Respiratory Medicine: Bronchodilators, Antitussives, Expectorants and Mucolytics

Question 1

Why are bronchodilators important?

Answer 1

Equine asthma.
Feline lower airway disease / feline asthma.
Canine chronic bronchitis.

Question 2

1. Pathophysiology of bronchodilation.
2. Drug types that cause bronchodilation.

Answer 2

1. Function of sympathetic stimulation.
   - adrenaline acts on alpha and beta adrenoreceptors to cause bronchodilation.
2. B-adrenergic receptor agonists.
   Anticholinergic drugs e.g. atropine.

Question 3

1. Example of short-acting non-specific B-adrenergic agonist.
2. Examples of long-acting specific B-adrenergic agonist.
3. Examples of anticholinergic drugs.
4. Example of methylxanthines.
5. Other less commonly used bronchodilator?

Answer 3

1. Adrenaline (emergency).
2. Terbutaline, Salbutamol, Clenbuterol.
3. Atropine, ipratropium.
4. Theophylline.
5. Sodium chromoglycate (Cromolyn).

Question 4

How do B-adrenergic receptor agonists work?

Answer 4

Relaxation of bronchial smooth muscle.
Stabilise mast cells - inhibit their degranulation – useful as many diseases that cause bronchoconstriction have an allergic component.
May increase mucociliary clearance.

Question 5

Adrenaline.

Answer 5

Short-acting non-specific B-adrenergic agonist:
- stims a and B adrenergic receptors.
- vasopressive and cardiac effects.
IV or IM.
Formulations = 1:1000 (1mg/ml) or 1:10000 (0.1mg/ml).
- short duration action bronchodilator.
- not suitable long term.
USED FOR LIFE-THREATENING BRONCHOCONSTRICTION!
- CPR.
- Anaphylactic shock.

Question 6

Terbutaline, Salbutamol, Clenbuterol.

Answer 6

Long-acting, specific B-adrenergic receptor agonists.
Developed to avoid cardiac effects of non-specific drugs.
Longer acting so suitable for long-term use.
Available in various formats - some as inhalation therapy.

Question 7

Terbutaline.

Answer 7

Bronchodilator.
Bricanyl - human med.
Lasts 6-8h.
Often used in cats w/ “asthma” off-license.
- prior to bronchoscopy or bronchoalveolar lavage.
- injectable in emergencies e.g. feline asthmatic crisis.
- orally for chronic therapy for feline asthma.

Question 8

Salbutamol.

Answer 8

Bronchodilator.
Ventolin - human med.
Similar action to Terbutaline.
Used in inhalers.

Question 9

Clenbuterol.

Answer 9

Bronchodilator.
- partial agonist – may be less effective.
Aids mucociliary clearance.
Available as syrup, granules and injectable.
Side effects incl. sweating, tremors, restlessness, tachycardia (beta stim).
Ventipulmin, Dilaterol - vet meds.
– horses –> equine asthma.
Planipart - vet med.
– uterine relaxant in cattle.

Question 10

Adverse effects of beta agonists.

Answer 10

CV - tachycardia.
– esp. w/ B1 agonists or high dose B2.
MSK - tremors.
– abused in people for muscle building.
– illegal use as growth promoter in cattle.
– risk to human health (esp. if heart disease or pregnant).
Tolerance w/ chronic use (wks).
- down-regulation of receptors.
- use for short-term Tx of bronchoconstriction.
- Drug-free break in between courses if ongoing Tx required.

Question 11

Sodium chromoglycate.

Answer 11

Bronchodilator.
Stabilises mast cells.
- inhibits release of histamine, leukotrienes etc.
– reduced bronchoconstriction.
Occasionally used in horses w/ Equine Asthma (not licensed).
- if increased mast cells on tracheal wash / bronchoalveolar lavage (usually increased neutrophils).
- inhalation once daily for 1-4d – effects last several days.
- must be given before horse exposed to allergen.

Question 12

Theophylline.

Answer 12

Corvental - vet med.
Methylxanthine.
MoA unclear: inhibition of phosphodiesterase 3 and 4?
Commonly used in dogs for chronic bronchitis, cats for feline lower airway disease, NOT for horses due to side effects.
Available as extended-release capsule.
- rapidly absorbed after oral administration.
- metabolised in liver.
- Plasma conc. monitoring sometimes recommended.

Question 13

1. Side effects of theophylline.
2. Why may drug interactions occur w/ theophylline?
3. Potential drugs it could interact with?
   – overcome this by…

Answer 13

1. Mild - nausea, vomiting, diuresis.
   Cardiac - tachycardia, increased contractility, arrhythmias.
   CNS - agitation and seizures (more common w/ caffeine).
2. Metabolised in the liver. Relies on cytochrome P450 enzymes. so its metabolism could be affected (inhibited or activated).
3. Fluoroquinolones, erythromycin, cimetidine.
   – dose reduction.
   Phenobarbitone, rifampicin.
   – dose increase.

Question 14

Anticholinergic drugs.

Answer 14

Muscarinic antagonists.
Sometimes used in horses w/ equine asthma but not used for this purpose in dogs and cats.
Hyoscine - Buscopan – vet med.
– mainly used for colic in horses but a useful emergency bronchodilator IV.
Atropine.
- Can be used IV in emergency in horses.
- Side effects = ileus, CNS toxicity, tachycardia.
- Ipratropium.
- Horses – by aerosol.
- Less side effects.

Question 15

What do antitussive drugs do?

Answer 15

Inhibit coughing.

Question 16

Cough reflex.

Answer 16

Irritation in bronchi/trachea > sensory receptors > sensory nerves > medulla oblongata > cough.

Question 17

MoA of antitussives.

Answer 17

Depression of cough centre in medulla oblongata.
Bronchodilation - B2 receptor agonist.

Question 18

1. When are antitussives not indicated.
2. When are antitussives indicated?

Answer 18

1. If cough is productive e.g. pneumonia.
2. Chronic cough - as can be harmful:
   – increase airway inflammation / irritation.
   – vicious cycle.
   Clear indication for dynamic airway disease e.g. tracheal collapse.

Question 19

Examples of antitussive drugs.

Answer 19

Codeine.
Hydrocodone.
Diphenoxylate.
Butorphanol.

Question 20

1. Codeine side effects.
2. How is hydrocodone different to codeine?
3. How is overuse of hydrocodone discouraged?

Answer 20

1. Sedation, constipation.
2. More potent.
3. Anti-cholinergic component (homatropine).

Question 21

1. Diphenoxylate trade names?
2. Action?
3. Traditional use?
4. side effects in dogs?

Answer 21

1. Lofenoxal, Lomotil.
2. Opioid agonist.
   Direct suppression of the cough centre.
3. Antidiarrheal agent - often combined w/ atropine – not appropriate for antitussive).
4. Minimal.

Question 22

1. Butorphanol tablet trade name.
2. Butorphanol injectable trade name.
3. Action?
4. Dose difference of oral butorphanol vs injectable butorphanol and why?

Answer 22

1. Torbutrol.
2. Torbugesic.
3. K-receptor agonist.
4. Dose much higher orally than injectable. Poor bioavailability when given orally.

Question 23

1. Non-opiate antitussive effectiveness compared to opiate antitussive.
2. Non-opiate antitussive.
3. Beware.
4. Action?

Answer 23

1. Not as effective.
2. Dextromethorphan.
   Some beta agonists (due to bronchodilation).
3. Some over-the-counter formulations may contain meds that are toxic or at toxic doses for pets e.g. paracetamol.
4. Uncompetitive NMDA receptor antagonist and sigma-1 receptor agonist.
   Central effect.
   Some evidence that it does not reach therapeutic levels in dogs.

Question 24

Mucolytic drug name and active ingredient.

Answer 24

Bisolvon, Bromhexine.

Question 25

1. Action of Bromhexine/ Bisolvon. 2. What is it administered simultaneously to in cattle and pigs? - why? 3. Forms of Bromhexine and licensing of these.

Answer 25

1. Increased secretion of fluid and breakdown of mucus - so secretions more watery (may make patient worse). Increase mucociliary clearance in calves w/ respiratory disease. 2. Oxytetracycline. - increases level of antibiotic in bronchial mucus (>40%). 3. Injectable licensed for cattle and pigs. Powder licensed for cattle, pigs, dogs, cats.

Question 26

1. Effect of expectorants. 2. Forms of expectorants.

Answer 26

1. Accelerate particle clearance. 2. Direct stimulants e.g. eucalyptus oil. - common in human cough sweets, not evaluated in vet med. Guaifenesin (glycerol guaiacoate) and guaiacol. - used in vet anaesthesia as muscle relaxants. - may also stim bronchial secretions (vagally mediated). - often in over-the-counter human cough medicine. -- limited evidence in people, not evaluated in vet med.

Question 27

1. 2 main methods of administering inhaled respiratory drugs. 2. Examples of inhaled respiratory drugs.

Answer 27

1. Nebulisation - small droplets of drug delivered to airways, less systemic absorption? - but can still see side effects e.g. steroids. Metered dose inhalers - often used in dogs and cats. -- AeroDawg/Aerokat -- and equine devices also available. 2. Salbutamol (B2 agonist). Glucocorticoids - fluticasone, beclomethasone. (Chromoglycate).

Question 28

Management of Equine Asthma.

Answer 28

Management changes - Reduce exposure to organic dusts and mould. Bronchodilators: - Oral clenbuterol (Vemtipulmin) or inhaled salbutamol -- tolerance develops if used alone. - Occasionally sodium chromoglycate -- if high mast cells. - Hyoscine butylbromide (Buscopan) -- injectable. Corticosteroids: - Oral (prednisolone), injectable (dexamethasone) or inhaled (beclomethasone or fluticasone). -- side effect laminitis. Mucolytics - Bromhexine (Bisolvon).

Question 29

Feline lower airway disease management.

Answer 29

Management strategies. Glucocorticoids: - oral prednisolone. - inhales fluticasone. Bronchodilators: - inhaled salbutamol. - injectable terbutaline -- emergency. - oral theophylline. - oral terbutaline -- risks w/ long term use?

Question 30

Management of dogs w/ chronic bronchitis.

Answer 30

Management changes. Bronchodilators: - oral theophylline (licensed for dogs). - inhaled salbutamol. Glucocorticoids: - inhaled fluticasone. - oral prednisolone. ABX if secondary infections. Antitussives v occasionally used in addition e.g. codeine. Mucolytics generally contraindicated.