Respiratory System Question And Answers

Respiratory System

Drugs Used In The Treatment Of Bronchial Asthma:

Bronchial asthma is characterized by dyspnea and wheezing due to increased resistance to the flow of air through the bronchi. Bronchospasm, mucosal congestion, and edema result in a narrowing of airways causing difficulty in breathing.

Two main groups of drugs are used to treat:

1. Bronchodilators—to reverse bronchospasm.
2. Anti-inflammatory drugs—to prevent and suppress= inflammatory response.

Read And Learn More: Pharmacology Question And Answers

Bronchial Asthma Classification:

Question 1. Write a short on Bronchial Asthma
Or
Classify Bronchial Asthma
Answer:

1. Bronchodilators:

Sympathomimetics:

• Selective β₂ agonists:
  • Short-acting — Salbutamol, terbutaline
  • Longer acting — Salmeterol, fenoterol, formoterol, pirbuterol, indacaterol

Nonselective agents — Adrenaline, isoprenaline, ephedrine

• Methylxanthines — Theophylline, aminophylline
• Anticholinergics — Ipratropium bromide, tiotropium, atropine

2. Anti  Inflammatory agents:

• LT receptor antagonists — Montelukast, zafirlukast
• Glucocorticoids:
  • Systemic — Glucocorticoids (hydrocortisone, prednisolone)
    Inhalational — Beclomethasone, budesonide, fluticasone, mometasone, ciclesonide
• Mast cell stabilizers — Disodium cromoglycate, nedocromil, ketotifen
• Anti-IgE antibody — Omalizumab
• PDE₄  inhibitor — Roflumilast

Bronchodilators

Question 2. Write a short on Bronchodilators
Or
Short-acting agonists  And Long-acting agonists on Bronchodilators.
Answer:

1. Sympathomimetic drugs: These are potent bronchodilators and are the most useful drugs to relieve bronchospasm.

Sympathomimetic drugs Mechanism of action:

Adrenergic agonists stimulate b₂ -receptors in the bronchial smooth muscles which leads to bronchodilatation.

1. Short-acting β₂-agonists (SABAs):

Salbutamol and terbutaline given by inhalation, are the fastest-acting bronchodilators with peak effect in 10 minutes and action lasts for 3–4 hours.

SABAs Adverse effects: Skeletal muscle tremors, palpitation, and nervousness.

SABAs Uses:

• Selective b₂ -agonists are the most commonly used bronchodilators as they are effective, convenient to use, and relatively safe bronchodilators.
• Available as metered dose inhalers, nebulizer solutions, injections, and also tablets.
• Dose: Salbutamol 100–200 mg inhalation, 1–4 mg oral. Terbutaline 250 mg inhalation, 2.5–5 mg oral.
• The proper technique in using the inhaler should be taught.
• ‘Spacers’ can be used in children and adults who cannot follow the right technique of inhalation.

Salbuyamol And Salmeterol:

Question 3. Difference between Salbutamol and Salmeterol:
Answer:

Long-acting β₂-agonists (LABAs):

• LABAs like salmeterol, are highly lipid-soluble and therefore, long-acting.
• They reach the bronchial smooth muscle and dissolve in their cell membrane in high enough concentrations to be long-acting (>12 hours).
• Formoterol is fast acting and the newer one bambuterol, indacaterol, oladaterol, and vilanterol are ultra-long-acting → given once daily.

LABAs Oral β₂-agonists:

Oral β₂-agonists have higher adverse effects than inhaled ones. Muscle tremors, palpitation, and nervousness can be significant and are used only in small children who cannot use inhalers and have occasional wheezing (1–4 mg 6 hourly).

LABAs Others:

• Adrenaline and isoprenaline produce prompt bronchodilation but they are not preferred due to the risk of adverse effects like palpitation, anxiety, restlessness, and tremors, and in higher doses cardiac arrhythmias.

Status of Sympathomimetics in Bronchial Asthma:

• b₂-agonists are the first-line drugs for the reversal of bronchospasm.
• Long-term use of b₂-agonists may result in tolerance. The b₂-receptors undergo downregulation on continued stimulation by the agonist.

2. Methylxanthines: Theophylline and its derivatives like aminophylline are good bronchodilators.

Methylxanthines Mechanism of Action:

1. Phosphodiesterase (PDE) is the enzyme that degrades cyclic-AMP. Methylxanthines inhibit PDE and thereby increase cAMP levels.
2.  Adenosine induces bronchospasm and stimulates histamine release cels. Methylxanthines are antagonists at adenosine receptors

Methylxanthines Pharmacokinetics:

• Theophylline is well absorbed from the gut, well distributed in the tissues, and metabolized in the liver
• Dose: Theophylline 200–400 mg TDS.
• Aminophylline: 250 mg slow IV over 20 minutes.

Methylxanthines Adverse effects:  Theophylline has a low therapeutic index and may cause many adverse effects:

• Gut –  Gastric irritation, vomiting
• CNS – Insomnia, tremors, kidney diuresis
• Higher doses cause restlessness, delirium, and convulsions.
• Children may develop behavioral abnormalities on prolonged use which should be avoided
• CVS – Palpitation, hypotension, arrhythmias.

Status in bronchial asthma: Theophylline is a second-line drug in bronchial asthma.

• Chronic asthma: Oral theophylline can be used to control mild to moderate asthma. Etophylline (IM) is used to relieve acute attacks. When used over the long term, plasma levels should be monitored.
• Acute bronchospasm:  Deriphylline IM inj. is an alternative to b₂-agonists.
• Apnea in premature infants: Theophylline or caffeine may be used for 1–3 weeks to reduce the duration of episodes of apnea in premature babies.

3. Anticholinergics:

• Atropine derivatives, ipratropium bromide, and tiotropium bromide are given by inhalation and their actions are largely confined to the respiratory tract.
• They block M1 and M3 receptors and are more effective in chronic bronchitis including chronic obstructive pulmonary disease (COPD) and are safe and well-tolerated.
• Unlike atropine, they do not dry up the secretions and hence do not inhibit mucociliary motility.
• As a bronchodilator, the efficacy of ipratropium bromide is lower than b₂-agonists but adds to the bronchodilator effects of b₂-agonists.
• They may also be used as alternatives to b₂-agonists.

Dose: 20–40 mg 3–4 times a day.

4. Tiotropium bromide: 

• Tiotropium bromide is longer acting—for 24 hours.
• Dose: 18 mcg 1 Rotacap OD.

Tiotropium Uses:

• As an adjunct to b₂ agonists particularly in severe bronchospasm and in acute severe episodes. Ipratropium 20–40 mg 2–4 puffs 3–4 times a day or tiotropium 18 mg 1 OD (they are also available in combination with salbutamol).
• As bronchodilators in chronic bronchitis and COPD.

Anti-Inflammatory Drugs

Question 4. Write a short on Leukotriene Antagonists.
Answer:

Leukotriene Antagonists:

• Leukotrienes (LT) are important mediators of inflammation and act on LT receptors, particularly LTB₄.
• Montelukast and zafirlukast are highly selective and competitive antagonists of leukotriene receptors.
• They block the effects of leukotrienes and thereby reduce mucosal edema and relieve bronchospasm.
• They decrease the response to allergens. They inhibit exercise-induced and aspirin-induced bronchospasm.

Leukotriene Antagonists Uses:

• Prophylaxis of mild to moderate asthma as an alternative to inhaled steroids or as add-on drugs.
• The oral route is an advantage, particularly in children.
• They also reduce the dose of the steroid required.
• The bronchodilator effect is additive with b₂-agonists.
• LT antagonists are particularly useful in aspirin-induced asthma as excess production of leukotrienes is thought to be responsible for bronchospasm.
• Montelukast (10 mg) is more commonly used—OD dose.

Leukotriene Antagonists Adverse effects:

• Rare headaches, rashes, and gastrointestinal disturbances can occur.
• Zileuton inhibits leukotriene synthesis by inhibiting the enzyme lipoxygenase but causes hepatotoxicity—hence not preferred.

Glucocorticoids:

Question 5. Write a short on Glucocorticoids.
Answer:

Since inflammation is the primary pathology in bronchial asthma, anti-inflammatory agents provide significant benefits.

Glucocorticoids Mechanism of action:

• Steroids are not bronchodilators.
• They suppress the inflammatory response to antigen–antibody reaction, reduce bronchial hyperactivity and thereby reduce mucosal edema and hyperirritability.
• Glucocorticoids bind to steroid receptors in the cytoplasm, drug–receptor complex moves to the nucleus, binds to DNA and induces the synthesis of specific mRNA, to bring about the effects.

Glucocorticoids Systemic:

• Glucocorticoids may be given systemically in acute episodes if the severity is not controlled by bronchodilators.
• Oral prednisolone is commonly used (dose 30–60 mg/day).
• The onset of response requires about 12 hours.
• In status asthmaticus, glucocorticoids, hydrocortisone, or prednisolone may be given IV.
• The use of systemic steroids should be restricted to short periods only.
• Chronic asthma requires prophylaxis with inhaled steroids.

Steroids for Inhalation:

• Beclomethasone, budesonide, fluticasone, ciclesonide, and mometasone are available as inhalers.
• Inhalational steroids require small doses → lower adverse effects.
• Not effective in acute attacks → only of prophylactic value → prevent episodes of acute asthma, reduce bronchial hyper-reactivity and effectively control symptoms.
• The effect develops after 1 week of treatment.

Side Effects of Inhaled Steroids:

• Hoarseness of voice (by a direct effect on the vocal cords)
• Sore throat and oropharyngeal candidiasis. Rinsing the mouth and throat with water after each use can reduce the incidence of candidiasis and sore throat. HPA axis suppression is generally not seen.
• The use of a ‘spacer’ reduces the adverse effects because the spacer reduces the deposition of the drug in the oropharynx and increases the delivery of the drug to the lungs.

1. Budesonide:

• Advantage—has topical activity and the absorbed portion is rapidly metabolized.
• Dose: 100–400 mcg 2–4 times a day.

2. Fluticasone:

Fluticasone Advantages:

• Poorly absorbed from the gut
• Undergoes high first-pass metabolism. Hence even when swallowed from an inhaled dose, systemic adverse effects are unlikely with fluticasone.
• Dose: 25–100 micrograms twice daily.

3. Ciclesonide:

• Ciclesonide has a unique way of reducing toxicity.
• It is a prodrug and is converted to an active drug in the bronchial epithelial cells.
• If absorbed, the plasma protein tightly binds the active metabolite.
• Such bound drug is unable to bind the glucocorticoid receptors in several
  tissues like the skin, eye, and bone, thereby avoiding toxicity to these structures

Status of Glucocorticoids in Asthma:

• Acute exacerbation: Oral prednisolone 30–60 mg/day for 5–7 days given with b2-agonists.
• Chronic asthma: Inhalation (2–4 times a day) for a long period for prophylaxis.
• Status asthmaticus: Intravenous hydrocortisone hemisuccinate 100–200 mg followed by another dose every 8 hours; may be switched over to oral prednisolone as soon as possible.

Mast Cell Stabilizers:

• Cromolyn sodium (disodium cromoglycate) prevents bronchospasm and inflammation following exposure to allergens and decreases bronchial hyper-reactivity.
• It is, therefore, used for prophylaxis.
• It is not a bronchodilator—hence not useful in acute episodes.
• Mechanism of action: The exact mechanism of action is not known. Cromolyn inhibits the release of mediators of inflammation.
• Cromolyn sodium is used as an inhaler—takes 2–4 weeks of treatment for the beneficial effects to develop. All patients do not respond—children are more likely to respond

Mast Cell  Adverse effects:

• Uncommon (<1 in 10,000 patients)—throat irritation, cough, and sometimes bronchospasm on inhalation due to deposition of the fine powder.
• Allergic reactions are rare.

Mast Cell  Uses:

1. Prophylaxis of bronchial asthma:
   • Cromolyn sodium used over a long period—2 puffs 3–4 times daily reduces episodes of acute asthma.
   • Cromolyn can also be used for prophylaxis before exposure to a known allergen—acute prophylaxis.
   • The use of cromolyn in bronchial asthma has declined as inhaled steroids are used.
2. Dose: 1–2 puffs 3–4 times a day.
3. Allergic rhinitis: Prophylactic nasal spray is effective.
4. Allergic conjunctivitis: Eye drops are used prophylactically—1–2 drops, 3–4 times a day.

Nedocromil: Nedocromil is similar to cromolyn sodium.

Ketotifen:

• Ketotifen is an antihistaminic with actions like cromolyn sodium. It inhibits airway inflammation but it is not a bronchodilator.
• It is given orally. Beneficial effects are seen after 6– 12 weeks of use. It is used for the prophylaxis of bronchial asthma and other allergic disorders like allergic rhinitis, atopic dermatitis, urticaria, and conjunctivitis.
• Dose: 1–2 mg BD.

Ketotifen Adverse effects: Drowsiness and dry mouth, dizziness, and weight gain.

Anti-Ige Antibody:

• Omalizumab is a monoclonal antibody against IgE.
• Omalizumab binds to IgE to form a complex and such bound IgE antibodies cannot bind to IgE receptors on mast cells and basophils.
• Thus the development of allergic response and the allergic process itself is inhibited.
• Omalizumab is given subcutaneously once in 2–4 weeks, has a long elimination t½ of 26 days.
• It is well-tolerated but can occasionally cause pain at the site of injection and allergic reactions.
• Few patients taking omalizumab developed different types of cancers but the correlation between the two is yet to be studied.
• Omalizumab can be used for prophylaxis in (>12 years age) moderate to severe asthma and in allergic rhinitis as it reduces the frequency and severity of acute exacerbations.

PDE₄ Inhibitors:

Roflumilast is a long-acting PDE₄ inhibitor effective orally. It has anti-inflammatory properties and may be used in COPD.

Treatment Of Asthma

Question 6. Write a short on the Treatment Of Asthma
Answer:

Mild Asthma:

• Occasional episodes of bronchospasm—inhaled b2 stimulants like salbutamol taken at the onset of bronchospasm.
• Mild chronic asthma → episodes of mild bronchospasm once a day—requires long-term steroids or cromoglycate.

Drugs that can Cause Bronchospasm:

• NSAIDs (like aspirin)
• Morphine
• β-blockers (like propranolol)
• Cholinergic drugs (for example, Bethanechol, Acetylcholine, and Organophosphorus compounds)
• Tubocurarine
• Zanamivir inhalation

Moderate Asthma:

Regular prophylaxis with cromoglycate or inhaled steroids. Acute episodes are managed with inhaled b₂-agonists. If inhaled steroids are contraindicated, leukotriene antagonists may be tried.

Acute Severe Asthma or Status Asthmaticus:

It is a medical emergency; trigger factors—acute respiratory infection, abrupt withdrawal of steroids after prolonged use, drugs, allergens, or emotional stress.

Asthma Treatment:

• Nebulization of a b₂ -agonist, and ipratropium alternately every 30 minutes. Additional salbutamol 0.4 mg IM/SC may be given. Severe tachycardia should be watched for.
• Hydrocortisone hemisuccinate IV 100 mg stat followed by 100 mg every 8 hours infusion (till the crisis is overcome) followed by a course of oral prednisolone.
• Oxygen inhalation is needed in most patients.
• Antibiotics—if the infection is present.
• IV fluids to correct dehydration and acidosis.
• Artificial ventilation may be required.
• K⁺ supplementation may be needed because repeated use of salbutamol may result in hypokalemia.

Drugs Used In Chronic Obstructive Pulmonary Disease (COPD):

Question  7. Write a short on COPD
Answer:

• Chronic obstructive pulmonary disease is an inflammatory response of the respiratory tract to innoxious gases with airflow limitation which is not fully reversible.
• It is mostly seen in chronic smokers.

Chronic exposure to dust and respiratory infection are other causative factors:

• Drugs used in asthma also help COPD but the response is not as good.
• Smoking should be stopped. For bronchospasm, inhalation of a b2-agonist or ipratropium is needed.
• Tiotropium or long-acting b₂ -agonists may be used for day-long bronchodilatation
• Theophylline may also relieve bronchospasm. Repeated exacerbation may require inhaled steroids for controlling the frequency and severity of episodes.
• PDE₄ inhibitor roflumilast is particularly effective in COPD.

Drugs Used In Treatment Of Cough:

Question 8. Write a short on the Treatment Of Cough
Answer:

• Cough is a protective reflex that clears the irritant matter and secretions from the respiratory tract. It could be due to infection, allergy, pleural diseases, and malignancy.
• The cause for the cough should be detected and treated whenever possible. Since it is a protective mechanism, undue suppression of cough can be more harmful.
• A dry annoying cough may serve no useful purpose and repeated coughing also causes exhaustion.
• In such situations, antitussives or cough suppressants may be used. Antitussives only provide symptomatic relief and do not alter the cause.

Antitussives:

Question 9. Write a short on Antitussives.

1. Central cough suppressants
   
2. Pharyngeal demulcents
   
3. Expectorants
   
4. Mucolytics
   

Answer:

1. Central Cough Suppressants: Codeine, pholcodine, noscapine, dextromethorphan, antihistamines, benzonatate.

Central cough suppressants act by inhibiting the cough center in the medulla:

1. Codeine:
   • Codeine is a good antitussive with less addiction liability.
   • It acts on µ opioid receptors and suppresses cough in sub-analgesic doses.
   • However, nausea, constipation, and drowsiness are common.
   • It should be avoided in patients with bronchial asthma since it is a respiratory depressant.
   • Dose: 10–15 mg every 6 hours.
2. Noscapine:
   • Noscapine is a natural opium alkaloid; dextromethorphan and pholcodine are synthetic opioid derivatives with antitussive actions like codeine but with lesser side effects.
   • They do not cause constipation and have no addiction liability but can cause nausea and drowsiness.
3. Benzonatate:
   • Chemically related to the local anesthetic procaine acts on the cough receptors in the lungs and also has a central effect.
   • It is given orally—100 mg thrice daily.
4.  Local anesthetics:
   • Like lignocaine, may be administered through nebulization to temporarily suppress coughing by anesthetizing the respiratory tract.
   • They are used to facilitate bronchoscopy.
5. Antihistamines: They are useful in cough due to allergy except that due to bronchial asthma.
   • They thicken the secretions which may be difficult to cough out. Their sedative property may be of additional value in suppressing cough.
   • Chlorpheniramine, promethazine, and diphenhydramine are the commonly used antihistamines.

2. Pharyngeal Demulcents: Lozenges, cough drops, linctuses

• Pharyngeal demulcents (demulcent = to caress soothingly—in Latin) increase the flow of saliva which produces a soothing effect on the pharyngeal mucosa and reduces afferent impulses arising from the irritated mucosa.
• Dry cough due to irritation of the pharyngeal mucosa is relieved. Candy sugar or a few drops of lemon also serve this purpose.

3. Expectorants: Potassium iodide, guaiphenesin, ammonium chloride

• (Latin—expectorate = to drive from the chest) increase the production of respiratory tract secretions that coat and cover the irritated mucosa.
• As the secretions become thin and less viscid, they can be easily coughed out.
• Expectorants (microkinetic agents) are used to treat a cough that results from irritation of the respiratory mucosa, for example, Alcohol, iodides, volatile oils like eucalyptus oil; cedarwood oil.

Bronchodilators:

• Salbutamol relieves cough that results from bronchospasm.
• The antitussive preparations generally have a combination of a central cough suppressant, an expectorant, an antihistaminic, and sometimes a bronchodilator and a mucolytic agent.

4. Mucolytics: Bromhexine, acetylcysteine, carbocysteine, ambroxol

Normally, the respiratory mucus is watery.  In respiratory diseases, the glycoproteins form larger polymers with plasma proteins present in the exudate and the secretions become thick and viscid. Mucolytics liquefy the sputum making it less viscid so that it can be easily expectorated.

• Bromhexine:
  • Bromhexine is a good mucolytic. It depolymerizes the mucopolysaccharides in the mucus and also liberates lysosomal enzymes which break the thick sputum.
  • It is given orally— 8–16 mg thrice daily. It is useful when respiratory secretions are thick or when mucus plugs make coughing strains.
  • Side effects are minor—may cause rhinorrhea and lacrimation. Bromhexine is highly bitter and therefore, tablet may be preferred to syrup. It is a commonly used mucolytic.
• Dose: 8–16 mg TDS.

Ambroxol:  Ambroxol is a metabolite of bromhexine with actions similar to it.

Acetylcysteine:

• Acetylcysteine and carbocysteine are well-tolerated.
• Carbocysteine can cause gastrointestinal irritation and rashes.
• Dose: 250–750 mg TDS.