CoughLecture 5

Professor Ahmed Shaaban

Professor of Pharmacology &

Senior Consultant of Endocrinology

Coughi.e. forcible expulsion of foreign body or gas out of respiratory tract.

A protective reflex to get rid of ... microbes, allergens, … more nocturnal.

A universal symptom of many important diseases.

Center : cough center, above RC.

Afferents: vagal, with central synapses via NMDA receptors fromrespiratory tract (mechanoreceptors above and chemoreceptors below),heart, stomach & ear.

Efferents: via phrenic & intercostal nerves to diaphragm & intercostal muscles.

Types of cough

Dry cough: useless and harmful (treated by antitussives).

Productive cough: useful cough (treated by expectorants & mucolytics).

Chronic cough (> 3 weeks): e.g. postnasal drip, asthma or GERD.

A)Treatment

Antitussives are used when cough is unproductive, distressing, painful, exhausting, increasing airway damage or causing morbidity as:

a. Sleep disturbances.

b. Chest pain.

c. Hernia.

d. Urinary incontinence.

e. Neuropsychiatric disorders.

Expectorants are used to get rid of excessive thick bronchial secretions

B)Adjuvants (new antitussive approach)Have some antitussive activity and also specific action in treatment of cough in different clinical diseases.

1)Upper respiratory tract infection (URTI) & common cold.

ttt. Lecture 6.

2)Upper airway syndrome (postnasal drip syndrome). Chronic, mainly sinusitis.

ttt. antihistaminics (1st generation due to multiple receptor block) & decongestants (α1 agonists).

3)Bronchial asthma & COPD.

Selective β2 agonists, M3 antagonists & theophylline: ↑ mucociliarytransport.

Inhaled steroids: anti-inflammatory.

4)Allergic : Anihistaminics & inhaled steroids.

5)GERD : proton pump inhibitors (PPIs) & H2 antagonists.

Antitussives

Central : ↓ cough c. Peripheral

A) Opioids

Narcotic Non-narcotic

(mild addictive)

1. Codeine 1. Dextromethorphan.

2. Dihydrocodiene 2. Propoxyphen.

more potent . 3. Noscapine.

B) Non opioids:

1) Carbetapentane.

2) Benzonatate.

3) Caramiphen (also bronchodialtor).

1- Cabetapentane:

local anesthetic &

atropine like .

2- Benzonatate: local

anesthetic, blocks

stretch receptor in

pulmonary alveoli

preventing afferent

stimuli stimuli for

cough reflex .

3- Dimulcents :

increase mucous

secretion forming a

Mild addictive opioid antitussivesAdvantages:

1. Potent cough center depressant.

2. Mild analgesic.

Disadvantages:

1. Mild narcotic addictive.

2. Constipation.

3. ↓ciliary activity.

Non addictive opioid antitussives Preferred:

1.Potent cough center depressant.

2. Less sedation & addiction.

3. Less constipation.

New antitussivesCough receptors stimulation increases glutamate release

in nucleus tractus solitarius leading to NMDA receptors stimulation.

This is potentiated by neurokinins.

1) NMDA antagonists. e.g. memantine.

2) Neurokinin antagonists.

3) GABA receptor agonists.

4) Leukotriene receptor antagonists.

5) Local anesthetics as inhaled lidocaine.

1 – 3 are central. 4 & 5 are peripheral.

Expectorantsi.e. drugs liquefying sputum (bronchial secretion) by ↓ viscosity &

↑ volume causing its expulsion out by cough reflex easily.

Used in bronchitis, bronchial asthma & emphysema.

A) Aromatic (stimulant) expectorants:

Mechanism:

1. Stimulation of bronchial mucus glands →↑ sputum volume (directly).

2. Stimulate repair & healing of destroyed epithelium in respiratory tract. 3. Antiseptic. 4. Deodorant.

Volatile oils as menthol, tr. tolu. & benzoin by inhalation via water vapor.

B) Na & K acetate or citrate, tr. ipecac & ammonium chloride or carbonate.

Mechanism: reflex stimulation of bronchial mucus glands (by irritation of gastric mucosa).

C) K iodide:Mechanism:

1. Excretion via bronchial gland → direct stimulation.

2. Irritate gastric mucosa → reflex stimulation of bronchial glands.

3.↑ Proteolytic activity of enzymes in sputum (mucolytic).

Adverse effects:

1. Bronchospasm (respiratory tract irritation).

2. Spread of TB (dissolves fibrous tissue).

3. GIT irritation.

4. Iodism: rhinorrhea, lacrimation, salivation &↑bronchial secretions.

5. Hypothyroidism.

6. Allergy.

Contraindications:1. Acute bronchitis (↑↑ bronchial secretions).

2. Bronchial asthma. 3. TB bronchitis.

4. Hypothyroidism. 5. Allergy.

Mucolyticsi.e. drugs which break mucus & ↓ sputum viscosity usually without affecting its volume.

Uses are similar to those of expectorants but in cases with thick sputum.

(1) Bromhexine:

Mechanism:

Depolymerization of mucopolysaccharides reducing sputum viscosity.

Adverse effects: mild GIT irritation.

(2) Carbocysteine:

Mechanism:

1. It breaks disulfide bonds of thick mucus reducing viscosity.

2. ↓ mucus glands hyperplasia & ↓ sputum volume .

3. It protects mucus membrane against infection.

(3) Acetyl cysteine:

Mechanism:

Disrupts disulfide bonds in thick sputum → ↓ viscosity.

Uses:

1. As mucolytic: oral & by inhalation.

2. Paracetamol toxicity (→ SH to liver).

Adverse effects :

1. Bronchospasm if by inhalation.

2. GIT irritation if oral.

3. Inactivates penicillin.

4. Allergy.