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Marc Imhotep Cray, M.D.

 Cough—forceful release of air from lungs—is a sudden, often
involuntary reflex and a major defense mechanism

 Airway irritation activates reflex, which forcefully removes irritants, by

stimulating airways, which then activates afferent nerves going from
respiratory passages through vagus nerve to medulla

 Activated cough receptors in medulla drive a reflex that initiates

inspiration (2.5 L of air) increases contraction of diaphragmatic,
abdominal, and intercostal (rib) muscles increases lung pressure and
emits air and irritants (at 100 mph)

Marc Imhotep Cray, M.D.
Cough (2)
 Coughs triggered by drainage of mucus from nasal passages into airways
are treated with cough suppressants (antitussives)

 Infection-related coughs (eg, in bronchitis) last for approximately 2 weeks

 Persistent, chronic coughs (eg, in smokers) must be evaluated

 Coughs occurring with blood, chest pain, shortness of breath, weight

loss, or dyspnea may indicate serious disease

 Coughs in infants may indicate a serious lung disorder

Marc Imhotep Cray, M.D.
Etiology of Chronic Cough With a Normal Chest
Cause Prevalence
Postnasal drip 28-41%
Asthma 24-33%
GERD 10-21%
Chronic bronchitis 5-10%
Postinfectious (often, viral URI) 10%
bronchial hyperresponsiveness
Bronchiectasis 4%
ACE inhibitors, tracheomalacia, 5%
eosinophilic bronchitis,
psychogenic, etc
Redrawn after Raffa RB. Netter's Illustrated Pharmacology, Updated
Ed. Elsevier, 2014

Marc Imhotep Cray, M.D.
Causes of Chronic Cough With Abnormal Chest

Marc Imhotep Cray, M.D.
Cough Suppressants (Antitussive Agents)
Cough suppressants are opioids that reduce sensitivity of central cough
receptors to peripherally activated afferents
Receptor desensitization disrupts reflex and minimizes coughing

Opioids include
opiates (morphine and drugs derived from opium poppy plant, such as
hydromorphone, hydrocodone, and codeine) and
synthetic drugs that mimic effects of morphine

Opioids desensitize central cough receptors, reduce airway mucous secretion,

and alter mucous composition

Marc Imhotep Cray, M.D.
Antitussive Agents (2)
 Opioids also produce many adverse effects, including
 analgesia
 addiction
 sedation
 euphoria
 respiratory depression
 nausea & vomiting and
 Constipation
 Doses of opioids needed to suppress cough are lower than doses that
evoke most of undesirable effects, particularly analgesia and addiction
 Dextromethorphan, a morphine derivative and glutamate antagonist,
suppresses cough center and has fewer adverse effects than other opioids,
which accounts for its popularity in over-the counter preparations

Marc Imhotep Cray, M.D.
Marc Imhotep Cray, M.D.
Other Cough Suppressants
Benzonatate [Tessalon]
 Benzonatate is a glycerol derivative chemically similar to procaine
 Benzonatate reduces activity of peripheral cough receptors and also
appears to reduce threshold of central cough center

 Diphenhydramine is an H1-receptor antagonist; however, antitussive
activity is probably not mediated at this receptor
 Diphenhydramine acts centrally to decrease sensitivity of the cough
center to afferents

Marc Imhotep Cray, M.D.
Marc Imhotep Cray, M.D.
Further study:
 Unit 7: Drugs Used In Disorders Of The Respiratory System. In: Digital Guidebook 2015
Integrated Scientific and Clinical Pharmacology
 IVMS MedPharm Cloud Folder

 Drugs Used In Disorders Of The Respiratory System Notes
 Autacoids, Ergots, Anti-inflammatory Agents, and Immunosuppressive Agents Notes
o Histamine and its Antagonists
o Eicosanoids

Marc Imhotep Cray, M.D.