Ischemic HD Tx

Question 1

Most important use of organic nitrates in IHD?

Answer 1

termination of stable and variant angina episodes

Question 2

Which vessels are more responsive to organic nitrates?

Answer 2

veins > arteries (decreased pre-load)

large vessels > small vessels

Question 3

How does NO relax smooth muscle?

Answer 3

• pro drugs are converted to NO by aldehyde dehydrogenase in the mito
• NO activates guanylate cyclase = inc cGMP
• inhibition of calcium channels

Question 4

How does the liver metabolize organic nitrates?

Answer 4

hepatic enzyme nitrate reductase pulls nitrate groups off

Question 5

How do the pharmacokinetics of NG and isosorbide dinitrate differ?

Answer 5

• NG = 2-5 minutes (great substrate for nitrate reductase); TERMINATION of angina; pro-phylaxis requires extended release
• ID = 1 hour; better oral viability – prophylaxis

Question 6

What is the most common method of using NG for termination of angina?

Answer 6

sublingual tablet (also spray, IV)

Question 7

What two forms of NG are formed for prophylaxis of angina?

Answer 7

• transdermal match (long duration)

- chest ointments (medium duration)

Question 8

WHat is the big problem with organic nitrates? How is this avoided?

Answer 8

• tolerance
• vascular smooth muscle loses ability to convert organic nitrates to NO (aldehyde dehydrogenase in mito)
• nitrate free periods every day to avoid tolerance

Question 9

Three adverse effects of organic nitrates?

Answer 9

• due to excessive vasodilation
• headaches (inc cerebral flow, avoid in migraneurs)
• hypotension (careful in the elderly; sit them down)
• tachycardia (reflex response to dec BP)

Question 10

When is an acute anginal episode Tx with organic nitrates considered an emergency?

Answer 10

doesn’t terminate within 15 minutes

Question 11

What is an absolute contraindication of nitrate use?

Answer 11

within 24 hours of sildenafil use (inhibits PDE 5 = inc cGMP)

Question 12

What calcium channels are usually inhibited by CCB’s?

Answer 12

L-type = cardiovascular contraction type

Question 13

How do half lives differ among dihydropyridine prototype drugs?

Answer 13

• amiodipine = 40 hours

- nifedipine = 2-4 hours

Question 14

Which CCB class is more often associated with reflex tachycardia?

Answer 14

• dihydropyridines

- non’s additionally directly inhibit SAN which compensates for reflex tachycardia in response to vasodilation

Question 15

DOC indication for CCB’s in myocardial ischemia?

Answer 15

variant angina (direct vasodilators, no drug-free periods)

Question 16

Why are fast-acting dihydropyridines avoided?

Answer 16

• significant reflex tachycardia because you experience a high, fast peak of drug causing a rapid drop in BP
• may exacerbate ischemia by increasing oxygen demand

Question 17

What two drug classes can cause gingival overgrowth?

Answer 17

• phenytoin

- dihydropyridines

Question 18

What is the new, anti-ischemic drug of last resort that is never used on its own?

Answer 18

Ranolazine = blocker of ‘late’ cardiac V-gated Na+ current seen in ischemia – prevents excessive entry of Na+ into cardiac myocytes during ischemia

Question 19

Indication of ranolazine?

Answer 19

• prophylaxis of stable angina resistant to other therapies

- symptomatic relief of ischemia resistant to other drugs in ACS

Question 20

What are the potential effects of this ‘late’ Na+ current?

Answer 20

• excess Na+ may cause abnormally high diastolic ventricular wall tension and stiffness by excess Na+ efflux and Ca influx which keeps myofilaments contracted
• inc tension/stiffness inc O2 consumption, compresses intramural small vessels

Question 21

What 4 agents decrease oxygen demand?

Answer 21

Dec HR, contractility, preload, after load

Question 22

What are the 3 ACS?

Answer 22

Unstable angina, NSTEMI, STEMI

Question 23

What differentiates stable and variant angina?

Answer 23

• stable is initiated by exercise and terminated by rest

- variant is neither initiated by exercise not terminated by rest = due to sudden construction of CA

Question 24

What is the most useful anti-ischemic drugs for ACS?

Answer 24

Metoprolol (BB)

Question 25

Which ischemic disease is not helped by BB?

Answer 25

Variant angina - BB don’t relax vasospasms

Question 26

What is the usual DOC for stable angina prophylaxis?

Answer 26

BB

Question 27

BB dose should be adjusted to achieve a HR range of:

Answer 27

55-60

Question 28

Why are CCB’s the DOC for prophylaxis of variant angina?

Answer 28

Direct vasodilator and drug free periods aren’t necessary like with the nitrates

Question 29

What kind of vasodilators are CCB’s?

Answer 29

Arteriolar - cause more edema than balanced vasodilators because there is increased capillary pressure

Question 30

Which drug is as effective as BB’s but has minimal effects on hemodynamics?

Answer 30

Ranolazine

Question 31

When and how is ranolazine used?

Answer 31

• when traditional therapies are ineffective

- in combination with dihydro’s, BB’s, or nitrates

Question 32

What are two drug interactions of ranolazine?

Answer 32

• CYP3A inhibitors increase plasma levels (diltiazem, verapamil)
• Ranolazine inc plasma levels of P glycoprotein substrates (digoxin)

Question 33

Two common AE’s? One uncommon AE? Potential arrhythmic AE?

Answer 33

• dizziness and constipation
• syncope
• blocks cardiac K+ channels and prolongs QT (but studies show it has a novel arrhythmic effect)

Question 34

Two vasodilator classes for IHD Tx?

Answer 34

CCB’s and nitrates