Leukotriene and Pulmonary Anti-Inflammatory Drugs

Question 1

What is arachidonic acid metabolized to?

Answer 1

Prostaglandins

Question 2

What are the three pathways?

Answer 2

5-lipoxygenase

other two not important (not well understood)

Question 3

What is the pathway for arachidonic acid to leukotrienes?

Answer 3

Arachidonic acid-> 5HPETE->LTA4-> LTB4 or LTC4

Question 4

What does zileuton inhibit?

Answer 4

Conversion of arachidonic acid to 5-HPETE by inhibiting 5-lipoxygenase and FLAP

Question 5

Why do COX-1 inhibitors sometimes precipitate asthma?

Answer 5

COX-1 inhibits the formation of prostaglandin forcing arachidonic acid to produce leukotrienes precipitating bronchoconstriction and mucus formation

Question 6

What do zafirlukast and montelukast do?

Answer 6

Competitively inhibit CysLT1 receptor

Question 7

Why is zileuton used for short term treatment?

Answer 7

It competitively inhibits CYP3A4 causing many drug interactions and increases liver enzymes

Question 8

What do leukotrienes cause?

Answer 8

Mucous formation and microvascular permeability

Question 9

Where is histamine synthesized?

Answer 9

In mast cells and neurons (not re-uptaken)

Question 10

Early phase reactants act on which receptor?

Answer 10

H1 receptor

Question 11

H1 receptor has two pathways what are they?

Answer 11

G-alpha q

G-beta-gamma

Question 12

Where are H1 receptors found?

Answer 12

Brain
Endothelium
Smooth muscle

Question 13

Where are H2 receptors found?

Answer 13

Gastric mucosa
Mast cells
Brain
Heart

Question 14

What G-proteins do H1 work through?

Answer 14

Gq increasing Calcium

Question 15

What G-proteins do H2 work through?

Answer 15

Gs increasing cAMP

Question 16

What does H1 activation cause?

Answer 16

Pain, itch
Vasodilation
Wakefulness
GI motility
Bronchospasm and secretion

Question 17

What does H2 activation cause?

Answer 17

Gastric secretions
Increased heart rate and contractility
Decreased T cell and Ab formation

Question 18

What are the H1 antagonists?

Answer 18

Diphenhydramine
Chlorpheniramine
Cetirizine
Hydroxyzine

Question 19

What are the H2 antagonists?

Answer 19

Cimetidine
Ranitidine
Famotidine

Question 20

Easy way to remember H1 2nd gen antagonists?

Answer 20

End in -dine

Except promethazine and hydroxyzine

Question 21

What causes the triple response in skin injury?

Answer 21

Reddening: vasodilation
Flare: axonal response
Wheal: vascular permeability

Question 22

Where is histamine constantly being released?

Answer 22

In the brain to keep you awake

Question 23

What do H1 selective drugs cause?

Answer 23

Sleepiness bc they cross BBB

Question 24

What are the non-sedating H1 selective drugs?

Answer 24

1st gen
Loratadine
Cetirizine 
2nd gen
Fexofenidine
Desloratadine

Question 25

What are the H1 selective drugs that cause sleepiness?

Answer 25

Diphenhydramine Chlorpheniramine Cetirizine Hydroxyzine

Question 26

What are the H2 selective drugs used for?

Answer 26

Limited to treatment of dyspepsia (GI acid secretion)

Question 27

What are the H2 selective drugs?

Answer 27

Cimetidine Ranitidine Famotidine

Question 28

What does H1 selective mean?

Answer 28

It is selective for H1 in the periphery not central

Question 29

What does H1 non selective mean?

Answer 29

It affects H1 in brain

Question 30

What does 1st generation and 2nd generation mean?

Answer 30

1st: anti-emetic 2nd: not an anti-emetic

Question 31

H1 first generation antihistamines:

Answer 31

``` Brompheniramine Chlorpheniramine Dimenhydrinate Diphenhydramine Hydroxyzine Promethazine ```

Question 32

What drug is an inhibitor of mast cell degranulation?

Answer 32

Cromolyn sodium

Question 33

How does Cromolyn sodium work?

Answer 33

Blocks mast cell degranulation

Question 34

Why is Cromolyn sodium only a prophylactic?

Answer 34

Because they only block mast cell degranulation they do not reverse it and are slow working