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Pharmacology I
Congestive Heart Failure Drugs Objectives

Learning Objectives:

Understand the cardiovascular consequences of CHF: e.g., how it affects BP, blood volume, renal function, and edema.

  1. Blood volume: Abnormal ’es in blood volume/interstitial fluid. The heart, veins, and capillaries are dilated with blood: CHF symptoms of fluid volume overload
  1. 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 ed BP. The compensatory mechanisms of ing BP will cause there to be an workload on the heart leading to a vicious cycle.
  2. 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.

  1. Reduce physical activity to ¯ myocardial work
  2. Reduce dietary intake of Na+
  3. Treatment with
    1. Vasodilators
    2. Diuretics
    3. Inotropes
  4. Avoid
    1. b -blockers
    2. Ca+2 channel blockers
    3. Certain antiarrhythmics

Relate the mechanisms of action of each class of drug to its efficacy in treating CHF.

  1. Vasodilators – used to both ¯ preload and afterload
  1. 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.
  1. 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.

Clinical problems (side effects) associated with each class of drug.

Vasodilators Diuretics Positive Inotropes

Digitalis glycosides:

Be able to compare pharmacokinetics of digoxin and digitoxin.

Digoxin Digitoxin

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 can’t 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 toxicity
Verapamil, Amiodarone, Quinidine (anti-arrhythmic drugs): can all cause dig toxicity by:

    1. displacing digitalis from plasma protein binding sites
    2. compete with dig for renal excretion
    3. Verapamil may increase dig levels by 50-75%.

Last updated 04/10/00 12:26 PM
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