Pharm S2B3 - Cv - Anti-Angina Drugs

Front 1

What is Coronary Artery Disease mainly due to?

Back 1

Obstruction of the coronaries by Atheromatous plaques

Front 2

When does Coronary Artery Disease start?

Back 2

silently in childhood

**everyone develops Coronary Artery Disease

Front 3

The primary symptom of heart disease; refers to chest pain caused by Myocardial Ischemia

Back 3

Angina Pectoris

Front 4

What characterizes Angina Pectoris?

Back 4

Chest discomfort occurring when the amount of blood delivered to the heart by the coronary arteries cannot supply enough oxygen to satisfy the Myocardial requirement so that OXYGEN NEED EXCEEDS OXYGEN SUPPLY

Front 5

How is Angina Pectoris typically relieved?

Back 5

within minutes by REST or use of NITROGLYCERIN

Front 6

Describe the chest pain associated with Angina Pectoris

Back 6

Strangling
Vise-like
Constricting
Suffocating
Crushing
Heavy
Squeezing

Front 7

Where is the site of chest discomfort in Angina Pectoris?

Back 7

Retrosternal often radiating down the Ulnar surface of the left arm or may also involve the right or both arms

Front 8

-

Back 8

-

Front 9

What does Oxygen supply to the heart depend on?

Back 9

Oxygen delivery

Extraction

Front 10

What does oxygen demand of the heart depend on?

Back 10

Cardiac workload
1. contractility
2. heart rate
3. ventricular wall tension
4. oxygen extraction is already maximal even at rest

Front 11

How can additional Oxygen be supplied to the heart?

Back 11

By increasing Oxygen delivery through coronary blood flow
1. directly proportional to Aortic Diastolic Pressure & duration of Diastole
2. inversely proportional to coronary vascular resistence determined by: metabolic products, autonomic activity, & various drugs

Front 12

Describe the "Coronary Steal Phenomenon"

Back 12

diseased atherosclerotic branch is unable to dilate as well as the normal branch in response to the vasodilator drug, the amount of blood supplied by the diseased branch is actually reduced because blood flow is diverted into the normal branch that is vasodilated

Front 13

Increasing Oxygen supply through coronary vasodilation releives only acute anginal attacks but is ineffective for chronic treatment because of _____________

Back 13

Coronary Steal

Front 14

-

Back 14

-

Front 15

What is the mechanism of action of Nitrates

Back 15

Decrease Preload

Front 16

All vascular smooth muscle cells are relaxed by Nitrates, but explain how the ensuing vasodilation is uneven

Back 16

Large veins are markedly dilated

Arterioles & Precapillary sphincters are dilated less

Front 17

What are the other effects of Nitrates aside from vasodilation? (2)

Back 17

1. Decrease platelet aggregation

2. produce Methemoglobin

Front 18

What are the beneficial effects of the Nitrates due to in anginal relief?

Back 18

1. Pronounced dilation of large veins = reduces Preload, myocardial oxygen demand, & cardia work

2. Redistribution of regional coronary blood flow from normal to ischemic areas due to preferential dilation of large epicardial arteries

3. Mild arteriolar dilation = reduces Afterload & myocardial oxygen demand

Front 19

What is the harmful effect of the Nitrates on angina?

Back 19

1. Reflex increases in HR & Contractility and therefore increases myocardial oxygen demand

2. Reflex tachycardia = reduced perfusion due to shorter diastole

Front 20

-

Back 20

-

Front 21

What are other uses of Nitrates (other than for angina)

Back 21

1. Treatment of Cyanide poisoning = sodium nitrite is used to induce formation of Methemoglobin which has very high affinity for Cyanide ion

2. Sex-enhancing drugs
-inhaled amyl nitrite to heighten climax by increasing coronary flow
-nitroglycerin patches or ointment for impotence

Front 22

What is the mechanism of action of Sildenafil?

Back 22

Inhibits cGMP Phosphodiesterase = increases cGMP -> vasodilation in the Corpus Cavernosum -> enhanced erection in 9 of 10 male patients

Front 23

What are common side-effects of Sildenafil? (5)

Back 23

1. Headache
2. Dyspepsia = indigestion
3. Nasal congestion
4. Visual disturbances = blue-green color vision
5. Priapism

"a guy taking Sildenafil has so much sex he sees Green & his dick hurts (priapism). So much sex gives him a headache & indigestion (b/c he just ate within 20 minutes). He also snots all over the girl"

Front 24

When is Sildenafil contraindicated?

Back 24

Elderly males with CV disease especially if they are receiving Nitrate Therapy for Angina or CAD

Front 25

Why are Sildenafil & Nitrates contraindicated?

Back 25

b/c nitrates increase cGMP systematically, Sildenafil can potentiate nitrate effects to cause extreme HYPOTENSION that is sometimes fatal

Front 26

What are the alternative uses of Sildenafil? (2)

Back 26

Postmenopausal women for Sexual dysfunction

Babies with Pulmonary HTN

Front 27

What are the 2 newer drugs related to Sildenafil?

Back 27

1. Vardenafil

2. Tadalafil = erection from single dose lasts 24-36 hours

Front 28

Which nitrates are metabolized rapidly & how?

Back 28

Oral nitrates

Hepatic reductase

Front 29

What are the routes of administration for nitrates in chronic treatment?

Back 29

1. Inhalation

2. Sublingual

3. Oral

4. Transdermal (skin patch or ointment)

Front 30

What is the preferred routed for Nitroglycerin & Isosorbide Dinitrate?

Back 30

Sublingual for rapid absorption & to avoid hepatic destruction

Front 31

What are the fast acting preparations fo Nitrates?

Back 31

1. inhaled Amyl nitrite

2. IV Sodium Nitroprusside = dilates arteries & veins equally

Front 32

What is Sublingual Nitroglycerin used for?

Back 32

Immediate anginal relief b/c its action is rapid (onset 1-3 min) & short (10-30 min)

**not suitable for maintenance of chronic therapy

Front 33

What is done to minimize tolerance of Nitrates during chronic treatment?

Back 33

Use lowest effective doses with nitrate-free intervals of 10-12 hours daily

Front 34

What are the Acute Toxicity symptoms of the Nitrates?

Back 34

Pronounced vasodilation resulting in Orthostatic Hypotension, Tachycardia, & throbbing Headaches

Front 35

What does frequent repeated exposure to Nitrates result in?

Back 35

Tolerance or a marked reduction in magnitude of most effects

Front 36

Describe "Monday Disease"

Back 36

Industrial exposure to Nitrates
-headache & dizziness on Mondays as tolerance diminishes on weekends; symptoms gradually disappear during weekdays when tolerance develops again with continuous exposure

Front 37

What are 2 important cardiovascular actions of intracellular calcium?

Back 37

1. triggers contraction in both the Myocardium & vascular smooth muscles

2. required for pacemaker activity of the SA node & for conduction thru the AV node

Front 38

What are the 2 major types of Cardiovascular Calcium channels?

Back 38

1. L-channel = long-lasting

2. T-channel = transient

**Calcium ions flow thru open pores in the calcium channels

Front 39

What are Calcium Channel Antagonists (CCA's)?

Back 39

Orally active drugs that bind to L-type Channels in the Myocardium & vascular smooth muscles

Front 40

What opens Calcium channels in the Heart & vascular smooth muscle?

Back 40

Beta-adrenergic stimulation enhances calcium entry

Front 41

What are the most sensitive smooth muscles to CCA's?

Back 41

Vascular but also bronchiolar, GI, & uterine muscles are relaxed

Front 42

Among the blood vessels, which are more sensitive to CCA's?

Back 42

Arterioles > Veins

Front 43

CCA:
-Chemical class = Dihydropyridine
-Binding site = 1A
-Tissue selectivity = Vascular

Back 43

Nifedipine

Front 44

CCA:
-Chemical Class = Benzothiazepine
-Binding site = 1B
-Tissue selectivity = in-between

Back 44

Diltiazem

Front 45

CCA:
-Chemical class = Phenylalkylamine
-Binding site = 1C
-Tissue selectivity = Myocardial

Back 45

Verapamil

Front 46

What are the major cardiac effects of the CCA's?

Back 46

1. Decreased contractility
2. reduced SA node impulse generation
2. slowed AV node conduction

Front 47

CCA that has the strongest Vasodilation effect

Back 47

Nifedipine

Front 48

CCA that has the strongest Cardiac Effects

Back 48

Verapamil

Front 49

CCA that has "in-between" effects on Vasodilation & Myocardial depression

Back 49

Diltiazem

Front 50

Which CCA is most likely to produce Reflex Tachycardia? Why?

Back 50

Nifedipine = causes most pronounced hypotension for reflex tachycardia, with little or no inhibition of SA or AV nodal function

Front 51

Why are Verapamil & Diltiazem not as likely to elicit Reflex Tachycardia?

Back 51

They are weaker Vasodilators & slow the heart by depressing SA & AV node function directly

Front 52

What are the beneficial effects of Nifedipine due to in the treatment of Angina?

Back 52

1. Coronary Vasodilation = increased myocardial oxygen supply

2. vasodilation of systemic arteries = decreased Afterload

***#1 is most significant

Front 53

What is the potential harmful effect of Nifedipine?

Back 53

Increased risk of MI resulting from:
-Pronounced hypotension -> reflex tachycardia -> increased cardiac workload

*especially applicable to Hypertensive patients with or without diabetes

Front 54

What are the beneficial effects of Verapamil & Diltiazem due to for the treatment of Angina?

Back 54

1. Reduced SA automaticity & AV conduction
2. decreased myocardial contractility & bradycardia
3. REDUCED CARDIAC WORKLOAD

Front 55

What are the potential harmful effects of Verapamil & Diltiazem?

Back 55

Serious cardiac depression that could result in:
1. cardiac arrest
2. AV block
3. CHF

Front 56

What are the "other" actions of CCA's? (2)

Back 56

1. inhibition of Insulin secretion
2. interference with Platelet aggregation

Front 57

What are the general side effects of the CCA's?

Back 57

1. flushing
2. edema
3. dizziness
4. nausea
5. constipation

CCA = Constipation, Color (red = flushing), Aversion (nausea)

Front 58

What may Verapamil & Diltiazem reduce the renal clearance of?

Back 58

Digoxin = could enhance its toxicity

Front 59

In what patients should Verapamil & Diltiazem not be used?

Back 59

pts with Ventricular dysfunction or SA-AV node disturbances

Front 60

What Beta blockers are commonly used for Angina treatment?

Back 60

Atenolol

Metoprolol

Propranolol

Nadolol

Front 61

What type of Angina are the Beta blockers extremely useful for the management of? Why?

Back 61

Angina associated with effort

B/c they reduce myocardial oxygen requirements at rest & during exercise

Front 62

T or F: Beta blockers produce better outcome & symptomatic treatment than CCA's

Back 62

True

Front 63

Aside from Angina, what else are the Beta blockers valuable for treating?

Back 63

Silent or Ambulatory ischemia which does not cause pain but is detected by appearance of ECG signs of ischemia

Long-term Beta-adrenergic blockade reduces the total amount of "ischemic time" per day

Front 64

What have studies on Beta-adrenergic Antagonist been shown to do?

Back 64

1. reduce mortality in patients with MI

2. improve survival & prevent stroke in hypertensive patients

Front 65

Beta blockers act by ____________________

Beta blockers do not _________________

Back 65

decreasing sympathetic tone to decrease Cardiac Output

dilate coronary arteries

Front 66

What does Anginal relief result from when using Beta blockers?

Back 66

Decrease sympathetic activity -> decreased contractility, HR, & vasoconstriction -> DECREASED CARDIAC WORKLOAD -> DECREASED OXYGEN DEMAND

Bradycardia also prolongs Diastole & increases Myocardial perfusion time

Front 67

What is the harmful effect of Beta blockade?

Back 67

may induce or worsen CHF whenever sympathetic activity prodives critical support for cardiac performance as in pts with Acute MI or Decompensated Heart Failure

Front 68

What do Beta blockers usually increase the tolerance to?

Back 68

Exercise when used for treatment of angina

BUT in patients with CHF exercise tolerance may be decreased by the reduction in CO

Front 69

In what type of patients should Beta blockers be used in caution when treating Angina? (4)

Back 69

1. Reduced Myocardial reserve
2. Asthma
3. Peripheral vascular insufficiency
4. Diabetes

Front 70

Why are Beta blockers potentially harmful in Variant Angina?

Back 70

Slow heart rate & prolong ejection time -> Left Ventricular End-Diastolic Volume increases -> increased Myocardial oxygen requirement

Front 71

Beta blockers:
1. may predispose to ______
2. Delays the recovery of _____

Back 71

1. Atherogenesis by increasing plasma triglycerides & decreasing HDL-cholesterol

2. Normoglycemia b/c it inhibits hyperglycemic responses mediated by Epinephrine = Beta-2 receptors in Pancreas

Front 72

What are the minor side-effects of Beta blockers? (2)

Back 72

GI = diarrhea, constipation, nausea, vomiting

CNS = insomnia, lassitude, nightmares, depression

Front 73

What effect will effective Antianginal therapy do?

Back 73

1. increase exercise tolerance

2. decrease frequency & duration of MI

Front 74

Which drugs are better for Variant/Angiospastic Angina?

Back 74

Nitrates & CCA's = dilate Coronary BV's

Front 75

What are the most effective drug combinations for Antianginal therapy?

Back 75

1. Beta blockers + CCA's

2. 2 CCA's (eg Nifedipine + Verapamil)

Front 76

How can the potentially harmful effects of the CCA's or Beta blockers be prevented?

Back 76

by combined treatment with Nitrates or vice versa

Front 77

How can Reflex Tachycardia be minimized when using Antianginal drugs?

Back 77

Combining Nitrates with CCA's or Beta blockers

Front 78

-

Back 78

-