1-8 and 9 Flashcards
True or False: TNF-a, CRP, CK-MB, Trop T/I, and BNP are all biomarkers for cardiac injury
True
How is initial cardiac dysfunction exhibited in HF/CHF?
Decrease in cardiac output
In HF/CHF, there is ultimately decreased perfusion of vessels and tissues, leading to ___deprivation and increased oxygen demand for the ____muscle (due to decreased coronary perfusion)
O2; heart
True or False: Activation of the RAAS System and Sympathetic Nervous System is an adaptive mechanism in HF/CHF
True
Eventually the compensatory mechanisms fail in CHF/HF, accompanied by ___ dysfunction
baroreceptor
In HF/CHF, increased RAAs activity results in what three effects?
1) Edema
2) Vascular dysfunction
3) Cardiac tissue damage
HF is accompanied by increased ____ and decrease ____
resistance; SV
Healthy heart muscles have HIGH adaptability to changing ____by regulating their own ___, as stated by Frank Starling
EDV; SV
(note: failing hearts do not follow this rule and this adaptive mechanism is lost)
What are the two types of CHF?
1) HF with reduced EF - Systolic Heart Failure
2) HF with preserved EF - Diastolic HF
In Heart Failure with Reduced Ejection Fraction (Systolic HF), there is impaired __ function and LCEF is ___ than 40%
systolic ; less than 40%
Which type of heart failure is associated with preserved ejection fraction and systolic function?
Disatolic Heart Failure (HF with preserved ejection fraction)
LVEF is greater than 50% in what type of HF?
Diastolic HF (HF w preserved EF)
What type of heart failure is associated with weakened pump and blood that backs up, overloading the heart
Systolic Heart Failure
Which type of heart failure is associated with thickened or stiff walls, as well as abnormal relaxation and inability to allow enough blood to fill heart prior to squeezizng?
Diastolic HF
Most common cause of acute decompensated HF?
LV or Diastolic Dysfunction
What is the compensation in acute decompensated HF? Why does it ultimately fail?
Compensation = increase in sympathetic activation, which results in increase in ventricular filling pressure
-Leads to leakage of fluids into lung alveoli and intersitium (congestion)
True or False: Acute decompensated HF is associated with rapid fluid accumulation in the lungs
True
What are two positive intotropic agents?
Digoxin, Lanoxin
___ inhibit the phosphorylated alpha subunit of the plasma membranes residing Na/K ATPase channel
Digoxin (and other positive introtropic agents)
How does Digoxin affect Na efflux via Na/K ATPase?
Decreases sodium efflux, increase cytosolic sodium
When digoxin acts, it increases cytosolic sodium, which REDUCES the requirement of Na entry through ___. As a result there is ___ retention in all cells, leading to increase in cytosolic ___, along with release of Ca2+ stores by ___, leading to myocyte contraction.
NCX; ca2+;ca2+;SERCA2
Chronic use of cardiac glycosides, like Digoxin, can result in ____ drug action. Why?
decreased drug action
- increased extracellular K promotes dephosphorylation of Na/K ATPase alpha subunit
Digoxin only has the ability to act on the ______ alpha subunit
phosphorylated state
How is digoxin typically excreted?
Renal route
What is the safe dose for digoxin maintenance therapy?
< 1 ng/mL
True or False: Digoxin has DDI with verapamil and spironolactone
True
True or False: Dopamine is an inotrope with vascular effects that acts on D1 and D2 receptors
True
How does dopamine behave at very low doses?
-Induces cAMP
-Vasorelaxation
In sympathetic neurons, dopamine acts via ___ receptors, inhibit __ release
D2; NE
How does dopamine behave at moderate doses (2-5 ug/kg/min)>
-Directly stimulates cardiac B1 receptors
-Increase cardiac contractility
-Increases sympathetic neuronal NE release
How does dopamine behave at higher doses?
-Stimulates alpha adrenergic receptors in arteries and veins
-Vasoconstriction
Clinical indications for high dose of dopamine infusion?
Circulatory collapse
Where is PDE-5 commonly found?
Lung
How can revatio/viagra be used in HF?
-Used to treat right ventricular systolic failure (due to: pulmonary artery hypertension)
___ is approved for short term in advanced CHF and can improve ventricular contractility and CO?
Inamrinone (PD3 Inhibitor)
True or False: Inamrinone is effective as a short term inotropic
True
AE for PDE3 Inhibitors (Inamrinone)?
Thrombocytopenia
What drug class do Inamirone and Sildenafil belong to?
PDE Inhibitors (includes PDE3 and 5 Inhibitors)
How does inhibiting PDE enzymes in HF affect cAMP levels?
-Raise or upregulate cellular cAMP
True or False: PDE results in a negative intropice effect in cardiac tissue, along with increases resistance in both arteries and veins
False
Clinical Benefits of PDE Inhibitors in HF?
(hint: preload/afterload)
Reduces preload and afterload
___is a non-specific beta agonist that can stimulate b1 receptors in cardiac tissue, resulting in increased contractility
Dobutamine
Dobutamine acts on ___ receptors on VSM, which results in ____ and ___ in vessel resistance
beta 2; vasodilation/decrease in vessels resistance
True or False: Dobutamine could be used to decrease inotropic effect and cause vasodilation
False - while Dobutamine can be used to cause vasodilation, it will INCREASE inotropic effect
Tolerance may develop follow 1 week of treatment with ____ due to increased PDE activity. Under those conditions ___ inhibitor addition will yield better pharmacological results.
Dobutamine; PDE3
What is the major role of diuretics in HF?
Decrease pre-load
Decrease edema
___: agents known to decrease ventricular filling pressure due to ability to decrease ECF volume
Diuretics
True or False: Diuretics typically decrease pre-load without significantly changing CO
True
What class of drugs are preferred for maintaining euvolemic state for patients suffering from hypervolemia?
Diuretics
What type of doses are initially required for diuretics, when used in CHF?
High doses
Since diuretics can cause hypokalemia, ___ are preferred in HF
K+ sparing diuretics
True or False: Bumetamide is a Loop Diuretic
True
What class of drugs are used to treat HYPERVOLEMIC patients with edema
Loop Diuretics
Why are Loop Diuretics also known as high ceiling diuretics?
They can expel max. Na/Cl/water
True or False: Thiazides result in loss of Na and K
True
True or False: Thiazides are only recommended for combinatorial therapy in CHF
True
Which drug class causes volume depletion and minimal K/Mg loss?
K Sparing Diuretics
True or False: MR Antagonists protect against cardiac/renal fibrosis, ischemia, and help prevent endothelial and vascular smooth muscle contraction, as well as damage/loss of elasticity
True
True or False: CHF patients have almost ___ more aldosterone in their circulation
20%
MR Antagonists, such as spironolactone, can be given in CHF. However, what is the AE associated?
Gynecomastia
- If this happens, substitute for Eplerenone
MR Antagonists can be used to treat CHF. However, about 2% of people develop ____. How can it be treated?
Hyperkalemia
-IV calcium OR glucose/insulin combination (IV)
-eventually switch to loop diuretics
Why does Diuretic Resistance occur in CHF treatment?
1) Non-adherence to na/fluid restriction
2) Non-compliance w med dose
3) Compensatory increase in sodium reabsorption following na loss from body by RAAS activation (mostly seen in Loop Diuretics)
____ and ___ are channel activating proteases (CAP1) present in tubular lumen that cleave GAMMA subunit of ENaC and activates it, resulting in enhanced reabsorption of __
Na
(Used if resistance to K sparing diuretics)
The endogenous prostaglandins enhance __ via RAAS
renal perfusion
Inhibition of prostaglandins (aspirin, NSAID) can decrease ____ and attenuate diuretic efficacy (there will be LESSER amount of filtrate in lumen)
renal perfusion
Hydralazine is also known as
Bidil
Bidil/Hydralizine is a ___
arterial dilator
Organic Nitrate primarily acts as a __dilator, thus reducing both ___ and ____
pre and afterload
What are two visodilators used in CHF?
1) Isosorbide Dinitrate
2) Hydralazine
____, a vasodilator used in CHF, gets converted to NO using ER residing CYP450 system
Isosorbide Dinitrate
____, an arterial dilator, decreases release of calcium from intracellular pools by inhibiting IP3 pathway and decreasing vascular contraction
Hydralazine
