Respiratory Medicine: Bronchodilators, Antitussives, Expectorants and Mucolytics Flashcards
Why are bronchodilators important?
Equine asthma.
Feline lower airway disease / feline asthma.
Canine chronic bronchitis.
- Pathophysiology of bronchodilation.
- Drug types that cause bronchodilation.
- Function of sympathetic stimulation.
- adrenaline acts on alpha and beta adrenoreceptors to cause bronchodilation. - B-adrenergic receptor agonists.
Anticholinergic drugs e.g. atropine.
- Example of short-acting non-specific B-adrenergic agonist.
- Examples of long-acting specific B-adrenergic agonist.
- Examples of anticholinergic drugs.
- Example of methylxanthines.
- Other less commonly used bronchodilator?
- Adrenaline (emergency).
- Terbutaline, Salbutamol, Clenbuterol.
- Atropine, ipratropium.
- Theophylline.
- Sodium chromoglycate (Cromolyn).
How do B-adrenergic receptor agonists work?
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.
Adrenaline.
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.
Terbutaline, Salbutamol, Clenbuterol.
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.
Terbutaline.
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.
Salbutamol.
Bronchodilator.
Ventolin - human med.
Similar action to Terbutaline.
Used in inhalers.
Clenbuterol.
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.
Adverse effects of beta agonists.
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.
Sodium chromoglycate.
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.
Theophylline.
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.
- Side effects of theophylline.
- Why may drug interactions occur w/ theophylline?
- Potential drugs it could interact with?
– overcome this by…
- Mild - nausea, vomiting, diuresis.
Cardiac - tachycardia, increased contractility, arrhythmias.
CNS - agitation and seizures (more common w/ caffeine). - Metabolised in the liver. Relies on cytochrome P450 enzymes. so its metabolism could be affected (inhibited or activated).
- Fluoroquinolones, erythromycin, cimetidine.
– dose reduction.
Phenobarbitone, rifampicin.
– dose increase.
Anticholinergic drugs.
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.
What do antitussive drugs do?
Inhibit coughing.
Cough reflex.
Irritation in bronchi/trachea > sensory receptors > sensory nerves > medulla oblongata > cough.
MoA of antitussives.
Depression of cough centre in medulla oblongata.
Bronchodilation - B2 receptor agonist.
- When are antitussives not indicated.
- When are antitussives indicated?
- If cough is productive e.g. pneumonia.
- Chronic cough - as can be harmful:
– increase airway inflammation / irritation.
– vicious cycle.
Clear indication for dynamic airway disease e.g. tracheal collapse.
Examples of antitussive drugs.
Codeine.
Hydrocodone.
Diphenoxylate.
Butorphanol.
- Codeine side effects.
- How is hydrocodone different to codeine?
- How is overuse of hydrocodone discouraged?
- Sedation, constipation.
- More potent.
- Anti-cholinergic component (homatropine).
- Diphenoxylate trade names?
- Action?
- Traditional use?
- side effects in dogs?
- Lofenoxal, Lomotil.
- Opioid agonist.
Direct suppression of the cough centre. - Antidiarrheal agent - often combined w/ atropine – not appropriate for antitussive).
- Minimal.
- Butorphanol tablet trade name.
- Butorphanol injectable trade name.
- Action?
- Dose difference of oral butorphanol vs injectable butorphanol and why?
- Torbutrol.
- Torbugesic.
- K-receptor agonist.
- Dose much higher orally than injectable. Poor bioavailability when given orally.
- Non-opiate antitussive effectiveness compared to opiate antitussive.
- Non-opiate antitussive.
- Beware.
- Action?
- Not as effective.
- Dextromethorphan.
Some beta agonists (due to bronchodilation). - Some over-the-counter formulations may contain meds that are toxic or at toxic doses for pets e.g. paracetamol.
- Uncompetitive NMDA receptor antagonist and sigma-1 receptor agonist.
Central effect.
Some evidence that it does not reach therapeutic levels in dogs.
Mucolytic drug name and active ingredient.
Bisolvon, Bromhexine.
- Action of Bromhexine/ Bisolvon.
- What is it administered simultaneously to in cattle and pigs? - why?
- Forms of Bromhexine and licensing of these.
- Increased secretion of fluid and breakdown of mucus - so secretions more watery (may make patient worse).
Increase mucociliary clearance in calves w/ respiratory disease. - Oxytetracycline. - increases level of antibiotic in bronchial mucus (>40%).
- Injectable licensed for cattle and pigs.
Powder licensed for cattle, pigs, dogs, cats.
- Effect of expectorants.
- Forms of expectorants.
- Accelerate particle clearance.
- 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.
- 2 main methods of administering inhaled respiratory drugs.
- Examples of inhaled respiratory drugs.
- 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. - Salbutamol (B2 agonist).
Glucocorticoids - fluticasone, beclomethasone.
(Chromoglycate).
Management of Equine Asthma.
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).
Feline lower airway disease management.
Management strategies.
Glucocorticoids:
- oral prednisolone.
- inhales fluticasone.
Bronchodilators:
- inhaled salbutamol.
- injectable terbutaline – emergency.
- oral theophylline.
- oral terbutaline – risks w/ long term use?
Management of dogs w/ chronic bronchitis.
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.
