Block 3: Positive Inotropic Drugs

Front 1

what is the term for any of the steroid and steroid glycoside compounds that exert typical positive inotropic and electrophysiologic effects on the heart

Back 1

digitalis

Front 2

what is the primary agent used clinically

Back 2

digoxin

Front 3

during what condition are the digitalis glycosides used to enhance cardiac output

Back 3

congestive heart failure

have no effect on cardiac output in normal patient

Front 4

these drugs are used to treat what type of arrhythmias even if toxic doses may cause cardiac arrhythmias

Back 4

supraventricular arrhythmias

Front 5

Where do digitalis compounds come from and what is their common structure

Back 5

foxglove plant

steroid nucleus with a lactone ring at position 17

Front 6

what has higher oral availability, digoxin or digitoxin

Back 6

digitoxin - 90-100%, compared to 70-80%

Front 7

what has higher oral absorption of digoxin- an encapsulated gel or a tablet

Back 7

encapsulated gel

Front 8

name three things that retard absorption

Back 8

food
antacids
steroid binding resins

Front 9

there is a close correlation between ___ ___ and plasma digoxin concentration

Back 9

creatinine clearance

Front 10

what is the consequence of the 10% of patients who metabolize digoxin to inactive products in the gut lumen by bacteria

Back 10

higher doses are needed

Front 11

what is a loading dose of digoxin called

Back 11

digitalizing dose

Front 12

name three ways drugs interact with digoxin

Back 12

1. inhibit absorption (cholestyramine)
2. antibiotics eradicate gut bacteria causing increased plasma concentrations
3. increase digoxin blood levels (antiarrhythmic agents like quinidine, verapamil)

Front 13

what is meant by positive inotropic action

Back 13

increased force and velocity of contraction by direct action on the heart, not mediated by catecholamines or by activation of adenylyl cyclase

Front 14

digitalis binds to the external portion of and inhibits which enzyme

Back 14

membrane bound Na-K-ATPase

Front 15

is digitalis binding to Na-K-ATPase enhanced or inhibited by hypokalemia

Back 15

enhanced

Front 16

What is the net effect of inhibition of the Na-K-ATPase enzyme

Back 16

increase in availability of Ca to myocardial contractile proteins

Front 17

digoxin increases the __ and __ of myocardial contraction by increasing intracellular __

Back 17

force
velocity
Ca

Front 18

how does digoxin help CHF

Back 18

direct positive inotropic action -> inc CO -> increased ejection fraction -> decreases cardiac filling pressure -> reflex reduction in heart rate and peripheral resistance

Front 19

digoxin causes improved renal perfusion, what does this result in

Back 19

inhanced sodium excretion and reduction in edema

Front 20

digoxin reduces venous pressure and left ventricular end diastolic volume, what does this allow?

Back 20

the distended heart to return to a smaller, more normal size, and relieves edema

Front 21

What is meant by "digitalis increases the efficency of the failing heart"

Back 21

CO and O2 consumption

Front 22

why does the hemodynamic outcome of digitalis administration differ between patients with CHF and those without CHF

Back 22

the DIRECT VASOCONSTRICTOR ACTION of digitalis

Front 23

What does digitalis do in patients without CHF

Back 23

it increases peripheral resistance and therefore afterload; no increased CO because of the increased afterload

Front 24

Why doesn't digitalis increase afterload in patients with CHF

Back 24

because the peripheral resistance is already very high due to compensatory vasoconstriction

Front 25

___ is a complex of signs and symptoms which comprise a recognizable clinical syndrome of pulmonary and peripheral tissue congestion with or without the effects of decreased cardiac output at rest

Back 25

CHF

Front 26

digoxin is used to treat CHF resulting from ___, which generally results from MI, myocarditis, toxins, or chronic mechanical overload

Back 26

left ventricular systolic dysfunction (dilated cardiomyopathy)

Front 27

does digoxin reduce the overall mortality of HF? does it reduce the rate of hospitalization?

Back 27

no
yes

Front 28

how does digoxin act as an anti-arrhythmic action

Back 28

enhances vagal tone- due to sensitized arterial baroreceptors, increased efferent vagal fiber excitability and increased sensitivity of heart to ACh

slows AV nodal conduction and sinus rate

Front 29

Name three anti-arrhythmic uses of digoxin

Back 29

a-fib
a-flutter
Paroxysmal supraventricular tachycardia (PSVT)

Front 30

what is the most frequent antiarrhythmic use of digoxin

Back 30

atrial fibrillation

Front 31

can digoxin achieve and maintain sinus rhythm during a-fib?

Back 31

no- other antiarrhythmic drugs or DC cardioversion are often needed

Front 32

name 8 predisposing factors for digtalis toxicity

Back 32

1. ionic imbalance
2. DECREASED K
3. increased Ca
4. heart disease
5. RENAL DYSFUNCTION - DIGOXIN
6. LIVER DYSFUNCTION- DIGITALIS
7. hypothyroidism
8. drug interactions

Front 33

name four manifestations of digitalis toxicity

Back 33

1. arrhythmias
2. stimulate "trigger zone"- anorexia, nausea, vomitting
3. visual changes
4. neurologic changes: HA, fatigue, insomnia, confusion, depression

Front 34

What particular arrhythmia is specific to digoxin toxicity?

Back 34

none- it can cause most any type of arrhythmia or conduction block

Front 35

what nerves to the heart are effected by digoxin

Back 35

both sympathetic and parasympathetic nerves are activated

Front 36

at toxic doses, the direct toxic effect of digoxin on the ventricle, combined with the enhanced sympathetic input to the ventricle can cause

Back 36

synergy- AV dissociation, premature ventricular beats, v-tach, and fibrillation

Front 37

name five steps to treat digoxin toxicity

Back 37

1. stop digoxin and monitor cardiac rhythm
2. correct electrolytes
3. KCl- unless AV block present
4. atropine or pacing for bradyarrhythmias
5. digoxin-immune Fab or lidocaine for ventricular arrhythmias

Front 38

except for ___, oral agents for chronic positive inotropic therapy have been show to increase mortality due to increased arrhythmias

Back 38

digoxin

Front 39

name two sympathomimetic amines parenterally administered primarily in cardiogenic shock, low output states which follow open heart surgery, and severe refractory CHF

Back 39

dopamine- i.v.
dobutamine- i.v.

Front 40

name two phophodiesterase inhibitors whose inotropic action is due to inhibition of cyclic nucleotide phophodiseterase isoenzyme III which leads to inc intracellular calcium

Back 40

inamrinone
milrinone

Front 41

what else do inamrinone and milrinone do

Back 41

vasodilators

Front 42

how are inamrinone and milrinone given

Back 42

parenterally

Front 43

toxicity of which, inamrinone or milrinone, includes reversible thrombocytopenia

Back 43

inamrinone

Front 44

which, inamrinone or milrinone, is the agent of choice for short term i.v therapy for severe CHF

Back 44

milrinone