Pulmonary Pharmacology

Question 1

How can anesthetic drugs be administered?

Answer 1

gases, vapors, or aerosols

Question 2

What are the features of anesthetic inhalants?

Answer 2

• volatile liquide or gases
• administered and eliminated from the respiratory tract
• low molecular weight and high lipid solubility
• low therapeutic indices
• under continuous control and given “to effect”

Question 3

In order to be distributed to tissues gases and vapors must…

Answer 3

attain a partial pressure in the blood

Question 4

In order to develop a partial pressure gases and vapors must…

Answer 4

dissolve in the blood

Question 5

Blood solubility

Answer 5

• delays anesthetic induction and recovery
• correlated with blood:gas partition coefficient
• The more soluble the drug is in blood the longer induction/recovery will take.
• High blood solubility and long recovery: Methoxyflurane>Isoflurane>NO2

Question 6

Anesthetic potency and lipid solubility

Answer 6

• lipid solubility determines how well the anesthetic drug can diffuse across cell membranes.
• High lipid solubility and low MAC value: Methoxyflurane>Isoflurane>NO2

Question 7

Minimum alveolar concentration (MAC)

Answer 7

the anesthetic dose that produces light anesthesia in 50% of a patient population.

Question 8

Normal diameter of the bronchi is set by…

Answer 8

• the balance of parasympathetic and sympathetic tone.
• ACh–> mAChR–> increased Ca2+–> bronchoconstriction
• NE–> alpha AR–> decrease cAMP–> bronchoconstriction
• Epinephrine–> Beta2 AR–> increase cAMP–> bronchodilation

Question 9

Bronchoconstrictive airway diseases

Answer 9

• due to recurrent airway inflammation–> smooth muscle hyperreactivity
• symptomatic treatment (bronchodilators)
• ex. asthma, chronic bronchitis, emphysema

Question 10

Neuroregulation of Airway function

Answer 10

• vagus–> acetylcholine–>muscarinic AChR–> [Ca2+] bronchoconstriction and thick mucus
• Adrenal gland–> epinephrine–> B2-AR–> [cAMP] bronchodilaiton, decreased mediators, and watery mucus

Question 11

Bronchodilators

Answer 11

• B2-adrenergic agonists
• Methylxanthines (theophylline)
• Muscarinic receptor blockers

Question 12

B2-adrenergic agonists

Answer 12

ex. albuterol (dogs & cats, oral or aerosolization) and clenbuterol (horses, oral or injection)
- most effective, increase diameter in small and large airway, increase mucociliary clearance, decrease in inflammatory mediators
- side effects: arrhythmias, mydriasis, excitement, sweating (horse)

Question 13

Methylxanthines (theophylline)

Answer 13

ex. aminophylline
- inhibits phosphodiesterase–> decrease cAMP breakdown
- competitive antagonist at adenosine receptors
- dilates large and small airways, increases ciliary beat frequency and decreases mucus viscosity
- good oral bioavailability, large Vd, hepatic phase 1 metabolism, low therapeutic index
- side effects: GI upset, seizures, arrhythmias, acute respiratory failure.

Question 14

Muscarinic receptor blockeres

Answer 14

ex. atropine, glycopyrolate, ipratropium
- not very effective
- use in severe asthmatic states, acute dyspnea, and bronchoconstriction produced by anti-cholinesterase agents
- low p.o. bioavailability
- injection or nebulization
- can be combined with glucocorticoids or B2-AR agonists
- side effects: tachycardia and decreased intestinal motility

Question 15

Glycopyrrolate and ipratropium vs. atropine

Answer 15

• 4 prime ammonium compounds don’t cross BBB
• ipratropium more effective than atropine
• glycopyrrolate has slower onset by longer duration of action than atropine

Question 16

Cough reflex

Answer 16

• Non-specific sign of respiratory tract disease
• rid airway of pathogenic microorganisms and irritating substances
• usually self resolving
• bronchoconstriction is an important stimulus for coughing

Question 17

Objective of antitussive therapy

Answer 17

• decrease frequency and severity of cough without compromising the effective evacuation of secretions
• usually given when cough is non-productive
• usually not used in animals

Question 18

Cough reflex pathway

Answer 18

site of irritation (use mucosal anesthetics, demulcents, mucokinetic agents, and brochodilators here)–> sensory/motor nerves to/from CNS cough center–> cough center in medulla (use opiates here)

Question 19

Opiate antitussive drugs

Answer 19

ex. codeine, butorphanol, dextromethorphan
- decrease sensitivity of cough center–> decrease awareness of airway irritation
- L-form more potent in producing “classical” opitae effcts.
- Codeine depresses respiration and has abuse potential
- Butophanol and dextromethorphan have little or no respiratory depressant effects or abuse potential.

Question 20

Dextromethorphan

Answer 20

• isomer of codeine
• no action at opioid receptors
• agonist at sigma receptors
• safe w/ no adverse effects
• used in small animal
• more effective when used with bronchodilator

Question 21

Butorphanol

Answer 21

• agonist at kappa-type opioid receptors
• naloxone reverses overdose
• some abuse liability but less sedation or respiratory depression than codeine
• approved in dogs and horses