Anti-Ischemic Medications

Question 1

what affects myocardial O2 supply?

Answer 1

carrying capacity (hemoglobin content and pulmonary O2 supply)
coronary flood flow volume

Question 2

What modulates coronary blood flow volume?

Answer 2

coronary artery perfusion pressure, compressive forces on coronary artery and intrinsic coronary artery resistance

Question 3

what is the coronary blood flow volume at its max?

Answer 3

ventricular diastole

Question 4

what is the key mediator of coronary blood flow?

Answer 4

NO messenger system at R2

Question 5

what are some key features of NO?

Answer 5

potent arteriolar and venodilator
produced by the endothelium from L-arginine thru activation of eNOS.
diffuses across endothelium and triggers vascular smooth muscle cell relaxation (converts GTP to cGMP) via enzyme guanylate cyclase which decreases Ca2+ concentration

Question 6

what causes increase in demand?

Answer 6

increased HR, contractility and wall stress

Question 7

what effects myocardial O2 consumption?

Answer 7

HR and SBP

Question 8

how do beta blockers work to treat myocardial ishcemia?

Answer 8

B1 adrenergic receptors normally activate Gs –> increased cAMP –> activate L-type Ca2+ channels –> Ca2+ induced Ca2+ channel release from SR –> increased contractility and O2 consumption
Blocking this prevents O2 consumption

Question 9

Laplace law

Answer 9

wall stress = (LVP X LV radius)/2h

h = myocardial wall thickness

Question 10

what are the different categories of anti-ischemic medications?

Answer 10

nitrates
beta-adrenergic receptor antagonists
Ca2+ channel antagonists

Question 11

where are B1 receptors located?

Answer 11

SA node, AV node, His-Purkinge, myocardium, JG apparatus, adipocytes

Question 12

What does stimulation of B1 receptors do?

Answer 12

increased contractility and O2 consumption

Question 13

Where are B2 receptors located?

Answer 13

peripheral and coronary vasculature, bronchi, peripheral muscle, uterine muscle

Question 14

what does stimulation of B2 receptors do?

Answer 14

dilation of peripheral vasculature and relaxation of pulmonary bronchioles

Question 15

what does antagonism of B2 receptors do?

Answer 15

claudication in patients with peripheral vascular disease, coronary vasospasm in patients with vasospastic angina and bronchospasm in patients with reactive airway disease (asthma)

Question 16

where are alpha receptors located?

Answer 16

peripheral circulation

Question 17

what does stimulation of alpha receptors do?

Answer 17

vasoconstriction

Question 18

what does blocking alpha receptors do?

Answer 18

vasodilation and decreased afterload

Question 19

what are some properties of beta blockers?

Answer 19

cardioselectivity –> block beta1 specifically, unless high dose
intrinsic sympathomimetic activity - weak beta agonist that block affects from more potent endogenous catecholamines
alpha adrenoreceptor blocking activity

Question 20

what is the usefulness of the alphaadrenoreceptor blocking activity of alpha receptors?

Answer 20

prevents unopposed receptor stimulation, treats hypertension, and increases survival in LV systolic dysfunction

Question 21

what are the adverse effects of nitrates?

Answer 21

Headache and flushing
Hypotension
Hypoxemia
Contraindicated with sildenafil
Methemoglobinemia

Question 22

what is nebivol?

Answer 22

3rd gen beta block (D isomer)
NO donor (L isomer)
cardioselective

Question 23

lipophillic drugs characteristics

Answer 23

metabolized by the liver with short t1/2 and crosses BBB

Question 24

hydrophillic drug characteristics

Answer 24

metabolized by the kidney with long t1/2 and does not cross BBB

Question 25

what are the adverse effects of beta blockers?

Answer 25

``` CNS effects Conduction abnormalities CHF Peripheral vascular disease Exacerbation of insulin associated hypoglycemia ```

Question 26

What is the mechanism of action of nitrates?

Answer 26

mitochondrial aldehyde dehydrogenase converts nitrates to NO (sulfhydryl group)

Question 27

What are the effects of low dose nitrates?

Answer 27

low dose - venodilation, decreased preload, myocardial wall tension, myocardial O2 demand

Question 28

what are the effects of high dose nitrates?

Answer 28

arterial vasodilation, which increases blood supply by recruiting collaterals

Question 29

what are contraindications for nitrates?

Answer 29

PDE inhibitors because it can lead to hypotension

Question 30

What is the metabolism of nitrates?

Answer 30

hepatic

Question 31

what are the categories of calcium channel antagonists?

Answer 31

dihydropyridines benzothiazepines phenylalkylamine

Question 32

what are adverse effects of calcium channel antagonists?

Answer 32

``` Hypotension Exacerbation of CHF Conduction abnormalities Edema Gastrointestinal Gingival hyperplasia Increase in cardiovascular mortality? ```

Question 33

what are dihydropyridines?

Answer 33

they are potent vasodilators with little effect on SA node function but may cause reflex tachy cardia the second generation are more vasoselective

Question 34

How do beta blockers with intrinsic sympathomimetic activity drugs compare to those without ISA?

Answer 34

less bradycardia and negative inotropic effect at rest, attenuates exercise induced increases in HR and myocardial contractility may increase mortality in patients with CAD, therefore not first line

Question 35

how do non-dihydropyridines compare to dihydropyridines?

Answer 35

more potent effect on sinus and AV nodal calcium channel recovery --> more pronounced negative chronotropic and dromotropic effects on cardiac conduction system --> symptomatic sinus bradycardia and AV nodal blockade

Question 36

what are benzothiazepines?

Answer 36

diatiazem effect sinus and AV node CA2+ channel recovery --> decreased chronotropic and dromotropic effects --> symptomatic sinus bradycardia + AV blockade can use with beta blocker and monitor HR and PR interval

Question 37

Phenylalkylamine

Answer 37

more potent effects on sinus and AV node Ca2+ channel recovery --> more decreased chronotropic and dromotropic effects DO NOT use with beta blocker --> increased risk of heart block monitor HR and PR interval

Question 38

how are calcium channel antagonists metabolized?

Answer 38

hepatically except for diltiazem which is hepatically metabolized and renally excreted

Question 39

what drugs increase the bioavailability of Ca2+ channel antagonists?

Answer 39

cimetidine (H2 blocker) phenytoin, carbamezapine

Question 40

what drug interaction does diltiazem have?

Answer 40

with verapamil it increases bioavailability of cyclosporine

Question 41

what drug interaction does verapamil have?

Answer 41

increases serum digoxin and with diltiazem it increases bioavailability of cyclosporine

Question 42

what is ranolazine?

Answer 42

its an anti-ischemic drug that may shift metabolism in ischemic myocyte from energy inefficient fatty acid oxidation to glucose metabolism to decrease myocardial O2 demand decrease myocardial oxygen demand thru prevention of intracellular Ca overload and improvement in diastolic relaxation and wall tension.

Question 43

adverse effects of ranolazine

Answer 43

QT prolongation and torsades de pointes

Question 44

what is the metabolism of ranolazine?

Answer 44

CYP3A (liver)

Question 45

what are some recommendations of ranolazine use?

Answer 45

Contraindicated in pts with liver disease. Do not use with strong CYP3a inhibitors. Modify dose with moderate CYP3a inhibitors. Modify dose with CKD. Can increase serum digoxin levels.

Question 46

what is the first line drug for myocardial ischemia?

Answer 46

beta blockers without ISA