Pharm Lecture 25 Chf

Front 1

CO equation

Back 1

CO=HRxSV

Front 2

BP equation

Back 2

BP=COxSVR

Front 3

Cardiac work equation

Back 3

Cardiac work=BPxCO

Front 4

Cardiac efficiency equation

Back 4

Efficiency=cardiac work/MVO2

MVO2=myocardial oxygen consumption

Front 5

LaPlace's Law

Back 5

T=(PxR)/h

T=myocardial wall tension
P=intraventricular pressure
R=radius
h=wall thickness

Front 6

CHF treatment goals

Back 6

1. improve contractility
2. reduce load on heart
3. eliminate salt & water
4. Improve functional status, exercise capacity, hemodynamics, and life expectancy.

Front 7

CHF drug classes

Back 7

1. Diuretics
2. Digitalis glycosides
3. Sympathomimetic amines & other inotropic agents (PDE inhibitors)
4. Vasodilators (ACEI's & AT1 blockers)
5. Beta blockers
6. Aldosterone antagonists
7. Vasopressin antagonists

Front 8

CHF diuretics

Back 8

Thiazides, loop diuretics, & aldosterone antagonists.
Reduce preload, afterload, sympathetic tone, & prevent remodeling after MI.

Front 9

2 mechanisms of action of digitalis

Back 9

1. +inotropic effect by inhibiting Na/K ATPase. Increase in intracellular Na, so Na/Ca exchanger doesn't work and Ca builds up in cell.
2. CNS: Increased vagal tone reduces cardiac work and sympathetic activity.
**Therapeutic actions are mainly due to enhanced vagal tone, while toxic actions are due to Na/K ATPase inhibition (afterdelpolarizations).

Front 10

Digitalis effects on normal heart

Back 10

Increased contractility.
No increase in CO.
Decreased PVR.

Front 11

Digitalis effects on failing heart

Back 11

Direct: increased contractility.
Indirect: increased vagal tone, decreased sympathetic activity & renin-angiotensin system, dilation of arterioles & veins.
Increased CO, P-R interval, Purkinje automaticity, work, & efficiency. Decreased HR, Q-T interval, blood volume, CVP, TPR, wall tension, MVO2. No change in arterial pressure.

Front 12

Digitalis toxicity

Back 12

Very low therapeutic index=2.
GI: anorexia, nausea, vomiting (young).
Visual:blurry, photophobia, green-yellow.
Neuro: tired/weak(elderly), anxiety, delirium.
CV: Cellular Ca overload=depolarizations & arrhythmias (A & V). Heart block (1st, 2nd, or complete)=excessive vagal tone (decreased conduction velocity thru AV node). CHF exaccerbation.
EKG: uncoupled P waves, bigeminy, trigeminy, V-tach, V-fib.

Front 13

Digoxin

Back 13

Cardiac glycoside.
Oral- 60-80% absorbed. 30% plama binding.
Not metabolized. Renal excretion. T1/2=1.6 days.
ASEs: quinidine competes for renal excretion & causes digoxin toxicity.

Front 14

Digitalis clinical uses

Back 14

Symptomatic use only; does not prolong life.
1. Systolic L heart failure (CHF).
2. Arrythmias (A-fib & flutter, paroxysmal supraventricular tach).

Front 15

Vasodilating agent actions in CHF treatment

Back 15

1. Reduce PVR to reduce afterload.
2. Venodilate to reduce preload.
3. Increase coronary blood flow or decrease O2 demand to decrease myocardial ischemia. (decrease wall tension).

Front 16

Venous bed vasodilators

Back 16

Nitroglycerin.
Isosorbide dinitrate.
Decrease LV EDV & MVO2.
No change in CO.
Only affect preload.

Front 17

Mixed action vasodilators

Back 17

Nitroprusside.
Captopril.
Enalapril.
Hydralazine+Nitrate.
Decrease LV EDV & MVO2.
Increase CO.
Decrease both preload & afterload.

Front 18

Arterial bed vasodilators

Back 18

Hydralazine.
No change in LV EDV.
Decrease MVO2.
Increase CO.
Only affect afterload.

Front 19

Nitroglycerin

Back 19

Venous venodilator; nitrate. Stimulates guanylate cyclase via NO.
Decrease RV & LV filling P (rest & exercise), pulm. congestion, ventricle size, wall stress, MVO2.
Increase coronary flow.
No change in CO.
Tolerance due to depletion of -SH groups. Limits long term use.

Front 20

Nitroprusside

Back 20

Mixed vasodilator; NO donor, increases cGMP.
Decreases LV EDV, MVO2, preload, afterload, wall tension, ventricle size.
Increases CO.
*Reduces LV filling P to a bit above normal.
IV administration only, begin slowly. Withdrawal symptoms (rebound hemodynamic effects) if abrupt.
Metabolized to cyanide.

Front 21

ACE inhibitors

Back 21

Mixed vasodilators; captopril & enalapril.
Begin slowly, 2-4 weeks.
Reduce LV filling P (rest & exercise), PVR.
Increases CO (usually), coronary flow.
No change in HR & contractility. No reflex tachycardia or tolerance.
Prolong life: slow cardiac dilation, prevent remodeling, prevent arrhythmias.
ASE: hypotension, dry cough (increase bradykinin which increases PG's), K+ retention.

Front 22

Losartan

Back 22

Mixed vasodilator; AT1 blocker.
Advantage of ACEI's: only block bad (AT1) effects of ACE but not good (AT2) effects.
Prolong life in CHF.

Front 23

Hydralazine

Back 23

Arterial vasodilator.
Decreases pulm, renal, & systemic vascular resistance, MVO2.
Increases renal blood flow, CO, SV.
No change in LV EDV.
Tolerance to monotherapy, so used with a nitrate.
Hydralazine+isosorbide dinitrate prolongs life, esp. in black ppl.

Front 24

Inotropic agents for CHF

Back 24

Digoxin, sympathomimetics, PDE inhibitors.
IV administration, used short-term for acute HF. (digitalis is oral).

Front 25

Dopamine

Back 25

Inotropic agent; beta receptor agonist. cAMP-dependent (Ca increases).
Low dose: DA1 stimulation, increase renal BF, natriuresis, vasodilation.
High dose: stimulates beta1, alpha 1&2 (vasoconstriction, given to patients in shock).
Short term effects.
Tolerance: receptor down-reg.
ASEs: ventricular arrhythmias, myocardial ischemia.

Front 26

Dobutamine

Back 26

Inotropic agent; beta1 receptor agonist. cAMP-dependent (Ca increases).
Safer than dopamine when patient is not in shock.
Short term effects.
Tolerance: receptor down-reg.
ASEs: ventricular arrhythmias, myocardial ischemia.

Front 27

Inamrinone

Back 27

Inotropic agent; PDE3 inhibitor to increase cAMP in heart & SMC (cause vasodilation too).
Short-term benefits.
ASE: ventricular arrhythmia, so only used in emergency situations.

Front 28

Nesiritide

Back 28

Inotropic agent; beta-type natriuretic peptide.
Balanced vasodilator effect.
Use: acute decompensated CHF & dyspnea at rest.

Front 29

Carvedilol

Back 29

Beta blocker: blocks beta 1&2, alpha1. Causes vasodilation.
Treats chronic CHF.
Increases beta receptor # & coupling to G protein.
Decreases preload & afterload, HR, LV EDV.
Antioxidant.
Used with diuretics, digoxin, &/or ACEI's.
Well-tolerated but hard to begin.
Start with low dose because initially ejection fraction decreases.
Prolongs life in CHF.

Front 30

Metoprolol

Back 30

Beta blocker; selective for beta1 (cardioselective).
No antioxidant effect.
Prolongs life in CHF.

Front 31

Aldosterone antagonists for CHF

Back 31

Spironolactone & eplerenone.
Reduce fibrosis of myocardium & blood vessels.
Reduces edema.
Anti-arrhythmia.
Prolong life in CHF.

Front 32

Conivaptan

Back 32

Vasopressin antagonist; blocks V1a & V2 receptors.
Short-term IV administration in patients with euvolemic or hypervolemic hyponatremia.
Potential use: CHF.

Front 33

Drugs that prolong life in CHF

Back 33

1. ACE inhibitors
2. AT1 blockers
3. Beta blockers
4. Aldosterone antagonists