Mbbs

1. Antitussive and
mucolytic drugs
Dr. Yusuf O. Ahmed, MBBS, Ph.D.
Department of Clinical Pharmacology & Therapeutics
Federal University of Health Sciences, Azare

2. Outline
• Introduction
• Classification of cough drugs
• Mucolytics (Expectorants)
• Antitussives
• Adjuvant antitussives

3. Introduction
• Cough is a common symptom of airway diseases, but its
mechanism is not well understood.
• Cough is a protective reflex that is intends to expel
respiratory secretions or foreign particles from airway.
• It occurs due to stimulation of mechano- or chemoreceptors
in throat, airway or stretch receptors in the lungs.

4. Introduction continued
• There are different etiology of cough (Table 1) but viral
infections of the URT are the most common cause of cough.
• Post-viral cough is usually self-limiting and commonly
patient-medicated.
• Notwithstanding, the wide use of over-the counter cough
medications are largely ineffective.

5. Introduction continued
• Because cough is a defensive reflex, its suppression may be
inappropriate in bacterial lung infection.
• Thus, before treatment of cough with antitussives, it is
important to understand the underlying causal mechanism
that may require therapy.
• Whenever possible treat underlying cause, not the cough.

6. Table 1. Different etiology of cough and therapeutic approach

7. Introduction – types of cough
• There are two types of cough:
1. Productive (useful) cough
2. Unproductive (useless) cough
• Productive cough serves to drain the airway, thus, it
should not be suppressed except if the amount of
expectoration is small and effect of continuous coughing is
very high.
• In unproductive cough, cough suppressants can be used to
treat this symptom.

8. Introduction – Physiology of cough
• The production and removal of bronchial secretions is a normal
function of the respiratory tract.
• The bronchial secretion consists of 2 phases, soluble and insoluble in
water.
• The soluble phase contain electrolytes and locally synthesized proteins.
• The insoluble phase contain a gel-like consistency that is
predominantly glycoprotein complexes called mucins.

9. Physiology of cough continued
• Mucociliary transportation is responsible for bronchial
excretion of mucus and foreign substances attached to the
mucus.
• The speed of mucus movement is from 4 to 20 mm per
minute.
• The cough reflex will be activated when there is disturbance
in this physiological mechanism, or if there is presence of
foreign substance in the respiratory tract.

10. Classes of Drugs used for cough
• Cough may be treated as a symptom (nonspecific
treatment) by the following class of drugs:
1. Pharyngeal demulcents examples are lozenges, cough
drops, glycerin, and liquorice.
2. Expectorants (mucokinetics)
3. Antitussives (cough center suppressants)
4. Adjuvant antitussives examples are salbutamol,
terbutaline and any other bronchodilator.

11. Demulcents and Expectorants
• Pharyngeal demulcents: sooth the throat and reduce
afferent impulses from the inflamed/irritated pharyngeal
mucosa.
• They provide symptomatic relief in dry cough arising from
throat.
• Expectorants (Mucokinetics): are drugs that increases
bronchial secretion or reduce its viscosity.
• They facilitate removal of bronchial secretion by coughing.

12. Demulcents and expectorant
continued
• Examples of expectorants are:
• Sodium and potassium citrate
• They are considered to increase bronchial secretion by salt action.
• Guaiphenesin, vasaka, and tolu balsum
• They are plants/botanical products that enhance bronchial secretion and
mucociliary function.
• Most of these expectorants are combined with antitussive
drugs, although efficacy of these drugs are non-conclusive.
• Infant steam inhalation and proper hydration maybe more
helpful.

13. Example of expectorant continued
• Mucolytics:
• Bromhexine: a derivative of alkaloid vasicine obtained from
Adhatoda vasica. It is a potent mucolytic and mucokinetic, capable
of inducing thin and copious bronchial secretion.
• Bromhexine depolymerizes mucopolysaccharides directly by
liberating lysosomal enzymes—network of fibers in tenacious
sputum is broken.
• It is particularly useful when there is mucus plugs.
• Common side effects of bromhexine are rhinorrhea and
lacrimation, nausea, gastric irritation, and hypersensitivity.

14. Mucolytics continued
• Other mucolytic drugs are:
• Ambroxol – a metabolite of bromhexine with similar mucolytic
action, uses, and side effects.
• Acetylcysteine – it opens disulfide bonds in mucoproteins present
in sputum to makes it less viscid.
• Carbocisteine – its action is similar with acetylcysteine. It is
beneficial to patients with chronic bronchitis. It is contraindicated
in PUD because of its ability to break gastric mucosal barrier.

15. Antitussive drugs
• They are also known as cough suppressant.
• They can act in the CNS to raise the threshold of cough center.
• They can also act peripherally in the respiratory tract to reduce tussal
impulses.
• Antitussives, goal is to control cough, thus, they should be used only
for dry nonproductive cough, cough that is unduly tiring, disturbs
sleep or is dangerous (hernia, piles, cardiac disease, ocular surgery).

16. Classification of antitussives
1. Opioids: Codeine, Ethyl morphine, and Pholcodeine.
2. Nonopioids: Noscapine, Dextromethorphan, and
Chlophedianol.
3. Antihistamines: Chlorpheniramine, Diphenhydramine, and
Promethazine.
4. Peripherally acting: Prenoxdiazine.

17. Opioids antitussives
• Codeine:
• It is a methyl-morphine that occurs naturally in opium alkaloid and
can be converted into morphine.
• It can be used as a centrally acting antitussive drug, usually in
combination with other substances.
• It has a weak narcotic (opiate) and analgesic effect; therefore, it can
used as a component of painkillers.
• By the nature of its action, codeine is close to morphine, but the
analgesic properties are less pronounced; the ability to reduce the
excitability of the cough centre is strongly expressed.
• To a lesser extent than morphine, it depresses respiration.

18. Codeine continued
• The activity of codeine is good activity when given by the
oral route.
• A single oral dose acts for 4–6 hours.
• The abuse liability is low.

19. Codeine continued
• Constipation is a prominent side effect especially when it is
used as analgesic.
• At higher doses respiratory depression and drowsiness can
occur, especially in children.
• It is contraindicated in asthmatics and in patients with
diminished respiratory reserve; should be avoided in
children

20. Non-opioids antitussives
• Noscapine (Narcotine)
• It is an opium alkaloid of the benzoisoquinoline derivatives.
• It depresses cough but has no narcotic, analgesic or dependence
inducing properties.
• It is nearly equipotent antitussive as codeine.
• Headache and nausea occur occasionally as side effect.
• It can release histamine and produce bronchoconstriction in
asthmatics.

21. Non-opioid antitussives continued
• Dextromethorphan
• A synthetic central NMDA (N-methyl D-aspartate) receptor
antagonist.
• Its d-isomer has antitussive action while l-isomer is analgesic.
• DXM does not depress mucociliary function of the airway mucosa
and is practically devoid of constipating action.
• They are considered non-addicting; some drug abusers indulge in
it.
• The antitussive action of DXM has been rated equivalent to codeine
but clinical studies suggest otherwise.
• Side effects - Dizziness, nausea, drowsiness; at high
• doses hallucinations and ataxia.

22. Antihistamine
• Many H1 antihistamines have been conventionally added to
antitussive/expectorant formulations.
• The relief in cough is due to there sedative and
anticholinergic actions, but lack selectivity for the cough
center.
• They have no expectorant property, may even reduce
secretions by anticholinergic action.

23. Antihistamine continued
• They have been specially promoted for cough in respiratory
allergic states.
• Examples of antihistamine are:
• Chlorpheniramine
• Promethazine
NB – Second generation antihistamines like fexofenadine,
loratadine, etc. are ineffective.

24. Peripheral acting antitussives
• Prenoxdiazine
• In contrast to other antitussives, it acts peripherally.
• It desensitizes the pulmonary stretch receptors and reduces tussal
impulses originating in the lungs.
• It is indicated in cough of bronchial origin.

25. Thank You