Cardiovascular I

Question 1

How is angina characterized on the ECG?

Answer 1

By S-T segment depression or elevation

Question 2

When does angina occur?

Answer 2

When oxygen supply to the myocardium is insufficient

Question 3

What agents decrease oxygen demand?

Answer 3

Vasodilators, Ca++ entry blockers, organic nitrates

Question 4

Typical Angina

1. Result of?
2. Induced by?

Answer 4

1. Atherosclerotic coronary artery disease
2. Excercise, eating, or emotional stress

Question 5

Varient or Prinzmetals Angina:

1. Result of?
2. When can it occur?

Answer 5

1. Coronary artery vasospasm possibly in conjunction with a coronary thrombosis
2. at rest

Question 6

What other things can cause myocardial ischemia?

Answer 6

Aortic valve disease, hypertrophic cardiomyopathy, stenosis of the coronary ostia, inflammation of the coronary arteries, and congenital anomalous origins of the coronary arteries arising from the pulmonary artery

Question 7

Early reversible ischemia:

1. Time period this occurs?
2. What occurs with glycolysis?
3. What occurs with phosphate?

Answer 7

1. 15 minutes
2. There is an increase in anaerobic glycolysis
3. There is greater use than production

Question 8

Early irreversible ischemia:

1. Time period?
2. What happens with high energy phosphates?
3. What occurs to the mitochondria and plasmalemma?
4. What ion influxes? Why is this important?

Answer 8

1. 60 minutes
2. Phosphate stores are depleted
3. Mito swells and plasmalemmal defects
4. Ca++ influx; stimulates lysozymes to destroy cells

Question 9

Late irreversible Ischemia

1. Time period?
2. What occurs to the membrane? Result?
3. What ion influxes? Why is this important?

Answer 9

1. 24 hours
2. It continues to pull apart and leak enzymes, co-factors and soluble cell components to the extracellular fluid
3. Ca++ influx; stimulates lysozymes for cell destruction

Question 10

The treatment of angina is targeted at imporvement of the balance between what?

What are the three classes of drugs traditionally used?

Answer 10

Balance between oxygen supply and demand in the heart

Beta blockers, Ca++ channel blockers, and organic nitrates

Question 11

What do organic nitrates do?

Main example?

Answer 11

Cause direct, endothelium INDEPENDENT, relaxation of most sources of smooth muscle including that from arteries and veins

Nitroglycerin

Question 12

Cellular mechanisms of action of nitrodilators:

Nitrodilators react with REDUCED _____ (example: ____) inside the cell to form unstable _____.

Answer 12

thiols; cysteine; nitrosothiols

Question 13

Cellular mechanisms of action of nitrodilators:

Nitrosothiol is believed to release ____ which binds to the ___ moiety of ____ cyclase. This binding activates the enzyme resulting in the production of ____ and subsequent activation of the ____ elicits relaxation of the vascular smooth muscle.

Answer 13

NO; heme; guanylate; cGMP; G-kinase

Question 14

Cellular mechanisms of action of nitrodilators:

No is not only a second messenger in vadodilation but it also has what other properties? (4)

What deactivates the conversion of GTP to cGMP?

Answer 14

Anti-thrombotic, anti-mitogenic, anti-atherogenic, and acts as an oxygen radical scavenger

Phosphodiesterases (PDEs)

Question 15

Hemodynamic systemic effects of nitrovasodilators:

What does it dilate?

The systemic dilatory effects reduce ___ and ___ as well as?

Consequently the systemic effects improve ischemia by ___ ___ ___ by the heart.

Answer 15

1. Veins and arteries with a preference for veins at low doses
2. preload; afterload; ventricular chamber size
3. reducing oxygen demand

Question 16

What is the primary effect of nitrodilators upon stable exertional angina?

Answer 16

To reduce oxygen demand by the heart

Question 17

Hemodynamic coronary effects of nitrovasodilators:

1. What coronaries are most sensitive? (size)
2. The dilating effect is of UNCERTAIN benefit but they may be important in what cases?
3. There is some evidence that decreased ___ pressure brought about by nitrodilators may facilitate blood flow to the ____.

Answer 17

1. Large are more sensitive than small
2. Eccentric coronary stenosis or in classic variant angina where vasospasm may be the primary cause
3. ventricular; endocardium

Question 18

Pharmacodynamics and Kinetics:

1. Speed of absorption?
2. Absorbed how?
3. Speed of metabolism?
4. Duration of action?

Answer 18

1. Rapid
2. Through mucous membranes
3. Fast
4. Short

Question 19

Nitroglycerin

1. Peak effect in how much time?
2. Duration of action?
3. Good for what 2 things?

Answer 19

1. 3 minutes
2. 20/30 minutes
3. Acute angina or prophylaxis before exertion

Question 20

Isosorbide dinitrate

1. Onset in how much time?
2. Peak effect time?
3. Duration?
4. Useful for?

Answer 20

1. 20/45 minutes
2. 45/120 minutes
3. 2-6 hours
4. Prevention of angina

Question 21

Side effects and limitations of nitrovasodilators:

The major drawback?

Answer 21

Tolerance

Question 22

What two ways is tolerance theorized to occur?

Answer 22

Counter-regulatory mechanism

Tissue metabolic mechanisms

Question 23

Counter-regulatory mechanisms of tolerance:

1. Decreased BP results in reflex activation of?
2. ____ ___ in response to these reflexes counteracts the ____ effect of the nitrodilator.

Answer 23

1. SNS as well as the Renin-angiotensin system
2. Volume retention; unloading

Question 24

Tissue metabolic mechanisms of tolerance:

1. Where does tolerance develop? What does this suggest?
2. Current research indicates a role for ___ in the development of tolerance
3. Sustained exposure to NO results in excessive production of what? This production then does that?

Answer 24

1. In isolated arteries suggesting that tolerance originates at the cellular level
2. ROS
3. ROS; Radicals inactivate NO, convert NO Synthase to a superoxide ion producing enzyme, and stimulate other superoxide enzymes

Question 25

Other side effects of nitrodilators? (extensions of their normal physiological effects) Why?

Answer 25

Postural hypotension (from preferred venodilation) Syncope (from too severe of a decrease in arterial pressure) Headache (from cerebral arterial vasodilation)

Question 26

What in conjunction with nitrodilators can result in severe hypotension and exacerbation of angina? What is this used as treatment for?

Answer 26

PDE5 inhibitors Erectile dysfunction

Question 27

Factors associated with ED parallel those of ___ \_\_\_ \_\_. What are these factors?

Answer 27

coronary artery disease; hypertension, diabetes, and hypercholesterolemia

Question 28

3 PDE5 inhibitors used for the treatment of ED?

Answer 28

Sildenafil (short), Vardenafil (short), and Tadafil (long)

Question 29

PDE5 inhibitors mechanism of action: What specific PDE do PDE5 inhibitors inhibit? Consequently what is increased? This is stimulated by?

Answer 29

They inhibit the cyclic GMP-specific PDE5 family of phosphodiesterases Intracellular concentrations of cGMP stimulated by cellular agonists, such as NO, that activate guanylate cyclase

Question 30

PDE5 inhibitors mechanism of action: Because they increase intracelullar concentrations of cGMP, they amplify the actions of?

Answer 30

NO

Question 31

PDE5 mechanism of action: 1. What is associated with excess oxygen radical formation? Excess ROS chemically reduces ___ concentration at target tissues. 2. What does diabetes do specifically?

Answer 31

1. Hypertension, diabetes, and hypercholesterolemia; NO 2. Damages nerves, including the NANC nerves, that release NO in the corpus cavernosum to induce penile erection.

Question 32

PDE5 inhibitors mechanism of action: PDE5 inhibitors counteract the effect of decreased NO bioavailabilty by enhancing the amount of ___ produced in the ___ \_\_\_\_ and ____ arteries.

Answer 32

cGMP; corpus cavernosum; penile

Question 33

Minor adverse events of PDE5 inhibitors?

Answer 33

Headache, flushing, rhinitis, possible dyspepsia (due to relaxation of the LES), weak inhibition of PDE6 (mediator of photoreceptor signal transduction)

Question 34

Major adverse effects of PDE5 inhibitors: 1. Taken alone? 2. Interaction with organic nitrates?

Answer 34

1. Only minimally decrease BP 2. Together they produce extreme reductions in BP

Question 35

PDE5 inhibitors are contraindicated in what patients?

Answer 35

Patients taking any form of nitrate or alpha adrenergic receptor ANtagonists

Question 36

Review Nitrodilator therapeutic mechanisms: 1. Venodilations --\> reduce \_\_\_ __ --\> reduce ventricular size, volume, and ____ --\> decreased wall stress. Overall decreased ___ \_\_\_\_. 2. Arterial dilation --\> decreased ventricular \_\_\_\_ 3. Dilate ____ free wall 4. Improve endocardial ___ \_\_

Answer 36

1. ventricular preload; pressure; oxygen demand 2. afterload 3. coronary 4. blood flow

Question 37

Review nitrodilator limitations: 1. What two things stimulate the SNS and cause reflex tachycardia and +inotropic effect? 2. Development of \_\_\_ 3. Complications associated with concurrent use of ___ \_\_\_.

Answer 37

1. Hypotension and decreased stroke volume 2. tolerance 3. PDE5 inhibitors

Question 38

Review Nitrodilator adverse reactions? Name 7.

Answer 38

Headache, dizziness, postural hypotension, syncope, palpitations, weakness, and Angina

Question 39

Why is angina an adverse reaction of nitrodilators if its used for the treatment of angina?

Answer 39

In coronary artery disease, if too much is taken, there can be exacerbation of the current angina and will drop BP/blood flow too low. It occurs when people take another one too soon

Question 40

Review - Beta adrenergic antagonist therapeutic mechanisms: 1. Limit catecholamine induced ___ \_\_ 2. Decrease ventricular ____ by decreasing \_\_\_. 3. Inhibit ___ aggregation 4. ___ stabilizing effect (although not all)

Answer 40

1. Increased HR 2. afterload; BP 3. platelet 4. membrane

Question 41

Review beta adrenergic antagonist limitations: 1. Potential for constriction of? 2. What occurs with withdrawl? 3. What occurs with sudden withdrawl?

Answer 41

1. vasculature and bronchi 2. Decompensation in borderline heart failure 3. Angina and possible MI

Question 42

Review - beta adrenergic antagonist adverse rxns: Name 8.

Answer 42

Bradycardia, heart block, hypotension, heart failure, bronchoconstriction, unrecognized hypoglycemia (in diabetes), cold extremities, claudication (too little blood flow during exercise)