Komiskey 9-27-07 Anti-Asthmatics And Antihistamines-1

Front 1

Treatment for intermittant asthma

Back 1

SABA prn

short-acting beta2 agonist

Front 2

First step to treat persistent asthma

Back 2

low-dose ICS

inhaled corticosteroid

Front 3

alternative to low-dose ICS?

Back 3

cromolyn or montelukast

Front 4

Summarized the step-ups of asthma therapy

Back 4

low-dose ICS --> medium-dose ICS -->
then add LABA (long-acting) or montelukast -->
then try high-dose ICS with LABA or montelukast -->
then add oral systemic corticosteroids

Front 5

Most prescribed drugs (ICS) to treat asthma

Back 5

Budesonide (Pulmicort)
Fluticasone (Flovent)

Front 6

Alternative but not perferred treatment of mild persistant Asthma

Back 6

Cromolyn sodium
Nedocromil (Tilade)

Front 7

Leukotriene modifiers

Back 7

Montelukast - leukotriene recep antagonist
Zafirlukast - leukotriene recep antagonist
Zileuton - blocks leukotriene synthesis by inhibiting 5-lipoxygenase,

Front 8

Adjunctive treatment of adults (12 & older) who have
moderate to severe persistant ALLERGIC asthma

Back 8

Immunomodulators:
Omalizumab (Xolair)

Front 9

Adjunctive treatment of adults (12 & older) who have
moderate to severe persistant asthma

Back 9

Long-Acting Beta2-agonists:
-Salmeterol
-Formoterol
Methylxanthines
-Theophylline

Front 10

multiple anti-inflammatory effects via ∆ gene expression e.g.:

Back 10

1.inhibit phosopholipase A2 --> decrease prostaglandins
2.Decreased cytokine & chemokine production
3.Inhibit the accumulation of basophils, eosinophils & other leukocytes in lung tissue
4.Decrease vascular permeability
5.Enhanced responsiveness of Beta2 receptors

Front 11

corticosteroids can also be given ____ if necessary (higher toxicity) for acute exacerbations or severe asthma

Back 11

orally

Front 12

_____ route for corticosteroids is used for ER visits for asthma attacks &  for Rx of status asthmaticus

Back 12

i.v.

Front 13

Inhaled Corticosteroids: (3)

Back 13

Beclomethasone (QVAR ®)
Budesonide (Pulmicort ®)
Fluticasone (Flovent ®)

Front 14

ICS:
Beneficial effects may be seen w/in when?

Back 14

a week, but  maximal improvement may require months of therapy

Front 15

Oral or I.V. Corticosteroids:

Back 15

Prednisone or Prednisolone (generic)(etc.)
Rx: acute asthma exacerbations & chronic severe asthma.

Front 16

Oral or I.V. Corticosteroids:
Adverse effects:

Back 16

: suppression of growth & adrenal axis; cataracts

Front 17

Rx of Chronic Asthma:
In Persistent or Chronic Asthma:*
Start:

Back 17

1. Inhaled corticosteroid (dose depends on severity)
If needed add
2. Long acting beta2 agonists
tachycardia and hypokalemia at 4-5 times recommended

Front 18

Rx of Chronic Asthma:
In Persistent or Chronic Asthma:*

Other options:

Back 18

3. Cromolyn sodium or Nedocromil
4. Leukotriene inhibitors
- can be taken orally (better adherence, esp. in kids)
- less efficacious than corticosteroids

Front 19

Long acting beta2 agonists

Back 19

Salmeterol (Serevent ®)
Formoterol (Foradil ®)

Front 20

Long acting beta2 agonists
quick facts

Back 20

highly lipid soluble (don’t diffuse away from 2R’s)
bronchodilation lasts >12 hrs
Typically added to drug regimen when a corticosteroid is “not enough” to control asthma(not used in place of a corticosteroid)

Front 21

Why use Formoterol
Salmeterol over albuterol?

Back 21

duration of action is much longer (12 hrs vs 4-8 hrs)

Front 22

Degranulation Inhibitors

aka Mast Cell Stabilizers

Back 22

Cromolyn sodium (Intal ®)
Nedocromil (Tilade ®)

Front 23

Degranulation Inhibitors
quick facts

Back 23

Inhibits release of cell mediatorsfrom eosinophiles & lung mast cells(mechanism ???)
Given by inhalation
Less potent than corticosteroids
Must be taken several times a dayor before an “attack”
Nedocromil is approved for pts 12 yrs & older; 15-20 % complain of unpleasant tasteCromolyn is approved for all ages

Front 24

Cromones: MOA

Back 24

inhibition of mast cell degranulation
inhibition of IL-4 induced IgE synthesis
inhibit the activation of inflammatory cells (in vitro)
local anesthetic effect
Promotes relaxation via interfering with Ca++ influx into the cell

Front 25

Leukotriene Synthesis Inhibitor

Back 25

Zileuton (Zyflo ®)
Montelukast (Singulair ®)*
Zafirlukast(Accolate ®)

Front 26

Zileuton (Zyflo ®)

facts

Back 26

- inhibits 5-lipoxygenase enz. - blocks formation of leukotrienes from arachidonic acid
- 4 times a day dosing
- occasional liver toxicity

Front 27

All three LK pathway inhibitors can be used to treat “aspirin _____- (but it is best to just avoid NSAIDs)

Back 27

allergy”

Front 28

Montelukast (Singulair ®)*
points about this drug

Back 28

- oral route (better compliance in kids)
- 1 time per day dosing (night time -asthma is more common at night) - approved for children 6 yrs & older
- good for exercise induced asthma

Front 29

Zafirlukast(Accolate ®)

points

Back 29

- 2 times per day dosing
- patients must be 12 yrs & older
- liver tests needed

Front 30

Rx for Acute Asthma and prevention of exercise induced asthma

Back 30

Short acting beta2 agonists

Front 31

SABAs are The most effective drugs for _____

Back 31

bronchodilation

Front 32

SABAs with Half lives of 6 hrs or less

Back 32

Albuterol (Proventil, Ventolin ®)
Terbutaline (Brethine, Bricanyl ®)

Front 33

Mechanism of SABAs:

Back 33

stimulate AdCyl -->
increase cAMP -->
decrease [Ca]I

Front 34

Adverse effects of SABAs

Back 34

tachycardia, skeletal muscle tremor

Front 35

If a beta2 efficacy is “lost” over time (destabilization of asthma), another drug such as an ____

Back 35

anti-inflammatory drug

Front 36

mechanism of theophylline

Back 36

Adenosine R antagonist
PDE inhibitor (toxic doses)
Bronchodilation & anti-inflammatory actions

Front 37

Vagal mediated broncho-_________ contributes to asthma in some patients (M3)

Back 37

constriction

Front 38

Ipratropium bromide (quaternary)
drugs: metered dose and metered dose with albuterol

Back 38

Atrovent ® - metered dose
Combivent ® - metered dose combo w/albuterol
Take every 4-6 hrs

Front 39

Muscarinic Antagonists for COPD

Back 39

Tiotropium (Spiriva®) –for COPD
24 hr duration of action
Slow dissociation from receptor
Capsule inhaled dose
Handihaler device(dry powder; no flurocarbons)

Front 40

Beta Agonists for acute asthma treatment

Back 40

Albuterol, levalbuterol, pirbuterol, bitolterol, isoproterenol, & epinephrine

Front 41

PDE inhibitors for acute asthma treatment

Back 41

Theophylline

Front 42

Anticholinergics for acute asthma treatment

Back 42

Ipratropium

Front 43

Inhaled beta-2 adrenergics

Back 43

salbutamol / Ventolin
fenoterol / Berpotec
procaterol / Pro-Air

Front 44

Cromoglycate / chromolyn

Back 44

inhaled nedocrimil sodium (Tilade)
Oral Ketotifen (Zaditen)

Front 45

Inhaled Steroids

Back 45

beclovent, budesonide

Front 46

Oral Steriods

Back 46

prednisone

Front 47

Anti-IgE Antibody drug

Back 47

Omalizumab (Xolair ®)

Front 48

What does Omalizumab (Xolair ®)
do?

Back 48

- Antibody targeted against the portion of IgE that binds to receptors on mast cells & other inflammatory cells (see next slide)
Lowers free circulating IgE & prevents antigen induced degranulation

Front 49

A multi week treatment w/ Omalizumab can lower plasma IgE & reduce______

Back 49

responses to antigens


Down regulation of FcRI binding sites on immune cells also occurs

Front 50

Omalizumab
humanized chimeric monoclonal antibody against high-affinity receptor-binding domain of human ____.
acts by complexing free ___, preventing its binding to effector cells.

Back 50

IgE

IgE

Front 51

enzyme converting histidine to histamine

Back 51

histadine decarboxylase

Front 52

H1 histamine receptor Found on ___-

Back 52

smooth muscle, endothelium, and central nervous system tissue

Front 53

H1 histamine receptor Activation results in vasodilatation, _____, smooth muscle activation, and separation of endothelial cells.

Back 53

bronchoconstriction

Front 54

H2 histamine receptor
Found on _____

Back 54

parietal cells

Front 55

H3 histamine receptor Found in the ______

Back 55

central nervous system

Front 56

H4 histamine receptor Recently discovered in different parts of the body including organs of the digestive tract, basophils, and ________ cells

Back 56

bone marrow

Front 57

When Histamine is Stimulated, what symptoms?

Back 57

Allergic Rhinitis

Allergic Bronchitis

Allergic Conjunctivitis

Allergic Dermatitis

Anaphylaxis,

Front 58

Stimulation of H2 Receptors causes what?

Back 58

Incr Gastric Acid and Pepsin --> Abdominal Pain
Incr Rate & Force of Myocardial Contraction --> tachycardia
Incr Vasodilation --> Hypotension, Flushing, HA

Front 59

H1 Type of receptor

Back 59

G-protein coupled, linked to intercellular Gq, which activates phospholipase C

Front 60

H2 type of receptor

Back 60

G-protein coupled, linked to intercellular Gs

Front 61

H3 type of receptor

Back 61

G-protein coupled, possibly linked to intercellular Gi

Front 62

H1 antagonists are really called ______ agonists

Back 62

inverse

b/c when they bind to receptor, they put it in an inactive state.

Front 63

H1 receptor Couples to G__?–protein to activate phospholipase C; inc. inositol triphosphate (IP3 ), diacylglycerol (DAG)

Back 63

q

Front 64

First Generation Antihistamines
Groups

Back 64

Ethylenediamines
Ethanolamines
Alkylamines
Piperazines
Tricyclics

Front 65

Oldest and most effective antihistamine on the market


Also inhibits the reuptake of serotonin, which led to the search for viable antidepressants with similar structures (prozac)

Back 65

Diphenhydramine (Benedryl)


(Ethanolamine)

Front 66

Ethanolamines:
Exhibits fewer side effects than most antihistamines
Widely used as an antiprurtic (stops itching)

Back 66

Clemastine (Tavist)

Front 67

Ethanolamines:
Anti-emetic (anti nausea)
Also causes strong sedation
Readily crosses the BBB

Back 67

Dimenhydrinate (Dramamine)

Front 68

Ethanolamines (4)

Back 68

Clemastine (Tavist®)
Dimenhydrinate (Dramamine®)
Diphenhydramine (Benadryl®)
Doxylamine (Unisom®)

Front 69

Second Generation Antihistamines More selective for H1 receptors where?

Back 69

peripheral

Doesn't cross the BBB like 1st generation

Front 70

examples of Second Generation Antihistamines

Back 70

loratadine [Claritin]
cetirizine (Zytric) #12
mizolastine

Front 71

Examples of "Next” Generation Antihistamines

Back 71

Fexofenadine
Desloratadine
Levocetirizine

Front 72

Piperidines:
Highly selective for H1 where?

Back 72

peripheral

Front 73

Piperidines Have no significant _____ effects

Back 73

anticholinergic

Front 74

Third generation H1-receptor antagonists

Back 74

Levocetirizine (Zyzal)
Deslortadine (Clarinex)
Fexofenadine (Allegra)

Front 75

What 3rd gen H1-receptor blocker?
It is the active metabolite of Lortadine
Even though it is thought to be more effective, there is no concrete evidence to prove this

Back 75

Deslortadine (Clarinex)

Front 76

Which 3rd gen H1 receptor blocker?
It was developed as an alternative to Terfenadine
It was proven to be more effective and safe

Back 76

Fexofenadine (Allegra)

Front 77

Ethanolamine to know for test

Back 77

Diphenhydramine

Front 78

Piperidines to know for the test

Back 78

Fexofenadine

Front 79

Others to know for the test

Back 79

Loratadine, Cetirizine

Front 80

Common side effects of 1st gen drugs?

Back 80

sedation, dizziness, tinnitus, blurred vision, euphoria, lack of coordination, anxiety, insomnia, tremor, nausea and vomiting, constipation, diarrhea, dry mouth, and dry cough

Front 81

Common side effects of 2nd gen drugs?

Back 81

drowsiness, fatigue, headache, nausea and dry mouth

Front 82

H4 receptors Couples with G__?-protein to inhibit adenylyl cyclase
Just recently discovered

Back 82

i

Front 83

The H4 receptor is highly expressed in peripheral blood leukocytes and ______ tissue, making this receptor a potentially interesting target in allergic and inflammatory diseases

Back 83

intestinal