Respiratory Pharmacology

Question 1

• Asthma is a complex disorder characterized by?

Answer 1

• Chronic inflammation of the airways
• Bronchial hyperresponsiveness
• Airflow obstruction

Question 2

• Inflammation of the airways results in?

Answer 2

• Bronchiolar Smooth Muscle Spasm
• Airway Hyperresponsiveness
• Airway Edema
• Increased Mucus Secretion
• These changes result in airflow obstruction

Question 3

Asthma Severity -Symptom Frequency(SF)- Nighttime Awakenings(NA)
Intermittent?
Mild Persistent?
Moderate Persistent?
Severe Persistent?

Answer 3

Intermittent: Symptom frequency-≤2 per week Night time awakenings-≤2 times/month

Mild persistent: SF- >2 but not daily, NA- 3-4 times/month

Moderate persistent: SF- Daily, NA->1 time/week but not nightly

Severe persistent SF- Throughout the day, NA- 4-7 times/week

Question 4

Types of drugs used to treat asthma?

Answer 4

Bronchodilators:
β2 Adrenergic agonists
Anticholinergics
Methylxanthines
Anti-inflammatory Drugs:
Corticosteroids
Release inhibitors
Immunomodulators
Leukotriene modifying agents

Question 5

Name three Inhaled short-acting β2 adrenergic agonists

SABAs

Answer 5

Albuterol
terbutaline,
pirbuterol

Question 6

Inhaled long-acting β2 adrenergic agonists

LABAs

Answer 6

• Salmeterol and formoterol.

Question 7

Inhaled β2 Adrenergic Agonists: MOA

Answer 7

• Bind to and activate β2 adrenergic receptors
on airway smooth muscle cells.
• Activation of β2 receptors stimulates adenylyl
cyclase and increases formation of cAMP.
• cAMP activates protein kinase A which
phosphorylates and inactivates myosin light
chain kinase.
• This results in relaxation of the airway smooth
muscle cells and bronchodilation.

Question 8

Inhaled B2 short acting agonists uses?

Answer 8

• SABAs are the DOC for relief of acute asthma
symptoms and prevention of exercise-induced
bronchospasm.

Question 9

Long acting B2 agonists uses?

Answer 9

• LABAs are combined with inhaled
corticosteroids (ICS) for long-term control in
moderate and severe persistent asthma.
• LABAs shouldn’t be used as monotherapy
for long-term control of asthma as they have
no anti-inflammatory action.
• LABAs are not used in the
treatment of acute symptoms
or exacerbations.

Question 10

β2 AdrenergicAgonists: Adverse Effects?

Answer 10

• Administration of these drug by inhalation
decreases the risk of systemic side effects such
as tachycardia, tremor, and hypokalemia.
• LABAs increase risk of serious asthma related
events (hospitalization, intubation, and
death).

Question 11

Name an Inhaled Short-Acting Muscarinic Antagonists
(SAMAs)?
Name an Inhaled Long-Acting Muscarinic Antagonists
(LAMAs)?

Answer 11

SAMA - Ipratropium

LAMA - Tiotropium

Question 12

Anticholinergics: MOA?

Answer 12

• Inhaled ipratropium and tiotropium block
muscarinic receptors on the airways causing
bronchodilation and reduction of respiratory
secretions

Question 13

Anticholinergics: Uses?

Answer 13

• Ipratropium is less effective than SABAs.
• Ipratropium provides additive benefit to
SABAs in the management of moderate to
severe exacerbations of asthma.
• Ipratropium is the DOC for β-blocker-induced
bronchospasm.
• Tiotropium may be added to ICS for long-term
control of severe persistent asthma.

Question 14

Anticholinergics: Adverse Effects?

Answer 14

• These agents are quaternary ammonium
compounds.
• Low access to the systemic circulation and
systemic adverse effects.
• Minor anticholinergic effects, e.g. xerostomia,
might occur.
• They may be safer than SABAs in patients
with cardiovascular disease.

Question 15

Name a Methylxanthine? MOA? Uses?

Answer 15

• Theophylline
MOA
• Inhibits phosphodiesterase.
• Increase in cAMP evokes bronchodilation
Uses
• Can be given orally or IV.
• Alternative therapy for patients with persistent
asthma.

Question 16

Theophylline: Adverse Effects?

Answer 16

• Largely replaced by β2 agonists and corticosteroids due to narrow therapeutic window, adverse effects, and potential for drug interactions.
• The most common adverse effects are headache, nausea, vomiting, abdominal discomfort, and restlessness.
• At high concentrations: cardiac arrhythmias
and seizures.

Question 17

Anti-Inflammatory Drugs: Corticosteroids?
Inhaled corticosteroids (ICS)?
Systemic corticosteroids?

Answer 17

Inhaled corticosteroids (ICS)
• Beclomethasone, budesonide, flunisolide, and
fluticasone

Systemic corticosteroids
• Prednisolone and dexamethasone

Question 18

Corticosteroids: MOA?

Answer 18

• Glucocorticoids inhibit phospholipase A2 and
inhibit transcription of COX-2, resulting in
reduced formation of leukotrienes and
prostaglandins.
• Prolonged use of SABAs results in β2
receptors desensitization.
• Corticosteroids prevent or reverse this
desensitization.

Question 19

Corticosteroids: Uses?

Answer 19

• ICS are the most effective long-term
control medication in the management of
persistent asthma.
• Oral prednisolone may be added to ICS for
long-term control of severe persistent asthma.
• A short course of systemic corticosteroids is
used for moderate and severe acute
exacerbations of asthma to speed recovery and
to prevent recurrence of exacerbations.

Question 20

Inhaled Corticosteroids: Adverse Effects?

Answer 20

• ICS have lower bioavailability than systemic
corticosteroids: risk of potential adverse
effects is reduced.
• Local adverse effects include oropharyngeal
candidiasis, dysphonia, reflex cough and
bronchospasm.
• Long term use may result in osteoporosis and
cataracts. It may cause deceleration of vertical
growth in children.
• Long term use of systemic glucocorticoids may
result in hypercortisolism and Cushing’s
syndrome.

Question 21

Name 2 Anti-Inflammatory Drugs: Release Inhibitors? MOA?

Answer 21

• Cromolyn
• Nedocromil
MOA
• Act by inhibiting mast cell degranulation, and
prevent both antigen- and exercise-induced
bronchospasm in asthmatic patients.
• Not useful in managing an acute asthma attack,
because they are not bronchodilators.

Question 22

Release Inhibitors: Uses?

Answer 22

• Cromolyn and nedocromil were once widely
used for asthma management, especially in
children, but have now been largely replaced by
other therapies.
• Alternative medications for patients with
mild persistent asthma.
• Also used to prevent exercise-induced
bronchospasm.

Question 23

Release Inhibitors: Adverse Effects?

Answer 23

• Throat irritation, cough, mouth dryness.
• Rarely, chest tightness and wheezing.
• Rare side effects include reversible dermatitis,
myositis, or gastroenteritis, pulmonary infiltration
with eosinophilia and anaphylaxis.

Question 24

Name an Anti-Inflammatory Drugs: Immunomodulator? MOA, use, and AE?

Answer 24

Omalizumab
• Monoclonal antibody.
• Prevents binding of IgE to basophils and mast
cells.
• Used in the management of patients with
severe persistent asthma with evidence of
allergy.
• Anaphylaxis may occur.

Question 25

Anti-Inflammatory Drugs: Leukotriene-Modifying Agents (LTMAs) Name 2 Leukotriene Receptor Antagonists (LTRAs): Name 1 5-Lipoxygenase Inhibitors :

Answer 25

``` Leukotriene Receptor Antagonists (LTRAs) • Montelukast • Zafirlukast 5-Lipoxygenase Inhibitors • Zileuton • All these drugs are taken orally. ```

Question 26

Leukotriene-Modifying Agents: MOA?

Answer 26

• Leukotriene-modifying agents (LTMAs) interfere with the pathway of leukotriene mediators, which are released from mast cells,eosinophils, and basophils.

Question 27

Leukotriene-Modifying Agents: Uses?

Answer 27

• Alternative therapy. • Used for prevention of exercise-induced bronchospasm. • Used in the management of NSAIDexacerbated respiratory disease (NERD).

Question 28

Leukotriene-modifying agents: | Adverse Effects?

Answer 28

• Montelukast: insomnia, anxiety, depression, suicidal thinking. • Zileuton: Hepatotoxicity.

Question 29

Acute exacerbations are managed with | quick relief medications:?

Answer 29

``` • Inhaled short-acting beta-2-adrenergic agonists (SABAs). • Inhaled short-acting muscarinic antagonists (SAMAs). • Systemic corticosteroids. ```

Question 30

``` Long term control differences treating different severity of asthma? Intermittent Mild persistent Moderate persistent Severe persistent ```

Answer 30

Intermittent: No Daily Medications Mild persistent: Low-dose ICS Moderate persistent: Low-dose ICS + LABA OR Medium-Dose ICS Severe persistent: Medium-Dose ICS + LABA OR High-Dose ICS + LABA

Question 31

Define COPD?

Answer 31

• COPD is characterized by chronic, progressive, irreversible obstruction of the airflow. • Smoking is the most important risk factor for COPD. • The three cardinal symptoms of COPD are dyspnea, chronic cough,and sputum production.

Question 32

Bronchodilators used in COPD?

Answer 32

Short-acting β2 agonists (SABAs) and Short-acting Muscarinic antagonists (SAMAs) : Used for symptomatic relief and in management of acute exacerbations of COPD. Long-acting β2 agonists (LABAs) and Long-acting muscarinic COPD antagonists (LAMAs) - Used for long-term control of

Question 33

Corticosteroids Used in COPD?

Answer 33

Fluticasone and budesonide - Used in the long-term management of COPD Oral prednisolone Used in the management of acute exacerbations of COPD

Question 34

Mucolytic Agents Used in COPD?

Answer 34

N-Acetylcysteine • Breaks disulfide linkages in mucus and lowers viscosity.

Question 35

What is Allergic Rhinitis?

Answer 35

• Inflammation of nasal mucosa induced by different allergens. • Characterized by nasal pruritus, sneezing, rhinorrhea, and nasal congestion. • Treatment includes allergen avoidance and pharmacotherapy.

Question 36

Pharmacotherapy of Allergic Rhinitis

Answer 36

* Glucocorticoid nasal sprays * Oral antihistamines * Cromolyn sodium * Montelukast * Nasal Decongestants

Question 37

Glucocorticoids: Uses in Allergic Rhinitis? AE?

Answer 37

``` • Glucocorticoid nasal sprays are the first-line treatment for allergic rhinitis. AE • Local irritation of the nasal mucosa • Nosebleed • Nasal septal perforation • Nasopharyngeal candidiasis ```

Question 38

Name 2 Nasal Decongestants, moa and AE?

Answer 38

• α adrenergic agonists. • Constrict dilated arterioles in the nasal mucosa. • Should be used no longer than 3 days due to risk of rebound nasal congestion.

Question 39

Which two drugs can be used for cough? MOA and AE?

Answer 39

Codeine and dextromethorphan • Suppress cough reflex via a direct action on the cough center in the medulla of the brain. • Adverse effects: constipation and drowsiness. • Dextromethorphan is safer and has lower abuse potential than codeine.