COPD, Classification of COPD, Pharmacodynamics, Pharmacokinetics, Side effects and Medicinal Uses, MCQs for GPAT, NIPER, DRUG INSPECTOR, PHARMACIST EXAMS.
COPD: Chronic obstructive pulmonary disease, a group of lung disease that blocks airflow and make it difficult to breathe.
Types of COPD: There are two main types of COPD.
- Chronic bronchitis: Which involves a long term cough with mucus.
- Emphysema: Which involves damage to the lungs over time.
Umbrella COPD: It is term used to describe progressive lung disease such as emphysema and chronic bronchitis.
Risk factor: Smoking is the main cause of COPD. The harmful chemical in smoke can damage the lining of the lungs and airways. Occupational dust and chemicals, environmental tobacco smoke (ETS), indoor and outdoor air pollution.
Sign and symptoms according to stages of COPD:
There are four stages of COPD:
Stage1: Symptoms are mild, but the damage to the lungs begins. Symptoms include, persistant cough, which could be dry or accompanied with mucus that is clear, white, yellow and green. Shortness of breath on exertion.
Stage2: Moderate COPD, persistant cough with mucus that may be worse in the morning, shortness of breath even with mild routine activity, wheezing on exertion, disturbed sleep and fatigue.
Stage3: Severe COPD, The symptoms in stage3 worsen considerably, frequent respiratory tract infections, swelling of the ankles, feet and legs, tightness in the chest, trouble taking a deep breathe, wheezing and other breathing issues when doing basic tasks.
Stage4: This the final stage of COPD. Occurs after years of continuous damage to the lungs. Patients have worsened symptoms, include, barrel shaped chest, constant wheezing, being out of breathe, delirium, increased heart rate, increased blood pressure and loss of appetite and weight.
Classification of drugs:
Table no: 1
| Sr. No. | Drugs | Mechanism of action | Pharmacokinetics | Side Effects | Uses | |||||
| 1 | Bronchodilators | |||||||||
| 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 as first line treatment in COPD, 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. | ||||||
| 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. | ||||||
| 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. | Corticosteroids | |||||||||
| 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. | ||||||
| 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 | Sneezing, nasal irritation.
Long use of these drugs cause puffiness of the face called ‘moon face’, weight gain, rounded lump between the shoulders called ‘buffalo hump’. |
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. | ||||||
| 3 | Phosphodiesterase 4 (PDE4) inhibitors:
|
|||||||||
| Roflumilast | PDE4 inhibitors causes bronchodilation by increasing intracellular cyclic adenosine 3’,5’ monophosphate in airway smooth muscle and inflammatory cells and also modulates lung inflammation. | The bioavailability of roflumilast is about 80%. Poorer blood brain barrier permeability, it is highly plasma protein bound (99%), roflumilast is metabolized to roflumilast N-oxide, the active metabolite of roflumilast in humans by CYP3A4 and CYP1A2, roflumilast is 70% excreted in the urine as roflumilast N-oxide, t1/2 of roflumilast is 17hrs and its metabolite is of 30 hrs. | Insomnia, loose stool, headache, drastic weightloss, GI upset. | Roflumilast use as adjunctive or alternate therapy to other COPD medications reduces COPD exacerbations and improves lung function. | ||||||
Other treatments for COPD:
Patients should receive a yearly influenza vaccine and the pneumococcal vaccine ever 5-7 years as preventive measure.
Oxygen therapy: It can be administered as long term continuous therapy, during exercise, or to prevent acute dyspnea. Long term oxygen therapy has been use to improve the patients quality of life and survival.
MCQs
1 What is COPD?
a. Mental disorder
b. Lung disese
c. Heart disease
d. Blood disorder.
2. Barrel shaped chest, constant wheezing, being out of breathe, delirium, increased heart rate are symptoms of which stage of COPD?
a. Stage I
b. Stage II
c. Stage III
d. Stage IV
3.Which of the following disease is included in the ‘umbrella term COPD’?
a. Emphysema
b. Chronic bronchitis
c. a&b
d. Lung cancer
4. Long term exposure to which of following can increase the risk of COPD?
a. Airborne chemicals
b. Pollutants
c. Lung irritants
d. All of above
5. Which of the following can improve your health, if you have COPD?
a. Not smoking
b. Exercise regularly
c. a & b
d. Drinking alcohol
6. How is COPD treated?
a. Bronchodilators
b. Oxygen therapy
c. Inhaled corticosteroids
d. All of above
7. COPD is associated with
a. Skeletal muscle dysfunction
b. Treatment with bronchodilators
c. Depression
d. Tachycardia
8. First line treatment of COPD
a. Short acting bronchodilators
b. Methyl xanthines
c. Corticosteroids
d. None of these
9.Long use of inhaled corticosteroids cause side effects like:
a. Puffiness of the face
b. Rounded lump between shoulders
c. Weight gain
d. All of above
10.Which drug is phosphodiestrase4 inhibitor?
a. Theophylline
b. Roflumilast
c. Doxophylline
d. Cholline theophylline
11. Which drug cause rapid weight loss?
a. Salbutamol
b. Theophylline
c. Terbutaline
d. Roflumilast
12. Which drug is use as round the clock bronchodilator in COPD?
a. Formeterol
b. Selmeterol
c. Terbutaline
d. Salbutamol
13. Which is the ester prodrug of terbutaline?
a. Bambuterol
b. Salbutamol
c. Selmeterol
d. Formeterol
14. Half life of Roflumilast?
a. 2hrs
b. 17hrs
c. 30hrs
d. 15hrs
15. Which drug has poor blood brain barrier?
a. Formeterol
b. Salbutamol
c. Ipratropium
d. Roflumilast
Answers:
- b
- d
- c
- d
- c
- d
- b
- a
- d
- b
- d
- a
- a
- b
- a
References:
- ‘K.D Tripathi’ Page no: 247-252, 8th edition 2018.
- ‘Dr. Muhammad Aslam’, medical.ppt. blog spot.com
- ‘Aaron M. Mulhal etal’, expert investing drugs, 2015
- Drug bank.com.