Pharmacology Test 2: Heart Failure

Front 1

Heart Failure

Back 1

The inability of the body to maintain adequate cardiac output to meet the metabolic demands of the body

Front 2

Types of Heart Failure

Back 2

High Output--normal CO; due to metabolic factors; normal CO is not enough; not very common

Low Output--decreased CO; the heart cannot generate enough output--pumping less blood; most common

Front 3

Primary Causes

Back 3

A problem with the heart itself

Coronary Artery Disease (CAD)
Infarction
Arrhythmia
Congenital
Valve Dysfunction
Drug Toxicity

Front 4

Secondary Causes

Back 4

Heart is affected second to some other process

Hypertension
Liver Disease
Renal Disease
COPD

Front 5

Left Side Heart Failure

Back 5

Leads to a back-up of blood into the LUNGS (Pulmonary Congestion)

Front 6

Early Stage of Heart Failure

Back 6

Someone just looks like they are out of shape; have trouble going up stairs

Front 7

Moderate Stage of Heart Failure

Back 7

Person will have trouble with Pulmonary Congestion at night, so may sleep with lots of pillows or upright in a lay-z-boy

Front 8

End Stage of Heart Failure

Back 8

Lots of PITTING EDEMA present, no exercise tolerance

Front 9

Treatment of CHF

Back 9

Often symptomatic

Want to treat the underlying cause

Overall Goals: decrease cardiac work (wall stress), increase CO, control Na+ and H2O

Drugs Used Include:
- diuretics
- vasodilators
- positive inotropic drugs
- beta receptor antagonists

Front 10

Goal of Diuretics

Back 10

Excrete Na+ and H2O by...
- decreasing Vascular volume
- decreasing Edema
- decreasing Preload
- decreasing Pulmonary Congestion

Front 11

Diuretics in the Treatment of HF: Classification and Mech. of Action

Back 11

Classification: Diuretics are drugs which eliminate Na and water by acting directly on the kidney.

The diuretics are the primary line of therapy for the majority of patients with heart failure and pulmonary congestion.

Mech. of Action: Diuretics (loop, thiazides and potassium-sparing) produce a net loss of Na and water acting directly on the kidney, decrease acute symptoms which result from fluid retention (dyspnea, edema).

Diuretic drugs are classically divided into three groups: 1) thiazides, 2) loop diuretics and 3) potassium-sparing

Front 12

Thiazide Diuretics

Back 12

Inhibit the active transport of Cl-Na in the cortical diluting segment of the Ascending Limb of the Loop of Henle

Front 13

Loop Diuretics

Back 13

Inhibit the transport of Cl-Na-K in the Thick portion of the Ascending Limb of the Loop of Henle

Front 14

Potassium-Sparing Diuretics

Back 14

Inhibit the reabsorption of Na in the distal convoluted and collecting tubules

Front 15

Loop Diuretics

Back 15

FUROSEMIDE
BUMETANIDE
TORSEMIDE

**BIG USE IN HEART FAILURE**

Front 16

Loop Diuretics: Mech. of Action and Use

Back 16

Mech. of Action: inhibit Na+ -K+ - 2Cl- symporter on Ascending Limb of Loop of Henle

Use: monotherapy for heart failure--reduce vascular volume, edema, pulmonary congestion
- IV administration for decompensated HF

*Improve symptoms but do not increase survival

Front 17

Compensated HF

Back 17

Living with it; still functioning

Front 18

Decompensated HF

Back 18

The people in trouble in the Emergency Room setting

Front 19

Thiazide Diuretics

Back 19

HYDROCHLOROTHIAZIDE

*Improve symptoms but do not increase survival

Front 20

HYDROCHLOROTHIAZIDE

Back 20

Mech. of Action: inhibit Na+ and Cl- co-transporter on the Distal Convoluted Tubule

Use: in resistance to loop, may be combined with loop, to produce synergistic natriuresis

*Improve symptoms but do not increase survival

Front 21

Potassium-Sparing Diuretics

Back 21

AMILORIDE
TRIAMTERENE
SPIRONOLACTONE

*Trials shows Spironolactone alone and in combo. with ACE(-) increase survival

Front 22

Potassium- Sparing Diuretics: Mech. of Action and Use

Back 22

Mech. of Action:
- Amiloride, Triamterene--block Na+ conductance channel
- Spironolactone--aldosterone antagonist

Use: limit K+ wasting; block the effects of aldosterone on the heart--attenuate remodeling

Front 23

Vasodilators Treatment Goal

Back 23

Decrease Peripheral Resistance by...
- decreasing Preload
- decreasing Afterload

Front 24

Angiotensin Converting Enzyme Inhibitors (ACE)

Back 24

CAPTOPRIL
ENALAPRIL
LISINOPRIL

Front 25

ACE Inhibitors

Back 25

Mech. of Action: decrease peripheral resistance--> decrease afterload and preload--> increase CO
- Decrease Aldosterone Release
- Decrease Na+ and H2O absorption
- Decrease Cardiac hypertrophy and remodeling

Side Effects: cough, can increase serum K+, hypotension

*Trials show ACE(-) have a significant increase on survival (longevity) and decrease hospital admissions

Front 26

Type 1 Angiotensin II Receptor (AT1) Antagonists

Back 26

LOSARTAN
CANDISARTAN

* Trials show them to be as effective as ACE(-) in treating CHF

Front 27

Type 1 Angiotensin II Receptor (AT1) Antagonists: Mech. of Action and Advantages

Back 27

Mech. of Action: block AT2 receptors, effects similar to ACE(-)

Potential Advantages: decrease side effects--bradykinin metabolism unaffected AT2 receptors not blocked

**ACE inhibitors or Angiotensin Receptor Antagonists are drugs of choice for heart failure**

Front 28

Other Vasodilators

Back 28

Sodium Nitroprusside
Nitroglycerin
Hydralazine
Isosorbide Dinitrite
Nesiritide

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SODIUM NITROPRUSSIDE

Back 29

IV administration ONLY--very potent and short-acting; used for decompensated pts.

Mech. of Action: converted to NO; preload and afterload reducer

Side Effects: hypotension, reflex tachycardia, ischemia

Front 30

NITROGLYCERIN

Back 30

Topical, Sublingual, IV

Mech. of Action: converted to NO; decrease preload and some effect on afterload

Side Effects: hypotension, reflex tachycardia, ischemia, tolerance

Decrease VR and decrease pulmonary congestion

Front 31

HYDRALAZINE

Back 31

Oral Administration

Mech. of Action: unknown; decrease afterload

**Isosorbide dinitrite and hydralazine often used in combination in pts who cannot take ACE(-). A synergistic vasodilator action

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ISOSORBIDE DINITRITE

Back 32

Oral Administration

Mech. of Action: converted to NO; decrease preload

**Isosorbide dinitrite and hydralazine often used in combination in pts who cannot take ACE(-). A synergistic vasodilator action

Front 33

NESIRITIDE

Back 33

Recombinant form of human brain natriuretic peptide (BNP)

IV infusion

Mech. of Action: increase cyclic GMP; produces natriuretic, diuretic, and vasodilator responses (decrease preload and afterload)

Use: acute treatment of dyspnea in CHF

* This is an emergency room drug; IV only; very short-acting

Front 34

Positive Inotropic Drugs

Back 34

DIGOXIN, Digitoxin (Cardiac Glycosides)
DOPAMINE
DOBUTAMINE
INAMRINONE and MILRINONE(Phosphodiesterase Inhibitors)

Front 35

Positive Inotropic Drugs: Treatment Goal

Back 35

Increase Ventricular Performance--> increase CO by increasing FC (very rarely used)

Front 36

DIGOXIN, Digitoxin (aka Digitalis Drugs): Cardiac Glycosides

Back 36

Absorption: Oral

Elimination: Renal

Mech. of Action: **inhibit (block) Na+/K+ ATPase--> increase intracellular Ca2+ and increase FC**
- increase FC--> increase CO
--> decrease preload and congestion, increase renal perfusion (decrease renin)

**FC is directly proportional to concentration of intracellular Ca2+

Other Effects: Increase parasympathetic tone; decrease automoticity, decrease speed of AV conduction

Side Effects: very narrow therapeutic index (S.E. are increased by low K+); GI effects; Cardiac Arrhythmias

Treatment of Side Effects: Lidocaine, potassium, beta blockers; Fab fragments (digitalis antibodies)

Use: Reserved for pts. in HF with ATRIAL ARRHYTHMIA, or if symptoms persist after ACE(-) and beta antagonists

Front 37

DOPAMINE

Back 37

D1, Beta 1, and Alpha 1 agonist

Mech. of Action: low dose, dilate renal artery

**Long term use is not recommended

Front 38

DOBUTAMINE

Back 38

Beta 1 agonist

Emergency Room drug, can only be given IV

Mech. of Action: increase FC without increasing HR

Side Effects: tolerance occurs which leads to tachycardia--so usually only used for a couple of weeks

**Long term use is not recommended

Front 39

Phosphodiesterase Inhibitors

Back 39

INAMRINONE
MILRINONE (given IV)

Front 40

Phosphodiesterase Inhibitors: Mech. of Action and Use

Back 40

Mech. of Action: increase intracellular levels of cAMP by inhibiting its breakdown; increase cAMP--> phosphorylation of Ca2+ channels--> increase intracellular Ca2+--> increase FC
- In Vascular Smooth Muscle
--> increase cGMP--> vasodilation and decrease preload and afterload

Use: short term severe failure

Front 41

Beta Receptor Antagonists

Back 41

CARVEDILOL (beta 1, beta 2, and alpha 1)--10x more potent as a beta than an alpha
METOPROLOL (beta 1)
BISPROLOL (beta 1)

Front 42

Beta Receptor Antagonists: Mech. of Action

Back 42

Decrease SNA to heart, decrease HR + O2 consumption

Decrease deleterious effects of catecholamines (decrease hypertrophy and remodeling)

Increase Ventricular Function (increase EF)

These hearts do not have to work as hard, the heart will actually work better

Beta therapy will decrease symptoms, increase longevity, and decrease hospital admissions in HF and post MI

Front 43

What 3 categories increase life expectancy?

Back 43

ACE Inhibitors
Beta Blockers
Ca Sparing Diuretics