Pb&t Integrative Inflammation Pharmacology: Asthma

Front 1

COPD is irreversible, clinically showing as emphysema or chronic bronchitis. Main cellular response is

Back 1

neutrophilic and monocytic
(neutrophils and resident macrohages release proteinases, particularly matrix metalloproteinases.

Front 2

Main cellular response of astma is:

Back 2

CD4 T lymphocytes
B lymphocytes
mast cells
eosinophils

Front 3

Beta 2 adrenergic receptors are activated by epinephrine which is secreted by the adrenal medulla and causes

Back 3

bronchodilation

Front 4

M3 receptors in airway smooth muscle when stimulated by acytelcholine can cause

Back 4

bronchoconstriction

Front 5

NANC fibers release neuropeptides including:
Neurokinin A, calcitonin gene related peptide, substance P, bradykinin, tachykinin and neuropeptide Y
All of which cause

Back 5

bronchoconstriction

Front 6

NANC fibers release neuropeptides including:
Nitric oxide and Vasoactive intestinal polypeptide (VIP)
All of which cause:

Back 6

bronchorelaxation

Front 7

_____ _______ Is a marker of the intensity of airway inflammation, and measurements have been used to assess the severity of asthma to titrate therapy accordingly.

Back 7

Nitric Oxide

Front 8

Inhaled corticosteroid use in COPD

Back 8

Is not a statistically significant benefit

Front 9

Cytokines produced by CD4 Th1 cells

Back 9

INF y
IL 2
TNF a

Front 10

Cytokines produced by CD4 Th2 cells

Back 10

IL4
IL5
IL6
IL9
IL13

Front 11

What type of CD4 Th cells guide the immune response towards a cellular response involving Th adn Tc cells?

Back 11

Th1

Front 12

What type of CD4 Th cells guide the immune response towards a humoral response based on ab production by B cells?

Back 12

Th2

Front 13

Th1 or Th2 predominates in Asthma?

Back 13

Th2

Front 14

Hypersensitivity vs Hyperreactivity
How do they each shift the stimulus response curves?

Back 14

Hypersensitivity- normal response at abnormally low levels of stimuli, possibly due to increase activity of mosin light chain kinase in asthma patients (left shift)

Hyperreactivity-exaggerated response at normal to high levels of stimuli. (upward shift)

Front 15

IL 4 in atopic patients can causes

Back 15

B cells to produce exaggerated amts of IgE ab directed against the allergen

Front 16

IgE ab bind to high affinity IgE receptors on mast cells, and crosslinking of the IgE receptors upon re-exposure to the allergen causes

Back 16

mast cell degranulaion

Front 17

IL-13 can cuse a type IV hypersensitivity rxn causing

Back 17

goblet cell hyperplasia
increased mucus production
Smooth muscle hyperresponsiveness

Front 18

Exposures to TB, viruses, siblings and day care w/in 6mo of life are associated with a _________ in incidence of asthma.

Back 18

decrease the incidence of asthma

(hygeine hypothesis)

Front 19

Activated Th2 cells bind and activate B cells via, They also produce ____ and ____ which induce B cell transformation into IgE producing plasma cells.

Back 19

CD40 on the B cell surface

IL4 and IL13

Front 20

Two broad classes of pharma agents to treat asthma

Back 20

Relievers (bronchodilators) and Controllers (antiinflammatories)

Front 21

Relievers (bronchodilators) or Controllers (antiinflammatories)
Methylxanthines

Back 21

Both

Front 22

Relievers (bronchodilators) or Controllers (antiinflammatories)
Inhaled Corticosteroids, cromolyns, leukotriene pathway modifying agents

Back 22

Controllers (anti-inflammatories)

Front 23

Relievers (bronchodilators) or Controllers (antiinflammatories)
Ipratropium
Tiotropium
Epinephrine
Isoproterenol
Isoetharine
Metaproternol
Terbutaline
Albuterol
Levabuterol
Pirbuerol
Bitolterol
Formoterol
Salmeterol

Back 23

Relievers (bronchodilators)

Front 24

Relievers (bronchodilators) or Controllers (antiinflammatories)
Anticholinergics and Beta-adrenergic agonists

Back 24

Relievers (bronchodilators)

Front 25

Relievers (bronchodilators) or Controllers (antiinflammatories)
Ipratropium
Tiotropium

Back 25

Relievers (bronchodilators)
Anticholinergics

Front 26

Relievers (bronchodilators) or Controllers (antiinflammatories)

Epinephrine
Isoproterenol
Isoetharine
Metaproternol
Terbutaline
Albuterol
Levabuterol
Pirbuerol
Bitolterol
Formoterol
Salmeterol

Back 26

Relievers (bronchodilators)
beta adrenergic agonists

Front 27

How do Anticholinergics work?

Back 27

antagonists at muscarinic receptors on airway sm muscle and glands leading to decrease bronchoconstriction.

Front 28

How do beta adrenergic agonists work?

Back 28

Agonists at beta adrenergic receptors on airway smooth muscle, act through a stimulatory G protien (Gs ie cAMP) to cause sm muscle relaxation and broncodilation.

Front 29

How do methylxanthines work?

Back 29

nonselective phosphodiesterase inhibitors the prevent the degredation of cAMP, and act as adenosine receptor antagonists; result is sm muscle relaxation and bronchodilation.

Front 30

How do inhaled corticosteroids work?

Back 30

Inhibit COX-2 action and prostiglandin biosynthesis by inducing lipocortins, activating endogenous anti-inflammatory pathways.

Front 31

How do cromolyns work?

Back 31

Inhibit chloride ion transport , which in turn affects calcium gating to prevent granule release, possibly decreasing mast cell response to inflammatory stimuli.

Front 32

Eosinophils are stimulated by ___ ___ and _______ produced by Th2 cells and mast cells

Back 32

IL3
IL5
GM-CSF

Front 33

How are eosinophils recruited to the airway from the blood stream?

Back 33

Bind to adhesion molecules such as VCAM 1 and by following chemokine gradients.

Front 34

Once recruited to the airway, what do eosinophils do?

Back 34

Release lipid mediators, secrete cytotoxic granules, and release cytokines and chemokines to attract other inflammatory cells

Front 35

List five substances released by eosinophils

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Major Basic Protein
Eosinophilic cationic protein
Eosinophil peroxidase
Eosinophil derived neurotoxin
Matrix metalloproteinases

Front 36

Antigen Presenting Cells

Back 36

Macrophages
B cells
Dendritic cells
Eosinophils (pg 830 Golan)

Front 37

What produces the following?
IL1 IL2 IL3 IL4 IL5 GM-CSF, TNFa, proteases, proteoglycans.
When?

Back 37

Mast cells
4-6 hourse after exposure to allergen

Front 38

What/Where are FcεRI receptors?

Back 38

High affinity IgE receptors on mast cells

Front 39

Preformed inflammatory mediators released from mast cells.
Mast cell degranulation acutely causes

Back 39

PAF, arachidonic acid, leukotriense, prostiglandin D2

Bronchoconstriction

Front 40

SRS-A (slow reacting substances of anaphylaxis)

Back 40

Original name of leukotrienes.
Leukotrienes have a slower, but more powerful and sustained effect than that of preformed mediators.

Front 41

_____________ __ is 1000x more potent than histamine in producing bronchoconstriction

Back 41

Leukotriene D4

Front 42

Anti-immunoglobulin E antibodies

Back 42

Omalizumab
(injections every 2-4 weeks, very costly, decreasing quantity of circulating IgE, affects both early and late phase asthmatic responses to challenge by inhaled allergen.)

Front 43

Ipratropium bromide is derived from atropine but is less

Back 43

absorbed, leading to minimized adverse effects (nausea, dry mouth.)

Front 44

What type of adverse effect are found due to anticholinergic drugs (Ipratropium Br and Tiotropium)?

Type of drug?

Back 44

Mild effects

These drugs are both quaternary ammonium salts

Competative antagonists at muscarinic acetylcholine receptors (M3)

Front 45

Long acting anticholinergic recently approved for COPD treatment.
Why is it long acting?

Back 45

Tiotropium

Long acting because of its slow dissociation from M1 and M3 receptors.

Front 46

Beta2 adrenergic stimulation of sm muscle leads to relaxation...so beta agonists....

Back 46

Bronchorelaxation...duh

Front 47

What epinephrine and where does it bind?

Back 47

Nonselective adrenergic agonist that binds to alpha, beta1 and beta2 receptors.

Front 48

Beta 1 receptors are also found in the heart, therefore, a side effect of epinephrine is...

Epinephrine causes________ via alpha receptors

Back 48

tachycardia, palpitations and potenial arrhythmias.

peripheral vasoconstriction leading to HTN

Front 49

Slightly more selective than epinephrine, isoproterenol targets ____ ____ receptors, but ideally we'd like to target only _____.

Back 49

Beta 1 and 2

Beta 2

Front 50

Beta 2 adrenergic receptors, found in smooth muscle of the airway, are also found in _______ _______ _________ , so beta 2 drugs can cauase a tremor

Back 50

Peripheral skeletal muscle

Front 51

beta 2 selective beta adrenergic agonists bind to beta 2 adrenergic receptors 2-400x more strongly than beta 1 receptor. The consequence of this is:
List the 4 drugs

Back 51

significantly fewer cardiac events

Albuterol
Terbutaline
Pirbuterol
Bitolterol

Front 52

Peak effect of beta2 adrenergic agonists? Duration?

What two drugs can be used as long acting beta agonists?

Back 52

30-60 min
4-6 hours

Formoterol
Salmeterol

Front 53

Two methylxanthines, theophylline & aminophylline, work via inhibition of phosphodiesterases III and IV via

Back 53

prevention of cAMP degredation (ie sm muscle relaxation, decreased intracellular Ca++, increased membrabe K+ conductance, and decreased myosin light chain kinase activity)

**They are bronchodilators and anti-inflammatory agents**

Front 54

Adverse effects of theophylline:
Susceptible to what type of drug-drug interactions?

Back 54

Tachycardia, psychomotor agitation, gastric acid secretion, and diuresis.

With P450 inhibitors

Front 55

Corticosteroids decrease the transcription of genes coding for many ....

Back 55

Proinflammatory proteins

(18!!! pg 834-835)

Front 56

Corticosteroids reduce the # of inflammatory cells in the airway, and reduces hyperresponsiveness.
Inhibition of IL-4 and IL-5 markedly reduces the inflammatory response in asthma. Bc IL-4..... and IL-5.....

Back 56

IL-4 typically induces B cell production of IgE

IL-5 is typically an important recruiter of eosinophils

Front 57

Why do the following corticosteroids have increased topical absorption?
Beclomethasone
Triamcinolone
Fluticasone
Budesonide
Flunisolide
Mometsone
Ciclesonide

Back 57

Substitution at the 17 alpha position increases topical absorption. (esp better if inhaled)

Front 58

Allergy antiinflammatory that is less efficacious but more safe than others:
(more effective in kids and young adults, prophylactic therapy in patients with allergic asthma associated with specific triggers)

Back 58

Cromolyns

Front 59

Disodium cromoglycate, and nedocromil are "mast-cell stabilizing agests"

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Cromolyns
(release of mediators of eos, neutros, monos, macros, and lymphocytes is also inhibited)