Respiratory Pharmacology Flashcards
• Asthma is a complex disorder characterized by?
- Chronic inflammation of the airways
- Bronchial hyperresponsiveness
- Airflow obstruction
• Inflammation of the airways results in?
- Bronchiolar Smooth Muscle Spasm
- Airway Hyperresponsiveness
- Airway Edema
- Increased Mucus Secretion
- These changes result in airflow obstruction
Asthma Severity -Symptom Frequency(SF)- Nighttime Awakenings(NA) Intermittent? Mild Persistent? Moderate Persistent? Severe Persistent?
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
Types of drugs used to treat asthma?
Bronchodilators: β2 Adrenergic agonists Anticholinergics Methylxanthines Anti-inflammatory Drugs: Corticosteroids Release inhibitors Immunomodulators Leukotriene modifying agents
Name three Inhaled short-acting β2 adrenergic agonists
SABAs
Albuterol
terbutaline,
pirbuterol
Inhaled long-acting β2 adrenergic agonists
LABAs
• Salmeterol and formoterol.
Inhaled β2 Adrenergic Agonists: MOA
• 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.
Inhaled B2 short acting agonists uses?
• SABAs are the DOC for relief of acute asthma
symptoms and prevention of exercise-induced
bronchospasm.
Long acting B2 agonists uses?
• 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.
β2 AdrenergicAgonists: Adverse Effects?
• 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).
Name an Inhaled Short-Acting Muscarinic Antagonists
(SAMAs)?
Name an Inhaled Long-Acting Muscarinic Antagonists
(LAMAs)?
SAMA - Ipratropium
LAMA - Tiotropium
Anticholinergics: MOA?
• Inhaled ipratropium and tiotropium block
muscarinic receptors on the airways causing
bronchodilation and reduction of respiratory
secretions
Anticholinergics: Uses?
• 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.
Anticholinergics: Adverse Effects?
• 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.
Name a Methylxanthine? MOA? Uses?
• Theophylline MOA • Inhibits phosphodiesterase. • Increase in cAMP evokes bronchodilation Uses • Can be given orally or IV. • Alternative therapy for patients with persistent asthma.
Theophylline: Adverse Effects?
• 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.
Anti-Inflammatory Drugs: Corticosteroids?
Inhaled corticosteroids (ICS)?
Systemic corticosteroids?
Inhaled corticosteroids (ICS)
• Beclomethasone, budesonide, flunisolide, and
fluticasone
Systemic corticosteroids
• Prednisolone and dexamethasone
Corticosteroids: MOA?
• 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.
Corticosteroids: Uses?
• 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.
Inhaled Corticosteroids: Adverse Effects?
• 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.
Name 2 Anti-Inflammatory Drugs: Release Inhibitors? MOA?
• 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.
Release Inhibitors: Uses?
• 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.
Release Inhibitors: Adverse Effects?
• 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.
Name an Anti-Inflammatory Drugs: Immunomodulator? MOA, use, and AE?
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.
Anti-Inflammatory Drugs: Leukotriene-Modifying Agents (LTMAs)
Name 2 Leukotriene Receptor Antagonists (LTRAs):
Name 1 5-Lipoxygenase Inhibitors :
Leukotriene Receptor Antagonists (LTRAs) • Montelukast • Zafirlukast 5-Lipoxygenase Inhibitors • Zileuton • All these drugs are taken orally.
Leukotriene-Modifying Agents: MOA?
• Leukotriene-modifying agents (LTMAs) interfere
with the pathway of leukotriene mediators,
which are released from mast cells,eosinophils,
and basophils.
Leukotriene-Modifying Agents: Uses?
• Alternative therapy.
• Used for prevention of exercise-induced
bronchospasm.
• Used in the management of NSAIDexacerbated
respiratory disease (NERD).
Leukotriene-modifying agents:
Adverse Effects?
• Montelukast: insomnia, anxiety, depression,
suicidal thinking.
• Zileuton: Hepatotoxicity.
Acute exacerbations are managed with
quick relief medications:?
• Inhaled short-acting beta-2-adrenergic agonists (SABAs). • Inhaled short-acting muscarinic antagonists (SAMAs). • Systemic corticosteroids.
Long term control differences treating different severity of asthma? Intermittent Mild persistent Moderate persistent Severe persistent
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
Define COPD?
• 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.
Bronchodilators used in COPD?
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
Corticosteroids Used in COPD?
Fluticasone and budesonide - Used in the long-term
management of COPD
Oral prednisolone Used in the management of
acute exacerbations of COPD
Mucolytic Agents Used in COPD?
N-Acetylcysteine
• Breaks disulfide linkages in mucus and lowers
viscosity.
What is Allergic Rhinitis?
• Inflammation of nasal mucosa induced by
different allergens.
• Characterized by nasal pruritus, sneezing,
rhinorrhea, and nasal congestion.
• Treatment includes allergen avoidance and
pharmacotherapy.
Pharmacotherapy of Allergic Rhinitis
- Glucocorticoid nasal sprays
- Oral antihistamines
- Cromolyn sodium
- Montelukast
- Nasal Decongestants
Glucocorticoids: Uses in Allergic Rhinitis? AE?
• Glucocorticoid nasal sprays are the first-line treatment for allergic rhinitis. AE • Local irritation of the nasal mucosa • Nosebleed • Nasal septal perforation • Nasopharyngeal candidiasis
Name 2 Nasal Decongestants, moa and AE?
• 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.
Which two drugs can be used for cough? MOA and AE?
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.
