In the medulla oblongata

Mu and kappa receptors

Give the drug class and MOA for each of the following:

Morphine

Codeine

Hydrocodone

Butorphanol

Dextromethorphan

Tramadol

Morphine: opiate, full mu and kappa agonist

Codeine: opiate, full mu and kappa agonist

Hydrocodone: opiate, full mu and kappa agonist

Butorphanol: opiate, partial mu and full kappa agonist

Dextromethorphan: opiate derivative; unknown - does not activate mu or kappa

Tramadol: opiate and non-opiate; activates serotonin and alpha-2 receptors, active metabolite is partial mu agonist

Very short T_1/2; not available in intravenous form

Human OTC formulations are compounded with acetaminophen, antihistamines and decongestants which should be avoided in veterinary patients

Tramadol is metabolized to its active form by CYP-2D enzymes; drugs that inhibit these enzymes (eg. SSRIs) reduce the efficacy of tramadol.

Use of tramadol with any serotonergic drug (SSRIs, TCAs, MAOIs) carries risk of causing serotonin syndrome.

What schedule is each of the following drugs?

Morphine

Codeine

Hydrocodone

Butorphanol

Tramadol

Morphine - II

Codeine - II

Hydrocodone - II

Butorphanol - IV

Tramadol - not scheduled

Feline asthma

Equine RAO (COPD)

Canine allergic bronchitis

These disease involve both bronchoconstriction and airway inflammation.

Methylxanthines - theophylline

Beta-2 adrenergic agonists - epinephrine, isoproteranol; clenbuterol, terbutaline

Anticholinergics - atropine, glycopyrrolate, ipratropium bromide

Methylxanthines (theophylline) inhibit PDE, resulting in increased intracellular cAMP which causes:

1) reduced mast-cell degranulation

2) antiinflammatory effects

3) bronchial smooth muscle relaxation

Theophylline is also an adenosine receptor antagonist, reducing adenosine receptor effects (bradycardia, bronchoconstriction)

tachycardia

nausea/vomiting, GI ulceration, anorexia

mild diuresis

CNS stimulation in horses

They are metabolized to inactive products by CYP 450 enzymes.  Thus:

1) Drugs that inhibit these enzymes (fluoroquinolones, cimetidine) increase plasma theophylline to toxic levels

2) Drugs that induce CYP 450 enzymes (phenobarbital, rifampin) reduce plasma theophylline to subtherapeutic levels

Stimulation of beta-2 adrenergic receptors:

1) increases intracellular cAMP causing bronchial smooth muscle relaxation

2) reduces mast cell degranulation

3) increases mucociliary clearance

Short-acting: epinephrine, isoproteranol

Long-acting: clenbuterol, albuterol, terbutaline

What are the negative effects of the following beta-2 adrenergic receptor agonists?

Epinephrine

Isoproteranol

Clenbuterol

Epinephrine: hypertension, tachycardia

Isoproteranol: tachycardia

Clenbuterol: cardiovascular toxicity, CNS stimulation, abuse potential

Long-term use is limited by negative side effects:

Tachycardia

Ileus, constipation, dry mouth

CNS excitation followed by depression

Decreased mucociliary clearance

Atropine - crosses BBB causing CNS effects; potential for colic

Glycopyrrolate - does not cross BBB

Ipratropium bromide - aerosol that is not absorbed, no systemic effects

Inhibits mast cell degranulation in the airways

Commonly administered via nebulization prior to exposure of a horse to a known, unavoidable allergen

Cromolyn

Corticosteroids

Leukotriene inhibitors

Augment beta-2 adrenergic agonist action

Synergistic action with theophylline

Decrease inflammation

Dogs: weight gain, GI ulceration, 2^o infections

Cats: weight gain, hyperglycemia, 2^o infections

Horses: weight gain, laminitis

Predniso(lo)ne

Depo-Medrol® injection for fractious cats

Dexamethasone for horses

Various inhalant drugs - all are much more potent than predniso(lo)ne

Lipoxygenase inhibitors - suppress production of all leukotrienes

LT receptor antagonists - block effects of all leukotrienes except one of the most important, LTB₄.

Lipoxygenase inhibitor: Zyflo®

LT receptor antagonist: Singulair®

Decreased viscosity of bronchial secretions

Enhanced clearance of bronchial exudates

Promote a more productive cough

Saline expectorants: believed to increase bronchial serous secretions by vagal stimulation.  Used in cattle for foot rot, lumpy jaw, wooden tongue and bronchitis.  Efficacy not proven.

Volatile oils: believed to directly increase serous bronchial secretions; efficacy not proven; not used in vet med

Guaifenesin: primary use is as muscle relaxant in anesthesia; believed to increase bronchial serous secretions by vagal stimulation

Acetylcysteine: the only true mucolytic proven to be effective; sulfhydryl groups break disulfide bonds on mucoproteins; strong odor can preclude its use in vet med

1) What decongestant drugs are available? 

2) How do they work?

3) What are they most commonly used for in vet med?

4) Why should they not be used on a long-term basis?

1) Phenylephrine, phenylpropanolamine (topical and systemic formulations); oxymetazoline, xylometazoline (topical only)

2) Decongestants stimulate alpha-adrenergic receptors in the mucosa causing vasoconstriction

3) Topical agents are used for idiopathic rhinitis in cats

4) Risk of "rebound vasodilation" resulting in increased mucus production

Doxapram

Stimulates the CNS (including the respiratory center) and carotid and aortic chemoreceptors.

Anesthetic emergencies, overdoses, neonates