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 2 types

COUGH

Non Productive (Dry) Productive (Tenacious)

Cough phases

Mechanism of cough

Stimulation of mechano or chemoreceptors (throat, respiratory passages or stretch receptors in lungs)

Afferent impulses to cough centre (medulla)

Efferent impulses via parasympathetic & motor nerves to diaphragm, intercostal muscles & lung

Increased contraction of diaghramatic, abdominal & intercostal (ribs) muscles noisy expiration

(cough)

Most common causes of cough

• Common cold,

• Upper/lower respiratory tract infection

• Allergic rhinitis

• Smoking

• Chronic bronchitis

• Pulmonary tuberculosis

• Asthma

• Gastroesophageal reflux

• Pneumonia

• Congestive heart failure

• Bronchiectasis

• Use of drugs (e.g.:ACEI)

Peripherally acting Centrally acting Peripherally& centrally

Pharyngeal demulcents

ExpectorantsOpioids Non Opioids

Classification of drugs

Mucokinetics Mucolytic

Benzonatate

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:- These are 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.

• Syrup of Ipecacuanha 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-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.

A/E:-It is dangerous in pts sensitive to iodine, and interfere with thyroid function.

• Prolong use - induce goiter and hypothyroidism

• Less popular now because of these potential hazards

• Guaiacol and Guaifenesin - 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.

• Admi orally 100-200mg BD

Mucolytic

• Mucolytics alter the chemical

characteristics of mucus to ↓ its viscosity

and facilitate its removal by ciliary action

• Commonly used mucolytics include acetyl

cysteine, carbocysteine,bromhexine,

ambroxol and dornase-alfa.

Bromhexine:- Alkaloid from vasaka plant .• It depolymerises mucopolysaccharides of

mucus directly and also by ↑ lysosomal enzyme activity that break the fiber network of tenacious sputum .

• Oral dose is 8-16mg TDS S/E:- GIT upset and rhinorrhoea

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

• Oral dose 30mg BD/TDS

Acetylcyseteine :- It is a mucolytic that ↓

viscosity of mucus by splitting the

disulfide –S-S- bonds of mucoproteins.

• It’s action facilitated by alkaline pH(7-9)

• Admi is done by nebulisation (3-5ml of

20%solution),also oral 200mg TDS but

efficacy is much less.

• S/E :- N, V, 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 pts of cystic fibrosis

• 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

• 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 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.

• Admi orally (10mg BD or TDS)

• Abuse liability is low at these dose.

S/E:- 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.

• Less addition liability, no analgesic action, least constipating effect, 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

S/E: At high doses may produce N, H and tremors.

Pipazethate:- Phenothiazine group of antitussive .Occasionally used in cough mixtures.

• Given orally 40mg TDS

Chlophedianol:- It is less effective

• Rarely used

• Dose 20mg BD orally

• High doses cause excitatory effects, tremors.

Centrally as well as peripherally acting antitussives

Benzonatate:- It is structurally related to LA 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 100-200mgS/E: D, N, H • High doses cause vertigo.

Specific treatment approach to cough

Etiology of cough Treatment

1) Upper/lower respiratory Appropriate antibiotics tract infections

2) Smoking/chronic bronchitis Cessation of smoking

3) Pulmonary tuberculosis Antibiotics

4) Asthmatic cough Inhaled β2-agonists/iprat-

ropium/corticosteroid

5) Postnasal drip (sinusitis) Antibiotics, nasal decon-

gestants, antihistamines