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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)
Classification of drugs
Peripherally acting

Peripherally& centrally
Benzonatate

Pharyngeal
demulcents

Expectorants

Mucokinetics

Mucolytic

Centrally acting

Opioids

Non Opioids
Peripherally acting
Expectorants:Pharyngeal demulcents
1.Mucokinetics
– Prenoxdiazine
– Ammonium chloride
– Glycerin
– Sodium citrate
– Liquo rice
– Potassium Iodide
– Lozenges
– Guaifenesin
– Linctus containing
– Ipecacuanha
2.Mucolytic
syrup.
–
–
–
–
–

Vasaka
Bromhexine
Ambroxal
Dornase alfa
Acetyl cysteine
Centrally acting
• Opioids
– Codeine
– Pholcodeine
– Morphine
– Ethylmorphine

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

Centrally and peripherally acting
• Benzonatate
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 100-200mg
S/E: D, N, H
• High doses cause vertigo.
Specific treatment approach to
cough
Etiology of cough
1) Upper/lower respiratory
tract infections
2) Smoking/chronic bronchitis

Treatment
Appropriate antibiotics
Cessation of smoking

3) Pulmonary tuberculosis

Antibiotics

4) Asthmatic cough

Inhaled β2-agonists/ipratropium/corticosteroid

5) Postnasal drip (sinusitis)

Antibiotics, nasal decongestants, antihistamines
Cough (VK)

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Cough (VK)

  • 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 COUGH Non Productive (Dry) Productive (Tenacious)
  • 5. 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 Benzonatate Pharyngeal demulcents Expectorants Mucokinetics Mucolytic Centrally acting Opioids Non Opioids
  • 8. Peripherally acting Expectorants:Pharyngeal demulcents 1.Mucokinetics – Prenoxdiazine – Ammonium chloride – Glycerin – Sodium citrate – Liquo rice – Potassium Iodide – Lozenges – Guaifenesin – Linctus containing – Ipecacuanha 2.Mucolytic syrup. – – – – – Vasaka Bromhexine Ambroxal Dornase alfa Acetyl cysteine
  • 9. Centrally acting • Opioids – Codeine – Pholcodeine – Morphine – Ethylmorphine • Non Opioids – Noscapine – Dexomethorphan – Pipazethate – Chlophedinol – Oxeladin Centrally and peripherally acting • Benzonatate
  • 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:- (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
  • 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 100-200mg 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
  • 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 .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 100-200mg S/E: D, N, H • High doses cause vertigo.
  • 27. Specific treatment approach to cough Etiology of cough 1) Upper/lower respiratory tract infections 2) Smoking/chronic bronchitis Treatment Appropriate antibiotics Cessation of smoking 3) Pulmonary tuberculosis Antibiotics 4) Asthmatic cough Inhaled β2-agonists/ipratropium/corticosteroid 5) Postnasal drip (sinusitis) Antibiotics, nasal decongestants, antihistamines

Editor's Notes

  1. (Water release from nose).
  2. Drowsiness