Pharmacology (Week 2)

Question 1

List some common Beta-2 Agonists

Answer 1

Salbutamol (short-acting - “SABA’s”)
Salmeterol (long-acting - “LABA’s”)
Indacaterol (ultra-long-acting)

Question 2

MOA of Beta-2 Agonists:

Answer 2

Stimulate Beta-2 R’s in smooth muscle –> activates adenylate cyclase –> converts ATP to cAMP –> relaxation –> larger airway –> less resistance

Question 3

Beta-2 Agonists typically used to treat what?

Answer 3

Asthma & COPD

Question 4

Side effects of Beta-2 Agonists:

Answer 4

Overstimulation of Beta-1 and Beta-2 may lead to:

Tachycardia, palpitations, or tremor

Question 5

Contraindications for giving Beta-2 Agonist:

Answer 5

Side effect is tachycardia so be cautious in patients where this would cause a problem:

• severe CAD
• arrhythmia
• aortic stenosis

Question 6

For Asthma, what is the recommended treatment?

Answer 6

Beta-2 Agonists (LABA’s) combined with corticosteroids (because long-term corticosteroid use will upregulate the Beta-2 R’s in lungs.

Question 7

Name a few prototypical anti-cholinergics.

Answer 7

Ipratropium

Long-acting muscarinic antagonists “LAMA” (tiotropium, aclidinium)

Question 8

Explain the MOA of anti-cholinergics.

Answer 8

Antagonizes the muscarinic receptors which prevents bronchoconstriction and reduces secretions.
Ipratropium is non-selective for M1, M2, & M3.
Newer agents are more selective for M3.

Question 9

How are anti-cholinergic drugs administered?

Answer 9

Inhalation.

They do not readily cross from alveoli into blood so ont much systemic absorption.

Question 10

When are anti-cholinergics indicated?

Answer 10

Mostly for COPD (acute exacerbations or chronic use)

Question 11

Contraindications of inhaled anti-cholinergics..

Answer 11

None of major significance

Question 12

Side effects of inhaled anti-cholinergics..

Answer 12

Due to decreased parasympathetic stimulation..

Dry mouth, nose bleeds, nasal irritation.

Question 13

What type of treatment is best for asthma?

Answer 13

Beta-2 Agonists

Question 14

What type of treatment is best for COPD?

Answer 14

Anti-cholinergics..
But often anti-cholinergics will be combined with Beta-2 Agonists.
Sometimes ICS ( Inhaled Corticosteroids) is added and this is called “triple therapy”

Question 15

Name some prototypical Leukotriene Receptor Antagonists (LTRA’s).

Answer 15

Montelukast

Zafirlukast

Question 16

Explain the MOA of Leukotriene Receptor Antagonists.

Answer 16

Oral administration.
Blocks the LT1 Receptor (in lipoxygenase pathway)
–> Inhibits Bronchoconstriction and inflammation.

Question 17

What are Leukotriene Receptor Antagonisits indicated for?

Answer 17

Used for asthma as a chronic and prophylactic medication (not for acute exacerbations).

Question 18

List some side effects of LTRA’s.

Answer 18

headache, vomiting, diarrhea, and rarely Churg-Strauss Syndrome (allergic granulomatosis).

Question 19

Name some prototypical Methylxanthines

Answer 19

Caffeine

Aminophylline

Question 20

Explain the MOA of Methylxanthines.

Answer 20

Methylxanthines inhibit phosphodiesterases and therefore prevent cAMP breakdown –> cAMP causes bronchodilation.

Methylxanthines also inhibit adenosine (leading to side effects).

Question 21

What are the indications for Methylxanthines?

Answer 21

As 2nd or 3rd line treatment of asthma & COPD.

Question 22

What are the contraindications for Methylxanthines?

Answer 22

Because cAMP leads to increased contractility and HR, Methylxanthines should be avoided in patients with coronary heart disease.

Question 23

What are some of the side effects of Methylxanthines?

Answer 23

Cardiac: arrhythmias
GI: nausea, vomiting
CNS: headache
Stimulatory effects: seizures, restlessness,

Question 24

What is the significance of Roflumilast?

Answer 24

Similar to Methylxanthines.
Selectively inhibits PDE-4.
(PDE-4 is found in inflam cells)
Roflumilast possesses more anti-inflam effect than methylxanthines.
May be used to treat COPD.

Question 25

List a couple prototypical Inhaled Corticosteroids.

Answer 25

Budesonide, Fluticasone.

Question 26

Explain the MOA of Inhaled Corticosteroids.

Answer 26

Reaches lung alveoli --> gets to nucleus of cells --> inhibit expression of pro-inflam cytokines & COX-2. Also have immunosuppresant effects.

Question 27

When are Inhaled Corticosteroids indicated?

Answer 27

COPD and asthma.

Question 28

What are some unwanted effects?

Answer 28

``` Catabolism: Inhibition of insulin --> increased blood glucose --> mobilization of Ca from bones --> increased muscle breakdown Anti-mitotic Water-retention ``` Thrush Hoarseness Sore throat Osteoporosis

Question 29

When would prednisone be used?

Answer 29

Only in severe asthma cases because it causes lots of side effects. (It is an oral medication).

Question 30

List the targets of drug therapy for asthma and COPD.

Answer 30

Bronchoconstriction Inflammation of airways Mucous plugs Remodelling

Question 31

Which drugs are bronchodilators?

Answer 31

Beta-2 Agonists (via adrenergic sm m relaxation) Anti-cholinergics (via decreased PSNS stimulation) Methylxanthines (via PDE inhibition & increased cAMP)

Question 32

What is omalizumab and how does it work?

Answer 32

It is a monoclonal antibody. | Prevents IgE from binding to allergen.

Question 33

What drugs are best for controlling the progression of disease in asthma (ie. not the main ones used for relieving symptoms, but just controlling progression).

Answer 33

Inhaled corticosteroids