Asthma, Antiasthmatic drugs, Pharmacodynamics , Pharmacokinetics, Side effects, Uses and MCQS for GPAT, NIPER, Pharmacist and Drug inspector exam
Bronchial Asthma:
It is chronic condition in which a person’s airways become inflamed swell, narrow and produce extra mucus which make difficulty in breathing.
Sign and symptoms:
Coughing, shortness of breath, chest tightness and wheezing sound (whistling sound in airways).
Risk factor that trigger Asthma:
Allergies, cold air, stress, irritants (household sprays, perfumes etc.), indoor and outdoor allergens, respiratory infections etc.
Inflammatory mediators in Asthma:
The inflammation in Bronchial Asthma is initiated by mast cells (present in lungs). The inflammatory reaction produces mediators like histamine, protease enzyme, prostaglandins, interleukins, leukotriene’s etc. These mediators together cause mucosal edema, constrict bronchial smooth muscles which will make breathing difficult.
Classification of Drugs for Asthma:
| Sr. No. | Drugs | Mechanism of action | Pharmacokinetics | Side Effects | Uses | |||||
| 1 | Bronchodilators | |||||||||
| A | Beta sympathomimetic
drugs |
|||||||||
| Salbutamol,
Terbutaline |
It stimulates β2 receptors of inflammatory cells, increased cAMP formation in bronchial smooth muscle cell and it will decrease the release of inflammatory mediators and dilates the bronchial smooth muscle. | Highly selective short acting β2 agonist. It is fastest acting bronchodilators, produces bronchodilation in 5 minutes and the action lasts for 2-4hrs. | Hypokalemia, tachyphylaxis throat irritation, nervousness, palpitation, restlessness, ankle edema. and muscle tremors. | Use for symptomatic relief, prevention of bronchospasm due to bronchial asthma and chronic bronchitis. | ||||||
| Salmeterol | Same as above | It is first long acting β2 agonist. Slow onset of action. | Headache, dizziness, cough, runny nose, stuffed nose, nervousness and ear pain | Used by inhalation for maintenance therapy and nocturnal asthma | ||||||
| Formeterol | Same as above | It is also long acting β2 agonist and acts for 12hr. It hs faster onset of action as compared to Salmeterol. | It is used on regular morning evening schedule for round the clock bronchodilation. | |||||||
| Bambuterol | Ester prodrug of terbutline has same mechanism of action | It is metabolised by hydrolysation in plasma and lungs by pseudocholinestrase enzyme to release active drug over 24 hrs. | Headache and feeling restless. | It is used in nocturnal and chronic asthma. | ||||||
| B | Methyl Xanthines | |||||||||
| Theophylline, Aminophylline, Choline theophylline, Hydroxyethyl theophylline and Doxophylline. | It is natural bronchodilator. It inhibits the phosphodiesterase enzyme, it also cause an intracellular increase in levels of cAMP and cGMP. This signal results in bronchial smooth muscle relaxation, pulmonary vessel vasodilation, CNS stimulation and cardiac stimulation. | Well absorbed orally, do no accumulate in organs and tissues, metabolised by liver. t1/2 is of 7-12 hrs and 2% of drug administered excreted unchanged in urine. | Gastric pain (with oral), rectal inflammation (with rectal suppostries), pain at the site of injection(i.m) and rapid iv can cause sudden death, convulsions and arrythmia | Used in COPD, bronchial astma and apnoea in premature infants. | ||||||
| C | Anticholinergics | |||||||||
| Ipratropium bromide, Tiotropium bromide | Bronchodilation by blocking cholinergic constrictor tone. | Poorly absorbed through g.i.t. The bioavailability of drug by inhalation is 0.03-6.9%. About 90% of inhaled dose is swallowed. T1/2 is of 2-3 hrs. | Dry mouth, upset stomach, vomiting, nosebleed, muscle pain. | Used for COPD and bronchial asthma. | ||||||
| 2 | Leukotriene antagonists | |||||||||
| Montelukast, Zafirlukast | Competitively antagonise cysLT1 receptor mediated bronchoconstriction, increased vasodilation. | These drugs inhibit leukotriene enzyme arachidonate 5 lipoxygenase , antagonise leukotriene receptor which opposed the action of leukotriene inflammatory mediators which are responsible for bronchoconstriction, inflammation and in mucus secretion. | Aggression, anxiety, hallucinations, depression, insomnia. | Used for prophylactic therapy of mild to moderate asthma. | ||||||
| 3 | Mast cell stabilizers | |||||||||
| Sodium chromoglycate, Ketotifen | It inhibits degranulation of mast cells of liver. It also inhibits the release of mediators like histamine, leukotrienes and interleukins which cause bronchoconstrictions. | It is not absorbed orally, administered as meterd dose inhalers. Half-life is of 8.5hrs. | Cough, throat irritation and bronchospasm | Allergic rhinitis, allergic conjunctivitis and in long term prophylaxis in mild to moderate bronchial asthma. | ||||||
| 4 | Corticosteroids | |||||||||
| A | Systemic corticosteroids:
Hydrocortisone, predinisolone |
These drugs bind with the cell nucleus to regulates that control transcription of pro-inflammatory gene products by reducing inflammation caused by inflammatory mediators. | It acts in 6-24 hrs. | Increased appetite, weight gain, changes in mood, increased growth of body hairs and cataract. and blurred vision | Used in bronchial asthma, staus asthmaticus and in COPD. | |||||
| B | Inhalational corticosteroids | |||||||||
| Beclomethasone | Same as above | Rapidly absorbed from pulmonary, nasal and GI tssue. Undergoes extensive first pass metabolism in the liver. 87% drug bind to protein | Sneeing, nasal irritation | Effective in perennial rhinitis | ||||||
| Budesonide | Same | Greater first pass metabolism than beclomethasone. Small fractionis absorbed is rapidly metabolised. | Itching of throat, nasal irritation, sneezing, throat dryness. | Used in seasonal perennial allergies. | ||||||
| Fluticasone | same | At higher dose systemic effects produce due to absorption from lungs. | Same | Used at higher doses in severe cases. | ||||||
| Ciclesonide | Same | It is absorbed from lungs. Bioavailability is 1%. Extensively bound to plasma proteins. | Unpleasant tase in mouth, dry mouth, hoarse voice, mild itching or skin rash. | Used to prevent difficult breathing, chest tightness, coughing and wheezing. | ||||||
| 4 | Anti- IgE antibody | Human monoclonal antibody. It neutralizes free igE in circulation without activating mast cells and inflammatory cells. |
|
No benefits noted in allergic asthma. | ||||||
MCQs:
1.What causes an asthma attack
a. Allergens
b. Smoke
c. Irritants
d. All of the above
2. Which one of the following anti-asthmatic drugs can cause arrhythmia and convulsions.
a. Prednisolone
b. Zafirlukast
c. Theophylline
3. Which anti-asthmatic drugs can cause cataracts.
a. Salmeterol
b. Salbutamol
c. Prednisolone
d. Montelukast
4. Which drugs are short-acting β2– agonist
a. Salbutamol
b. Prednisolone
c. Terbutaline
d. a&c
5. Which drugs are long-acting β2 – agonist
a. Salbutamol
b. Formoterol
c. Salmeterol
d. b&c
6. Asthma is characterized by recurrent episodes of
a. Wheezing
b. Chest tightness
c. Coughing
d. All of the above
7. Identify leukotriene inhibitors
a. Zafirlukast
b. Salbutamol
c. Theophylline
d. Ipratropium
8. Which anti-asthmatic drugs show first pass metabolism
a. Budesonide
b. Salmeterol
c. Beclomethasone
d. a&c
9. Which anti asthmatic drugs act as bronchodilators
a. Salbutamol
b. Ipratropium
c. Theophylline
d. All of above
10. Which is natural bronchodilator
a. Theophylline
b. Prednisolone
c. Budesonide
d. Ipratropium
11. Which is drug inhibit (phosphodiesterase) enzyme
a. Theophylline(Methyl Xanthine)
b. Salbutamol
c. Terbutalline
d. Ipratropium
12. Acute attack of asthma treated with
a. Bronchodilators
b. Steroids
c. Methyl xanthines
d. Anticholinergics
13. Side effects of β-2 agonist
a. Hypokalemia
b. Tachyphylaxis
c. Muscle tremor
d. All of above
14. LT1 Receptor antagonist used in asthma
a. Zafirlukast
b. Montelukast
c. Both
d. None
15. Which drug inhibit 5- lipoxygenase enzyme.
a. Salbutamol
b. Montelukast
c. Ketotifen
d. Flutikasone
Answers:
1. d
2. d
3. c
4. d
5. d
6. d
7. a
8. d
9. d
10. a
11. a
12. a
13.d
14. c
15.b
References: ‘K.D. Tripathi’, 8thedition 2018, page no-242-251.
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