This document discusses different types of antitussive drugs used to suppress cough. There are three main types - centrally acting drugs that work in the brain cough center, antihistamines, and bronchodilators. Centrally acting drugs include codeine, noscapine, and dextromethorphan which work by penetrating the brain and suppressing the cough reflex. Antihistamines like chlorpheniramine are used when cough is due to allergies. Salbutamol is a bronchodilator that relieves cough by dilating constricted bronchioles. The effectiveness of centrally acting drugs is debated as they may not work as well for upper airway coughs. New mechanisms

1. Antitussive
(Drugs for Dry cough)

2. • Cough is a normal physiological reflex action
to irritation in larynx, trachea or in bronchi
• It functions to expel irritating materials or
mucus secretions from the respiratory tract
• Cough is useful but frequent, severe and
nonproductive cough can be irritating, painful
or disturb sleep and needs to be controlled
• Cough is not a disease but a symptom of
underlying diseases

3. larynx, trachea and bronchi

4. Causes of different coughs
Dry cough Productive cough
•Bronchospasm. •Smoking, Tobacco
•Allergies •Nasal Discharge
•ACE inhibitors •GERD
•Asthma •COPD
•Exposure to dust,
fumes, and chemicals
•pneumonia,
bronchitis, sinusitis, or
tuberculosis
•Dry cough needs to be suppressed
•Productive cough needs to be promoted

5. There are three types of antitussives
• Centrally acting : Codiene, Noscapine,
Dextromorphan
• Antihistamines : Chlorpheniramine
• Bronchodilators : Salbutamol

6. Centrally acting (CNS acting)
• The cough center of the brain located in the
medulla oblongata area of the brain is a
region of the brain which controls coughing.
• Drugs that act this way need to have good
penetration into the brain ie they are very
liphophillic

8. Codiene
• It is a weak opiod agonist that shows activity by action
on cough centre in the brain
• Weak opiod activity limits its addiction potential but it
has sedative effects and it is metabolized into
morphine
• Thus addicts take the OCT formulation of codeine in
higher amounts to counter withdrawal effects of heroin
• It’s safer alternative is pholcodeine since among it’s 7
different metabolites in human, morphine only occurs
in trace amounts
• http://www.ncbi.nlm.nih.gov/pubmed/2383296

9. Noscapine
• It is a benzylisoquinoline alkaloid from plants of
the Papaveraceae family
• It is found in street heroin as a contaminant
• Noscapine is non-addictive and has a low side-
effect incidence
• This agent is primarily used for its antitussive
effects
• It is under study for possible cancer cure

10. Dextromethorphan(DXM)
• It is a morphinan type opiod anonist
that has less sedation potential than codiene
• DXM is also used recreationally. When
exceeding label-specified maximum dosages,
dextromethorphan acts as a dissociative
hallucinogen
• Primary metabolite is a NMDA receptor
antagonist ie has a CNS depressant effect
• Used in an OTC antitussive medication and

11. Antihistamines
• The antitussive activity of antihistamines are
established from clinical trials (not enough
research to establish MOA)
• Following effect has been linked to antitussive
action of Antihistamines but no research is
conclusive enough
– Sedative (study shows non-sedating Antihistamines
are not antitussive)
– Anticholinergic (no rank based action)
– histamine H1 receptor binding strength (no rank
based action)
Ref: Older-Generation Antihistamines and Cough Due to Upper Airway Cough
Syndrome (UACS): Efficacy and Mechanism. Lung 2008

12. Chlorpheniramine
• It is a first-generation alkylamine antihistamine used in
the prevention of the symptoms of allergic conditions
such as rhinitis and urticaria(skin rash).
• Its sedative effects are relatively weak compared to
other first-generation antihistamines.(this is an
advantage)
• Combined with opiods for OTC cough preparations
• The antihistamine is helpful in cases where allergy is the
reason for the cough

13. Bronchodilators: Salbutamol
• It is short-acting β2-adrenergic receptor agonist.
• Constriction of bronchioles caused by allergen,
asthma or exercise induced leads to cough
• Salbutamol dilates bronchioles thus providing
relief
• It is absorbed through the lungs and administered
by an inhaler.
• (R)/Levo-salbutamol has a 100-fold greater
binding affinity than (S)/Dextro-salbutamol for
the β2-adrenergic receptor.

14. THANK YOU

15. Spot the difference!
Target site- lungs
Targetsite - Brain
Look at the two molecules. Based on the differences in their
site of action and in structure what GENERAL difference in
Their design can you conclude?

16. Review of Antitussives
Topics covered
• Current and future of centrally acting
antitussives
Ref: Respir Physiol Neurobiol. 2006 July 28; 152(3): 349–355
• Antitussive effect of 2nd generation
antihistamines
Ref: Br J Clin Pharmacol, 2003, 56, 501–504

18. Current and future of centrally acting
antitussives
• The efficacy of codeine and
dextromethorphan in humans has recently
been questioned
• They are less effective on cough induced by
upper airway disorders than conditions
involving the lower airways in humans.
• The reasons are not clear.

19. • Codeine was effective against cough in
patients with lower airway disease (Sevelius
and Colmore, 1966; Sevelius et al., 1971)
• Codeine was found to be ineffective in
patients with cough due to upper airway
disorders (Aylward et al., 1984)

20. Is there no future scope for centrally
acting antitussives???
• peripherally acting antitussives have worked
in animal models and are proposed as a safer
alternative
• there is no rationale that would support
greater efficacy i those that act peripherally
acting ones

21. New directions
i) There is an urge to cough. The more we cough,
more we want to do it again
ii) Also we can sometimes voluntarily block
cough
These two observation indicate novel
mechanism of cough control that are different
from the old cough centre theory
Thus Drugs designed to act on these novel
mechanism are hypothized to be better
centrally acting antitussives

22. 2nd generation Antihistamines
• First-generation antihistamines block both
histaminic and muscarinic receptors as well as
passing the blood-brain barrier.
• Second-generation antihistamines mainly
block histaminic receptors and do not pass
the blood-brain barrier.

23. 2nd gen antihistamines are useless in cough
• Fexofenadine demonstrated no antitussive
activity against capsaicin-induced cough in 12
healthy volunteers and 12 patients with
Upper respiratory tract infection.

24. 2nd gen antihistamines are useless in stopping
sneezing
Loratadine, failed to suppress sneezing in
rhinovirus induced cold in 66 adults
Ref: Clin Infect Dis., 2001, 33 (9), 1483-1488