COUGH AND DRUGS USED IN THE TREATMENT OF COUGH
Cough: Cough is one of the most common symptom of respiratory diseases. It is a protective reflex—to expel out unwanted material, excessive secretions or foreign particles from the respiratory tract. It could be due to infection, allergy, pleural diseases and malignancy. Cough is of two types: Productive and Non-productive.
Productive Cough: Here coughing results in removal of secretions or foreign particles. It is also called useful (serves the purpose) cough. It is commonly seen in Bronchial Asthma, acute and chronic Bronchitis, Bronchiectasis, Pneumonia, Pulmonary Tuberculosis (expectorants to be avoided), Lung cancer, etc.
- This type of cough is symptomatically treated with drugs like the expectorants, mucolytics or with steam inhalation. Antimicrobial agents may or may not be used (depending on the presence or absence of bacterial infection).
Note
- This type of cough should not be suppressed (unless stress of coughing must be avoided).
- Drugs that tend to increase the viscosity of the secretions by drying it such as anti-cholinergics and anti-histaminics (due to their anti-cholinergic property) should be avoided in productive cough.
Non-productive or Dry-irritating Cough: It results from irritation in the respiratory tract because of the dust or fumes or other environmental pollutants. It is also seen in Upper Respiratory Tract Infections (e.g. Pharyngitis). Coughing does not result in removal of anything (very little or no sputum) from the respiratory tract, does not serve any purpose and therefore it is also called ‘useless’ cough.
- Dry cough is treated with cough suppressants mainly acting centrally, or ‘peripherally acting suppressants’ or anti-histaminics or rarely with expectorants (only for irritation below the epiglottis).
That the treatment of the two types of cough are different.
Classification
- Pharyngeal demulcents: Lozenges, Cough drops, Linctuses.
- Expectorants: Potassium iodide, Guaiphenesin, Ammonium, chloride, Ipecacuanha.
- Central cough suppressants: Codeine, Noscapine, Dextromethorphan, Antihistamines, Benzonatate.
Drugs Used in the Treatment of Productive Cough
Expectorants: Expectorants (Latin—expectorate=to drive from the chest). They are the drugs that help in removal (expectorating out) of sputum. Expectorants increase water content of the respiratory secretions making them more thin and easy to remove. Total volume of secretions (sputum) increase.
Examples: Potassium iodide, Potassium citrate, Sodium citrate, Ammonium chloride, Ipecacuanha, Vasaka, Terpin hydrate, Eucalyptus oil, Guaiphenesin, Guaiacol, etc.
- Direct stimulants Volatile oils like eucalyptus oil; creosotes, alcohol, cidar wood oil—when administered by inhalation with steam can increase respiratory secretions.
- Reflex expectorants are given orally, they are gastric irritants and reflexly increase respiratory secretions.
- Potassium iodide, acts both; directly and reflexly. Ipecacuanha is an emetic. In subemetic dose it is used as an expectorant.
Extemporaneous Expectorant Formulation: (One dose)
i. Potassium iodide | 0.2 g |
ii. Potassium citrate | 1.0 g |
iii. Sodium bicarbonate | 1.0 g |
iv. Tincture ipecacuanha | 0.6 ml |
v. Syrup tolu | 2.0 ml |
vi. Water up to | 30.0 ml. |
Mucolytics: Mucolytics liquify the sputum by breaking down muco-polysaccharide strands. Liquifaction helps in easy removal of the secretions. They do not increase the water content or total volume of the secretions.
Examples: Bromhexine, Ambroxol, Serratiopeptidase, Carbocysteine, Acetylcysteine
- Normally the respiratory mucous is watery. The glycoproteins in the mucous are linked by disulphide bonds to form polymers making it slimy link the glycoproteins in the mucous.
- In respiratory diseases, the glycoproteins form larger polymers with plasma proteins present in the exudate and the secretions become thick and viscid. Mucolytics liquify the sputum making it less viscid so that it can be easily expectorated.
- Bromhexine obtained from the plant Adhatada vasica is a good mucolytic. It depolymerises the mucopolysaccharides in the mucous. It is given orally (8–16 mg thrice daily). Side effects are minor-may cause rhinorrhea.
- Acetylcysteine opens disulfide bonds in mucoprotein of the sputum reducing its viscosity. It is given by aerosol. Side effects are common and hence not preferred.
- Carbocysteine is similar to acetylcysteine and is used orally.
Steam inhalation offers an effective and inexpensive alternative to drugs. In presence of dehydration, just rehydrating the patient is found to be beneficial.
Note
Expectorants and Mucolytics, both have similar indications (uses) - in treatment of ‘Productive’ cough - where there are excessive, thick and tenacious secretions which are difficult to remove. As they act by different mechanisms, they may be used together.
Decongestants: Decongestants are the drugs that reduce mucosal congestion resulting from allergic or inflammatory reaction. These are sympathomimetic agents. They relieve congestion by vasoconstrictor action (with possible cardiovascular side effects - caution in elderly). They are also used as nasal decongestants.
Examples: Phenylephrine, Phenylpropanolamine, Pseudoephedrine, Ephedrine, Oxymetazoline
Pharyngeal Demulcents: Pharyngeal demulcents (demulcere=to care soothingly-in LATIN). These drugs increase the flow of saliva which produces a soothing effect on the pharyngeal mucosa and reduce 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.
Bronchodilators: These are the agents, which relieve cough that is resulting 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.
Drugs Used in Treatment of Non-productive Cough
Centrally Acting Cough Suppressants: They inhibit the medullary cough center and thereby inhibit the ‘reflex’. They should be used ONLY in non-productive cough (i.e. without sputum), to suppress the cough reflex arising out of irritation.
Examples: Codeine, Pholcodeine, Noscapine, Dextromethorphan, Ethylmorphine.
Note
- Cough suppressants SHOULD NOT BE USED in cases with productive cough.
- Cough suppressants should not be COMBINED with expectorants or mucolytics - it amounts to combining two drugs with opposite actions.
- Central cough suppressants act by inhibiting cough centre in the medulla (CNS).
- Codeine is a good antitussive with less addiction liability; nausea, constipation and drowsiness are common. Does 10–15 mg every 6 hours.
- Noscapine is a potent antitussive; no other CNS effects are prominent in therapeutic doses. Nausea is the only occasional side effect. Dose 15–30 mg every 6 hours.
- Dextromethorphan and pholcodeine are synthetic opioid derivatives with antitussive actions like codeine but with less side effects. Pholcodeine is longer-acting-given twice daily.
- Benzonatate is chemically related to the local anesthetic procaine. It acts on the cough receptors in the lungs and also has a central effect. It is given orally-100 mg thrice daily.
- Antihistamines are useful in cough due to allergy except that due to bronchial asthma.
Antihistaminics: Histamine is one of the mediators of allergic reaction. Anti-histamines antagonize (block) the actions of histamine. This may be useful in patients with cough due allergic conditions. Some of them have CNS depressant 131properties and cause sedation. Such antihistaminic also depress cough center. Extra caution is required while using such drugs that cause sedation during day time as they slow down body reflexes and this may be dangerous during driving a vehicle and handling machines. Some anti-histaminics have anticholinergic activity also. They tend to make secretions more thick and tenacious. This is not desirable if the patient has productive cough.
Examples: Triprolidine, Terfenadine, Azatidine, Diphenylpyraline (less sedation, less anti-M), Chlorpheniramine maleate, Pheniramine maleate (sedatives), Promethazine, Diphenhydramine, Carbinoxamine, Methdilazine (pronounced sedation + Anti-Muscarinic).
Soothing agents: Popular among the cough remedies is the cough-drops available in the form of lozenges. Their action is simply to increase salivation (sialagogues) which lubricates upper pharynx and thereby reduces irritation. Such drugs are however not effective if the irritation is deep seated (below epiglottis). So called ‘medicated’ lozenges containing menthol, eucalyptus oil, etc. have value comparable only to placebo. A few lemon drops or a lump of sugar serves similar purpose.
Trade Preparations: Formulations available in the market (and listed as cough remedies) contain 57 different drugs in different combinations which can be placed under 8 different categories :
- – Expectorants
- – Mucolytics
- – Central cough suppressants
- – Anti-histaminics
- – Bronchodilators
- – Decongestants
- – Correctives and preservatives
- – Miscellaneous
- As against this, WHO Essential Drug List for treatment of cough includes only one drug (Codeine). As per the National Formulary 4–5 ingredients are sufficient for an Expectorant and only 1–2 as cough suppressant.
- Availability of large number of products in the market, requires that a doctor should be able to select the right formulation and avoid undesirable drug combinations, in different clinical settings.
Bronchodilators: They cause relaxation of bronchial smooth muscles. This is believed to relieve cough resulting from spasm of the smooth muscles. Stimulation of β2 receptors inhibit the release of Histamine and other mediators from mast cells, this may be an additional mechanism for the use of such drugs in treatment of cough associated with allergic conditions.
Examples: Terbutaline (β2), Salbutamol (β2), Ephedrine (α+β), etc.
Doses of some commonly used ingredients in cough remedies:
Expectorants: These are included in expectorant formulations in different combinations, given 3–4 times a day.
Potassium Iodide : | 200–300 mg |
Potassium Citrate : | 1–2 g |
Sodium Citrate : | 1–2 g |
Ammonium chloride : | 300 mg |
Ipecacuanha syrup : | 0.6–1.0 ml |
Vasaka : | 1–2 ml |
Eucalyptus oil : | 0.06–0.2 ml |
Guaiacolate : | 100–200 mg |
Terpin hydrate : | 200 mg 4 hourly |
Guaiphenesin : | 400 mg in adults; |
in children: 2–6 yrs = 50–100 mg; | |
6–12 yrs = 100–200 mg (given 4 hourly) |