Respiratory Pharmacology

Front 1

What are the respiratory effects of Epinephrine?

Back 1

1. Bronchodilation via direct stimulation of beta-2-adrenoceptors

2. Vasoconstriction of small blood vessels decreases local congestion & edema

3. Acts in the CNS to increase respiratory rate & tidal volume and thus dec. CO2 in the alveoli

4. Rapid onset of action (30 sec) when given s.c.

Front 2

What are the respiratory effects of Isoproterenol?

Back 2

1. Bronchodilation via direct stimulation of beta-2-adrenoceptors

2. Rebound bronchoconstriction may occur after prolonged use

3. Arterial pO2 may decline in some pts/ b/c perfusion is increased (CO) more than ventilation
(give O2 to prevent problem)

4. Limited use in asthma due to adverse cardio effects and dev. of tolerance due to B2 receptor down reg.
(down reg. reversed by inhaled corticosteroids)

Front 3

What drug are for outpatient use that cause bronchodilation via beta-2-adrenoceptor stimulation?

Back 3

1. Salmeterol
2. Albuterol
3. Terbutaline

Front 4

What are the effects of Salmeterol, Albuterol, Terbutaline?

Back 4

1. Preferentially dilate the smaller & more peripheral airways
2. Inhibit the release of inflammatory compounds from mast cells
3. Inhibit the accumulation of eosinophils
4. Improve mucociliary transport in proximal and distal airways
5. Tolerance develops due to beta-2 receptor downregulation

Front 5

Is Salmeterol a LABA or a SABA? Do you still need to give a SABA? Is it a substitiute for corticosteroids?

Back 5

1. LABA --> slow onset, long lasting
(bronchodilation ~ 24 hrs)
2. Still give a SABA
3. NOT a substitute for corticosteroids

* Do NOT use in patients w/ deteriorating asthma

Front 6

What are the S/E's of the beta-2-adrenoceptor agonists?

Back 6

May cause a paradoxical bronchospasm after excessive inhalation

Front 7

What is the MOA of Corticosteroids?

Back 7

Inhibit the recruitment of leukocytes & monocytes & prevents the release of PGs, LTs, PAF, TNF, and IL-1

Front 8

What is the preferred route of administration of Corticosteroids for the treatment of asthma?

Back 8

Inhaled (Aerosol) Corticosteroids

* If the response to inhaled CS is inadequate, the dose may be inc. up to 4-fold before resorting to p.o. therapy

Front 9

When would systemic administration of corticosteroids for the treatment of asthma be appropriate?
(Descending dose pack)

Back 9

Treatment of acute exacerbations for 5-10 days exerts little toxicity, and adrenal suppression dissipates within 1-2 weeks

Front 10

What are the adverse effects of inhaled corticosteroids?

Back 10

1. Bone resorption may occur--dose dependent
2. Adrenal suppression w/ higher doses
3. Pupura may occur--dose related

Front 11

What are the major adverse effects of Inhaled corticosteroids?

Back 11

1. Dysphonia
2. oropharyngeal Candidiasis

*mitigate BOTH by rinsing the mouth & throat w/ water after use & employing spacer or reservoir devices

Front 12

What are two corticosteroids are good for children because they have a high "first-pass" metabolism?

Back 12

1. Budesonide
2. Fluticasone

*50% first-pass metabolism if swallowed

Front 13

What are the general properties of Muscarinic receptor antagonists in the airways?

Back 13

1. Poorly lipid-soluble quaternary compounds which do not enter CNS or cross placenta

2. Dilated large and small sized airways

Front 14

What is the MOA of Muscarinic receptor antagonists?

Back 14

Muscarinic receptor blockade prevents bronchoconstriction and bronchial secretion

Front 15

What are the two Muscarinic receptor antagonists? (on the drug list)

Back 15

1. Ipratropium
2. Tiotropium

Front 16

Which has a longer bronchodilatory effect? Ipratropium or Tiotroprium.

Back 16

Tiotroprium --persists for 24 hrs

Ipratroprium --persists for 4-8 hrs

Front 17

What are the clinical uses of Muscarinic receptors antagonists?

Back 17

1. TERTIARY therapeutic agent in asthma

2. Prophylaxis to prevent attacks in patients w/ a poor response or intolerance to the beta-2 agonists

Front 18

What M receptor antagonist is the DOC for patients with COPD?

Back 18

Tiotropium

Front 19

What are the toxicities and S/E of Muscarinic receptor antagonists?

Back 19

1. Dry mouth and bitter taste
2. Use w/ caution in pts. with angle-closure glaucoma, GI or GU obstruction of prostatic hypertrophy

Front 20

What are the pulmonary toxicities of leukotrienes?

Back 20

1. Bronchoconstriction
2. Increased mucus production
3. Increased vascular permeability
4. Chemotaxis for eos/neutrophils
5. Increased leukocyte adhesion

Front 21

What drugs are Leukotriene receptor antagonists and what specific receptors are they antagonistic against?

Back 21

1. Zafirlukast

2. Montelukast

*LTC4 & LTD4

Front 22

What are the effects of the LT receptor antagonists?

Back 22

Decrease the late bronchoconstriction cause by challenge w/ allergens

Maximal therapeutic effect occurs after 1 wk of therapy; decreased need for rescue w/ a SABA

Used as an ALTERNATIVE to inhaled corticosteroids, but not as effective

Major adverse side effect is HEADACHE

Front 23

Zafirlukast can increase the plasma concentration of other drugs by inhibiting ____________

Back 23

CYP2C9

Front 24

What is a really good drug for exercise induced Asthma?

Back 24

Cromolyn sodium

Front 25

What is the bioavailability of Cromolyn sodium?

Back 25

low, only 10% absorbed from the LUNGS and GI tract

Front 26

What forms does Cromolyn sodium come in?

Back 26

1. Powder in capsules for inhalation
2. Powder in aerosol
3. Nasal spray & opthalamic drops

Front 27

What is the MOA of Cromolyn sodium?

Back 27

1. PROPHYLACTIC thearpy prevents immediate and delayed antigen-induced degranulation of mast cells

2. Prevents the release of chemical mediators from mast cells by preventing the increase in intracellular calcium concentration induced by the formation of IgE-antigen bridges on the cell surface

*Use 10-15 minutes prior to exposure to antigen

Front 28

What are the pharmacologic effects of Cromolyn sodium?

Back 28

1. Reduces the frequency & severity of the bronchospasm
(beneficial effects may take 3-4 wks to develop)

2. Long-term therapy can reduce the overall reactivity to histamine and leukotrienes by preventing the bronchial damage caused by mast cell products

Front 29

What are the toxicities and S/Es of Cromolyn sodium?

Back 29

No contraindications

Use aerosol w/ care in patients w/ CAD or cardiac arrhythmias: hydrocarbon propellants can elicit adverse cardiac effects

Few adverse effects during long-term therapy --> throat irritation, cough, dry mouth and wheezing

Front 30

What is the MOA of Theophylline?

Back 30

Inhibition of phosphodiesterase which degrades cAMP

A specfic adenosine receptor antagonist

Front 31

What are the general properties of Theophylline/Aminophylline?

Back 31

Hepatic merabolism; t1/2 decreased in smokers

Crosses the placenta

Secreted in milk: usually no effect in nursing children

Aminophylline is more water soluble than Theophyline

Found in OTC asthma remedies

Front 32

What are the pharmacolgical effects of Theophylline/Aminophylline?

Back 32

*See pages 336-337*

Front 33

What are the toxicities and S/E's of Theophylline/Aminophylline?

Back 33

*See pg. 337

Front 34

In patients with what disease is Theophyline contraindicated?

Back 34

Active gastic ulcer disease

Front 35

The toxic effects of Theophylline appear at __________ and are prominent at ___________.

(plasma concentrations)

Back 35

15 mg/L

20+ mg/L

Front 36

What is periodic deep and shallow breathing occuring in cycles of 45 seconds to 3 minutes called?

Back 36

Cheyne-Stokes breathing

Front 37

When does Cheyne-Stokes breathing usually occur?

Back 37

Heart failure--delay of blood flow from lungs to CNS

CNS injury--increased gain in respiratory center response to CO2

Front 38

What is the treatment for Cheyne-Stokes breathing?

Back 38

Aminophylline--normalized respiration

Front 39

What is neonatal apnea?

Back 39

Apnea of greater than 15 seconds in duration that causes recurrent cerebral hypoxia which may produce serious neurological damage

Front 40

What drugs increase respiratory rate and improve blood gases in preterm infants w/ intermittent apnea?

Back 40

Aminophylline or Caffeine (iv)