Congestive Heart Failure Drugs Objectives
Understand the cardiovascular consequences of CHF: e.g., how it affects BP,
blood volume, renal function, and edema.
- Blood volume: Abnormal es in blood
volume/interstitial fluid. The heart, veins, and capillaries are dilated with
blood: CHF symptoms of fluid volume overload
- Pulmonary congestion with left heart failure
- Peripheral edema with right heart failure
- Blood pressure: the failing heart evokes 3 major compensatory mechanisms
to enhance CO due to low BP. Baroreceptors trigger activation of b
AR receptors in the heart, which s HR and
force of contraction. Also a 1
mediated vasoconstriction enhances venous return and
s preload. (These compensatory responses
the work of the heart and can contribute to further decline in cardiac
function.) The subsequent ¯ in renal blood flow
resulting from the ¯ BP will cause the RAA
system activity to
which will aldosterone which will
Na+ and H2O
retention which leads to edema as well as
BP. The compensatory mechanisms of ing BP will
cause there to be an
workload on the heart
leading to a vicious cycle.
- Hypertrophy: The heart
s in size and the
chambers dilate (Remember this info from the last test in physio) Eccentric
is a result of afterload and concentric is a
result of preload.
Know the therapeutic strategy for pts with CHF.
- Reduce physical activity to ¯ myocardial work
- Reduce dietary intake of Na+
- Treatment with
- b -blockers
- Ca+2 channel blockers
- Certain antiarrhythmics
Relate the mechanisms of action of each class of drug to its efficacy in
- Vasodilators used to both ¯ preload and
- ACE inhibitors (captopril, enalapril): The agents of choice in CHF®
superior to other vasodilators. They block the enzyme that cleaves angio I
to angio II. They also ¯ the rate of bradykinin
inactivation (bradykinin is a perfect vasodilator). By ¯
ing the circulating angio II levels, ACE inhibitors also ¯
aldosterone secretion which ¯ Na+ and
Þ ACE inhibitors affect on the heart - ¯
vasc resistance, ¯ venous tone, ¯
BP to CO. They also blunt the usual angio II
mediated increase in Epi and Aldosterone and they block the remodeling
associated with hypertrophy post damage.
- Direct smooth muscle relaxants hydralazine, isosorbide, NTG, SNP,
- dilation of venous blood vessels leads to a ¯
in cardiac preload by ing venous
- arterial dilators reduce systemic arteriolar resistance and ¯
- Nitrates (NTG and SNP) reduce afterload. NTG can also increase
- Diuretics- work to relieve pulmonary congestion and peripheral edema,
which is useful in relieving symptoms of volume overload. They ¯
plasma volume, thus ¯ ing venous return
(preload) and ¯ cardiac workload and O2
Demand. They also ¯ afterload by reducing plasma
volume, thus ¯ ing BP.
- Loop furosemide inhibits reabsorption of Na+ and Cl-
from the loop of Henle and distal tubules thus
ing excretion of water and Na+.
- Thiazides- HCTZ- s excretion of Na+
- Positive Inotropes enhance cardiac muscle contractility, thus
ing CO. Although these drugs act by different mechanisms, in each case the
inotropic action is the result of an increase in cytoplasmic calcium
concentration that enhances the contractility of the heart.
- Cardiac glycosides digoxin, digitoxin
- b - agonists dobutamine
- phosphodiesterase inhibitors amrinone, milrinone
Clinical problems (side effects) associated with each class of drug.
- Cause Na+ and water retention if not given with a diuretic
- Excessive vasodilation may
- Orthostatic hypotension
- Electrolyte imbalances (Hypokalemia which can increase the
likelihood of dig toxicity)
- PVCs and other dysrhythmias
Be able to compare pharmacokinetics of digoxin and digitoxin.
- Relatively short ½ life (better tx of toxic reactions)
- More rapid onset of action than digitoxin makes it useful for cardiac
- Eliminated largely unchanged in the urine
- Low volume of distribution which makes it more accessible
- Binds strongly to plasma proteins in extravascular space resulting in a
large volume of distribution
- Extensive hepatic metabolism, hepatic disease may require a ¯
- Long ½ life due to protein binding.
- Long onset of action
Understand the cellular mechanisms of toxicity of digitalis glycosides.
There is a very narrow therapeutic range.
Electrolyte disturbances can occur especially hypokalemia, which can precipitate
serious arrhythmias. The hypokalemia probably increases myocardial binding of
cardiac glycosides, resulting in excess drug effect. Hypercalcemia and
hypomagnesiumia can also occur.
Digoxin by inhibiting the Na/K/ATPase pump, affects the membrane potential and
keeps the cell depolarized longer and brings the resting membrane potential
closer to +. The Na+/Ca+2 exchanger will then try to take
more sodium out but in the process brings in too much calcium, which can cause
contraction. Digoxin also alters AV nodal conduction, which is very sensitive to
membrane potentials. Dig has a high affinity for the AV nodal cells and can make
the membrane so less that it can depol to the point where it cant fire
anymore and you get AV nodal block.
Know what factors can affect digitalis sensitivity of the heart and the
consequences of interaction with the following drugs:
Loop and thiazide diuretics: Causes loss of K+ and possible dig
Verapamil, Amiodarone, Quinidine (anti-arrhythmic drugs): can all cause
dig toxicity by:
- displacing digitalis from plasma protein binding sites
- compete with dig for renal excretion
- Verapamil may increase dig levels by 50-75%.
Last updated 04/10/00 12:26 PM
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