Respiratory Pharms

Question 1

• Butorphanol

Answer 1

• Given per os (higher dose; why?) or parenterally
• Added analgesic benefit but can cause sedation
• Minimal CVS/respiratory suppression
• More potent than codeine

Question 2

• Codeine

Answer 2

• 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

Question 3

• Dextromethorphan

Answer 3

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

Question 3

• Dextromethorphan

Answer 3

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

Question 4

• Antihistamines

Answer 4

Can reduce coughing by central effect that alters mucus secretion in the respiratory tract

Question 5

Expectorants

Answer 5

• 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

Question 6

Mucolytics

Answer 6

• 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

Question 7

Bromhexine (Bisolvon®)

Answer 7

• 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

Question 8

Na-acetylcysteine/carbocysteine (Mucomyst®)

Answer 8

• 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.

Question 9

Bronchoconstriction

Answer 9

•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

Question 10

Sympathomimetics

Answer 10

•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

Question 11

Adrenaline, isoproterenol

Answer 11

• 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.

Question 12

Terbutaline, albuterol, salbutamol

Answer 12

• Used in an inhalant → long term use for asthma

Question 13

Clenbutarol

Answer 13

• For COPD in horses

* Beware late pregnant horses (tocolytic)

Question 14

Parasympatholytic/cholinergic blocking agents

Answer 14

•Atropine, glycopyrrolate, ipratropium

Question 15

Methylxanthines (theophylline, aminophylline)

Answer 15

• 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

Question 16

Disodium cromoglycate (mast cell stabiliser)

Answer 16

• Inhibits release of histamine and other autacoids
• These may cause bronchoconstriction
• Used for specific types of COPD (prophylactic)
• Expensive

Question 17

Diphenhydramine and chlorpheniramine

Answer 17

• Usually administered by nebulization

* These are H1 blockers used to prevent histamine binding to mast cells.

Question 18

Corticosteroids

Answer 18

• 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

Question 19

Nasal (and eye) decongestants

Answer 19

•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.

Question 20

Nebulization

Answer 20

• 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).

Question 21

Drugs that can be added with nebulization:

Answer 21

• 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.

Question 22

Nebulisation considerations

Answer 22

• 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.

Question 23

Doxapram

Answer 23

• Used for reversal of barbiturates and inhalation anesthetics
- CNS stimulant
• Caesarian-born puppies

Question 24

Antidotes:

Answer 24

• In the case of narcotic overdose e.g., naltrexone

* In the case of α2 agonistic sedation reversal e.g., yohimbine for xylazine

Question 25

In production animals?

Answer 25

• Vaccinate against the infectious agents mostly involved in respiratory pathology
• Sound management practices
• Environmental control
• Of particular importance in feedlot animals

Question 26

Ipratropium bromide

Answer 26

• Anti cholinergic bronchodilator
• Used for asthma and chronic obstructive pulmonary disease.
• Does not cause tachycardia, tremors or significantly affect mucus production
• Not commonly used in vet medicine

Question 27

Atropine

Answer 27

• Anti-muscarinics
• Cause bronchodilatation but cause undesirable increases in the viscosity of bronchial mucous and reduced ciliary activity.
• Given in hospital setting/ GA /anaesthesia due to its side effects.