L31 Drugs Used in The Treatment of Respiratory Diseases→↑↓

Question 1

Name, Type MoA and Side effects of Bronchodilators

Answer 1

B2-Agonists (a first line drug in asthma therapy)
→ Short-acting b2-agonists (SABA), e.g. →→Salbutamol (Albuterol) and
Terbutaline
Benefits
→Rapid relief of symptoms and
suitable for use in exacerbations
→Long-acting b2-agonists (LABA), 
→→e.g. Salmeterol and Formoterol
Benefits
→Improved lung function
→ Less symptoms
→ Less nocturnal asthma
→ Decreased rescue medications
→ Steroid-sparing in adults and
children
→ Reduced number of exacerbations
when added to inhaled steroid
→ Improved quality of life

MoA
B2 bind to b2 receptor which is G protein couple recetpor which link to adenylyl cyclase (AC) which converts ATP to cAMP lead to muscle relaxation.
↓ vascular permeability and oedema
↑ mucociliary clearance due to ↑ ciliary beat frequency
Marked protection against all non-specific bronchoconstrictor
stimuli such as methacholine (an inhaled drug that causes mild
narrowing of the airways in the lungs)

Common side (adverse) effects – tremor, tachycardia, hypokalaemia and the development of the followings:
→Desensitization (tachyphylaxis, tolerance)

→↓ b2AR responsiveness - due to uncoupling

→Down-regulation of b2-receptors

↓ b2AR numbers - due to internalization, degradation
→Phosphodiesterase inhibitors (methylxanthines; a second line
of drug in asthma therapy)
→→ e.g. Theophylline and Aminophylline

→↑cAMP →smooth muscle relaxation
→ block adenosine receptors → ↓contraction of airway smooth
muscle & ↓ histamine release

Side (adverse) effects: given orally
→ ↑ CNS → nervousness
→ ↑ CVS →(+) chronotropic & inotropic
→ ↑ GI secretion (nausea, vomiting)
→ Kidney → diuresis (↑ urine excretion)

→Muscarinic Receptor Antagonists (Anticholinergics)
→→Short-acting muscarinic receptor antagonists (SAMA), e.g. Ipratropium
→→Long-acting muscarinic receptor antagonists (LAMA), e.g. Tiotropium

MOA: inhibit Ach-mediated bronchospasm by binding to all muscarinic
receptors
→ ↓vagal cholinergic tone
→ ↓mucus secretion

Side (adverse) effects: few by inhalation
→ Dry mouth
→ Irritating cough

Question 2

Name, Type MoA and Side effects of Leukotriene Pathway Modifiers

Answer 2

Cysteinyl Leukotriene Receptor Antagonists, e.g. Montelukast (Singulair
) and Zafirlukast

MOA: inhibit LTC 4 & LTD 4-mediated bronchospasm by binding to LTC 4 & LTD 4 receptors

5-Lipoxygenase Inhibitors - e.g. Zileuton
⎼ MOA: prevent synthesis of leukotrienes

Side (adverse) effects:
→ Nausea
→ Diarrhea
→ Headache

Question 3

Anti-inflammatory Drugs

Answer 3

Inhaled
→ Budesonide 
→ Fluticasone
→ Mometasone
→ Ciclesonide
Oral
→ Prednisolone
→Prednisone
→ Hydrocortisone – systemic (i.v.)

Side (adverse) effects: oral >> inhaled steroids
→ Osteoporosis
→ Cataracts
→ Glucose intolerance
→ Depressed immunity
→ Cushingoid changes

Question 4

Anti-allergic Drugs

Answer 4

Mast cell stabilisers: e.g. cromolyn sodium (= sodium cromoglycate), nedocromil sodium
MOA:
→inhibit mast cell degranulation and activation
→ depress the exaggerated neuronal reflexes triggered by irritant
receptors in the airways

Side (adverse) effects:
→ Dry mouth
→ Irritating cough

Question 5

Anti-IgE Monoclonal Antibody

Answer 5

Omalizumab
MOA: the reductions in circulating levels of IgE leads to downregulation in IgE receptors (FceRI) on mast cells,
basophils and dendritic cells, thus preventing the release of inflammatory mediators

Side (adverse) effects: anaphylaxis, the severe (and sometimes fatal) systemic reaction to an allergen

Question 6

Anti-IL-5 Therapy Agents

Answer 6

Mepolizumab : humanized IgG1 mAB against IL‐5
→ Binds to IL‐5 ligand
→ Prevents IL‐5 from binding to its receptor

Reslizumab : humanized IgG4 mAB against IL‐5
→ Binds to IL‐5 ligand
→Prevents IL‐5 from binding to its receptor

Benralizumab
humanized Ab targeting the α‐chain of IL‐5 receptor
→ Binds to IL‐5 receptor
→ Causes apoptosis of eosinophils and basophils

Question 7

Anti-IL-4 Therapy Agent

Answer 7

Dupilumab : a fully human IgG4 mAB directed against the α subunit of the interleukin (IL)‐4 receptor (IL‐4Rα)

Side (adverse) effects:
→ Headache
→ Diarrhea
→ Local reaction

Question 8

Combination Therapy

Answer 8

Rationale: glucocorticoids reverse and restore b2AR function and number in lung in vivo

Inhaled corticosteroid (ICS) in combination with inhaled long-acting b2-agonist (LABA)

Question 9

Treatment for Asthma

Answer 9

Controllers – medications taken daily on a long-term basis
→Inhaled glucocorticoids (ICS), e.g. budesonide, fluticasone
→ Leukotriene pathway modifiers, e.g. montelukast
→Long-acting inhaled anticholinergics (LAMA), e.g. tiotropium
→ Inhaled corticosteroid (ICS) in combination with long-acting inhaled
b2-agonists (LABA), e.g. fluticasone/salmeterol, budnesonide / formoterol
→ Mast cell stabilisers, e.g. cromolyn sodium
→ Sustained-release theophylline
→ Anti-IgE monoclonal antibody or other anti-cytokine biologics

Relievers – medications used on an as-needed basis
→ Short-acting inhaled
b2-agonists, e.g. salbutamol or ICS-formoterol in combination (first line)
→ Inhaled anticholinergics, e.g. ipratropium

Question 10

Drugs Provoke Asthma

Answer 10

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs, e.g.
ibuprofen)

Beta-adrenergic receptor antagonists (blockers): e.g. propranolol
Through blockade of b2-receptors

Question 11

COPD: Medication (I)

Answer 11

Bronchodilators: to induce bronchodilation
→b2-agonists
Salbutamol (short-acting)
Salmeterol and formoterol (long-acting)
Indacaterol (Onbrez; ultra long-acting)

→Muscarinic receptor antagonists (anticholinergics)
Ipratropium (short-acting)
Tiotropium (long-acting)
Aclidinium (Tudorza Pressair ; ultra long-acting)
Glycopyrronium (Seebri Breezhaler ; ultra long-acting)

Anti-inflammatory drugs: to decrease inflammatory response
→ Glucocorticoids
→ Selective PDE4 inhibitor: e.g. roflumilast (Daxas)
→Theophylline

Question 12

COPD: Medication (II) Dual therapy

Answer 12

→ Anticholinergics /b2-agonists
Ipratropium/salbutamol (Combivent) (SAMA + SABA)
Umeclidinium/vilanterol (Anoro Ellipta) (LAMA + LABA)
Glycopyrronium/indacaterol (Ultibro Breezhaler)
Aclidinium/formoterol (Duaklir Genuair)

→Glucocorticoids /b2-agonists (ICS + LABA)
Budesonide/formoterol (Symbicot)
Fluticasone/salmeterol (Seretide)
Fluticasone/vilanterol (Relvar/Breo Ellipta)
Fluticasone/formoterol (Flutiform)

Question 13

COPD: Medication (III) Triple therapy

Answer 13

(glucocorticoids / anticholinergics /2-agonists; ICS + LAMA + LABA)
→ Beclometasone/glycopyrronium/formoterol (Trimbow)
→ Fluticasone/umeclidinium/vilanterol (Trelegy Ellipta)
→ Budesonide/glycopyrrolate/formoterol (Breztri AerosphereTM)

Question 14

Types of Drugs to Treat Cough

Answer 14

Antitussives

Expectorants

Mucolytics

Question 15

Name MoA and Adverse effect Antitussives

Answer 15

Codeine and Noscapine
Strongly effective cough suppressant

Use for dry cough
MoA: suppress the cough reflex through
direct action on the cough centre in the medulla

Side effects: dry mouth, constipation, nausea, respiratory depression and dependence

Dextromethorphan
Mechanism of action: selectively depresses the cough center in the medulla

Side effects are mild and rare:
→ dizziness
→ drowsiness
→ nausea

Question 16

Name MoA and Adverse effect Expectorants

Answer 16

Used to assist in the removal of secretions or exudates from the trachea, bronchi, or lung

Mechanism of action:
→Stimulate the mucin secreting cells to hyperactively produce mucin,
which is thinner with a high water content
→ The increased volume of thinner mucin helps to stimulate coughing
e.g. guaifenesin, potassium iodide

Question 17

Name MoA and Adverse effect of Mucolytics

Answer 17

reduce the viscosity of bronchial secretions
N-acetylcysteine

Mechanism of action:
 Breaks the disulphide bonds cross-linking mucus glycoprotein molecules,
thus making the mucin thinner and more easily transported out of the lungs

In Bronchitis: thick sputum with polysaccharide fibres
⎼ Other mucolytics:
→ Carbocisteine – similar to NAC
→ Bromhexine – disrupts the structure of acid mucopolysaccharide fibres
in sputum, causing it to become less viscous

Question 18

Drugs for Allergic Rhinitis

Answer 18

H1 receptor antagonists (also known as H1 Antihistamines)

1st generation (sedative): cross the blood brain barrier
e.g. chlorphenamine (chlorpheniramine; Piriton)
diphenhydramine (Benadryl)
Side effects: drowsiness, dizziness, hypotension and dry mouth

2nd generation (non-sedative): work peripherally
→e.g. cetirizine (Zyrtec)
→loratadine (Claritin)
→fexofenadine (Telfast)

Question 19

Decongestants

Answer 19

Drugs that reduce congestion of nasal passages, which in turn open clogged nasal passages and enhances drainages of the sinuses

phenylephrine (a selective a1-adrenergic agonist)

Mechanism of action: constricts dilated arterioles in the nasal mucosa & reduces airway resistance

pseudoephedrine – a sympathomimetic

Question 20

Other Classes of Drugs

Answer 20

Combination therapy (H1 antihistamine-pseudoephedrine)

Glucocorticoids
e.g. beclomethasone (nasal sprays)

Anti-allergic mast-cell stabilisers
e.g. cromolyn sodium (intranasal)