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Flashcards in Inotropic Drugs Deck (24):
1

Glycosides - Primary Mechanism

Glycosides block the Na+/K+ pump, decreasing the rate of extrusion of Na+

Increased intracellular Na+ augments the rate of Ca2+ influx through the NCX as it pumps to remove excess Na+

Increased Ca2+ leads to increased inotropy by virtue of more Ca2+ available to bind Tn-C

2

Effects of cardiac glycosides

Increased inotropy leads to: increased CO, increased EF, increased SV, decreased ESV and EDV

Decreased ESV and EDV result in decreased transmural wall pressure and reduced myocardial work

Increased CO also increases renal perfusion and GFR, resulting in diuresis and decreased blood volume

2

Alpha adrenergic agonists - Mechanism

Alpha adrenergic receptors activate Gq protein, which activates phospholipase C to produce DAG and IP3

IP3 activates Ca2+ release from the SR via IP3 receptors

3

Pro-arrhythmic effects of cardiac glycosides

Increased intracellular Ca2+ can lead to Ca2+ overload in the SR; if Ca2+ oscillation is large enough to depolarize the cell beyond threshold, it can lead to afterdepolarization and premature ventricular contraction or ventricular tachycardia or fibrillation

4

Beta-adrenergic agonists - Mechanism

Binding of agonist to the B-adrenergic receptor activates the Gs protein, which activates adenylylcyclase to produce cAMP; cAMP activates PKA which phosphorylates many protein targets including LTCCs and Phospholamban, increasing Ca2+ flux into the cell

5

Epinephrine / Adrenaline

Non-glycoside positive inotrope; sympathomimetic with B-adrenergic activity, binds both B1 and B2 adrenergic receptors

6

Phosphodiesterase Inhibitors

Prevent breakdown of cAMP by phosphodiesterase and increase the affinity of Tn-C for Ca2+

Persistent cAMP-PKA mediated phosphorylation of phospholamban increases the reuptake of Ca2+ into the SR

7

Norepinephrine

Non-glycoside positive inotrope; sympathomimetic with B-adrenergic activity, binds alpha1 receptors, B1 receptors, and B2 receptors with B1 activity > B2

Reduces vasodilation

8

Cardiac Glycosides - Secondary Mechanism

Glycosides increase CO, which increases renal blood flow; increased renal perfusion decreases circulating blood volume and diminishing activation of the RAS system

***Over time the positive inotropic effects of cardiac glycosides decrease sympathetic tone by resolving the symptoms of CHF

9

Digoxin - Pharmacokinetics

Polar compound with addition of an -OH group; compound administered IV and is excreted unchanged by the kidney with a half life of ~1.7 days

10

Digitalis- Side Effects

AV block
PVCs
Bradyarrythmias

11

Digitalis - DDIs

ACEIs - Increase K+ which displaces binding of Digoxin from Na+/K+ ATPase

Diuretics - can increase or decrease K+

Ca2+ channel blockers and B-blockers also slow AV nodal conduction

12

Digitoxin - Pharmacokinetics

Administered IV, excreted renally following hepatic degradation with a half life of ~7 days

13

Electrophysiologic effects of Digitalis on SA node

Decreased conduction velocity

14

Electrophysiologic effect of Digitalis on AV node

Decreased conduction velocity
Increased effective refractory period

15

Electrophysiologic effect of Digitalis on Purkinje fibers

Increased conduction velocity (therapeutic)
Decreased conduction velocity (pathological)

16

Electrophysiologic effect of Digitalis on Ventricular muscle

Decreased effective refractory period

17

Norepinephrine - Receptor Targets

alpha-1 adrenergic
B1 adrenergic > B2 adrenergic

18

Epinephrine - Receptor Targets

alpha-1 adrenergic
beta-1 adrenergic = beta-2 adrenergic

19

Dopamine - Receptor Targets

alpha-1 adrenergic
beta-1 adrenergic > beta-2 adrenergic

20

Isoproterenol - receptor targets

Beta 1 adrenergic = Beta-2 adrenergic

NO alpha-1 adrenergic activity

21

Dobutamine - Receptor targets

Primarily beta-1 adrenergic

Some beta-2 adrenergic

22

2 main effects of Digoxin

1. Improve contractility of the failing heart

2. Prolong refractory period of the AV node in patients with supraventricular arrhythmias

23

Uses of Digoxin

Symptom improvement in systolic dysfunciton (NYHA II, III, IV)

Control of ventricular rate during atrial fibrillation