Respiratory Pharms Flashcards
• Butorphanol
- Given per os (higher dose; why?) or parenterally
- Added analgesic benefit but can cause sedation
- Minimal CVS/respiratory suppression
- More potent than codeine
• Codeine
- Use human pediatric formulations
- Oral absorption is inconsistent in veterinary species
- Less CNS suppression and constipation than morphine
- Antitussive effects at sub-analgesic doses more potent than morphine
- Often used in combination with other respiratory agents
E.g. antihistamines (chlorampheniramine), expectorants (GGE), decongestants (phenylephrine) and bronchodilators
• Dextromethorphan
o Not a true opiate, similar potency to codeine but less opioid side effects
o In many over-the-counter cold and cough medicines
o Human drug; extra label use and be careful of formulation (usually combined with other drugs e.g., pseudoephedrine which causes excitement)
o Short effect in dogs
• Dextromethorphan
o Not a true opiate, similar potency to codeine but less opioid side effects
o In many over-the-counter cold and cough medicines
o Human drug; extra label use and be careful of formulation (usually combined with other drugs e.g., pseudoephedrine which causes excitement)
o Short effect in dogs
• Antihistamines
Can reduce coughing by central effect that alters mucus secretion in the respiratory tract
Expectorants
• Act by increasing pulmonary mucous secretions BUT decreasing the viscosity thereof
o Act directly or by reflex action* on the tubulo-acinar mucous cells in the bronchi
o Assist with removal of excessive exudates and secretions in the upper respiratory tract
o Moderately beneficial adjunctive respiratory treatment
Mucolytics
- Used to loosen viscid or inspissated pulmonary secretions and help “expectoration”
- Do not increase volume of secretion like expectorants but help to remove mucous plugs from smaller airways
- Rehydration of the patient is also important; “steaming” for short periods works well
Bromhexine (Bisolvon®)
- Interferes with the production of acid mucopolysaccharide fibres by the goblet cells in the nasal and bronchial mucosa
- Very effective and antitussive properties at higher doses
- Can be used for longer periods than Na-acetylcysteine
Na-acetylcysteine/carbocysteine (Mucomyst®)
- Break disulphide bonds and change mucous ion characteristics = altered mucous composition
- Can be given orally or nebulized
- SEs: coughing, bronchospasm, ciliary depression
- Note: Acetylcysteine is also used for treating paracetamol toxicity in cats! Expensive. SEs include hypersensitivity and bronchospasm.
- Bromhexine is cheaper, safer and good for long term treatment.
Bronchoconstriction
•Tightening of smooth muscle in the lower airway
•Causes coughing, wheezing and dyspnea
•Can be due to:
- The release of histamine (local or systemic release)
- Cholinergic stimulation (also increased mucous secretion)
- Respiratory mononuclear phagocyte system inflammation releasing histamine, serotonin, prostaglandins etc.
o Particularly NB in cats
o Mononuclear phagocytic system is first line defense in the lungs. Involves monocytes, macrophages and dendritic cells
•Production of reactive oxidative species
o Pollutant particles are linked to development of respiratory track inflammation and asthma
Sympathomimetics
•ß2-agonists stimulate a GPCR-2cnd messaging system
o Activate cAMP production
o Ca2+ is bound to the cell membrane and ER
o Not available to cause muscle contraction
o Down-regulate mast cell autacoid release
Adrenaline, isoproterenol
• i/v → emergencies
- Reduce histamine release
- Increased activity of the ciliary epithelium of the bronchial mucosa.
• Side effects: tachycardia (β1 receptors) and tremors. May effect blood pressure.
Terbutaline, albuterol, salbutamol
• Used in an inhalant → long term use for asthma
Clenbutarol
- For COPD in horses
* Beware late pregnant horses (tocolytic)
Parasympatholytic/cholinergic blocking agents
•Atropine, glycopyrrolate, ipratropium
Methylxanthines (theophylline, aminophylline)
- Inhibit phosphodiesterase, reduce breakdown of cAMP.
- Blocks breakdown of cyclic AMP to 5’ AMP.
- The increase in cyclic AMP causes bronchodilatation.
- Side effects: nausea and vomition, diuresis (adenosine receptor antagonism) and hypotension
- Admin: Slow i/v in emergencies OR orally for maintenance
Disodium cromoglycate (mast cell stabiliser)
- Inhibits release of histamine and other autacoids
- These may cause bronchoconstriction
- Used for specific types of COPD (prophylactic)
- Expensive
Diphenhydramine and chlorpheniramine
- Usually administered by nebulization
* These are H1 blockers used to prevent histamine binding to mast cells.
Corticosteroids
• DoC for decreasing inflammatory pulmonary disease such as asthma
• Indirect bronchodilators; decrease autacoid release
• Very effective for allergic bronchoconstrictive disease e.g., feline asthma
o Fluticasone and beclomethasone often used in inhalers
o Can also use prednisolone and dexamethasone systemically.
o Inhalation or topical use reduces systemic side effects
o Can be combined with β2 specific agonists
Nasal (and eye) decongestants
•Not commonly used because of rebound effects; makes nasal discharge worse than before (occurs 3 – 5 days after treatment).
•Sympathomimetic / α1 agonists,
o Mostly used topically into nasal passages to decrease oedema and secretions for easier breathing
• Phenylephrine, naphazoline.
• Other SE: hypertension, tachycardia or reflex bradycardias, irritability, insomnia.
Nebulization
- Administration of drugs dissolved in tiny (ultrasound-formed) droplets
- Administered via a mask or closed chamber
- Saline is usually the “vehicle” or sometimes the only ingredient
- Required frequency is 3 to 4 times a day for 30 – 45 min at a time
- Droplets are small enough to reach smallest airways (0,5 - 3μm ideal size).
Drugs that can be added with nebulization:
- Antibiotics – gentamicin
- Corticosteroids – beclomethasone
- Mucolytics – Na-acetylcysteine
- Bronchodilators – terbutaline
- Detergents – allevaire
- Proteolytic enzymes – deoxyribonuclease
- Proteolytic enzymes break down secretion viscosity, like mucolytics.
- Detergents also decrease the surface tension and thus the viscosity of secretions.
Nebulisation considerations
- Check that drugs are compatible with fluid vehicle and with each other
- Note that saline alone produces good expectoration effect
- Nebulization of antibiotics is effective in producing effective drug concentration in respiratory tract but is time consuming, expensive and offers no advantage over systemic administration
- Some agents can be irritating (mucolytics)
- Don’t overhydrate; respiratory embarrassment can occur
- Water particles on deposited on the mucosa of small airways; if rate of deposition exceeds epithelial absorption ability, then will cause increased resistance and blockage of small airway
- Do not overheat small (< 4kg) and febrile animals as they cannot cool themselves at high humidity
- Ensure that the components of the nebulization fluid are compatible when preparing a mixture.
- In many instances drugs are not added to the nebulizing fluid. Nebulization is then mainly used to deposit fluid in the trachea-pulmonary tree to achieve expectoration.
- Respiratory embarrassment = pulmonary oedema secondary to overhydration.
Doxapram
• Used for reversal of barbiturates and inhalation anesthetics
- CNS stimulant
• Caesarian-born puppies
