E3: Inotropes/Glycosides

Question 1

Dobutamine
Classification
Indication
MOA (5)
Pharmacologic effects
ADR
DI

Answer 1

Classification: B1 selective adrenergic AGONIST
Indication: IV short term use in cases of ADHF to support cardiac function
MOA (5):
B1 stimulation of cardiac cells&raquo_space;B2, a1
Increase cAMP –> increased PKA (Keeps Ca2+ channels open, increased SR Ca2+ release)
Calcium enters cardiomyocytes
Actin + myosin shortening of cardiac muscle fibers
Contraction of cardiac muscle

Pharmacologic effects: inotropic agent, increase force of contraction
ADR: Increase HR, SBP, VPC
DI: MOA and COMT inhibitors, TCA

Question 2

Digoxin-Lanoxin, Digitek, Lanoxicaps
Classification
Indication
MOA (5)
Pharmacologic effects
ADR
DI

Answer 2

Classification: Cardiac glycoside

Indication:
-Chronic HF maintenance (HFrEF only): decreased hospitalizations, no decreased mortality
-Arrhythmia’s: control ventricular rates in atrial fibrillation (3rd line antiarrhythmic)

MOA (5)
reversible inhibition of myocyte Na+/K+ ATPase
–block ability to move Na+ out of cell
–less Na+ extracellularly = ↑ Ca2+ intracellularly
**↑Ca2+ to interact w/actin and myosin to ↑ contractile force
–↑ force of cardiac cell contraction –> positive inotropic agent
Pharmacologic effects
-positive inotropic effect, ↑ ventricular ejection of blood
-↑PNS stimulation to the heart (neg. chronotropic effect… ↑ vagus nerve stimulation in SA and AV node… ↓HR)

ADR:
-visual disturbances (photophobia, scotoma, blurred/dim vision, chromatopsia, xathopsia,)
-digitalis delirium: mental depression/personality changes

DI:
-verapamil, ↑ dig levels
-drugs/conditions that cause ion disturbances
–↑K = ↑ dig and vice versa
–↑ Ca2+ = ↑ dig

Question 3

Digoxin has a ________ therapeutic plasma range and is primarily excreted through the ______

Answer 3

NARROW therapeutic range
excretion via the KIDNEY

Question 4

2 main components of digoxin structure

Answer 4

1. Aglycone portion: steroid backbone and lactone ring
2. Glycone portion: 3 sugars ↑ absorption and distribution of drug in body

Question 5

Milirnone (Primacor) IV
Indication (4)
MOA (5)
Pharmacologic effects (2)
ADR
DI

Answer 5

Indication (4):
1. acute decompensated HF (hospitalization: water retention, SOB, fatigue)
2. patient w/ventricular assist device/waiting for heart transplant
3. provide marginal symptomatic relief
4. ↑mortality w/LT use

MOA (5)
1. cAMP dependent PDE3 inhibitor
–inhibits breakdown of cAMP
–↑cAMP
–↑PKA (keeps Ca2+ channels open, ↑SR Ca2+ release
–↑Ca intracellularly
–↑contractile force

Pharmacologic effects
A. Inotropic vasodilator/inodilator
–Significant inotropic effect on failing heart, little chronotropic effect
–cause arterial & venous vasodilation of blood vessels

ADR: arrhythmias, hypotension, angina, headache

DI: other PDE inhibitors (viagra, tadalafil-Cialis, avanafil-Stendra)

Question 6

CoQ10
Indication
MOA
Pharmacologic effects
ADR
DI

Answer 6

Indication: Not approved for any treatment by FDA (OTC product), used as supplement for HMG-CoA reductase inhibitors (statins)

MOA: mitochondrial oxidative phosphorylation pathways (direct free radical scavenging activity

Pharmacologic effects
1. Minimal positive inotropic effect
2. Prevention of atherosclerosis (antioxidant effect)

ADR: abdominal discomfort, headache, nausea, vomitting

DI: diminish the anticoagulant effect of Vit K antagonist (warfarin)

Question 7

Ivabradine (Corlanor) PO
Indication
MOA
Pharmacologic effects
ADR
DI

Answer 7

Indication: Chronic stable symptomatic HF w/resting HR at least 70BPM (↓ rate of hospitalization in chronic stable HFrEF)
MOA: binds K+/Na+ hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) receptors selectively inhibits the pacemaker I_f current in SA node
*binds K+/Na+ HCN4 to inhibit If current in SA node

Pharmacologic effects
-↓HR NOT contractility
-↓ spontaneous firing of SA node (↓automaticity)
-allows more time for blood to fill into ventricles

ADR:
1. lumnious phenomena, phsophenes (sensations of enhanced brightness in the eye)
2. bradycardia
3. headaches

DI: CYP3A4 substrate (Major)