Drugs for Angina

Question 1

What is angina?

Answer 1

chest pain caused by transient ischemic episodes

Question 2

What are the 3 types of angina and their causes?

Answer 2

1. Stable angina –> chest pain on exertion due to atherosclerotic occlusion of a coronary artery. 70% occlusion prevents adequate O2 to reach active cardiac tissues.
2. Unstable angina –> chest pain at rest. Fissures of atherosclerotic plaques cause transient platelet aggregation (thrombosis) of a coronary artery (incomplete occlusion)
3. Prinzmetal’s Angina –> Chest pain anytime, unrelated to atherosclerosis. VASOSPASTIC.

Question 3

What is the general (layman’s terms) goal of angina drugs?

Answer 3

Therapies can either :

1. DECREASE THE HEART’S OXYGEN DEMAND via negative inotropic and chronotropic effects OR by decreasing afterload/preload.
2. INCREASE THE OXYGEN SUPPLY by increasing coronary bloodflow

(Ideal drugs cause both to happen)

3. Prevent platelet aggregation –> NSAIDS

Question 4

Heart work is determined by what 3 factors?

Answer 4

HR

Contractility

Afterload

Question 5

O2 supply is determined by what 4 factors?

Answer 5

Vascular resistance or coronary arteries

Perfusion pressure

Collateral blood flow

Heart rate and mechanics

Question 6

WHich of the 3 types of angina has the best prognosis?

Answer 6

Prinzmetal’s

Question 7

Perfusion of the heart occurs during diastole. How can this concept be used for drug therapy?

Answer 7

Any therapy that decreases HR will increase the time the heart spends in diastole, resulting in greater O2 delivery time to the heart.

Question 8

What is the #1 drug choice for angina (mentioned in Robbins too)?

What is a unique result of taking this drug?

Answer 8

NITRATES! (Nitroglycerin)

Decreases the Preload –> decreased ventricular pressure during diastole reduces wall stress, and subendocardial bloodflow is increased.

Question 9

MOA of Nitrates

Answer 9

NO activates gualylyl cyclase in the smooth muscle cells of the VEINS, resulting in increased cGMP levels.

This causes relaxation of venous smooth muscle (VENODILATION), reducing the PRELOAD.

NITRATES ARE THE ONLY DRUGS THAT REDUCES PRELOAD

They also cause CORONARY VASODILATION

Question 10

Adverse effects of nitrates?

Answer 10

1. Hypotension - at high doses resulting from vasodilation in addition to ventilation.
2. Headache (most common)- due to vasodilation of meningeal arteries
3. Rash –> seen with long lasting nitrates (patches)

Question 11

What’s the drug/drug interaction to worry about with Nitrates?

Answer 11

PDE (phosphodiesterase) INHIBITORS like Viagra/Cialis.

Nitrates cause up regulation of cGMP and PEDI’s prevent its breakdown.

Question 12

What is the generic name of Viagra?

Answer 12

Sildenifil

It’s “Silly to take Sildenifil with Nitrates”

Question 13

Why are “nitrate-free” periods recommended for people taking them regularly?

Answer 13

Tolerance to the beneficial effects of Nitrates occurs with repeated use, but is quickly fixed.

Even the headaches are tolerated after a while.

Question 14

How do you prevent the headache that comes from Nitrates?

Answer 14

NSAIDS.

Question 15

Describe the theoretical mechanism of Nitrate tolerance.

Answer 15

Depletion of CYSTEINE–> necessary for the metabolism of Nitrates into their active form.

Question 16

How do you take a patient off to Nitrates? Stop abruptly or Step down?

Answer 16

Step down, because coronary vasospasm (collapse) has been observed following abrupt cessation of nitrates.

Question 17

How do Ca2+ channel blockers help angina?

Answer 17

They increase the time the SA nodal cells spend in phase 4.

Decrease HR by increasing the amount of time the Ca2+ channels stay closed!

(increase threshold for opening of L-type Ca2+ channels)

Question 18

CCB’s specifically block ________ calcium channels.

Answer 18

L-type

only present in heart and vasculature, nowhere else in the body.

Question 19

Which CCBs are cardio-selective in their actions? What do they do to the heart?

Answer 19

Verapamil and Diltiazem, the Non-dihydripyridines.

1. SA node - slow pacemaker firing (phase 4 prolongation)
2. Reduce isotropy of atrial myocardium
3. Slow AV conduction of AP.

Question 20

You give a B-blocker and Diltiazem simultaneously. What happens?

Answer 20

The patient’s heart can’t be stimulated cause you’ve blocked all the inotropic receptors.

Bradycardia, Asystole, even death can occur.

Question 21

You give a B-blocker and Nifedipine simultaneously. What happens?

Answer 21

Nifedipine decreases TPR via VASODILATION.

DECREASES AFTERLOAD

Remember the MOA of dihydropyridines is blocking Ca2+ influx channels in the vasculature, preventing smooth muscle contraction.

The decrease in TPR lowers the MAP, therefore lowers the CO and SV. The body’s compensatory response is usually to activate sympathetic receptors on the heart (B1) to speed the heart back up.

B-blockers prevent this from happening, and keep the HR down.

SYNERGISTIC EFFECT.

Question 22

Do Dihydropyridine CCBs cause venodilation, vasodilation, or both?

Answer 22

VASODILATION (arteries) Vasodilation lowers BP.

No effect on venodilation. Venodilation doesn’t really lower the BP much.

Nitrates are the ones that VENOdilate at low concentrations and do both at high toxic concentrations.

Question 23

Why do dihydropyridines and non-dihydropyridines bind to L-type calcium channels in different locations?

Answer 23

DIFFERENT BINDING SITES:

Non-dyhydropyridines bind the L-type calcium channel INSIDE THE CHANNEL, so they bind channels that are constantly in use (in the heart)

Dihydropyridines bind the L-type calcium channel AT A CERTAIN VOLTAGE. The voltage of Ca2+ channels in the heart changes so rapidly, drugs like Nifedipine don’t have time to bind. The voltage of Ca2+ channels in smooth muscle changes more slowly, so there is time to bind.

Question 24

What is ONE common effect between Verapamil and Nefidipine?

Answer 24

Both non-dihydropyridines and dihydropyridines cause CORONARY ARTERY VASODILATION.

Question 25

T/F: CYPs have no effect on Verapamil

Answer 25

FALSE: Verapamil is a CYP substrate and inhibitor.

Don’t take with other CYP inhibitors either… Grapefruit Juice, CLONIDINE,

Question 26

WHen should you NOT use a (-) inotropic drug like Verapamil?

Answer 26

When you have AV conduction defects or advanced heart failure.

Question 27

You have heart failure, and are having angina symptoms as well. What do you do now?

Answer 27

Give nitrates or dihydropyridines+ B=blocker.

NOT non-dyhydropyridines. They’re contraindicated with any previous heat problem.

Question 28

You’re an asthmatic diabetic, and are developing angina. What do you take for it?

Answer 28

You can’t take B-blockers because they’d induce vasospasms and hypoglycemia.

Take Verapamil.

Question 29

WHat’s the order in treatment you give to an angina patient?

Answer 29

B-blocker first.

B-blocker and Nitrates to refractory.

B-blocker, nitrates, and CCB to even more refractory.

Question 30

If you’re going to give nitrates or dihydropyridine CCBs, do you always give a B-blocker?

Answer 30

YES –> prevents the reflex tachycardia dan positive inotropic response to decreased CO with the preload decrease if nitrates and the after load decrease of dihydropyridine CCBs.

Question 31

Which type of Angina can B-blockers NOT help?

Answer 31

Prinzmetal’s. B-blockers have no vasodilatory effects, and can’t stop vasospasm of coronary arteries as a result.

Question 32

MOA of Ranolazine.

Answer 32

Ranolazine is an angina treatment drug with NO EFFECT on hemodynamics.

It’s a pure metabolic inhibitor, meaning it’s a partial Fatty Acid Oxidase inhibitor, which increases glucose oxidation and efficiency of O2 utilization in the heart.

Only good for patients refractory to B-blockers, Nitrates, and CCBs OR people who have exercise induced angina. This allows them to exercise for longer before symptoms occur.

Question 33

What drug should ALL patients with stable or unstable angina be on? (don’t really need it with vasospastic angina)

Answer 33

ASPIRIN