Pharmacology - Drugs and Chronic Heart Failure Flashcards
What is Chronic Heart Failure ?
Major causes of chronic heart failure include hypertension and ischaemic heart disease. Under normal circumstances the ejection fraction of the left ventricle is about 60%. In systolic dysfunction, weaken ventricular muscle reduces the ejection fraction to some 40%, enlarging ventricular size. In diastolic dysfunction, ventricular stiffness reduces ventricular filling and although the ejection fraction may not change, the stroke volume is decreased.
Why do you not always see a reduced cardiac output in heart failure ?
The body has 2 major compensatory systems to try and maintain the cardiac output in chronic heart failure.
1- Activation of the sympathetic nervous system stimulates the heart, increasing both heart rate, a positive chronotropic effect, and the force of contraction of cardiac muscle, a positive inotropic effect.
2- A reduction in renal perfusion causes salt and water retention influencing the preload on the heart increasing the filling pressures.
The renin angiotensin system plays an important role in both responses. However, these very compensatory events also produce some of the major symptoms of compensated heart failure. Systemic vasoconstriction induced by increased sympathetic tone, increases the afterload on the heart while the retention of salt and water, produces oedema, pulmonary oedema inhibiting respiration and peripheral oedema, which falls under gravity, generating swollen ankles.
What drug increases the force of cardiac constriction of cardiac muscle without activating heart rate?
Digoxin
Explain the Inotropic action of Digoxin
Digoxin stimulates the force of contraction of the heart muscle by inhibiting the Na/K ATP-ase enzyme.
Digoxin induces an increase in intracellular sodium that will drive an influx of calcium in the heart and cause an increase in contractility.
This allows more contraction of the heart.
What are some adverse effects of Digoxin ?
-Digoxin has a narrow therapeutic index - and needs blood levels measured.
- ATPase inhibition in the conducting system can generate many types of arrhythmia
-One type of arrhythmia produced is called bigeminy or coupled beats where after depolarisation can trigger another action potential.
How can Digoxin be used to treat Supraventricular tachycardias ?
- Slows conduction
- Can stop the AV nodes reaching the ventricles
Slowing AV conduction means digoxin can inhibit the effect of atrial or nodal arrhythmias on ventricular function although, at higher doses, digoxin can produce AV block.
How does Oedema occur in heart failure?
Odema is formed due to fluid movement across the capillary wall -
Oedema is produced by an imbalance in the 2 major forces determining fluid movement across the wall of capillaries, the hydrostatic pressure of the blood moving fluid out into the interstitium and the oncotic pressure of plasma protein acting to retain fluid within the capillary vessel. Normally these two forces balance each other with any excess fluid being removed from the interstitium by the lymphatic system. In heart failure, the elevated venous pressure, increases the hydrostatic pressure gradient reducing the force required for fluid absorption back into the capillary. The result of diuretic therapy is to reduce the elevated venous pressure including the filling pressure to the heart. The change in capillary dynamics results in the removal of oedema fluid in the lung, relieving congestion and in the periphery removing the swollen ankles. A picture of papable oedema is shown on the right hand side.
How do you manage odema in heart failure ?
Take fluid out through the kidney by a loop diuretic
What are some examples of diuretics ?
furosemide and bumetanide
How do fruesimide and bumetanide work in congestive heart failire
They include furosemide and bumetanide which both increase the urine flow by inhibiting the NKCC2 co-transporter in the ascending limb of the loop of Henle which reabsorbs about 25% of the filtered load of fluid and sodium. The NKCC2 pump is located in the luminal membrane. Loop diuretics work from the inside of the renal tubule binding to the chloride binding site on the transporter. Loop diuretics are natriuretic as well as diuretic and increase the excretion of other ions including potassium, magnesium and calcium.
What are the adverse effect of Loop Diuretics ?
- Excess diuresis
(I) volume depletion, weakness, dizziness, cramp (II) azotaemia (III) metabolic alkalosis - Flow-dependent excretion
Hypokalemia (especially if aldosterone is high), Mg, Ca. - Extra-renal pump inhibition
reversible deafness cochlea, Na/K high in endolymph, a/p generation to sound reduced.
What is the Interaction between Loop Diuretics and Digoxin
The hypokalaemia induced by loop diuretics has the potential to increase the toxicity of digoxin.
In hypokalaemia, the reduction in plasma potassium reduces its activation of the pump which becomes partially inhibited adding to the pharmacological effect of digoxin. If plasma potassium is maintained at normal levels, no interaction is seen.
Do loop diuretics have an effect on CHF mortality ?
No
Does Digoxin have an effect on CHF mortality?
No
Does Enanipril (ACE) inhibitor improve mortality rate in patients who are already on furosemide and digoxin?
What can be given instead that has a similar effect if they have a intolerance to ACE ?
Consensus study was the first drug to be shown to reduce the probability of death in chronic heart failure, decreasing heart size, and improving 1 year survival by 25% although with no effect on sudden death.
Angiotensin receptor blocker
