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Heart Failure Medications- Part Three: Add-on Agents. Lecture for Pharmacy Students & Pharmacists.

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In part three of this four-part lecture on Heart Failure medications, we will:

Heart failure medications part 3 add-on agents in part 3 we’ll talk about adding on additional medications to traditional drug therapies let’s first talk about evaporadine prior studies have shown that an elevated resting heart rate is a risk factor for heart failure for adverse outcomes this provides evidence for the benefit of lowering the heart rate in patients

With heart failure if aberdeen is a selective if or funny current inhibitor which lowers heart rate by acting on the sinoatrial node or the pacemaker it does not affect blood pressure myocardial contractility or intracardiac conduction here’s where evaporadine works it blocks the sympathetic nervous system along with the beta blockers to decrease heart rate the

Benefits of aberdeen were demonstrated in the shift trial which was published in the lancet in 2010 6505 symptomatic heart failure patients mostly new york heart association class 2 and class 3 were studied their ejection fractions were less than or equal to 35 percent their resting heart rates had to be at least 70 beats per minute they needed to be taking beta

Blockers at their highest tolerable dose and hospitalized for heart failure within the past year approximately 92 percent of patients were receiving ace inhibitors or arbs in both groups if aberdeen was titrated to 7.5 milligrams twice a day to maintain a resting heart rate between 50 and 60 beats per minute the trial lasted for 23 months the results of the shift

Trial showed that compared to placebo evaporating significantly decreased death from cardiovascular causes or hospitalization for heart failure with a p-value less than .0001 this was driven primarily by a reduction in the need for re-hospitalization for heart failure this was a significant finding with a p-value of .001 more on the shift study showed that most

Of the benefit was observed in patients with heart rates greater than 77 only twenty six percent of patients were taking target doses of beta blockers ten percent of all patients were not taking a beta blocker and patients treated with aberdeen had an average reduction in heart rate of 8 beats per minute as stated earlier if aberdeen is a selective sinus node

Inhibitor via the if funny current it has no other hemodynamic effects it affects heart rate only and it has no ionotropic effect the indication is to reduce the risk of hospitalization for worsening heart failure in adult patients with stable symptomatic chronic heart failure would reduce left ventricular ejection fraction evaporadine is known as corlinor and

It’s manufactured by amgen the initial dose is 2.5 to 5 milligrams twice a day orally it needs to be taken with food the usual target dose is 7.5 milligrams po twice a day titrated to a heart rate of 50 to 60 beats per minute the price per month is about five hundred dollars wholesale acquisition cost evaporadine caused symptomatic bradycardia in five percent

Of patients compared to one percent in placebo which was statistically significant if aberdeen decreased heart rate by 15 beats per minute over placebo evaporating also can cause a temporary vision disturbance or flashes of light caused by phosgenes in three percent of patients versus one percent of placebo and evaporating needs to be avoided in pregnancy so the

Recommendation for evapodine is that it’s indicated as an add-on drug for patients with heart failure in sinus rhythm with a heart rate of 70 beats per minute or greater despite maximally tolerated beta blockers according to published guidelines if aberdeen may be considered inappropriate patience but the beta blocker should first be titrated to the target dosage

If tolerated let’s move on and talk a little bit about vasopressin and antagonists we know that vasopressin or adh concentrations are elevated in acute heart failure adh can activate the vasopressin receptors and there’s two types the first type is called v1a receptors which when activated in the systemic vasculature causes vasoconstriction the second type are

V2 receptors which are more important in heart failure where activation in the kidneys leads to a decrease in free water clearance this can lead to fluid retention and hyponatremia thereby worsening heart failure so can we use vasopressin receptor antagonists in heart failure to block the increase in adh basopressin receptor antagonists include a drug called

Canavaptan which is a dual vasopressin 1a and vasopressin 2 receptor antagonist unfortunately conovaptan is only available as an injection injectable tobaptin on the other hand is a selective v2 receptor antagonist it’s an oral tablet and it increases urine output without causing sodium loss so would vasopressin receptor antagonists be beneficial in heart failure

This was studied in the everest trial the everest trial studied the efficacy of vasopressin antagonism using tovaptan and heart failure 4133 patients with acute decompensated heart failure with the new york heart association class 304 rating and left ventricular ejection fraction of less than 40 percent were studied all patients also received standard therapy ace

Inhibitors arbs beta blockers diuretics nitrates and hydrolyzine the patients were randomly assigned within 48 hours of hospitalization to 30 milligrams per day of tovaptan or placebo the results of the trial showed that tovap10 modestly improved patient global clinical score body weight and congested symptoms and overall hemodynamic profile at day 7. the main

Clinical benefit was driven primarily by weight loss unfortunately there was no significant benefit in other clinical outcomes no improvement in long-term outcome the trial failed to show any significant differences between tovaptan and placebo in all cause mortality cardiovascular mortality or hospitalizations for heart failure the combination of hydrolyzing and

Isosorbide dinitrate results in vasodilation thus improving prognosis in patients with heart failure with reduced ejection fraction hydrolyzing provides symptomatic relief of heart failure by decreasing afterload nitrates have venous dilating properties that decrease preload used in combination these two agents have additive benefits in alleviating the symptoms of

Heart failure and increasing exercise tolerance the benefits of this combination of drugs was demonstrated in the aheph trial or the african-american heart failure trial 1050 black patients with heart failure and new york heart association class to four symptoms were studied hydralazine and isosorbite dinitrate were added to optimal doses of base inhibitors and beta

Blockers initial dose was hydrolyzing 25 milligrams twice a day plus isosorbidinitrate 20 milligrams three times a day with a target dose of hydrolyzing 75 milligrams three times a day plus isosorbite 40 milligrams three times a day the results showed a compared to placebo hydrolyzine and isosorbide decreased all-cause mortality as well as decreased hospitalization

For heart failure the ahep trial showed that the addition of hydrolyzine combined with isosorbidinitrate to standard heart failure therapy with an ace inhibitor and a beta blocker improved survival and reduced heart failure hospitalizations hydrolyzing isosorbidite added therapy should be considered for use in black patients with persistent symptomatic heart failure

With reduced ejection fraction with an lvef at or below 35 percent despite conventional therapies of ace inhibitors beta blockers and diuretics hydrolyzing isoscele by dinitrate is also an option for those intolerant of ace inhibitors and arbs because of renal disease please remember to avoid using isosorbide concurrently with phosphodiesterase inhibitors such

As sildenafil viagra due to additive hypotensive effects with nitrates some adverse reactions to monitor for are hypotension headache dizziness hydrolysis alone can cause lupus-like syndrome and tachycardia isosorbidinitrate hydralazine is taken three times a day making compliance a challenge diuretics diuretic therapy loop and thiazide is essential when needed

To manage volume status in patients with heart failure however diuretics do not provide mortality benefit or improve survival in heart failure patients so they should be used only when needed to relieve symptoms treat pulmonary congestion and or to control fluid retention they produce rapid symptomatic relief once the excess volume is removed therapy is aimed

At maintaining sodium balance and preventing accumulation of new fluid while avoiding dehydration loop diuretics such as furosemide bumetanide and torsomide are the preferred initial diuretic agents in the setting of loop diuretic resistance thiazide-like agents most commonly metallozone might be added for a synergistic effect monetary electrolytes especially for

Hypokalemia here’s a nice table that reviews the dose equivalency and duration of action of various loop diuretics digoxin digoxin works as a positive ionotrope and can also be arrhythmogenic digoxin should be considered for those who remain symptomatic despite therapy with all other heart failure agents in the only large controlled trial of digoxin in patients

With heart failure digoxin had no impact on mortality but decreased hospitalization rates unless the risk of toxicity outweighs the benefit this continuation of deduction is generally discouraged because an association between withdrawal therapy and worsening heart failure has been well documented it is important not to withdraw digoxin and heart failure patients

Who were stable and tolerating digoxin especially those experiencing frequent hospitalization to summarize we previously stated which type of heart failure patient will benefit most from the addition of aberdeen based on the shift trial we explained why vasopressin receptor antagonists are not recommended for heart failure patients we identified which group of

Patients would benefit most from the addition of hydrolyzine isosorbide and we defined the current role of the use of digoxin and diuretics in heart failure coming up next in part four of this series we’re going to describe the mechanism of action of sglt2 inhibitors outline the heart failure indications for sglt2 inhibitors explain the mechanism of action of

Varus sigwat define vera sigwat’s fda indication for heart failure and discuss very sigwatt’s dose kinetics drug interactions and adverse reactions so stay tuned thanks for tuning in to watch this installment of the farm easy tutor i hope you learned something that you could use at school or in practice if you’d like to continue to see more of these types of

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Heart Failure Medications- Part Three: Add-on Agents. Lecture for Pharmacy Students & Pharmacists. By The PharmEZ Tutor