Cardiovascular I Flashcards Preview

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Flashcards in Cardiovascular I Deck (42):
1

How is angina characterized on the ECG?

By S-T segment depression or elevation

2

When does angina occur?

When oxygen supply to the myocardium is insufficient

3

What agents decrease oxygen demand?

Vasodilators, Ca++ entry blockers, organic nitrates

4

Typical Angina

1. Result of?

2. Induced by?

1. Atherosclerotic coronary artery disease

2. Excercise, eating, or emotional stress

5

Varient or Prinzmetals Angina:

1. Result of?

2. When can it occur?

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

2. at rest

6

What other things can cause myocardial ischemia?

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

7

Early reversible ischemia:

1. Time period this occurs?

2. What occurs with glycolysis?

3. What occurs with phosphate?

1. 15 minutes

2. There is an increase in anaerobic glycolysis

3. There is greater use than production

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?

1. 60 minutes

2. Phosphate stores are depleted

3. Mito swells and plasmalemmal defects

4. Ca++ influx; stimulates lysozymes to destroy cells

9

Late irreversible Ischemia

1. Time period?

2. What occurs to the membrane? Result?

3. What ion influxes? Why is this important?

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

10

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

What are the three classes of drugs traditionally used?

Balance between oxygen supply and demand in the heart

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

11

What do organic nitrates do?

Main example?

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

Nitroglycerin

12

Cellular mechanisms of action of nitrodilators:

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

thiols; cysteine; nitrosothiols

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.

NO; heme; guanylate; cGMP; G-kinase

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?

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

Phosphodiesterases (PDEs)

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.

1. Veins and arteries with a preference for veins at low doses

2. preload; afterload; ventricular chamber size

3. reducing oxygen demand

16

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

To reduce oxygen demand by the heart

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 ____.

 

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

18

Pharmacodynamics and Kinetics:

1. Speed of absorption?

2. Absorbed how?

3. Speed of metabolism?

4. Duration of action?

1. Rapid

2. Through mucous membranes

3. Fast

4. Short

19

Nitroglycerin

1. Peak effect in how much time?

2. Duration of action?

3. Good for what 2 things?

1. 3 minutes

2. 20/30 minutes

3. Acute angina or prophylaxis before exertion

 

20

Isosorbide dinitrate

1. Onset in how much time?

2. Peak effect time?

3. Duration?

4. Useful for?

1. 20/45 minutes

2. 45/120 minutes

3. 2-6 hours

4. Prevention of angina

21

Side effects and limitations of nitrovasodilators:

The major drawback?

Tolerance

22

What two ways is tolerance theorized to occur?

Counter-regulatory mechanism

Tissue metabolic mechanisms

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.

1. SNS as well as the Renin-angiotensin system

2. Volume retention; unloading

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?

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

25

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

Postural hypotension (from preferred venodilation)

Syncope (from too severe of a decrease in arterial pressure)

Headache (from cerebral arterial vasodilation)

26

What in conjunction with nitrodilators can result in severe hypotension and exacerbation of angina?

What is this used as treatment for?

PDE5 inhibitors

Erectile dysfunction

27

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

coronary artery disease; hypertension, diabetes, and hypercholesterolemia

28

3 PDE5 inhibitors used for the treatment of ED?

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

29

PDE5 inhibitors mechanism of action:

What specific PDE do PDE5 inhibitors inhibit?

Consequently what is increased? This is stimulated by?

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

30

PDE5 inhibitors mechanism of action:

Because they increase intracelullar concentrations of cGMP, they amplify the actions of?

 

NO

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?

1. Hypertension, diabetes, and hypercholesterolemia; NO

2. Damages nerves, including the NANC nerves, that release NO in the corpus cavernosum to induce penile erection.

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.

cGMP; corpus cavernosum; penile

33

Minor adverse events of PDE5 inhibitors?

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

34

Major adverse effects of PDE5 inhibitors:

1. Taken alone?

2. Interaction with organic nitrates?

 

1. Only minimally decrease BP

2. Together they produce extreme reductions in BP

 

35

PDE5 inhibitors are contraindicated in what patients?

Patients taking any form of nitrate or alpha adrenergic receptor ANtagonists

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 ___ __

1. ventricular preload; pressure; oxygen demand

2. afterload

3. coronary

4. blood flow

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 ___ ___.

1. Hypotension and decreased stroke volume

2. tolerance

3. PDE5 inhibitors

38

Review Nitrodilator adverse reactions?

Name 7.

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

39

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

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

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)

1. Increased HR

2. afterload; BP

3. platelet

4. membrane

41

Review beta adrenergic antagonist limitations:

1. Potential for constriction of?

2. What occurs with withdrawl?

3. What occurs with sudden withdrawl?

1. vasculature and bronchi

2. Decompensation in borderline heart failure

3. Angina and possible MI

42

Review - beta adrenergic antagonist adverse rxns:

Name 8.

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