Drugs Acting on Respiratory System | Animals | Pharmacology

After reading this article you will learn about the various drugs acting on respiratory system.

Expectorants:

(Mucokinetic agents/Brochomucotropic drugs):

Are the drugs which increase respiratory secretions or sputum volume and reduce the viscosity of sputum.

The word expectorant comes from a Latin word “expectorare” which means to derive from chest.

Cough:

Cough may be of two types:

(i) Less frequent and productive-occurs in acute inflammatory stage.

(ii) Frequent and non-productive-occurs in chronic inflammatory stage.

Chronic inflammatory stage may be converted to acute form by drugs so that the secretions may be removed.

All animal species apparently do not respond to expectorant drugs, e.g., Pot. citrate and ipecae markedly increase respiratory secretions in rats, but to a lesser extent in dogs, cats and chickens. In guinea pigs and rabbits, these drugs are having no effect; rather a slight decrease in respiratory secretions occurs.

Classification of Expectorants:

A. According to their Mechanism of Action:

1. Direct acting expectorants – (stimulates bronchial glands):

(a) Sodium citrate or acetate.

(b) Potassium citrate or acetate.

(c) Potassium iodide

(d) Guaiacol

(e) Guaiphenesin (Glyceryl guaiacolate)

(f) Balsam of Tolu.

(g) Vasaka

(h) Terpin hydrate.

2. Reflex acting expectorants- (Irritate gastric or bronchial mucosa):

(i) Ammonium chloride or carbonate.

(ii) Potassium iodide.

(iii) Ipecacuanha (Ipecac)

(iv) Squill (scilla)

3. Mucolytic expectorants:

(i) Bromhexine

(ii) Acetyl cysteine

(iii) Pancreatic dornase

4. Central expectorants-(sub-emetic dose):

(i) Apomorphine

(ii) Tarter-emetic

(iii) ipecac.

B. According to their Therapeutic Uses:

1. Sedative expectorants:

(a) Saline expectorants:

(i) Potassium iodide

(ii) Ammonium carbonate and chloride

(iii) Sodium bicarbonate

(iv) Sodium citrate

(v) Sodium Chloride

(vi) Potassium Citrate

(b) Demulcent expectorants:

(i) liquorice

(ii) Syrups (e.g., syrup of vasaka)

(iii) Mucilages

(iv) Glycerol, etc.

(c) Nauseant expectorants:

(i) Antimony Potassium tartrate

(ii) Ipecac

(iii) Apomorphine

(iv) Scilla (squill)

(v) Vasaka

2. Stimulant expectorants:

(i) Wood tar derivatives:

(a) Guaiacol

(b) Guaifenesin

(ii) Volatile oils:

(a) Oil of turpentine

(b) Oil of eucalyptus

(c) Oil of Lemon

(d) Oil of Pine

(e) Oil of anise

(iii) Others:

(a) Oleo-resins e.g., benzoin-volatile, tincture benzoin co. (Friar’s balsam)

(b) Camphor

(c) Creasote, etc.

3. Anodyne expectorants:

(i) Camphorated tincture of opium (paregoric)

4. Miscellaneous expectorants:

(i) Water aerosols

(ii) Gases (e.g. carbon dioxide → CO₂)

(O₂ acts as anti-expectorant)

5. Mucolytic expectorants:

(i) Sodium acetyl cysteine

(ii) Bromhexine

There is no synergistic action among the various ingredients (expectorants) com­monly used in cough mixture. Although they induce an increase in respiratory tract fluid, the sum of the individual drug effects as expectorants is equal to that of the total cough mixture.

Mechanism of Action:

Sedative expectorants:

They stimulate secretion of mucus, which protects and reduces acute inflammatory conditions in the respiratory tract. When coughing occurs, it is more productive and effective but less frequent. They have little, if any, antitussive activity.

A. Saline Expectorants:

(a) Ammonium Salts:

They are gastric irritants. They reflexly enhance bronchial secretion and sweating. Expectorant doses are sub-emetic but often nauseat­ing.

In toxic doses, the ammonium ion (NH₄⁺), as present in ammonium salts, produce acute pulmonary oedema. Dose → Man : 0.3-1 gm.

(b) Pot. iodide:

It acts both directly and reflexly. Directly: it is secreted by bron­chial glands and in this process irritates them, increasing the volume of secretion. Reflexly: It is also a gastric irritant, acts reflexly to increase bron­chial secretion.

[Drugs → gastric irritation → stimulate vomiting and associated cough centre of medulla oblongata → ↑ bronchial secretion.] Potassium iodide increases respiratory tract secretions by about 150%.

It is not desirable if bronchial mucosa is acutely inflammed. KI is used in the treatment of cough associated with chronic bronchitis, bronchial asthma and pulmonary emphysema.

Use of iodine preparations in advance pregnancy and hyperthyroid condition is contraindicated. They should not be recommended to animals whose milk is con­sumed by human. Iodides (sodium and potassium) are too irritating to use in treat­ment of acute inflammatory conditions of the respiratory tract.

Dose – KI:

200-300 mg, TD, orally, in a mixture containing other bronchial antispasmodics.

Demulcent Expectorants:

They protect the mucosa of the respiratory tract from irritation and so reduce the frequency of cough. Alone, syrup has no expectorant value. It does not increase fluid secretions of respiratory tract but may serve as a vehicle for an expectorant drug (e.g. : Syrup of vasaka; vasaka is an expectorant).

Nauseant Expectorants:

(a) Antimony Potassium Tartrate (Tarter Emetic):

It increases secretions of the respiratory tract by producing nausea, which serves to loosen a dry, harsh cough. But this is too toxic to be used as an expectorant or emetic.

(b) Ipecac:

Ipecac or ipecacuanha consists of dried roots or rhizome of Cephaelis ipecacuanha or Cephaelis acuminata or a mixture of both. It contains an alkaloid “emetine.”

The drug apparently induces nausea that results in reflex secretions of the respira­tory tract.

Due to its local irritant action and bitter taste, it reflexly increases salivary and gastric secretions.

Nausea and vomiting (by stimulating vomiting centre reflexly) may occur when large doses are administered orally or when emetine is excreted into the stomach following parenteral injection.

In sub-emetic doses, ipecac acts as an expectorant, and makes the bronchial secretion more fluid. It is used in the form of tincture in common cold, acute and chronic bronchitis and bronchopneumonia. It is often combined with (NH₄)₂ CO₃ and syrup of vasaka.

Ipecac has toxic effects. So, it should be used with sufficient precaution.

Dose – Man:

Syrup ipecac – 0.6 – 1.8 ml. [Seldom used in veterinary practice.]

(c) Vasaka:

It consists of fresh and dried leaves of Adhatoda vasica. It contains a bitter crystalline alkaloid “vasicine” (peganine) and an organic acid. It is used in India as an expectorant. It is a gastric irritant and in large doses vomiting and diarrhoea may occur. It is usually employed as a liquid extract or syrup. The dried leaves have been smoked in cigarettes for the relief of asthma. The syrup is used in a dose of 2-4 ml. per animal.

Stimulant Expectorants:

These drugs produce mild irritation of the bronchial mucous membrane during their excretion. These are used to stimulate or promote repair of chronic inflammatory processes. Many of these expectorants are aromatic compounds that probably are eliminated in part by the respiratory mucosa. Some of them tend to reduce bronchial secretion.

Guaiacol and Guaifenesin:

Guaiacol and its less irritating derivative. Guaifenesin (skeletal muscle relaxant) are believed to directly increase bronchial secretion and mucosal ciliary action, when after absorption from gut they are secreted by tracheobronchial glands. They reduce the stickiness of mucus in chronic bronchitis.

Dose:

Man: 100-200 mg. [Not used now a days]

Anodyne Expectorants:

Camphorated tincture of opium (paregoric) increases respi­ratory secretions by 400%. It acts by reflex action through the G1 tract, causing elevation in output of fluid in the respiratory tract. In addition, paregoric has antitussive activity in presence of opium alkaloids such as morphine and codeine. [Not used now-a-days]

Mucolytic Expectorants:

Mucolytics are relatively modern addition to the range of drugs which aim to make bronchial secretions easier to propel by ciliary action or to expel by coughing.

(a) Bromhexine:

A derivative of the alkaloid vasicine obtained from Adhatoda vasica (vasaka), is a potent mucolytic and mucokinetic, capable of inducing thin copious bronchial secretion. It depolymerizes mucopolysaccharides directly as well as by liberating lysosomal enzymes –> network of fibres in tenacious sputum is broken. It is particularly useful if mucus plugs are present.

Side Effects:

Rhinorrhoea and lacrymation.

Dose:

Small animals – 1mg/ kg, BD, orally or parenterally, for 7 days.

Horse – 0.1 – 0.25 mg/kg, orally or parenterally for 7 days.

(b) Acetyl Cysteine:

It opens disulphide bonds in mucoproteins present in sputum and makes it less viscid, but it has to be administered directly into the respiratory tract by aerosol (3-5 ml of 10-20% sol) or by tracheal instillation (in tracheostomy patient). It is irritating to the mucosa, often induces bronchoconstriction (specially in asthmatics,); a bronchodilator is generally included in the aerosol.

Side Effects:

Running of nose, nausea, stomatitis etc.

(c) Pancreatic Dornase:

It is de-oxy-ribonuclease which degrades nucleoproteins present in purulent sputum. Not commonly used.

Antitussive Drugs:

Definition:

Antitussive agents are preparations used to relief or suppress coughing. The objective of antitussive therapy is to decrease severity and frequency of cough without concommitant impairment of evacuation of broncho-pulmonary secretions .

Classification:

1. Centrally acting antitussive drugs:

(a) Narcotic antitussive agents:

(i) Codeine phosphate and sulfate.

(ii) Terpin hydrate (condiene elixir)

(iii) Morphine sulfate

(iv) Hydrocodone bitartrate (Hycodan)

(v) Pholcodeine

(b) Non-narcotic antitussives:

(i) Dextromethorphan

(ii) Noscapine

(iii) Butorphanol tartrate.

(iv) Carbetapentane

(v) Oxeladin

(vi) Chlophedianol

(vii) Pipazethate.

2. Peripherally acting antitussives:

(a) Local anaesthetics:

(i) Benzonatate

(ii) Oxolamine

(b) Antihistamines:

(i) Diphenhydramine

(ii) Chlorpheniramine

(iii) Promethazine

(iv) Trimeprazine tartrate + Prednisolone (Temaril-P)

Cough:

Cough is a protective reflex, its purpose being expulsion of respiratory secretions or foreign particles from air passages.

It occurs due to stimulation of mechano- and chemoreceptors in throat, respiratory passage or stretch receptors in the lungs.

Types of Cough:

Cough may be useful or useless. Useless (nonproductive) cough should be suppressed. Useful (productive) cough serves to drain the airways, its suppression is not desirable, may even be harmful, except if the amount of expecto­ration achieved is small compared to the effort of continuous coughing.

Site of action of antitussives:

Antitussives are the drugs that act in the CNS to raise the threshold of cough centre or act peripherally in the respiratory tract to reduce tussal (cough) impulses, or both these actions,

They should be used primarily for dry unproductive cough or if cough is unduely tiring or hazardous (hernia, piles, cardiac disease, ocular surgery).

Antitussive Acting on CNS:

Codeine Phosphate:

Codeine phosphate and sulphate are available primarily in combination with antihistamine (chlorpheniramine), expectorant (Guaifenesin), decon­gestant (phenylephrine), and other combination of drugs for respiratory ailments.

Terpin hydrate (codeine elixir) is also available and contains 10 mg of codeine in each 5 ml . The majority of codeine antitussive preparations contain this quantity of codeine, which is the limit for nonprescription use.

Codeine (methyl morphine) is a naturally occurring opioid alkaloid, quantitatively similar to morphine as cough-centre depressant depress a dry and irritating cough.

It is more selective for cough centre and is treated as the standard antitussive because codeine is less depressant on the respiratory centre and has less constipating action than morphine. Condeine is contraindicated in patient with copious respiratory secretions be­cause the secretion may accumulate in the lungs and airways with disastrous results.

Doses:

Dogs – 1-2 mg/kg, orally in a cough mixture

– 10-65 mg, s.c. inj.

Horse & Cattle – 0.2 – 2 gm., total dose, orally in a cough mixture

Adverse effect-constipation.

Other opiate Derivative Antitussives:

(i) Hydro codeine

(ii) Nascapine

(iii) Codoxime

(iv) Pholcodeine

Non narcotic antitussives (acting at peripheral sites).

(i) Dextio methorphan hyrdochloride-It is similar to Codeine in potency.

(ii) Trimeprazine – It has beneficial effect in respiratory allergies including bronchial asthma, rhinitis and chronic cough. Preparations available –

(a) Tablets of Trimeprazine (5mg) + Prednisolone (2 mg)

Capsules of (b) Trimeprazine (375 mg) + Prednisolone (1 mg)

Trimeprazine (7.5 mg) + Prednisolone (2 mg)

(iii) Diphenhydramine hydrochloride (Benadryl):

It is beneficial in cough release in respiratory allergies.