Drugs for HF - Kruse Flashcards
_ occurs when cardiac output is inadequate to provide the oxygen needed by the body
heart failure
What are some causes of HF?
- diminished coronary blood flow
- damaged heart valves
- external pressure around the heart
vitamin B deficiency - primary cardiac muscle disease
- others
What are some current therapies mechanisms that which are targeted for HF?
- RAAS
- sympathetic nervous system.
- Current therapies shown to reduce mortality, while historic therapy treated end-point components and did not reduce mortality.
what are the three classes of drugs used to treat HF?
- Diuretics
- Vasodilators
- Inotropic agent
Which diuretics is known to be used in HF?
- Loop diuretics particularly furosemide and ethacrynic acid.
besides HF, what else is loop diuretics indicated for?
- edema
- HTN
- AKI
- Hypercalcemia
What adverse effects are associated with loop diuretics?
- Hypokalemia
- Alkalosis
- Hypocalcemia
- Hypomagnesemia
- Hyperuricemia
- Ototoxicity
- Sulfonamide (hypersensitivity)
promotion of arrhythmias, vascular and cardiac hypertrophy and remodeling, and stimulation of myocyte death has also been implicated by what factor of the RAAS mechanism?
Ang II
_ is the only cardiac glycoside available in the US
Digoxin
What are the therapeutic application of digoxin?
- HF implicated with an 3rd heart sound. ( if there’s no third 3rd sound this woun’t be the first choice)
- Tachyarrhythmias
- Shock
_ is a combination of steroid nucleus, lactone ring, and sugar that which inhibits the membrane-bound Na/K ATPase and increase myocardial contractility
Digoxin
Explain the normal physiology of sarcolemmal exchange of Na and Ca during cell depolarization and repolarization
During depolarization, Na and Ca enter cell. Ca once inside goes to the RyR and indices further Ca release from the SR. THe increased Ca inside the cell allows for muscle contraction.
During repolarization: Sarcoplasmic recticular Ca ATPase pumps Ca back into the SR. Also, 3 Na leaves while 2K comes into the cell via the Na/K ATPase (main ATPase to maintain the voltage gradient) on the sarcolemma. this builds a gradient on the outer leaflet of the cell for the Na/Ca exchanger (NCX) to function which trades Ca leaving the cell and 3 Na coming into the cell.
So if you block the Na/K ATPase, there’s no Na gradient on the outside for which NCX to work. and so that’s blocked and Ca builds up inside the cell.
On what channel does digoxin work?
Digoxin works to block the Na/K ATpase that is open during repolarization of sarcolemma. This blockage builds up Ca inside the cell and thus stronger and longer muscle contraction occurs.
Digoxin increases the activity of Ca-dependent K channels. Increased Ca dependent K channel activity promotes K efflux and a more rapid repolarization thus shortened cardiac action potential
At therapeutic level of digoxin parasympathomimetic effects predominate on cardiac tissue. explain how.
- Parasympathomimetic effects involve sensitization of the baroreceptors, central vagal stimulation, and facilitation of muscarinic transmission at the cardiac muscle cell.
- Cholinergic innervation is more concentrated in the atria, resulting in increased action of digoxin on atrial and AV nodes compared to Purkinje or ventricular function.
what is the most common cardiac manifestation of digoxin toxicity?
Increased after potential –> Arrhythmia, paroxysmal atrial tachycardia. If allowed to progress, the tachycardia may deteriorate into fibrillation that could be fatal.
At therapeutic effects of digoxin explain how the following is effected: A. Sinus node B. Atrial muscle C. AV node D. Purknje system, ventricular muscle E. EKG changes
A. Decrease B. decrease refractory period C. Decrease conduction velocity and incrase refractory period D. Slight decrease refractory period E. Increase PR interval, and decrease QT interval
What effects does the following have on Digoxin?
A. Hyperkalemia
B. Hypokalemia
A. reduce effects of digoxin (esp the toxic effects)
B. potentiate the toxic effects of digoxin
What effects does hypercalcemia and hypomagnesemia have on digoxin?
They increase the risk of digoxin-induced arrhythmia
What is the MOA of bypyridines (Milrinone)
selective inhibition of PDE3 phosphodiesterase enzyme (PDE3 degrades cAMP).
- increase concentration of cAMP in heart result in direct stimulation of myocardial contractility and acceleration of myocardial relaxation
- increased concentration of cAMP in the vasculature cause balanced arterial and venous dilation
When there is the decrease in CO indicate what happens to the following as a reflex mechanism A. Carotid sinus firing B. sympathetic discharge C. Force and rate of heart D. Preload E. Afterload
A. Decrease B. increase C. Increase D. Increase E. Increase
which of the following meds may, at high doses, potentiate the toxic effects of digoxin? A. Lasartan B. Ibuprofen C. Furosemide D. Ranitidine E. Citalopram
C. Furosemide. The idea here is that K digoxin bind to similar area on the Na/K ATPase
Loop diuretics and thiaziade diuretics all cause hypokalemia as an AE, so at high dose of either will lead to hypokalemia and when combined with tx with digoxin may affect therapeutic efficiacy of digoxin. even at stanard dose of it.
which of the following increase both force of heart contraction and produces vasodilation? A. ACEI B. Beta blocker C. Bipyridines D. cardiac glycosides E. Venodilators
C. Bipyridines.
Wrong ans:
A. ACEI can vasodilate but can’t really have an effect on contraction.
B. Can have an effect on contractility but cannot vasodilate.
D. do not vasodilate
E. does not affect contractility
Digoxin toxicity includes what signs and symptoms?
- Blurry yellow vision
- Cholingeric effects (nausea, vomiting, diarrhea)
- arrhythmias (increased PR, decreased QT, T inversion)
- Hyperkalemia initially, but with increasing digoxin toxicity leads to hypokalemia
- renal insufficiency with increasing digoxin tox
A 67-year old male with congestive heart failure with systolic dysfunction presents to the emergency department with several days of nausea, vomiting, and decreased appetite. He denies fever, chest pain, abdominal pain, or sick contacts. He reports shortness of breath at baseline. His heart rate is 84 beats/min and his blood pressure is 118/87. Physical exam is remarkable for +1 pitting edema in his bilateral lower extremities. His current medications include furosemide, lisinopril, carvedilol, and digoxin. At a recent cardiologist visit, his furosemide dose was increased due to worsening lower extremity edema. EKG shows PR interval increased, with QT interval interval decreased. Management of this patient will likely entail which of the following?
- Atropine administration
- Potassium and magnesium repletion
- Hemodialysis
- Cardiac catheterization
- Cardiac pacemaker implantation
- Potassium and magnesium repletion.
Digoxin toxicity can present with nausea, vomiting, and decreased appetite in conjunction with a wide array of EKG changes. Treatment includes correcting electrolytes disturbances, especially potassium and magnesium repletion as necessary.
