Antianginal drugs

Question 1

How do nitrates and nitrites have their action?

Answer 1

Cause vasodilation via NO which is converted into cGMP.

Question 2

What kind of vasodilation is caused by nitrates?

Answer 2

Uneven, large veins are dilated more, so preload is reduced more than afterload, but afterload is still reduced, thus decreasing cardiac workload and decreasing oxygen demand

Question 3

What is the DOC for any acute anginal attack (classic or variant)?

Answer 3

Nitrates

Question 4

What is the downside of nitrate therapy?

Answer 4

A decrease in BP causes baroreflex and an increased HR and contractility, thus decreasing diastolic perfusion time and increasing O2 demand again

Question 5

What is the predominant mechanism of anginal relief by nitrates?

Answer 5

to decrease myocardial O2 requirements

Question 6

What is the secondary mechanism of anginal relief by nitrates?

Answer 6

redistribution of regional coronary BF from normal to ischemic areas even though total flow remains unchanged

Question 7

What are the pharmacokinetics of nitrates?

Answer 7

Rapid metabolization and very fast acting, hence sublingual is the route of choice because it avoids hepatic destruction, effects only last about 30 minutes

Question 8

What is the inhaled nitrate?

Answer 8

Amyl nitrite

Question 9

What is sublingual nitrate?

Answer 9

isosorbide dinitrate

Question 10

What is the IV nitrate?

Answer 10

sodium nitroprusside

Question 11

What are some adverse side effects of nitrates?

Answer 11

Orthostatic hypo, tachycardia, throbbing HA, TOLERANCE– evidenced by “Monday disease” exhibited by explosive manufacturers– symptoms disappear by Friday due to tolerance

Question 12

Where do CCBs have their action?

Answer 12

At all smooth muscles that depend on calcium for normal resting tone and contraction

Question 13

How does nifedipine lead to reflex tachy if it is vascular specific?

Answer 13

reflex tachycardia causes increase in HR

Question 14

When is the only time slow release nifedipine is indicated?

Answer 14

For HTN, not for angina (may actually provoke angina)

Question 15

How are CCBs used to treat angina?

Answer 15

As chronic treatment, not immediate relief

Question 16

What is the most harmful effect of nondihydropyridines and angina?

Answer 16

The potential for serious cardiac depression that could end in cardiac arrest, A-V block, or CHF (don’t use in CHF patients for this reason)

Question 17

Where does anginal relief from BBlockers come from?

Answer 17

decreased SNS activation, decreased vasoconstriction, hypotension and bradycardia, and decreased demand. Bradycardia has an added benefit for increasing myocardial perfusion time

Question 18

Why are BBlockers not used for variant angina?

Answer 18

They do not cause direct vasodilation of coronary arteries, it is good to maintaining heart rate to prevent repeat ischemia (see metoprolol graph)

Question 19

Who are BBlockers contraindicated in?

Answer 19

Asthmatics and diabetics!

Question 20

How could BBlockers be harmful in variant angina?

Answer 20

Slow HR and long ejection time leads to an increase in LV EDV, which will increase myocardial O2 requirement

Question 21

What kind of treatment can BBlockers be used for?

Answer 21

Classic angina, NOT VARIANT

Question 22

What is the MOA of ranolazine? When is it indicated?

Answer 22

It is a partial fatty-acid oxidation inhibitor, so it decreases O2 consumption in ischemic tissue and decreases contractility by inhibiting late inward sodium current; used when other anti-anginal drugs don’t work- it decreases left ventricular wall stiffness and improves coronary circulation

Question 23

What methods are used to treat variant or angiospastic angina?

Answer 23

Nitrates and CCBs are preferred because BBlockers will not dilate spastic coronary vessels.

Question 24

What is the most effective drug combo for angina?

Answer 24

B-blockers and a vasodilator (start with nitrates, move to CCBs)

Question 25

How do you avoid reflex tachycardia with the use of nitrates?

Answer 25

Use CCBs and BBlockers

Question 26

Why would you never prescribe nifedipine and a nitrate?

Answer 26

Nifedipine causes reflex tachy and so does a nitrate, double reflex tachy is BAD NEWS!

Question 27

What is the MOA for Sildenafil?

Answer 27

acts as a selective inhibitor of cGMP PDE5 to maintain relaxation of blood vessels

Question 28

What are indications for Sildenafil use?

Answer 28

Tx for male ED, pulmonary HTN

Question 29

Max concentrations are reached in ____ minutes with sildenafil and the half-life is ____ hours

Answer 29

30-120, 4 hours

Question 30

How is Viagra metabolized?

Answer 30

In the liver by CYP3A4

Question 31

What are two side effects of sildenafil?

Answer 31

Vasodilation side effects, visual impairment due to inhibition of PDE-6 (blue color, photophobia or blurred vision)

Question 32

What are contraindications for sildenafil?

Answer 32

Pregnant or lactating women, no use in infants or children.

Current use of nitrates or nitrates (causes very low BP) or alpha blockers (not as extreme, but still low BP)

Question 33

Why does GRAPEFRUIT, cimetidine, erythromycin, quinidine, etc cause an excess in side effects when taken with Sildenafil?

Answer 33

Because they inhibit CYP3A4 and 2C9 enzymes which are supposed to be around to metabolize sildenafil

Question 34

What are the more selective PDE-5 inhibitors? Why is that a good thing?

Answer 34

Vardenafil (Levitra) and Tadalafil (Cialis); less visual disturbances

Question 35

What sets vardenafil apart from other PDE5 inhibitors?

Answer 35

It achieves plasma concentration sooner than sildenafil and tadalafil, which may result in faster onset of action

Question 36

What sets tadalafil from other PDE5 inhibitors?

Answer 36

Duration of action is longer than sildenafil and vardenafil leads to increased spontaneity