PHARMACOLOGY – III PREPAIRED BY: MR.

RAHUL SINGH SHAKTAWAT

[UNIT – I, PART – A, CHAPTER – 3] WEBSITE LINK: https://drugee.wordpress.com/

[CHAPTER – 3]
Expectorants and Antitussives:
1. Definition
• Expectorants: Drugs that increase the secretion of mucus in the respiratory tract, making
it less viscous and easier to expel by coughing. They are used in conditions where
excessive mucus production causes airway obstruction.
• Antitussives: Drugs that suppress cough reflex either centrally (by acting on the
medullary cough center) or peripherally (by soothing irritated airways). They are used
in non-productive coughs where coughing is distressing or harmful.
2. Principles of Toxicology and Treatment of Various Poisonings
A. Toxicology of Expectorants and Antitussives
Some cough medications contain opioid derivatives (e.g., codeine) or other CNS depressants (e.g.,
dextromethorphan), which may cause serious toxicity in overdose cases.
1. Expectorants (e.g., Guaifenesin, Ammonium chloride)
• Generally safe but may cause nausea, vomiting, dizziness in high doses.
• Chronic excessive use may lead to kidney stones (Guaifenesin-related lithiasis).
2. Antitussives
• Opioid-based (Codeine, Hydrocodone)
• Overdose can cause respiratory depression, sedation, hypotension, and
coma.
• Non-opioid (Dextromethorphan, Benzonatate)
• Overdose may cause hallucinations, ataxia, CNS depression, serotonin
syndrome (especially when combined with SSRIs/MAOIs).
B. Treatment of Poisoning
• Opioid Antitussive Overdose (e.g., Codeine, Hydrocodone)
• Naloxone (opioid antagonist) IV for respiratory depression.
• Supportive care (oxygen, ventilation, IV fluids) if necessary.
• Dextromethorphan Overdose
• Activated charcoal if ingested within 1 hour.
• Benzodiazepines for seizures/agitation.
• Supportive measures (IV fluids, monitoring of cardiac function).
3. Classification with Dosage
A. Expectorants
1. Mucolytics (Reduce Mucus Viscosity)
• Examples: Acetylcysteine, Carbocisteine

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 PHARMACOLOGY – III PREPAIRED BY: MR. RAHUL SINGH SHAKTAWAT
[UNIT – I, PART – A, CHAPTER – 3] WEBSITE LINK: https://drugee.wordpress.com/

• Dose: 200-600 mg orally three times daily

2. Reflex Stimulants (Enhance Bronchial Secretion by Gastric Irritation)
• Examples: Guaifenesin, Ammonium chloride
• Dose: 200-400 mg every 4-6 hours
3. Direct Stimulants (Increase Bronchial Gland Activity Directly)
• Examples: Potassium iodide
• Dose: 300-600 mg orally three times daily
B. Antitussives
1. Central-Acting (Medullary Cough Center Suppression)
• Opioid Derivatives
• Examples: Codeine (10-30 mg every 6-8 hours), Hydrocodone (5-10 mg every
4-6 hours)
• Non-Opioid
• Examples: Dextromethorphan (10-20 mg every 4-6 hours)
2. Peripheral-Acting (Suppress Cough by Reducing Airway Irritation)
• Examples: Benzonatate (100-200 mg three times daily)
4. Mechanism of Drug Action and Its Relevance in Treatment: Cough is a protective
reflex that helps clear secretions and foreign materials from the respiratory tract. However,
excessive coughing — whether productive (with mucus) or non-productive (dry cough) — can
be harmful and distressing. The mechanism of action of expectorants and antitussives varies
based on their target pathways in the respiratory system.
A. Expectorants
Function: Expectorants increase mucus secretion or reduce mucus viscosity, facilitating
easier expectoration (coughing up phlegm).
1. Mucolytics (Reduce Mucus Viscosity)
• Examples: Acetylcysteine, Carbocisteine, Bromhexine
• Mechanism of Action:
1. Acetylcysteine and carbocisteine break down disulfide bonds in mucoproteins.
2. This reduces mucus viscosity, making it thinner and easier to expel.
3. In addition, acetylcysteine replenishes glutathione levels, providing antioxidant
effects beneficial in COPD and cystic fibrosis.
• Relevance in Treatment:
• Used in chronic lung diseases like COPD, chronic bronchitis, cystic fibrosis, and
pneumonia, where mucus build-up obstructs airflow.

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 PHARMACOLOGY – III PREPAIRED BY: MR. RAHUL SINGH SHAKTAWAT
[UNIT – I, PART – A, CHAPTER – 3] WEBSITE LINK: https://drugee.wordpress.com/

• Prevents mucus plugging, reducing the risk of respiratory infections and

exacerbations.
2. Reflex Stimulants (Increase Bronchial Secretion by Gastric Irritation)
• Examples: Guaifenesin, Ammonium chloride
• Mechanism of Action:
1. These drugs act on gastric mucosa, stimulating vagal sensory fibers.
2. This triggers a reflex increase in bronchial gland secretion, leading to thinner
mucus.
3. The increase in mucus volume reduces its viscosity, facilitating easier clearance.
• Relevance in Treatment:
• Effective in productive cough due to common cold, influenza, or mild
respiratory infections.
• Helps prevent airway obstruction by thick mucus, especially in children and
elderly patients.
3. Direct Stimulants (Increase Bronchial Gland Activity Directly)
• Examples: Potassium iodide, Sodium citrate
• Mechanism of Action:
1. These drugs are absorbed into the bloodstream and directly act on bronchial
glands.
2. This leads to increased mucus secretion, reducing mucus thickness and
adhesiveness.
• Relevance in Treatment:
• Used in chronic bronchitis and asthma where excessive mucus retention occurs.
• Potassium iodide has additional anti-inflammatory properties, reducing airway
irritation.
B. Antitussives
Function: Antitussives suppress excessive coughing by acting on the central nervous system
(CNS) or peripheral sensory receptors in the airways.
1. Central-Acting Antitussives (Medullary Cough Center Suppression)
• Opioid Derivatives (Codeine, Hydrocodone)
• Mechanism of Action:
1. Codeine and hydrocodone bind to µ-opioid receptors in the medullary cough
center (in the brainstem).
2. This suppresses the cough reflex, reducing the frequency and severity of coughing.

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 PHARMACOLOGY – III PREPAIRED BY: MR. RAHUL SINGH SHAKTAWAT
[UNIT – I, PART – A, CHAPTER – 3] WEBSITE LINK: https://drugee.wordpress.com/

3. They also have mild sedative and analgesic effects, which help soothe airway
irritation.
• Relevance in Treatment:
• Used for severe, dry coughs that interfere with sleep or cause chest pain.
• Contraindicated in COPD patients due to risk of respiratory depression.
• Risk of addiction and dependence with prolonged use.
• Non-Opioid (Dextromethorphan, Pholcodine)
• Mechanism of Action:
1. Dextromethorphan acts on σ-opioid receptors and NMDA receptors in the
medulla.
2. This inhibits cough center activity, reducing cough frequency.
3. Unlike codeine, it lacks significant sedative or analgesic effects.
• Relevance in Treatment:
• Used for mild-to-moderate non-productive coughs.
• Safer alternative to opioid-based antitussives, as it has lower addiction
potential.
2. Peripheral-Acting Antitussives (Suppress Cough by Reducing Airway Irritation)
• Example: Benzonatate
• Mechanism of Action:
1. Benzonatate is an ester-linked local anesthetic.
2. It numbs stretch receptors in the lungs and airways, preventing cough signals
from reaching the brain.
3. This reduces cough reflex sensitivity, without affecting CNS function.
• Relevance in Treatment:
• Used in coughs associated with lung cancer, pneumonia, and post-surgical
conditions.
• Preferred when opioid use is contraindicated (e.g., in elderly patients).

C. Combination Therapy for Cough Management

• In productive coughs, expectorants (e.g., guaifenesin, acetylcysteine) loosen mucus,
making it easier to expel.
• In dry, persistent coughs, antitussives (e.g., dextromethorphan, codeine) suppress
excessive coughing.
• In cases of cough with airway inflammation, a combination of anti-inflammatory agents
(e.g., steroids) and expectorants is effective.

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 PHARMACOLOGY – III PREPAIRED BY: MR. RAHUL SINGH SHAKTAWAT
[UNIT – I, PART – A, CHAPTER – 3] WEBSITE LINK: https://drugee.wordpress.com/

Summary of Mechanisms and Treatment Relevance

Drug Class Mechanism of Action Relevance in Treatment
Mucolytics (Acetylcysteine, Used in COPD, cystic
Breaks disulfide bonds in mucus
Bromhexine) fibrosis, pneumonia
Reflex Expectorants (Guaifenesin, Stimulate gastric receptors → reflex Used in common cold,
Ammonium chloride) bronchial secretion bronchitis
Direct Expectorants (Potassium
Stimulate bronchial glands directly Used in chronic bronchitis
iodide, Sodium citrate)
Opioid Antitussives (Codeine, Suppress medullary cough Used in severe dry coughs
Hydrocodone) center via µ-opioid receptors (lung cancer, pleurisy)
Non-Opioid Antitussives Inhibits σ-opioid and NMDA Used in mild-to-moderate
(Dextromethorphan) receptors in the brain dry coughs
Numbs cough receptors in the Used in post-surgical cough,
Peripheral Antitussives (Benzonatate)
airways pneumonia
5. Therapeutic Effects
1. Expectorants
• Promote mucus clearance, improving breathing in respiratory infections, COPD,
bronchitis.
2. Antitussives
• Suppress distressing dry cough, reducing airway irritation and discomfort.
6. Clinical Uses
1. Expectorants
• Mucolytics: COPD, bronchitis, cystic fibrosis, pneumonia.
• Reflex expectorants: Common cold, productive cough.
2. Antitussives
• Opioid-based: Severe dry coughs, lung cancer, post-surgical cough.
• Non-opioid: Mild dry cough, upper respiratory infections.
7. Side Effects and Contraindications
Drug Type Side Effects Contraindications
Expectorants Nausea, dizziness, hypersensitivity Renal impairment (Potassium iodide)
Opioid Antitussives Drowsiness, constipation, COPD, respiratory depression, addiction-
respiratory depression prone individuals
Non-Opioid Dizziness, hallucinations, serotonin MAOI use (Dextromethorphan), children < 2
Antitussives syndrome years
8. Pharmacological Actions
Category Action
Expectorants Increases mucus production (Guaifenesin) or reduces mucus
viscosity (Acetylcysteine).
Opioid Suppresses cough reflex centrally (Codeine, Hydrocodone).
Antitussives
Non-Opioid Blocks cough receptors peripherally (Benzonatate) or acts on NMDA receptors
Antitussives centrally (Dextromethorphan).
9. Correlation of Pharmacology with Related Medical Sciences

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 PHARMACOLOGY – III PREPAIRED BY: MR. RAHUL SINGH SHAKTAWAT
[UNIT – I, PART – A, CHAPTER – 3] WEBSITE LINK: https://drugee.wordpress.com/

• Physiology: Understanding airway dynamics and mucus clearance helps optimize

expectorant therapy.
• Pathophysiology: Chronic cough in conditions like COPD, asthma, or lung infections
requires differentiated drug therapy.
• Toxicology: Monitoring opioid addiction potential and serotonin syndrome risk with
dextromethorphan.
• Public Health: Over-the-counter (OTC) misuse of codeine & dextromethorphan has led
to regulatory controls.

End

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