Flashcards in Inotropes Deck (59):
What is digoxin?
Cardiac glycoside that competes with K+ and blocks Na+/K+ pump leaving more Na+ in the cell to pump out in exchange for Ca2+ on Na/Ca exchanger
Does digoxin inc HR?
No, inc inotropy w/o inc in HR
List some pharmacological properties of digoxin
How is digoxin eliminated?
What does digoxin do to the CO?
What does digoxin do to the LVEF?
What does digoxin do to the LVEDP?
Decrease (ie preload)
What does digoxin do to exercise tolerance?
What does digoxin do to natriuresis?
Inc (Excretion of Na and H2O from kidney)
What does digoxin do to the neurohormonal activation?
-Hrt works better, body doesn't need as many hormones
What does digoxin do to the levels of plasma norpei
What does digoxin do to the peripheral NS activation?
What does digoxin do to the RAAS activity?
What does digoxin do to vagal tone?
Increases, helps with HR control and normalizes arterial baroreceptors (were desensitized before administration of drug-->drug dec preload)
What is digoxin's effects on the Atrial and AV node?
Decreases "automaticity" via increase in vagal tone and decrease in sympathetic activity (i.e. dec how quickly cells can cycle and fire again)
Increases refractory period of AV node in toxicity (high levels) and can lead to bradycardia and heart block
-->i.e. increase in PR invterval
What are digoxin's effects on the ventricles?
Increases isotropy at therapeutic doses
At toxic doses, can inc sympathetic tone and directly inc automaticity leading to increased risk of ventricular tachycardia and fibrillation
What are inotropes?
Agents that increase cardiac contractility for our purposes by increasing intracellular Ca2+ and cAMP
Why are inotropes helpful in HF?
In HF, there is a reduction in the rate and extent of Ca2+ delivery to myofilaments, resulting in reduced contractility
What do inotropes do to the frank-starling curve?
Shifts them upward and left (greater end diastolic volume/preload and greater SV)
What are the clinical uses of Digoxin?
-A fib with rapid ventricular response (increase AV nodal refractory period, more effective at rest than with exercise)
-CHF symptoms despite medical therapy (don't give an asymptomatic person the drug because you'll only get the negative effects without the pos dec in symptoms)
-Can be combined with other drugs
What are the negative long term effects of digoxin?
More serious arrhythmias--vent tacky or fib
What are the positive long term effects of digoxin?
Fewer hx admissions for heart failure
What factors predispose people to digoxin toxicity?
Hypokalemia, hypomg, hypothyroidism, hypoxia
Drug interactions are common!
What are the contraindications for digoxin?
-Advanced AV block without a pacemaker (will cause complete heart block)
-Bradycardia or sick sinus syndrome without a pacemaker
-Wolf-Parkinson-White with atria fibrillation (increases conduction through the bypass tract)
What are the cardiac consequences of digoxin toxicity?
-Ventricular-->PVCs, tachycardia, fib
-Supravent-->premature atrial contractions and supraventricular tachycarida
-SA and/or AV
Heart Failure Exacerbation
-Typically due to heart block/bradycardia
What are the extra cardiac consequences of digoxin?
GI: nausea, vomiting, diarrhea
Nervous: depression, disorientation, paresthesias
Visual: blurred vision, scotomas, yellow-green vision
Hyperestrogenism: Gynecomastia, galactorrhea
How do you treat digoxin toxicity?
-Antibody rapidly reverses inhibition of myocardial sodium pump
-Avoid hypo or hyperkalemia
Where are the catecholamine effects on peripheral excitatory action on smooth muscle?
-BVs of skin and mucous membranes
-Salivary and sweat glands
Where do catecholamines have peripheral inhibitory action?
Gut, bronchial tree, BVs in skeletal muscle
Catecholamine actions on metabolic activity
-inc glycogenolysis in liver and muscle
-liberation of free fatty acids from adipose
Catecholamine actions on endocrine activity
Modulation of insulin, renin, pituitary actions
Catecholamine actions on CNS
Resp stim, inc wakefulness, dec appetite
Where is beta 1 located?
Myocardium, SA node, AV node
Where is beta 2 located?
Where is alpha located?
What neurohormone usually stimulates SNS?
What triggers eli and norepi release?
Stress causes release from adrenal medulla
Where does dopamine have its effects?
CNS and periphery
What are the dose-dependent responses of dopamine?
-DA1 receptor: low dose, post-synaptic-->vasodilation of renal, mesenteric, coronary and cerebral
-DA2 receptor: medium dose, pre-synaptic-->inhibits re-uptake of norepi allowing for indirect beta stimulation
-Beta1 and Alpha receptors stimulated directly at high dose
What is the half life of dopamine?
Dopamine side effects
-Tachycardia (as dose inc)
-Infiltration of IV site can lead to necrosis of skin or gangrene of fingers/toes (large vasoconstriction if dopamine binds)
What is dobutamine?
A synthetic catecholamine
How does dobutamine work?
Decreases afterload while increasing inotropy, esp at low doses and has beta and alpha adrenergic activity- (more isotropy than vasodilation)
Side effects of dobutamine
-Rapid vent response to a fib due to inc in A-V conduction
-Nausea, headache, palpitations
How can dobutamine be used as a diagnostic agent?
You can take advantage of the ischemic potential of dobutamine to diagnose coronary disease. It's like pharma stimulating exercise. See what parts of the heart are not being perfused when it squeezes harder
When do we use epinephrine?
After cardiopulmonary bypass or in resuscitations. Useful in denervated post-transplanted heart to stimulate rhythm
How long is the epinephrine half life?
What are the side effects of epinephrine?
Tachycardia, ischemia, platelet agg and infarction, anxiety, fear, restlessness
What does norepi do.?
Powerful vasoconstrictor, but only modest inotrope
What is isoproterenol?
Non-selective beta agonist with powerful chronotropic effect
When is isoproterenol used?
After heart transplant to drive HR and decrease pul vasc resistance
What are phosphodiesterase inhibitors?
Type III: associated with the sarcoplasmic reticulum, increasing contractility without an increase in HR, esp at low dose. Act independently of beta receptors
They are potent vasodilators and therefore decrease preload
Why don't we use amrinone often?
Can cause significant thrombocytopenia
How is milrinone eliminated?
What was the disappointment with PDE inhibitors?
they increase mortality
What is vesnarinone?
PDE inhibitor inotrope and type III atriarrhythmic
What is a problem with vesnarinone?
Improves quality of life, but inc morality and risks of arrhythmias
Why use beta-adrenergic inotropic therapy in HF?