Respiratory pharmacology

Question 1

Classes of respiratory drugs

Answer 1

Bronchodilators: beta adrenergic agonists, anticholinergics, methylxanthines

Drugs for allergic and inflammatory disorders: antihistamines, sodium cromoglycolate, corticosteroids, NSAIDS, leukotriene inhibitors

Antitussives

Mucolytics and expectorants

Decongestants

Question 2

Sympathetic control of bronchial tone

Answer 2

Sympathetic: no innervation but dilation d/t circulating adrenaline

B2 adrenoceptors: G protein coupled receptors–>increase cAMP in bronchial smooth muscle–> relaxation of bronchial smooth muscle

Also, inhbit release of histamine from mast cells–> inhibit release of inflammatory mediators, so some benefit in allergic reaction

Question 3

Parasympathetic control of bronchial tone

Answer 3

vagal influence in lungs

Muscarinic: M3–>linked to phospholipase C–>increase IP3–>increase cytosolic concentration of calcium–> constriction of bronchial smooth muscle

To relax: stimulate B2 adrenoceptors or inhibit muscarinic pathways

Question 4

Beta-adrenergic agonists

Answer 4

Endogenous pathway: circulating adrenaline

Adrenaline (epinephrine): lots of side effects, not appropriate for routine use–>very short duration of action (endogenous molecule and body has lots of ways of breaking it down)– used for emergency treatment of life threatening bronchoconstriction.

Question 5

B2 specific agonists

Answer 5

Terbutaline, salbutamol, salmeterol, clenbuterol

Commonly used in RAO

still not often used in long-term treatment

down regulation of Beta 2 adrenoceptors–>lose efficacy

used for rescue therapy

Side effects (can be reduced by aerosol inhalation): CVS: increased HR, palpitations; skeletal muscle tremors; tolerance–>use in acute circumstances or intermittently.

Question 6

Anticholinergics

Answer 6

e.g. atropine, glycopyrrolate, propantheline, ipratropium

Side effects: increased CV activity; slow gut motility,stasis

Administration: topical vs. systemic–> atropine, even when given topically, still goes systemc

Ipratropium: charged molecule–>can’t pass through membrane–> therefore localized action and not absorbed systemically.

NB: overactive muscarinic pathway implicated in RAO.

Question 7

Methylxanthines

Answer 7

e.g. theobromine, caffeine, theophylline, etamiphylline

Mechanism of action: Phosphodiesterase (PDE) inhibitors

increase cAMP–>cAMP produced d/t noradrenaline synthesis–>cAMP inhibits contraction

PDE breaks down cAMP –>PDE inhibitor increases cAMP–>bronchial smooth muscle relaxation.

Methylxanthines also decrease inflammatory mediators

adenosine inhibition: circulating substance that causes bronchoconstriction

Question 8

Pharmacokinetics of methylxanthines

Answer 8

oral admin–>high bioavailability

rapid,complete absorption

hepatic metabolism–>not rapid, good bioavailability

Side effects: increased cAMP, but mild around the body

GI: nausea, vomiting

CV: increased HR

CNS: increase in alertness, agitation, in v. high doses, convulsions.

Question 9

Drugs for allergic and inflammatory disorders

Answer 9

Antihistamines, sodium cromoglycate, corticosteroids, NSAIDS, leukotriene inhibitors

Question 10

Antihistamines

Answer 10

histamine involved in hypersensitivty reactions–>mediated through H1 receptor.

H1-receptor antagonists: diphenhydramine, cyproheptadine

Histamine–>bronchoconstriction, local edema, stimulate vagal nerve

Uses: control of allergic respiratory disease and also skin allergies

Side effects: sedation d/t histamine receptors in CNS

Question 11

Sodium cromoglycate

Answer 11

Mechanism of action: inhibit release of inflammatory mediatorys (histamine, leukotrienes, etc) from mast cells

NO bronchodilator action, just prevents bronchoconstriction

Aerosol inhalation in horses

Limitation: must be given prophylactically

Question 12

Corticosteroids

Answer 12

decrease inflammation associated with inflammatory pulmonary diseases- inhibition of transcription of certain genes involved in producing inflammatory mediators

e.g. fluticasone, prednisolone, dexamethasone

oral vs. inhaled (effective in tx. of asthma)

benefit: act to enhance action of beta 2 adrenoceptors. slow down down-regulation process–> enhance length of efficacy of beta agonist.

Question 13

NSAIDs

Answer 13

e. g. flunixin, ketoprofen
uses: bovine respiratory disease- useful with inflammatory process i.e. PG mediated

Question 14

Leukotriene inhibitors

Answer 14

lipoxygenase–>leukotrienes

1) lipoxygenase inhibitors (Zileuton)
2) leukotriene receptor blocks (Zafirlukast, Montelukast)

Question 15

Antitussives

Answer 15

Cough reflex: sensory input from bronchial/tracheal airways–>stimulate cough center

Opiates: directly depress cough center

e.g. morphine, codeine, hydrocodone, detromethorphan, butorphanol, tramadol

Mu and kappa receptors

some of the opioids have a greater effect than others, but their efficacy for analgesia has v. litle to do with efficacy as an antitussive

Question 16

Mucolytics and expectorants

Answer 16

Mucolytic: drug alters structure of mucus, decreasing viscosity and making it easier to remove from tract

Expectorants: make a greater volume of mucus and stimulates coughing

Saline expectorants: direct: eucalyptus oil, lemon oil

Guaifensesin compounds: muscle relaxant at high dose- can be used to scavenge free radicals– treatment of certain toxicoses

Acetylcysteine: anti-oxidant compound->chemically interferes with mucus–>mucolytic

Question 17

Decongestant

Answer 17

upper respiratory congestion

alpha agonists–>vasoconstriction of BVs in upper respiratory tract–> decreased production of mucous (phenylephrine)

Antihistamines–>decrease inflammation