3. Home remedy for cough
Honey is the better treatment than
most commonly available OTC drugs
and almost have equal activity as
dextromethorphan in reducing
frequency of cough in children 2-5
yrs - Cochrane review
4. Objectives of the class
At the end of the class you should be able to
• Explain the physiology of cough
• Classify antitussives and their pharmacology
• Classify the drugs used in productive cough and their pharmacology
5. PHYSIOLOGY OF COUGH
• A physiological protective reflex, happens spontaneous and voluntary act
• Stimuli - irritation of the lining of the trachea and extrapulmonary bronchi
• It tries to clear away the foreign bodies or its secretions
• Receptors:– RAR, SAR, and C fibers; -mechanical 2-10um and chemical irritants
• Afferent: Vagus nerve – trachea-bronchial tree, larynx, pharynx
• Centre: medulla oblongata – dorsal side
• Efferents vagus, phrenic and spinal motor neurons - expiratory muscles
6. PHYSIOLOGY OF COUGH
• Receptorial phase: stimulation of cough receptors – vagus nerve – cough centre
• Inspiratory phase: wide opening of the glottis with rapid inhalation
• Compressive phase: prompt closure of the glottis- strong contraction of the
abdominal muscles, expiratory muscles - intrapulmonary pressure (100mmHg) -
compression of the alveoli and bronchioles.
• Expiratory phase: vocal cords and epiglottis open suddenly – explosion of air
(965 km) from the lungs to the outside.
7. COUGH as a SYMPTOM
• People seek medicines – the distressing and exhausting nature of the cough
• In chronic conditions worrisome
• Cough more than 3 weeks – problematic
• Cough can be a pathological symptom
• Bronchitis, bronchiectasis, cancer, cigarette smoking etc
Cough helps clear secretions
Always treat the underlying cause not the symptom
8. Treat the Underlying cause
Cause Treatment
Viral URTI Symptomatic
Bacterial URTI Appropriate antibacterial drugs
Pulmonary TB Antitubercular drugs
Smoking, bronchiectasis,
chronic bronchitis
Cessation of smoking, avoidance of pollutants; steam
inhalation, postural drainage
Asthma Drugs for Asthma
GERD Prokinetics, PPIs and other drugs for GERD
Drug-induced Change the drug; symptomatic
9. TYPES OF COUGH
• Productive Cough
• Cough with Expectoration
• Non-productive Cough
• Dry Cough
13. EXPECTORANTS – Mucokinetics
• Guaifenesin,
• Most commonly used
• Increases secretion - ↓ viscosity and adhesiveness
• Soothing effect
• ADR: Nausea, abdominal pain, drowsiness, and rashes
• Potassium iodide – ↑ secretion by irritation, not used due to thyroid interactions
• Sodium/ Potassium citrate- ↑ Secretion by salt action
• Essential oils- Stimuate endo tracheal gland secretions
• Ammonium chloride – acts indirectly by ↑ Parasympathetic secretions
14. EXPECTORANTS – Mucolytics
• Bromhexine – Adathodai
• Copious secretion of glands - Mucokinetic
• Mucolytic - depolymerizing mucopolysaccharides – lysosomal enzymes
• ADR: rhinorrhea, lacrimation and gastric secretions
• Ambroxol – metabolite of Bromhexine
• Acetylcysteine & Carbocisteine
• Breaks the disulphide bonds in the sputum proteins
• Both has favourable role in tracheostomy, cystic fibrosis, mucus plugs
• Used as directs instillation and nebulisations
• ADR: Breaks gastric mucus barrier – CI in Peptic ulcer
15. EXPECTORANTS – Mucolytics
Acetylcysteine : Other uses
• Acute paracetamol poisoning: oral, IV
• Dry eye (keratoconjunctivitis sicca): 0.5% eye drop
• Hemorrhagic cystitis due to cyclophosphamide/ ifosfamide: intravesical
• DORNASE Alpha
• Highly purified solution of human DNAase
• Secretions in cystic fibrosis contain large amount of extracellular DNA
• Dornase selectively breaks down DNA
• Dornase Alfa is administered through inhalation to reduce viscosity of
respiratory secretions in cystic fibrosis
• Used 2.5 mg inhalation
17. ANTI-TUSSIVES
• Drugs that supresses cough by reducing threshold
• Opioids – acts by opioid receptors – abuse liability
• Codeine , Pholcodeine and ethyl morphine
• Non Opioids
• Centrally acting -Dextromethorphan, Noscapine, clophendianol
• Peripherally acting - Prenoxdiazine, benzonatate
• Anti-histaminics H1– sedation and anti-cholinergic action
• Diphenhydramine, Chlorpheniramine, promethazine
18. ANTI-TUSSIVES- Therapy
• For treatment of troublesome dry cough in cases such as:
• Distressing in day time
• Patient not able to sleep in night
• Consequences of persistent cough are serious, eg, post-cardiac surgery, post-
ocular surgery, hernia, etc
• Absolutely avoid in cough with expectoration
• Problems with antitussives (codeine): constipation, abuse liability, asthma
worsening, respiratory depression
19. ANTI-TUSSIVES - Opioids
• Codeine – acts by opioid receptors -action reversed by antagonist naloxone
• Weak opioid receptor agonist
• Cures cough, causes constipation
• Abuse liability minor, but present
• High doses: drowsiness, respiratory depression (especially in children)
• Histamine release bronchoconstriction: avoided in asthmatics
Pholcodeine, Ethylmorphine
• Similar to codeine, but less constipating and lower abuse liability
20. ANTI-TUSSIVES – Non-Opioids
Dextromethorphan – equipotent to codeine but no constipation
• Opioid by origin, but has no action on opioid receptors
• NMDA receptor agonist; involvement in cough suppression-not established
• Raises cough threshold: exact MoA still unknown
• ADRs: histamine release (avoid in asthmatics); nausea, headache
Noscapine
• Opioid by origin, but no action on opioid receptors
• But at higher doses-bronchoconstriction & hypotension due to release of
histamine
21. ANTI-TUSSIVES – Non-Opioids
Prenoxdiazine – Peripherally acting
• Desensitizes pulmonary stretch receptors reduces tussal impulses originating
in the lungs.
• Poor efficacy -May be used in cough of bronchial origin
Benzonatate - related to local anaesthetic- tetracaine.
• Usefull in diagnostic laryngoscopy
• Has both central as well as peripheral action-
• Suppress cough center & Inhibits pulmonary stretch receptors
• ADR-dizziness, dysphagia, severe allergic reaction
22. ANTI-TUSSIVES – Antihistaminics
Diphenhydramine
• H1 Antihistamine
• No direct antitussive mechanisms
• Relieve cough by their sedative effect day time sedation is undesirable
• Due to their anticholinergic action, secretions may dry up harmful
• Chlorpheniramine and Promethazine were also been used
24. Other drugs
Pharyngeal demulcents
• Coats Pharynx sensory receptors
• Soothing effects
• Only useful in cough of above larynx origin – eg sorethroat
Bronchodilators
• Salbutamol - Relieve cough if it is due to bronchospasm
• Asthma, asthmatic bronchitis, eosinophilic bronchitis
• Use is irrational in other types of cough
Aeromatic chest rubs - studies shows usefull only in healthy volunteers
25. Other Modalities
Steam inhalation
• Economic & safe method of treating cough.
• Effective in cough originating below larynx
• Helpful for adequate and desired liquefaction of sputum required for mucociliary
action to expel out.
• Addition of eucalyptus oil or menthol not usefull but for aroma
Hydration
• Dehydration increase the viscosity of bronchial secretion.
• Maintaining hydration by adequate intake of fluid reduces the viscosity.
26. Novel drugs
Transient receptor Potential Antagonists (Vanilloid receptors)
Airway sensory receptor ion channel
In trial
promising in chronic persistent cough
drug induced cough by bradykinin esp. capsaicin
Gefapixant
ATP receptor P2Xa Antagonist
Chronic idiopathic cough
Dysguesia
27. FDC in COUGH
• Majority of ‘cough syrups’ available in market are irrational
• Expectorant + antitussive: irrational
• Expectorant + antihistaminic: irrational (antihistaminic dries up secretions)
• Antitussive + antihistaminic: irrational (antihistaminic has no additional
antitussive MoA; causes undesirable sedation)
• Any drug for cough + bronchodilator: irrational, except in cases where
bronchodilators are indicated
• Any drug for cough + antibiotic: irrational, costlier, HARMFU
