Pharm S2B3 - Cv - Inotropic Drugs & Chf

Front 1

When does CHF result?

Back 1

when the heart can no longer supply oxygenated blood adequately to peripheral tissues during stress or even at rest

*heart is unable to pump blood at a rate sufficient to satisfy the needs of the metabolizing tissues

Front 2

What does CHF most frequently result from?

Back 2

Coronary Artery Disease

Front 3

What is CHF primarily a disease of?

Back 3

Aging = 75% of existing & new cases occur in people over 65

Front 4

Among survivors of CHF, the qualiity of life is adversely affected by these 3 things

Back 4

1. Progressive fatigue
2. shortness of breath
3. functional disability

Front 5

What is the long-term prognosis of CHF even with treatment?

Back 5

5-year survival of 37% in men & 57% in women

30-50% of CHF patients with severe symptoms die within one year

Front 6

What can the mortality of CHF be reduced by?

Back 6

Drug treatment

Front 7

What are 4 causes of "high-output" CHF?

Back 7

1. Hyperthyroidism = upregulation of Beta-1 receptors in heart; increased oxygen consumption & BMR

2. Anemia

3. AV shunts

4. Thiamine deficiency -> wet beriberi

Front 8

What is the heart work condition in "high-output" CHF?

Back 8

Healthy heart exhausted by working too hard

Front 9

What are the main causes of "low-output" CHF?

Back 9

1. Coronary Artery Disease
2. HTN
3. MI
4. Persistent arrhythmias
5. Rheumatic Heart Disease
6. General Carciomyopathy

Front 10

What is the heart work condition in "low-output" CHF?

Back 10

heart is unable to pump enough blood to meet tissue needs

Front 11

Which one has poor Inotropic drug response, high-output or low output?

Back 11

High-output

Front 12

Describe the Hemodynamic characeteristic of CHF

Back 12

1. Subnormal Cardiac Output causing decreased exercise tolerance with rapid muscle fatigue, tachycardia, pulmonary edema, & cardiomegaly

2. Myocardial Hypertrophy to maintain cardiac performance; increased myocardial muscle mass & muscle wall thickness

3. Neurohumoral Reflex compensation arises from increased activity of sympathetic nerves, Renin-angiotensin-Aldosterone system

Front 13

Describe the normal cardiovascular regulation

Back 13

-Strong afferent signals from the Carotid & Cardiopulmonary Baroreceptors
-Efferent signals predominantly Parasympathetic & relatively weak sympathetic

Front 14

Describe the Cardiovascular Regulation in CHF

Back 14

-generalized SYMPATHETIC activation with reciprocal Parasympathetic withdrawal
-Sympathetic predominance then causes: 1) Arterial constriction 2) increased renin secretion 3) reflex tachycardia

Front 15

What is Preload?

Back 15

equivalent to End-diastolic Volume, which is related to Right-Atrial pressure

when venous return increases, End-diastolic volume increases & stretches or lengthens the ventricular muscle fibers

Front 16

In CHF, what is Preload elevated by?

Back 16

Increases in Blood Volume & Venous tone

Front 17

Treatment with __1__ drugs reduces Preload by dilating peripheral veins to retain more blood & keep blood away from the heart

Treatment with __2__ reduces Preload by decreasing blood volume

Back 17

1. Venodilator

2. Diuretics

Front 18

Define Afterload

Back 18

Arterial resistence against which the heart pumps blood which is determined by Aortic impedence & vascular resistance

Front 19

In CHF why does Afterload rise?

Back 19

Increases in Sympathetic & Renin-Angiotensin activity which elevate peripheral resistance via Arterial constriction

Front 20

Treatment with ________ drugs reduces Afterload by decreasing peripheral resistance

Back 20

Arteriodilator

Front 21

Why is Myocardial Contractility reduced in CHF?

Back 21

Myocardial muscle fibers are stretched beyond their elastic limits as ventricles become dilated

Front 22

Myocardial contractility is increased by __1__ drugs, but reduced by __2__

Back 22

1. Inotropic drugs

2. Beta-blockers

Front 23

What does Reflex Tachycardia result from in CHF?

Back 23

Sympathetic overactivity due to Baroreflex activation brought about by the reduction in Cardiac Output

Front 24

_______ drugs reduce cardiac work by slowing the Heart Rate

Back 24

Beta blockers

Front 25

-

Back 25

-

Front 26

What are the "cornerstones" of CHF drug therapy?

Back 26

1. ACE inhibitors & other Vasodilators to reduce Cardiac workload

2. Diuretics to reduce Preload by correcting salt & water retention
-Loop diuretics prefered b/c of their potency

3. Digoxin = improves cardiac pumping & output

Front 27

What is a reasonable therapeutic approach in starting treatment for CHF?

Back 27

Use ACE Inhibitor alone & if the response is inadequate then add a Loop Diuretic & then finally Digoxin if needed

**b/c fo potential Digoxin toxicity

Front 28

What do ACE Inhibitors counteract in CHF?

Back 28

counteract the increased Renin-Angiotensin system activity

Front 29

What are the factors that increase the Renin-Angiotensin activity in CHF?

Back 29

1. Reduced renal perfusion activating Renal baroreceptors = Renin release

2. Increased Sympathetic activity stimulating Beta-1 receptors on the JG apparatus

3. Anti-hypertensive drugs that stimulate Renin secretion:
-Diuretics by decreasing delivery of Na+ to macula densa
-Vasodilators by reducing Renal perfusion pressure

Front 30

What 2 drugs specifically counteract the increased Renin-Angiotensin system in CHF? How do they diminish Cardiac Workload?

Back 30

ACE inhibitors & Angiotensin II Antagonists

1. decrease Afterload = reduce Angiotensin vasoconstriction

2. decrease Preload = reduce Aldosterone release & fluid volume

Front 31

List some effective ACE inhibitors used to treat CHF

Back 31

Captopril
Enalapril
Lisinopril
Ramipril
Quinapril

Front 32

By how much can ACE inhibitor therapy reduce CHF mortality?

Back 32

by 28-40%

Front 33

List the common ending for Angiotensin-II receptor Antagonists

Back 33

-SARTAN

Front 34

List the common ending for the ACE inhibitors

Back 34

-PRIL

Front 35

There are 2 type of Angiotensin II receptors: AT1 & AT2

What receptor do AT-II Antagonists block & where are these receptors predominantly located?

Back 35

AT1

Vascular Smooth Muscle

Front 36

What are 2 important differences between AT-II blockers & ACE inhibitors?

Back 36

1. AT-II blockers are more specific than ACE inhibitors b/c AT-II antagonists do not affect BRADYKININ metabolism = no coughing or angioneurotic edema

2. AT-II antagonists have more complete inhibition of Antiotensin action b/c enzymes other than ACE can generate Antiotensin II

Front 37

What are the adverse effects of Angiotensin-II receptor Antagonists?

Back 37

1. Hyperkalemia

2. reduced renal function (fetal renal toxicity)

"The Sargeant (Sartan) has alot of Potassium & his kid has Fetal Renal Toxicity"

Front 38

Vasodilator that is infused IV in acute decompensated CHF as long as Cerebral & Renal persusion can be maintained despirte the reduction in systemic BP

Back 38

Sodium Nitroprusside

Front 39

Describe the vasodilating effects of Sodium Nitroprusside

Back 39

Balanced vasodilator = dilates both veins & arteries to produce both Preload & Afterload

Front 40

What is the most common adverse effect of Sodium Nitroprusside?

Back 40

excessive Hypotension

Front 41

Discuss the effects of Nitroglycerin & Isosorbide Dinitrate for CHF treatment

Back 41

Dilate VEINS > Arteries = lower Preload > Afterload

Tolerance precludes their long-term use

Front 42

Which Calcium-channel antagonists should not be used for CHF? Why?

Back 42

Verapamil & Diltiazem b/c their cardiac effects may worsen CHF symptoms & increase mortality
-reduce muscle contractility

Front 43

Which CCA may be given to treat CHF? Why?

Back 43

Nifedipine

Blocks slow calcium channels to reduce intracellular calcium = relaxes Arteriolar smooth muscles -> Vasodilation
-has little effect on Cardiac L-type Ca++ channels

Front 44

How do Beta-blockers improve the symptoms of CHF? What do they improve?

Back 44

1. Slow heart rate
2. slow contraction velocity


1. CO
2. Exercise tolerance
3. Ventricular function

Front 45

What are the proposed mechanisms of how Beta-blockers have beneficial effects in CHF?

Back 45

1. Decreased HR & Cardiac Work
2. Attenuation of responses to high catecholamine concentrations
3. Up-regulation of Beta-adrenergic receptors
4. reduced myocardial remodeling

Front 46

What do Diuretics do to help in the treatment of CHF?

Back 46

reduce extracellular fluid volume & thereby reduce Preload

Front 47

What is chronic diuretic treatment only used for?

Back 47

patients with advanced disease & symptoms

Front 48

Which diuretics are the 1st choice drug for CHF?

Back 48

Loop Diuretics
-Furosemide, Bumetanide, Torsemide
-Ethacrynic acid is used only for patients allergic to sulfonamides

Front 49

What type of CHF are Thiazide diuretics only used for?

Back 49

Mild CHF

Front 50

What concurrent treatment may inhibit Diuretic efficacy?

Back 50

with Vasodilators = reduce renal blood flow

Front 51

What are the 2 parts of the chemical structure of Digoxin?

Back 51

1. Algycone or Genin is responsible for all biological activity

2. 3 molecules of sugar (Digitoxose) influence pharmacokinetics including absorption, half-life, & metabolism

Front 52

What is the mechanical effect of Digoxin?

Back 52

Positive Inotropy = increased myocardial contractility/Stroke volume

Front 53

What is the inotropic mechanism of action of Digoxin?

Back 53

1. inhibition of Na+/K+ ATPase
2. intracellular increase in Na+ & decrease in K+
3. decreased expulsion of intracellular Ca+
4. increased intracellular Ca+
5. increased actin-myosin interaction by IC Ca++
6. increased force of myocardial contraction

Front 54

What counteracts Digoxin's toxicity & reduces abnormal cardiac automaticity?

Back 54

Potassium b/c it inhibits Digoxin's binding to Na+/K+ ATPase receptor

Digoxin toxicity should be treated with Potassium

Front 55

What increases Digoxin's toxicity?

Back 55

Calcium & hypokalemia

Front 56

Why is Heart Rate decreased when using Digoxin for CHF?

Back 56

In untreated CHF, sympathetic activity is already high but upon Digoxin treatment, contractility & CO will be increased thus removing the stimulus for increased Sympathetic tone

Front 57

Why is Cardiac Output increased in patients with CHF who are on Digoxin?

Back 57

1. Increased contractility

2. increased CO removes the stimulus for Sympathetic overactivity = reduction in sympathetic tone
-Venodilation = reduced Preload
-Arteriodilation = reduced Afterload

Front 58

What electrical effects does Digoxin have at therapeutic doses?

Back 58

1. Decrease automaticity

2. Prolongs Refractory Period

3. Slow AV node conduction

Front 59

What can toxic doses of Digoxin cause in the heart?

Back 59

Arrhythmias by increasing Sympathetic activity & automaticity to form ectopic foci
-slowed conduction may cause Sinus Bradycardia or Heart Block
-may produce almost every variety of arrhythmia

Front 60

Based on the reduction in Conduction Velocity in the AV node, what is Digoxin used for in the pretreatment of?

Back 60

Atrial Fibrillation before Antiarrhythmic drugs are used
-antiarrhythmic drugs when given alone may cause paradoxical ventricular tachycardia which can be prevented by pretreatment digoxin which will slow the ventricular rate

Front 61

-

Back 61

-

Front 62

What vascular effect does Digoxin have on normal hearts?

Back 62

contract smooth muscle = Vasoconstriction

Front 63

What vascular effect does Digoxin have on Failing hearts?

Back 63

Increase CO -> remove stimulus Sympathetic hyperactivity -> reduced Sympathetic activity -> Vasodilation

Front 64

What are Digoxin's effects on the Kidney?

Back 64

Diuresis, but only in CHF patients
-increased GFR is due to Cardiac, not renal actions
-digoxin causes Diuresis only in edematous patients with CHF
-no diuresis in normal subjects or other types of edema

Front 65

What are the GI effects of Digoxin?

Back 65

1. Anorexia & diarrhea due to direct irritation
2. Vomiting due to stimulation of the Chemoreceptor Trigger Zone
3. Abdominal pain due to Mesenteric Arteriolar Constriction

Front 66

Why does Digoxin have a narrow Margin of Safety?

MoS = amount between a therapeutic dose and a lethal dose of a drug

Back 66

Because the Therapeutic Dose is 50-60% of the Toxic dose & side-effects often occur even with Therapeutic doses; toxicity leads to discontinuing Digoxin in 5-25% of patients

Front 67

What are the earliest signs of Digoxin intoxication?

Back 67

GI
-anorexia, NVD, abdominal discomfort
-copious salivation often accompanies the nausea
-vomiting can be harmful as it requires great physical effort
-GI symptoms disappear a few days after discontinuing Digoxin

Front 68

What are the most dangerous adverse effects of Digoxin?

Back 68

Cardiac = can simulate almost all arrhythmias including Sinus Bradycardia, Ectopic ventricular beats, AV block, & Bigeminy

Front 69

What is the most common cause of death due to Digoxin?

Back 69

Ventricular Fibrillation

Front 70

How do you monitor the adverse cardiac effects of Digoxin?

Back 70

1. Routine measurements of ECG

2. Serum Digoxin & Potassium

Front 71

What are the CNS side effects of Digoxin?

Back 71

Headache
Fatigue
Malaise
Drowsiness
Trigeminal neuralgia
Mental symptoms

Front 72

Aside from GI, Cardiac, & CNS...what are other adverse effects of Digoxin?

Back 72

1. Color & Visual Disturbances = Blurry yellow vision
2. Skin rashes
3. Eosinophilia
4. Gynecomastia
5. in severe intoxication, antiarrhythmic drugs may result in cardiac arrest

"Upon DIGGING you find an OX with who has Yellow vision, a skin rash, red cells, & large breasts"

Front 73

What should treatment of Digoxin intoxication include?

Back 73

1. discontinue Digoxin
2. oral or IV Potassium (K+)
3. Lidocaine
4. Digoxin antibodies (Anti-Dig Fab fragments)

Front 74

What drugs enhance Digoxin toxicity by decreasing its Renal Clearance?

Back 74

Quinidine
Amiodarone
Captopril
Verapamil
Diltiazem
Cyclosporin

*CDC-VAQ

Front 75

What increases Digoxin's renal clearance?

Back 75

Thyroxine

Front 76

What decreases Digoxin's GI absorption?

Back 76

Cholestyramine

Bran

Front 77

What are Digoxin's interactions with Quinidine?

Back 77

1. Quinidine displaces Digoxin from tissue binding sites

2. Quinidine depresses Digoxin's renal clearance

**may result in sudden death

Front 78

What diuretics may enhance Digoxin toxicity? Why?

Back 78

Thiazides & Loop Diuretics

produce Hypokalemia
-Potassium blocks Digoxin's action at the Na+/K+ ATPase

Front 79

What drugs enhance Digoxin's toxicity by inhibiting SA or AV node activity?

Back 79

Beta blockers

Front 80

What drugs enhance Digoxin toxicity by inhibiting myocardial contractility?

Back 80

CCA's
-Verapamil
-Diltiazem
-Nifedipine -> but probably not so much

Front 81

What group of people are mosre susceptible to Digoxin intoxication? Why?

Back 81

Elderly patients b/c their serum Digoxin levels are elevated by Hypochlorhydria or reduced Renal Clearance

Front 82

What patients usually require larger doses of Digoxin?

Back 82

Infants

Front 83

What condition predisposes to intoxication of Digoxin by reducing renal clearance to elevate serum Digoxin levels?

Back 83

Hypothyroidism

Front 84

List 3 PDE inhibitors used to treat CHF

Back 84

Amrinone

Milrinone

Vesnarinone

**-RINONE

Front 85

What do the "-RINONE's" inhibit?

Back 85

type III Phosphodiesterase = inhibit cAMP degradation

Front 86

Whta is the mechanism of action of the "-RINONE's"?
-AmRINONE
-MilRINONE
-VesnaRINONE

Back 86

increase Myocardial contractility by increasing cAMP & inward calcium flux in the heart

Inhibit Phosphodiesterase-3 = increase cAMP
-also relax vascular smooth muscles to cause Vasodilation

Front 87

What are the -RINONE's only used for?

Back 87

Short-term treatment in advanced heart failure

**long-term trials produce intolerable side effects & increase mortality in CHF patients

Front 88

These drugs are infused IV to increase Myocardial Contractility only in Acute CHF

Back 88

Dopamine

Beta-1 adrenergic agonists = Dobutamine

Front 89

What 2 drugs may increase Digoxin toxicity by increasing it GI absorption?

Back 89

1. Erythromycin

2. Omeprazole