconstrictions
increased vascular permeability
chemotaxis

28

What enzyme converts Arachadonic Acid to LTA4?

5-lipoxygenase

29

What enzyme converts LTA4 to LTB4?

LTA hydrolase

30

What enzyme converts LTA4 to LTC4 (D4, E4)? What molecule is being added?

LTC4 synthase adds glutathione

31

Interaction of peptidoleukotrienes with what receptor is responsible for bronchoconstriction?

Cys LTR1

32

What are the leukotrienes most important in asthma?

LTC4 and LTD4

33

MOA Zileuton

5-lipoxygenase inhibitor

Prevents synthesis of LTB4 and LTC4 (D4, E4)

34

MOA Zafirlukast

Leukotriene receptor antagonist (LTD4 receptor, Cys LTR1)

*Inhibits Cyt P450 - significant drug interactions

35

MOA Montelukast

Leukotriene receptor antagonist (LTD4 receptor, Cys LTR1)

*used in asthma

36

Role of PGI2 (prostacyclin)

Vasodilates
Increases vascular permeability
OPPOSES platelet aggregation

37

Role of TXA2 (thromboxane)

Vasoconstriction
Platelet aggregation

38

MOA of aspirin?

IRREVERSIBLY acetylates (inhibits) COX

39

Why are there a lot of hypersensitivites associated with aspirin?

Blocking COX shifts to utilization of LOX pathway -- increases leukotriene production leading to symptoms of hypersensitivity

(Also PGE2 can no longer inhibit 5-lipoxygenase)

40

Ibuprofen

Inhibits COX1 &2

41

Naproxen

Inhibts COX1 & 2

42

Ketorlac

Inhibits COX1 & 2

43

Ketoprofen

Inhibits COX1 & 2

44

Indomethacin

**Most potent NSAID
Inhibits COX1 & 2

**Can cause severe frontal headache and blood disorders

45

Sulindac

Inhibits COX1 & 2

46

Piroxicam

Inhibits COX1 & 2

47

Celecoxib

COX 2 inhibitor

*Thrombus - shifted balance too much

48

Acetaminophen

NOT NSAID!!!

Analgesic
Antipyretic (BUT NOT anti-inflammatory!)

Effectively inhibits COX in the brain but not at sites of inflammation

Overdose can cause serious hepatic injury

49

What does kallikrein do and where is it found?

Found in tissues and blood stream

Makes bradykinin and kallidin

50

What does carboxypeptidase N do?

Removes carboxy terminal arginine

this allows bradykinin and kallidin to bind the B1 receptor better

This receptor is induced after trauma

51

What does Kininase II (Angiotensin converting enzyme) do?

Degrades bradykinin (vasodilator)

**Degrades a dilator and makes a constrictor**

52

What happens to blood pressure if you prevent the degradation of kinins by inhibiting angiotensin converting enzyme (ACE)?

Decreased blood pressure

53

What are the main actions kallidin and bradykinin when binding to the B2 receptor?

Hypotension
Edema
Pain

54

What are the main actions kallidin and bradykinin when binding to the B1 receptor?

Chronic inflammatory effects
*Induced after trauma

55

What is a key biochemical event in the anti-inflammatory mechanism of the glucocorticoid nasal spray?

Steroid has to get inside the cell (intracellular receptor)

Interacts with glucocorticoid receptor within the cell

Signal transduction → into the nucleus

Acts as transcription factor

56

What do glucocorticoids do to cells in circulation? How do they do that?

-found in many cell types and tissues
-Changes cell numbers in circulation
-Increases neutrophils
-Decreases lymphocytes
-Does this by effecting synthesis and release of inflammatory mediators

57

What cell is the focus of durg treatment to prevent rejection of transplanted organs?

T-cells!

58

What adverse consequences would you predict from inhibition of the functions of this cell type?

-Immunosuppression
-Reduced cancer surveillance
-Increased infections

59

What is so important about IL-2? Why is it such a good drug target?

IL-2 activates T-cells (won't affect resting T-cells)

60

MOA of
predinsone
Methylprednisolone
Betamethasone
Dexamethasone?

Affects cell movement in circulation
-Increases neutrophils
-Decreases Everything else
-Effects synthesis/ release of inflammatory mediators:
-reduced COX2
-Inhibits release of AA- decreased PG and LTKs
-Inhibits degranulation of mast cells and basophils
-Inhibits synthesis and release of cytokines

61

MOA Cyclosporine

Binds to cyclophilin → inhibits calcineurin → decreased NFAT activation → decreased IL-2 production

62

MOA Tacrolimus

Binds to FKBP → inhibits calcineurine → decreased NFAT activation → decreased IL-2 production

63

MOA Sirolimus

Inhibits mTOR (protein kinase involved in cell-cycle progression)

64

MOA Mycophenolate mofetil

Inhibits activity of inosine monophosphate dehydrogenase

65

MOA Anti-thymocyte globulin

Antibody binds to thymocytes in the circulation, resulting in lymphopenia and impaired T-cell immune response

66

MOA Muromonab- CD3

Antibody that blocks antigen recognition of the T-cell receptor complex

67

MOA Dacilzumab and Basiliximab?

Antibody that blocks the IL-2 receptor to prevent T-cell proliferation