DRUG THERAPY OF COUGH

Cough is physiologically useful protective reflex that clears the respiratory tract of the accumulated mucus and foreign substances.

It occurs due to stimulation of mechano / chemo receptors in throat, respiratory passage or stretch receptors in the lung.

Types of cough

• Cough is two types

• Non productive:- cough is considered as serving no useful purpose., rather it increased discomfort to the patient.

• For treatment antitussive agents are useful.

• Productive cough:-It is characterized by presence of excessive sputum and may be associated with conditions such as chronic bronchitis and bronchiectasis.

• In this condition expectorants are useful.

• Ideal antitussive should suppress the frequency as well as intensity of coughing with out affecting the normal elimination of excessive secretions from the respiratory tract.

• Expectorants:- Increase the volume and decrease the viscosity of secretions to enhance the propulsion of the secretion upward and outward by ciliary movement and coughing.

Peripherally acting Centrally acting Peripherally& centrally

Pharyngeal demulcents

ExpectorantsOpioids Non Opioids

Classification of drugs

Mucokinetics Mucolytic

Peripherally actingPharyngeal demulcents

– Prenoxdiazine– Glycerin– Liquo rice– Lozenges– Linctus containing

syrup.

Expectorants:- 1.Mucokinetics

– Ammonium chloride – Sodium citrate– Potassium Iodide – Guaifenesin– Ipecacuanha

2.Mucolytic– Vasaka – Bromhexine– Ambroxal – Dornase alfa– Acetyl cysteine

Centrally acting

• Opioids– Codeine– Pholcodeine– Morphine– Ethylmorphine

• Benzonatate

• Non Opioids– Noscapine– Dexomethorphan– Pipazethate– Chlophedinol– Oxeladin

Centrally and peripherally acting

Demulcents:- Indirect peripherally acting cough suppressants.

• They provide a protective coat over sensory receptors on pharynx and reduce afferent impulses from the inflamed / irritated mucosa.

• They provide relief in dry cough arising from throat.

• Ex:- Honey, liquorice

Expectorants

• Mucokinetics:- These expectorants stimulate the flow of respiratory tract secretions by stimulating bronchial secretory cells( to inc. volume) and the ciliary movement (to facilitate their removal)

Ex:- Volatile oils, certain emetics in sub emetic doses, ammonium chloride, Na citrate, guaiacol and guaifenesin.

Essential oils:- Provide only mild expectoration by directly stimulating the bronchial secretory cells.

• know its use has declined.

Sodium and potassium citrate:- (0.3-1g) After absorption citrates get converted to bicarbonates in vivo and mucus becomes less viscous in alkaline pH.

Ammonium chloride:- It is a gastric irritant which reflexly enhances bronchial secretions.

• Large doses it can produce metabolic acidosis.

• KI:- (0.2-0.3g) It is secreted by bronchial glands and in this process irritates them, increasing the volume of secretions.

• It also gastric irritant acts reflexly as well.

ADE:-It is dangerous in patients sensitive to iodine and interfere with thyroid function.

• Prolong use can induce goiter and hypothyroidism

• Less popular now because of hazards

• Guaiacol and Guaifenesin are obtained from creosote wood but nowadays are prepared synthetically.

• These safe expectorants with proven efficacy.

• Guaifenesin is less irritating derivate of guaiacol. • After absorption, guaifenesin is secreted

through bronchial glands to increase airway secretion and mucosal ciliary activity.

• It is administered orally 100-200mg BD

MucolyticMucolytics alter the chemical characteristics

of mucus to decrease its viscosity and facilitate its removal by ciliary action

Commonly used mucolytics include acetyl cysteine, carbocysteine, bromhexine, ambroxol and dornase-alfa.

Bromhexine:- It is an alkaloid from vaska plant .

• It depolymerises mucopolysaccharides of mucus and also increase lysosomal enzyme activity that break the fiber network of tenacious sputum .

• Oral dose is 8-16mg TDS

• Side effects:- GIT upset and rhinorrhoea (Water release from nose).

• Ambroxol:-Metabolite of bromhexine and has a similar mode of action

• Oral dose 30mg BD/TDS

Acetylcyseteine :- It is a mucolytic that decrease the viscosity of mucus by splitting the disulfide –S -- S- bonds of mucoproteins.

• Action facilitated by alkaline pH(7-9)• Administratation is done by nebulisation

(3-5ml of 20%solution),also oral 200mg TDS but efficacy is much less.

• Side effects :- Nausea, vomiting, stomatitis and bronchospasam

• Dornase-alfa:- It is highly purified solution of recombinant human deoxyribonuclease (DNase). These enzyme that selectively cleaves DNA.

• Purulent (Pus) pulmonary secretions in cystic fibrosis contain very high amounts of extra cellular DNA.

• Dornase alfa inhalation (2.5mg once daily) hydrolysis this accumulated DNA in the sputum of the patients of cystic fibrosis

Other

Drinking warm water, inhaling warm moist air

or menthol vapours, surfactants such as

tyloxapol, proteolytic enzymes such as

chymotrypsin or trypsin are also used for

their hydrating and mucolytic action.

Centrally acting• Drugs that act in the CNS to raise the

threshold of cough centre to reduce tussal impulses

• Main aim to control rather then eliminate cough

• These are mainly useful for dry unproductive cough or if cough is disturbs sleep or is hazardous.

Codeine:- An opium alkaloid (Semi synthetic opioid), qualitatively similar to but less potent then morphine.

• It is more selective for cough centre and it is treated as standard antitussive.

• It suppress cough center for 6hr.• Administered orally (10mg BD or TDS)• Abuse liability is low at these dose.• Side effects:- High dose cause respiratory

depression, convulsions, postural hypotension, constipation.

Pholcodeine:- It is structurally related to codeine but it is slightly more potent, longer acting and better tolerated than codeine.

• It cause lesser constipation and drowsiness than codeine.

• More suited for long term use

• Orally 10-15mg BD

Dextromethorphan:-It is methyl ester of the dextroisomer of levorphanol.

• It has less addition liability, no analgesic action, least constipating effect and minimal drowsiness

• It is as potent as codeine and given orally 10mg TDS

• Most popular cough suppressant

• Combination available with antihistamines and bronchodilators in cough mixtures.

Noscapine:- It is naturally occurring opium alkaloid belonging to benzylisoquinoline group.

• Popular cough suppressant• Given orally 15mg TDS.• Less addiction liability, drowsiness,

analgesic activity

• Side effect: At high doses may produce nausea, headache and tremors.

Pipazethate:- Phenothiazine group of antitussive. Occasionally used.

• Given by orally 40mg TDS

Chlophedianol:- It is less effective • Rarely used• Dose 20mg BD orally• High doses cause excitatory effects,

tremors.

Centrally & peripherally acting antitussives

Benzonatate:- It is structurally related to local anesthetic tetracaine.

• It not only inhibits the afferent cough impulses to suppress the central cough center, but also inhibits the pulmonary stretch receptors and also posses local anaesthetic action

• Administered orally 100-200mg Orally

Side effects: Drowsiness, nausea, headache • High doses cause vertigo.