1. DRUG THERAPY OF COUGH

2. 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.

3. Types of cough
Cough is 2 types

4. Cough phases

5. Afferent impulses to cough centre (medulla)
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)

6. 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)

7. Classification of drugs
Peripherally acting
Peripherally& centrally
Centrally acting
Benzonatate
Opioids
Non Opioids
Pharyngeal
demulcents
Expectorants
Mucokinetics
Mucolytic

8. Peripherally acting Expectorants:- Pharyngeal demulcents
1.Mucokinetics
Ammonium chloride
Sodium citrate
Potassium Iodide
Guaifenesin
Ipecacuanha
Pharyngeal demulcents
Prenoxdiazine
Glycerin
Liquo rice
Lozenges
Linctus containing syrup.
2.Mucolytic
Vasaka
Bromhexine
Ambroxal
Dornase alfa
Acetyl cysteine

9. Centrally and peripherally acting
Centrally acting
Opioids
Codeine
Pholcodeine
Morphine
Ethylmorphine
Benzonatate
Non Opioids
Noscapine
Dexomethorphan
Pipazethate
Chlophedinol
Oxeladin
Centrally and peripherally acting

10. 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

11. 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.

12. 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.

13. KI:- ( g) 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

14. 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 mg BD

15. 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.

16. 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
(Water release from nose).

17. 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

18. 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

19. 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.

20. 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.

21. 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.

22. 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

23. 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.

24. 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.

25. Pipazethate:- Phenothiazine group of antitussive
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.

26. 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 mg
S/E: D, N, H
High doses cause vertigo.
Drowsiness

27. 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

28. Thank Q