Drugs useful in cough. Dry cough Productive cough

3. Dr Bikash Meher,MBBS,MD
Asso prof.
Dept. of pharmacology
Pharmacotherapy
of
Cough

4. Learning objectives
Cough
Definition
Types
C0ugh reflex
Common causes
Classification of drugs
Individual drugs
Other treatment modalities
Mode of approach

5. Cough
 Protective reflex mechanism which removes foreign material
and excess respiratory secretion
 Involuntary reflex and major defensive mechanism
 Not to be suppress- Indiscriminately
 Many situations do not serve any purpose
 Disturb patient ,its rest and sleep

6.  Mechanism of Cough is complex
 Central and peripheral nervous systems involved
 Changes in Bronchial smooth muscle and bronchial mucosa
Is responsible
 Cough centre-Medulla
 Cough receptor-stretch receptor-pharynx,Larynx,Lungs
Mechanism of cough

8. The cough reflex.
Hadjikoutis S et al. QJM 1999;92:487-494

9. Irritation of bronchial mucosa cause broncho constriction
Stimulation of cough receptor
Afferent impulses to cough centre (medulla)
Efferent impulses via parasympathetic & motor nerves to
diaphragm, inter costal muscles & lung
Increased contraction of diaphragmatic, abdominal &
Inter costal muscles
Noisy expiration (cough)
Mechanism of Cough

10. Types of cough
Productive cough
Non-productive/Dry cough

11. Common causes of cough
 Upper/lower respiratory tract infection
 Allergic rhinitis
 Smoking
 Chronic bronchitis
 Pulmonary tuberculosis
 Asthma
 Gastro esophageal reflux
 Pneumonia
 Congestive heart failure
 Bronchiectasis
 Use of drugs ( ACE inhibitors)

12. Drugs which induce cough
ACE inhibitors
Amiodarone
Iodide
Beta blocker

13. Anti tussive – Cough suppressant ( tussis-cough)
Expectorants-Increase volume of mucus secretion
Mucolytic- Reduce viscosity of mucus
Mucokinetic-Increase mobility of cough

14. Classification of Drugs for cough
1.Antitussives
Centrally acting
Opioid mechanism (Codeine,pholcodeine,Levoopropoxyphene)
Non opioid mechanism (Noscapine,dextromethorphan)
Peripherally acting
Pharyngeal demulcent
Syrup,lozences
Steam inhalation

15. 2.Expectorants
Directly acting
Guaiphensin, sodium citrate
Indirectly acting
Ipepcac,Ammonium salt
3.Mucolytic
Bromhexine,ambroxol,acetylcysteine,methyl cysteine
4. Others
Antihistamine,Bronchodilators,Local anesthetic

16. Antitussives
 Ideally cough should not be suppressed
 Treatment of underlying cause
 Drugs which suppress cough-Antitussives
M.O.A
 Raise threshold of cough centre in medulla
 In respiratory tract reduce tussal impulse
 Useful for dry cough

17.  Semi synthetic opioid analgesic
 Less potent than morphine
 More selective for cough centre
 Potent cough suppressant action at low dose (10 mg BD)
 Anti tussive action –blocked by Naloxone
 Has less addiction
S/E
 Constipation ,Drowsiness, Respiratory depression
 Contraindicated in bronchial asthma
Codeine

18. Pholcodeine
 Antitussive efficacy similar to codeine
 No analgesic/addictive effect
 Longer acting
 Dose 10-15mg 3-4 times a day

19. Noscapine
Opium alkaloids belongs to benzyl isoquinoline group
No addictive, analgesic & constipating properties
Do not interfere with mucocilliary movement
Different mechanism
Release histamine
S/E
Nausea,headache,tremor,bronchoconstriction
Dose 15 mg

20. Dextromethorphan
D-isomer of methorphan
Raise threshold for cough centre
Antitussive action not blocked by Naloxone
M.O.A
NMDA receptor antagonist
Least addiction and constipation, Minimal drowsiness
No analgesic action, No affect on mucocilliary action
Uses
Use along with antihistamine and bronchodilator as suppressant
S/E
Nausea, vomiting, ataxia
Dose- 10mg TDS

21. Pharyngeal demulcents
Demulcent –Demulcere ( Caress)
Sooth throat
Reduce afferent impulse from inflamed pharyngeal mucosa
Symptomatic relief in dry cough
Syrup, Lozenges

22. Q.A young patient is diagnosed with asthma. His primary
symptom is frequent cough ,not bronchospasm and
wheezing.Ashthma medication started but until their
effect develop we want to suppress the cough without
running risk of suppressing ventilatory drive or causing
sedation. Which is the best drug for this?
A.Codeine
B.Dexomethorphan
C.Promethazine
D.None of the above

23. Expectorants
Expectorare- drive from chest
↑Bronchial secretion,↓Viscoscity
Facilitates removal
Directly acting
Guaifenesin ,Na+ & K+ citrate or acetate
Reflex acting
Ammonium salt
Both
Potassium Iodide

24. Sodium & potassium citrate or Acetate
M.O.A
 Bronchial secretion by salt action
Guaifenesin
 Expectorant drug usually taken by mouth
M.O.A
 Increase airway secretion and mucocilliary activity
 Dose 100-200mg BD
Ammonium chloride,Ipecac
 Reflexly increase respiratory secretion
 Gastric irritant

25. Potassium Iodide
 Direct
 Indirect
 Liquefaction of tenacious sputum
A/E
 Metallic taste, Swelling of salivary and lacrimal gland
 Hypothyroidism
 Dose-300mg TDS

26. Mucolytics
Acetyl cysteine
M.O.A
 Reduce viscosity of sputum by opening disulfide bond of
mucoprotein
S/E
 Nausea,vomiting,stomatitis,bronchospasm,rhinorrhea
 Dose 200mg
 Administer directly to respiratory tract

27. Carbocysteine
 Liquefies viscid sputum
 Other mode of action
S/E
 G.I irritation
 Dose 250-750mg TDS

28. Bromhexine
 Synthetic derivative of vasicine (Vasaka)
M.O.A
 Depolymerization of muco polysaccharide
 Increasing lysosomal enzyme activity
 ↑ volume & ↓ viscosity of sputum
S/E
 GIT upset, rhinorrhea,lacrimation
Uses
Useful where mucus plug present(tracheostomy,emphysema,CF)
Dose 30mg TDS

29. Ambroxol
 Metabolite of bromhexine
 Similar properties
 Dose 15-30 mg TDS
Dornase alfa
 Human recombinant DNAse
 Cleaves DNA
 Useful in Cystic fibrosis
 Given by inhalation
 Dose 2.5mg OD

30. Q.Which of the following statements regarding opiate action
is correct?
A. Trigger vagal reflex to suppress cough
B.Cause diarrhea
C.Stimulate production of cough
D.Suppress cough centre

31. Q.Which is NOT a mucolytic?
A.Ambroxol
B.Acetylcysteine
C.Bromhexine
D.Potassium iodide

32. Antihistamines
Added to antitussives/expectorant formulation
Relief in cough due to sedative & anticholinergic actions
Lack selectivity for cough centre
No expectorant action
↓Secretions (anticholinergic effect)
Suitable for allergic cough but not for asthma
Ex.Chlorpheniramine, diphenhydramine, promethazine

33. Bronchodilators
Bronchospasm induce or aggravate cough
M.O.A
↑Surface velocity of air flow during cough
 Clear secretions of airway
Not used routinely for every type of cough
Use only when bronchoconstriction is present ( Bronchial
asthma)
Ex. β2-agonist (salbutamol, terbutaline)

34. Local anesthetic
 Lignocaine
 For intractable cough of Bronchial carcinoma
 Administer by nebulizer
 To prevent cough during endoscopy
 Instill topically in airway

35. Role of hydration in cough
DeHydration increase viscosity of secretion
Adequate fluid –decrease viscosity
Highly effective
Role of steam inhalation
Useful for liquefaction of tenacious sputum
Role of other agents

36. Specific treatment approach to cough
Etiology of cough Treatment approach
1.Upper/lower respiratory Appropriate antibiotics
tract infections
2. Smoking/chronic bronchitis Cessation of smoking
3. Pulmonary tuberculosis Antitubercular drug
4. Asthmatic cough Inhaled β2-agonists/iprat-
ropium/corticosteroid
5. Postnasal drip (sinusitis) Antibiotics, nasal decongestants
Antihistamine
6.Gastroesophageal reflux PPI,diet modification
7.ACE inhibitor Losartan

37. Summary
Cough-protective reflex
Treat underlying cause
Provides symptomatic treatment
Antitussive –Suppress cough centre
Opioid&non opiod
Mucolytic-Lysis
Mucokinetic –Facilitates expulsion
Adjuvants-Anti-histamine,Bronchodilator

38. Thank you