Mod2 Respiratory Pharm

Front 1

Name the sympathomimetic drugs.

Back 1

Epinephrine
Salmeterol
Terubtaline
Albuterol

Front 2

epinephrine

Back 2

B2>B1>a

--produces bronchodialation via direct stimulation of B2 adrenoreceptors
--vasoconstriction via a-adrenoceptors decreases local congestion and edema
--also acts in the CNS to increase resp rate and tidal volume and thus decrease CO2 in the alveoli

**very rapid onset of action when given s.c. (30s)

Front 3

salmeterol, terbutaline and albuterol effects, use?

Back 3

1. bronchodilation via B2-adrenoceptor stimulation
2. preferentially dilate smaller and more periph airways
3. inhib release of inflamm cmpds from mast cells
4. inhib accumulation of eosinophils
5. improve mucociliary transport in prox and distal airways
6. tolerance develops due to down-regulation of B2-adrenoceptors

Front 4

What is special about salmeterol?

Back 4

It has a very slow onset of action, but is very long acting
-- bronchodilation may persist for 24h
-- therapy w/ short-acting B2-agonist is STILL req'd
-- do NOT use in patients with deteriorating asthma
-- NOT a substitute for corticosteroids

Front 5

Side effects of the B-adrenoceptor agonists?

Back 5

- few adverse effects when given via inhaler
- may cayse paradoxical bronchospasm after excessive inhalation
- When given p.o.:
-- cardiac arrhythmias, hyperglycemia, hypokalemia, dizziness, headache, nervousness, and tremor may occur

Front 6

Corticosteroids used in respiratory pharmacology?

Back 6

beclomethasone
budesonide (high "first pass" metab)
flunisolide
fluticasone

Front 7

corticosteroid MOA?

Back 7

1. inhibit recruitment of leukocytes and monocytes-macrophages into affected areas and prevent autocoid release from these cells
2. prevent and reverse the early phase of inflamm process (edema, fibrin deposition, capillary dilation, migration)
3. prevent and reverse late phase inflamm response (prolif of capillaries and fibroblasts, collagen deposition)
4. inhib synth and/or release of PGs and LTs, PAF, TNF, IL-1, and plasminogen activator

Front 8

aerosol formulations of corticosteroids?

Back 8

direct application of corticosteroids to the lungs by inhalation is usually effective in the treatment of asthma and obviates the adverse effects of systemic admin

**if inhaled response inadequate, may be increased 4-fold before resorting to p.o. therapy with corticosteroids

Front 9

How long is normal for systemic admin of corticosteroids?

Back 9

treat acute exascerbations for 5-10 days -- will exert little toxicity and any adrenal suppression dissipates within 1-2wks

Front 10

Adverse effects of corticosteroid use via inhalation?

Back 10

minimal:
- NO growth retardation
- bone resorption may occur, but is dose-dependent
- NO CHO/lipid metabolism
- adrenal suppression with higher doses
- purpura may occur, dose-related
- NO cataracts
MAJOR adverse effects:
- dysphonia
- oropharyngeal candidiasis
- BOTH can be mitigated by rincing mouth and throat with water after use ane by using spacers or reservoirs

Front 11

Adverse effects of corticosteroid use systemically?

Back 11

Long-term therapy requires alternate day therapy and the usual precautions upon cessation.

Many possible effects PREDNISONE mnemonic.

Front 12

General properties of ipratroprium?

Back 12

--poorly lipid-soluble quarternary cmpd
--does not enter CNS or cross placenta
--Bronchodilation w/in 10m of inhalation, peaks at 1-2h and persists for 4-8h

Front 13

Ipratropium MOA?

Back 13

-- Muscarinic receptor blockade in smooth muscle of large and small airways prevents vagally induced bronchoconstriction
-- no antihistaminic or anti-inflamm effects
-- does not inhib mast cell degran

Front 14

Iprotropium effect on lungs?

Back 14

-- dilates large and small sized airways
-- does NOT effect mucus production, viscosity, or clearance (no ciliary affect)
-- No effect on pulmonary gas exchange or arterial CO2

Front 15

Ipratropium clinical use?

Back 15

--a secondary therapeutic agent
--used prophylactically to prevent attacks in patients with either a poor response or intolerance to the B-adrenoceptor agonists
-- patiente response is highly variable but tolerance DOES NOT develop
-- After FEV1 is increased by ipratropium, a B2-adrenoceptor agonist will elicit a further increase in FEV1

Front 16

Ipratropium toxicity and S/Es?

Back 16

-- Most common are dry mouth and bitter taste
-- use with caution in presence of angle-closure glaucoma, GI or GU obstruction, and prostatic hypertrophy

Front 17

How do leukotrienes (LTs) exhibit pulmonary toxicity?

Back 17

-- bronchoconstriction
-- increased mucus production
-- increased vasc permeability
-- chemotaxis for eosinophils/PMNs
-- increased leukocyte adhesion

Front 18

Name the 5-LO inhibitor.

Back 18

zileutonf

Front 19

Zileuton action, use?

Back 19

-- prevents LT synth
-- increases FEV1, decreases asthma symptoms and use of B2-agonists and corticosteroids
-- used in prophylaxis and chronic tx of mild/moderate asthma
-- prevents aspirin induced asthma

Front 20

Zileuton interactions?

Back 20

Can increase plasma conc. of other drugs by inhibiting CYP450

Front 21

Name the LT receptor antagonists.

Back 21

zafirlukast
montelukast

Front 22

zafirlukast and montelukast action, use?

Back 22

-- both drugs are competitive receptor antag of receptors for LTC4 and LTD4 (SRS-A cmpds)
-- decrease late bronchoconstriction caused by allergen challenge
-- max therapeutic effect occurs after one week of therapy and is assoc w/ decreased need for rescue B-agonist like albuterol
-- alternative to low-dose corticosteroids or cromolyn sodium

Front 23

zafirlukast, montelukast S/Es?

Back 23

major S/E is headache (13%)

Front 24

zafirlukast interactions?

Back 24

can increase plasma conc. of other drugs by inhibiting CYP450

Front 25

cromolyn sodium general properties?

Back 25

-- lipid soluble, but only 10% absorbed from lungs and GI tract
-- available as powder in capsules for inhalation, powder in aerosol, nasal spray, and opthalmic drops

Front 26

Chromolyn sodium MOA?

Back 26

***prevents immediate and delayed Ag-induced degranulation of mast cells
-- prevents release of chemical mediators from mast cells by preventing increase in intracellular Ca conc induced by formation of IgE-Ag bridges on cell surface
-- Does NOT affect binding of IgE to mast cells or binding of Ag to IgE
-- No effect on basal tone of bronchial smooth muscle or the bronchoconstriction caused by ACh, LTs, or histamine
-- No direct antihist or anti-inflamm effects
-- Must be used prophylactically (10-15min) prior to exposure of Ag

Front 27

Chromolyn sodium pharm effects?

Back 27

-- reduces freq and severity of bronchospasm
-- beneficial effect may take 3-4 wks to develop
-- long-term therapy can reduce overall bronchial reactivity to histamine and LTs by preventing bronchial damage caused by mast cell products

Front 28

Chromolyn sodium toxicity, S/Es?

Back 28

-- no contraindications
-- use aerosol with care in patients with CAD or arrhythmias b/c hydrpcarbon propellants can elicit adverse cardiac effects
-- few adverse effects during long-term therapy
- may cause throat irritation, cough, dry mouth, wheezing

Front 29

What is a good adjunctive therapy for asthma?

Back 29

antihistamines -- block actions of histamine at H1 receptors, and the older drugs also block muscarinic receptors and aid in bronchodilation

Front 30

Name the PDEase inhibitors used in asthma treatment?

Back 30

theophylline
aminophylline

Front 31

theophylline and aminophylline general properties?

Back 31

-- elim by hepatic metab and half-life decreased in cigarette smokers
-- crosses placenta
-- secreted in milk; usually no effect on nursing children but may cause irritability/excitation
-- aminophylline is more water soluble than theophylline
-- found in OTC asthma remedies

Front 32

theophylline and aminophylline MOA?

Back 32

-- inhibition of PDEase which degrades cAMP
-- increased cAMP allows increased excitability
-- a specific adenosine receptor antagonist

Front 33

theophylline and aminophylline effects in the lungs?

Back 33

--dilates large and periph airways by relaxation of smooth m.
-- improves ventilation by increasing contraction of the diaphragm and accessory resp m.
-- produces dose-related increase in FEV1 and FVC
-- tolerance DOES NOT develop

Front 34

theophylline and aminophylline effects in the mast cell?

Back 34

***iinhibit mast cell degran
-- prevents histamine release and LT synth

Front 35

theophylline and aminophylline effects in the CNS?

Back 35

-- increases ventilation by increasing the sensitivity of the medullary resp centers to CO2
-- causes central stim
-- can produce nervousness, excitation, insomnia, tremor, and seizures

Front 36

theophylline and aminophylline effects on the heart and blood vessels?

Back 36

-- slight decrease in TPR w/ increased HR and dp/dt elicits a transient rise in CO and organ perfusion
-- central venous pressure and cardiac preload decrease
-- direct effect on adrenal increases plasma epi
-- causes cerebral vasoconstriction, possibly by release of NE

Front 37

theophylline and aminophylline effects on kidney, GI?

Back 37

kidney - transient diuresis and weak natriuresis via a decrease in the filtration fraction

GI - enhances gastric acid secretion

Front 38

theophylline and aminophylline toxicity and S/Es?

Back 38

**serious toxicity is NOT always preceded by less severe S/Es
-- careful dose titration necessary to max benefit and min S/Es
-- monitor plasma conc b/c 5-8mg/L min conc for therapeutic effect while toxic effects appear at 15mg/L and are prominent at 20+mg/L
-- contraindicated in presence of active ulcer
-- use with care in presence of CAD ore recent MI, and CHF or hepatic disease
-- GI tract
- nausea, GI discomfort common b/c both meds are highly alkaline and cause direct gastric irritation
- emesis if conc >15mg/L via action on chemoreceptor trigger zone
-- CNS - restlessness, nervousness, excitation, headache and tremor
- seizures usually occur at 40+mg/L; control w/ diazepam
-- CV - rapid i.v. injection can cause hypotension and arrhyhmias

Front 39

theophylline and aminophylline drug interactions?

Back 39

cimetidine, diltiazem, ERYTHROMYCIN, verapamil, and OCP's increase plasma theophylline by blocking hepatic metab

Front 40

What is Cheyne-Stokes breathing?

Back 40

--periodic deep and shallow breathing which occurs in cycles of 45 seconds to 3 minutes

-- usually occurs in heart failure or after CNS injury

Front 41

How do you treat Cheyne-Stokes?

Back 41

aminophylline (i.v.) often normalizes respiration b/c it sensitizes respiratory center to CO2

Front 42

What is neonatal apnea?

Back 42

--apnea of greater than 15 seconds in duration which can cause recurrent cerebral hypoxia and may produce serious neurological damage

Front 43

Tx for neonatal apnea?

Back 43

aminophylline or caffeine (i.v.) increases resp rate and improves blood gasses in preterm infants w/ intermittent apnea

Front 44

Neonatal hypoxic respiratory failure...

Back 44

-- assoc w/ signs/symptoms of pulm HTN due to increased pulm vasc resistance

-- treat with NO gas given by inhalation
-- improves pulmonary perfusion by decreasing pulmonary vascular resistance