Pharmacology: Test 3: Positive Inotropic Drugs Lec 53

Front 1

Digitalis: Digoxin

Back 1

any of the steroid or steroid glycoside that exert positive inotropic and electrophysiologic effect on heart

Primary agent used clinically is called DIGOXIN

Front 2

Digoxin

Back 2

used to enhance CO during CHF but no effect on CO of normal pt.

used to trt supraventricular cardiac arrhythmias (tox may also cause arrhythmias)

Front 3

Digoxin vs. digitoxin

Back 3

Digitoxin does not have a 12' hydroxyl group that digoxin does.


Digitoxin has better oral bioavailability, slower onset of action, reach peak in 4-6 hrs (vs. digoxin in 1.5- 4 hrs). It's is highly protein bound (97% vs. 23% for digoxin) Better Therapeautic plasma conc. (14-26) then digoxin (.5-1.2) and toxic plasma conc also better, 34 vs >2.4 for digoxin.

Front 4

Why is digoxin not so great in emergency?

Back 4

Peak effect takes hours, upto 4 hours for digoxin or 6 hours for digitoxin (IV)

Front 5

Digoxin elimination and renal status

Back 5

T1/2 is 1.6 dz but depends on renal function, and clear slowly with age and renal dysfunction.

May clear faster in some where it is also metabolized by gut bacteria

Front 6

Digoxin: Drug interractions

Back 6

Most important ones are certain antiarrhythmia drugs: Quinidine, Verapamil, Amiodarone... these drugs cause [digoxin] to double.

So decrease digoxin dose by 50% and monitor serum levels as necessary.

Front 7

Digoxin: Mechanism

Back 7

normally Na-K ATPase maintains sodium gradient within the cell by removing Na from cell and bringing in K. The Low Na in the cell allows for Na-Ca exchange where Na flows into the cell and Ca is kicked out of the cell.

When Na-K ATPase is out of business by digoxin binding and inhibiting Na-K ATPase pump, the Na builds up in the cell and so intracellular Na gradient is high and extracellular Na doesn't go in, and can't kick out Ca, hence leading to ACCUMULATION OF CALCIUM



This causes increase in force and velocity of contraction.

Front 8

Digoxin and hypokalemia

Back 8

since digoxin binds the same site as K, in hypokalemia, digoxin can more readily bind and disable the Na, K ATPase and its action is enhanced.

Front 9

Digoxin Effects: Pt with Heart Failure

Back 9

positive inotropic action causes >> Increase CO > increase renal perfusion > enhanced sodium excretion and reduction in edema.

Enhanced CO > Increased EF > decrease cardiac filling pressure > reflex reduction in HR and peripheral resistance > Sx improvement

Decreased venous pressure and LV end diastolic vol allows distended heart to return to smaller, more normal size and relieve edema.

Front 10

Digitalis and O2 consumption

Back 10

while increase contractility cause more o2 consumption, this is offset by decrease in HR and Heart size.

Front 11

Digitalis in normal pts

Back 11

Digitalis posses DIRECT VASOCONTRICTOR action, which causes incrase peripheral resistance in normal pts, but increased inotropic state of the heart doesn't translate to increase CO because of increase Afterload.

In pts with CHF, their peripheral resistance is already high due to compensatory vasocontriction, so the inotropic effects are realized.

Front 12

Digoxin and CHF

Back 12

should be used in pts with LV systolic dysfunction (dilated cardiomyopathy) usually doe to ischemia or infarct, myocarditis, toxins, or chronic mechanical overload. Used to treat Type II, III and IV heart failure symptoms.

DIGOXIN DOESN'T REDUCE MORTALITY BUT REDUCE HOSPITALIZATION.

Front 13

Digoxin as Anti-Arrhythmic drug

Back 13

Mech: enhance vagal tone (increase baroreceptor sensititivy, increase heart sensitivity to Ach, slow AV nodal conduction)

used in ATRIAL fibrillation, atrial flutter, Paroxysmal supraventricular tachcarydia (PSVT).

Front 14

Digitalis Toxicity

Back 14

Predisposing factors: DECREASED plasma K (or Mg) and increased plasma Ca

Renal (digoxin) or hepatic (digitoxin) dysfunctin.

Hypothyroidism

Drug Interractions: verapamil, diltiazem, beta blockers, Kaliuretic diuretics, sympathomimetics

Front 15

Digitalis: manifestations of toxicity

Back 15

Arrhythmias, anorexia, nausea (stim. of area postrema), visual changes such as distortion of color vision or appearance of Halos on dark, headache, fatique, depression, confusion.

Front 16

Arrhthmias as Toxic effect of digitalis

Back 16

toxic dose can cause most any type of arrhythmias or conduction block.

Mech: Neurally via activatin of both Symp and parasymp nerve to heart.

Directly, by overinhibition of too many Na, K ATPases, causing alt. in Ca, K and Na fluxes.

The neural and direct effect synergize resulting in AV dissociation and arrhythmias.

Front 17

Therapy for Digoxin toxicity

Back 17

STOP drug, ECG monitoring, correct electrolytes, Low K or Mg common, High K likely to be fatal, Use atropine (pacing contraindicated)

Give Fab "Digibind", MgSO4

Front 18

Other inotropic agents

Back 18

symp amines (dopamine, dobutamine), PDE3 inhibitor (3 is spec for heart, leads to elecated intracellular Ca).