Angina

Question 1

classes of drugs to treat stable angina

Answer 1

Nitrates: venodilation thereby decreasing preload and
thus the oxygen demands of the heart; some dilation of
coronary vessels to increase oxygen delivery
2. B-blockers: decrease the oxygen demands of the heart
3. Ca++ channel blockers: cause vasodilation of smooth
muscle in peripheral vasculature to decrease the oxygen
demands of the heart; dilation of coronary vessels to
increase oxygen delivery

Question 2

classes of drugs to treat variant angina

Answer 2

1. Nitrates: relaxation of coronary vessels and reducing
   spasm
2. CCBs: relaxation of coronary vessels and reducing spasm

Question 3

drugs to treat unstable angina

Answer 3

aspirin
heparin (IV)
nitroglycerin & B blockers
CCB

Question 4

Other Therapies Commmonly Used in Angina Patients

Answer 4

Prior MI = use -blockers

Diabetes = add ACEI

All patients with CAD and LDL > 130 = use “statins”

Antiplatelet drugs: Aspirin (alternative is clopidogrel or prasugrel)

Question 5

Organic Nitrates

Answer 5

Nitroglycerin

Isosorbide mononitrate and isosorbide dinitrate

Question 6

Nitroglycerin use

Answer 6

DOC for prompt relief of an ongoing angina attack; prophylaxis of stable or vasospastic angina

Question 7

Nitroglycerin action

Answer 7

relaxes vascular smooth muscle by intracellular conversion to nitrite ions and then to nitric oxide (NO); NO activates guanylyl cyclase which increases cGMP; elevated cGMP ultimately leads to dephosphorylation of the myosin light chain resulting in vascular smooth muscle relaxation; veins tend to respond at a lower concentration than arteries

Question 8

Nitroglycerin effects on the CV system

Answer 8

1) at moderate to high doses, dilation of the large veins, resulting in pooling of blood in the veins; this diminishes preload (venous return to the heart) and reduces the work of the heart; 2) at all doses, dilation of coronary vasculature providing increased blood supply to the heart muscle

Question 9

Nitroglycerin pharmacokinetics

Answer 9

very rapid (2 min.) onset of action when given sublingually; transdermal patch for prophylaxis

Question 10

Nitroglycerin adverse

Answer 10

most common effect of all the nitrates is headache; reflex tachycardia; orthostatic hypotension

Question 11

Nitroglycerin tolerance

Answer 11

(tachyphylaxis): tolerance to the actions of nitrates develops rapidly and is overcome by a daily “nitrate-free interval” to restore sensitivity to the drug (usually 6-8 hrs at night when there is decreased demand on the heart); nitroglycerin patches are worn for 12 hours and removed for 12 hours; in patients with variant angina, their angina worsens early in the morning perhaps due to circadian catecholamine urges so their nitrate-free interval should be late afternoon

Question 12

Isosorbide mononitrate and isosorbide dinitrate info

Answer 12

therapeutic use: prevention of angina attacks
mechanism of action: same as for nitroglycerin
. cardiovascular effects: same as for nitroglycerin
pharmacokinetics: much longer onset of action and longer duration of action than nitroglycerin; given orally
adverse effects: same as for nitroglycerin
. tolerance: same as for nitroglycerin

Question 13

Organic Nitrates

work place

Answer 13

there can be continuous exposure to nitrates in the chemical industry (explosives)
when contamination of the workplace with volatile organic nitrate compounds occurs, workers find that upon starting their work week (Monday), they suffer headache and transient dizziness
after a day or so these symptoms disappear
What is happening?
tolerance

Question 14

Organic Nitrates dependence

Answer 14

an even more serious hazard of industrial exposure is the development of dependence
after months or years of exposure, the workers may develop variant angina during the weekend (away from the nitrates)

Question 15

Organic Nitrates drug interactions

Answer 15

Nitrates + phosphodiesterase 5 inhibitors
(sildenafil, vardenafil, tadalafil); erectile dysfunction is frequently seen in people with risk factors parallel to those of coronary artery disease; taking nitrates and PDE 5 inhibitors at the same time can result in extreme hypotension and death

Question 16

B-Adrenergic Blockers use & MOA

Answer 16

use: stable angina; not vasospastic
Mechanism of action: relieve angina by modifying sympathetic tone and thereby reducing heart rate and cardiac contractility; the specific mechanism is blockade of 1 receptors; these drugs reduce the frequency and severity of angina attacks

Question 17

B blockers drugs

Answer 17

propranolol, metoprolol, atenolol are useful in angina treatment; drugs with intrinsic sympathomimetic activity (partial agonists) such as pindolol, and maybe acebutolol, are less effective

Question 18

which reduce mortality in pts w stable angina

Answer 18

Beta blocker, nitrates, and aspirin
have been shown to reduce mortality in patients
with stable angina.

Question 19

CCB use & MOA

Answer 19

use: stable or vasospastic angina
Mechanism of action: these drugs interfere with Ca++ influx required for excitation-contraction coupling in smooth and cardiac muscle, resulting in vasodilation; the net effect is reduction in systemic vascular resistance, reduction in coronary vasospasm, and decreased myocardial oxygen demand

Question 20

CCB drugs

Answer 20

verapamil, diltiazem, and all the dihydropyridines

Question 21

what treats raynaud’s

Answer 21

CCBs are also useful for Raynaud’s phenomenon, a condition

associated with vasospasm and cold extremities

Question 22

Ranolazine use & MOA

Answer 22

use: adjunct to other standard therapies
Mechanism of action: not fully understood (does not reduce
HR or BP) metabolic modifier (changes in cardiac metabolism)

Question 23

Ranolazine adverse

Answer 23

prolongs the QT interval (may cause torsades)