14. Chronic ischemia Drugs

Question 1

Nitrates IG are vasodialator but have most effect on:

Answer 1

venous blood vessels

Question 2

Mech of action of nitrates

Answer 2

Become denitrated in Smooth muscle–> free nitrate converts to NO
NO–> activate GC which increases cGMP
cGMP–> activates cGMP protein kinase (PKG)
PKG phosphoylates stuff leading to decreased Ca and dephosphorylation of myosin

Question 3

How do nitrates affect preload

Answer 3

Increase venous capacitance to DECREASE preload
this reduces diastolic wall tension thus Oxygen deman
Decreased preload has small increase in subendo blood flow

Question 4

What effect do nitrates have on afterload?

Answer 4

SMALL REDUCTION to afterload or small reduciton in systemic atrial pressure
see reduction in systolic wall tension
slight reflex tachycardia

Question 5

When are nitrates valuble as a coronary dialator?

Answer 5

if ischemia is dt vasospasm… not so much is pt has angina with maximal dilation d/t accumulation of local metabolites

Question 6

How are nitrates activated?

Answer 6

by organic nitrate reductase in the liver: low bioavailability d/t 1st pass effect

Question 7

What form of nitrate is biologically active?

Answer 7

Mononitrate: doesn’t need to be metabolized while isosorbide dinitrate gets metabolized in liver–> mono form

Question 8

How can we acheive high conc of nitrates rapidly?

Answer 8

sublingual to avoid 1st pass affect; last 30 mins or so

Question 9

Can we use nitrates for chronic angina?

Answer 9

yes, provides prophylaxsis against angina episodes

Question 10

Nitrate with no first pass metabolism and 1/2 life of 5 hours

Answer 10

mononitrate

Question 11

has 25% bioavailability with longer DOA (4-6hrs) and metabolized to be active

Answer 11

dinitrate

Question 12

Nitrate that is orally controlled release tabs/capsules and available as patch and ointment/paste applied to skin

Answer 12

Nitroglycerin

Question 13

Do pts devo tolerance to nitrates?

Answer 13

yes; if used constantly w/in in a few hours, but rapid reversal…. limits how effective slow release forms are so use small dose and schedule nitrate free period

Question 14

Adverse effects of nitrates

Answer 14

headache, hypotension, reflex tachycardia, flushing

Question 15

Why are beta blockers recommended for IHD?

Answer 15

have anti-anginal effect by reducing oxygen demand dt decrease force of ventricular cnx and HR; because blocks effects of catecholamines on B1 receptors

Question 16

Propanolol and timolol are examples of

Answer 16

non-selective B blockers

Question 17

metoprolol and atenolol are examples of

Answer 17

selective B1 antagonists

Question 18

when are B blockers ineffecient at tx angina?

Answer 18

when its dt vasospasm (use nitroglycerin!)

Question 19

How do Beta blockers decrease oxygen demand in an ischemic heart?

Answer 19

Decreases HR, decreases contractility, decreases BP (afterload)

Question 20

Do Beta blockers help increase oxygen to ischemic areas?

Answer 20

a little– they slow the HR so that heart spends more time in diastole thus longer time in coronary perfusion

Question 21

When we have decreased CO we can have ______ prelaod that can lead to _______ wall tension

Answer 21

increased

increased

Question 22

Can we use B blockers in patients with COPD?

Answer 22

NOPE

Question 23

Pt comes in with IHD and you recommend he be treated with a Beta Blocker. Pt has:
elevated LDL
family hx of HTN
heart block
insulin-tx diabetes
Which of these prevents you from tx with beta blockers?

Answer 23

Insulin dependent diabetes and heart block (as well as bradycardia) are contraindicated for Beta Blocker

Question 24

Nifedipine and Amlodipine are examples of:

Answer 24

Dihydropyridine Ca+ channel blockers

Question 25

Verapamil and Diltiazem are examples of:

Answer 25

Non-dihydropyridine Ca+channel blockers

Question 26

Which are more potent vasoD; non-dihydropyridine or dihydropyridine

Answer 26

dihydropyridine: such as nifedipine and amlodipine

Question 27

How do dihydropyridine (nifedipine and amlodipine) relieve ischemia?

Answer 27

Decrease O demand via vasoD which will decrease Afterload thereby reducing wall stress

Question 28

What channel blockers are potent agents for relief of vasospasm?

Answer 28

Nifedipine or amlodipine

Question 29

Nondihydropyridine; verapamil or diltiazem relieve ischemia by:

Answer 29

decreasing O demand by reducing force of contraction and heart rate

Question 30

Which drug works by decreasing O demand by reducing force of contraction and heart rate

Answer 30

Nondihydropyridine; verapamil or diltiazem

Question 31

What negative effects are seen in all Ca+channel blockers?

Answer 31

headache and flushing

Question 32

Constipation is a side effect seen in which Ca+ blocker

Answer 32

Verapamil

Question 33

Which Ca+ blockers cause Edema the worse

Answer 33

Nifedipine and diltiazem

Question 34

Which Ca+ blocker cause bradycardia and decrease contractility?

Answer 34

verapamil and diltazem

Question 35

What benefits do we see from combinding a nitrate with a Beta Blocker?

Answer 35

Beta blocker prevents potential reflex increase in HR and contractility produced by nitrates Nitrates prevent the potential increase in wall tension from beta blockers

Question 36

What do we need to be worried about when combinding a Beta blocker with Verapamil or Diltiazem Ca+ channel blocker?

Answer 36

additive negative inotropic effect can cause excessive cardiodepression

Question 37

How does RANOLAZINE work?

Answer 37

anti-ischemic tx; decreases frequency of anginal episodes and increases exercise capacity: but no effect on HR via vasodialation Its works to inhibit late Na current in cardiac myocytes

Question 38

Which anti-ischemic tx works to inhibit late sodium current in cardiac myocytes

Answer 38

Ranolazine