Lecture 31: Angina and Hypertension Drugs

Question 1

Drugs used to treat angina (classes, 4)

Answer 1

Nitrates, Ca2+ channel blockers, beta blockers, late Na+ channel blocker

Question 2

Drugs used to treat HT (classes, 7)

Answer 2

Diuretics, ACEis etc, Ca2+ channel blockers, beta blockers, alpha blockers, combo beta and alpha blockers, alpha agonists, other vasodilators

Question 3

What is the primary goal of pharmacological treatment of angina. What three things determines this?

Answer 3

Decrease mycoardial oxygen demand (ventricular wall stress, heart rate, contractility)

Question 4

What determines ventricular wall stress?

Answer 4

Afterload (AS/HTN), preload (volume), ventricular wall thickness

Question 5

Three key nitrates

Answer 5

Nitrogylcerin, isosorbide dinitrate, nitroprusside

Question 6

Nitrates: mechanism

Answer 6

Nitrates release NO –> cGMP –> dephosphorylation of myoslin light chain phosphate –> relaxation

Question 7

What vessels do nitrates dilate? And what does this all do?

Answer 7

Veins (decrease preload) > arteries (decrease afterload, may help increase coronary flow) > arterioles (decrease afterload)

Question 8

How can nitrates affect the HR?

Answer 8

Reflex tachycardia

Question 9

Primary clinical indication for nitrates

Answer 9

Angina

Question 10

What nitrate can be used in hypertensive emergency

Answer 10

Nitroprusside

Question 11

Besides tachycardia, what other SEs do you get with nitrates?

Answer 11

Orthostatic hypotension, headache (vasodilationof meningeal artery)

Question 12

Do not use nitrates with…why? Mechanism?

Answer 12

PDE-5 inhibitor (sildenafil) because they will cause PROFOUND hypotension; PDE inhibits cGMP –> GMP, so you get more cGMP –> MORE RELAXATION

Question 13

Nitroprusside: PKs. What does this mean?

Answer 13

Nitroprusside can be metabolized into CN, so LT use can cause cyanide poisoning, especially with renal failure; only use until a pt is OUT OF A HYPERTENSIVE EMERGENCY

Question 14

Prolonged nitrate use causes…How to avoid this?

Answer 14

Tolerance (tachyphylaxis); discontinue nitrate use for 8-12 hours/day

Question 15

Two classes of Ca2+ channel blockers and associated drugs

Answer 15

Dihydropyridines (nifedipine, amlodipine); Non-dihydropyridines (dilitiazem, verapamil)

Question 16

Ca2+ channel blockers: mechanism

Answer 16

Blocks VG L-type CA2+ channel –> less phosphorylated myosin light chain –> relaxation of SM

Question 17

What vessels are dilated with Ca2+ channel blockers?

Answer 17

Aterioles and arteries (afterload reduction)

Question 18

Do Ca2+ channel blockers affect preload?

Answer 18

Not really

Question 19

Where else do Ca2+ channel blockers work?

Answer 19

Uterus, bronchi, gut

Question 20

What’s important about non-dihydropyridines

Answer 20

More potent on cardiac L-type Ca2+ channels –> decrease cardiac contractility AND decrease HR (via affect on AV/SA node)

Question 21

So, what are non-dihydropyridines heart affects?

Answer 21

Negative inotrope, dromotrope, chronotrope

Question 22

What’s important about dihydropyridines?

Answer 22

Does not decrease cardiac contractility, but does cause greater vasodilation –> reflex tachycardia

Question 23

Which dihydropyridines causes greater reflex tachycardia?

Answer 23

Nifedipine > amlodipine

Question 24

Order HR affects of Ca2+ channel blockers

Answer 24

Fast –> slow: nifedipine –> amlodipine –> verapamil, diltiazem

Question 25

Clinical indications of Ca2+ channel blockers

Answer 25

Angia, HTN, supraventricular tachycardia (for non-dihydropyridines)

Question 26

Ca2+ channel blockers: SEs

Answer 26

Hypotension, edema (decreased renal perfusion --> aldosterone), constipation (gut relaxation)

Question 27

Verapamil and diltiazem: SEs

Answer 27

Exacerbates CHF (decreae contractility), bradycardia

Question 28

Nifedipine: SEs

Answer 28

Reflex tachycardia

Question 29

Ranolazine: mechanism

Answer 29

Late Na+ current inhibitor; in ischemia causes prolonged activation of late Na+ current --> high Na+ in cell --> NCX FLIPS --> high Ca2+ in cell --> myocyte dysfunction and increased O2 demand

Question 30

Summarize the mechanism of Ranolazine and point out a cool effect

Answer 30

Keeps Ca2+ in cell NORMAL --> improves O2 consumption in ischemic cell; only effects ischemic cells!

Question 31

Primary clinical indication for ranolazine

Answer 31

Stable angina

Question 32

T/F: Does ranolazine affect BP?

Answer 32

Nope

Question 33

Ranolazine: SEs

Answer 33

Prolongs QT interval (blocks IKr)

Question 34

T/F: Ranolazine can cause torsades de pointes

Answer 34

Low risk due to balanced effect of IKr and late sodium current inhibition

Question 35

Thiazides: mechanism

Answer 35

Inhibit NaCl symporter in distal convoluted tubule

Question 36

Thiazides: SEs

Answer 36

Hypokalemia (same mechanism as furosemide), volme depletion, hypotension

Question 37

Thiazides: clinical indications (2) and one note

Answer 37

Hypertension, edema (CHF, cirrhosis, renal failure/proteinuria); note: NOT AS GOOD AT EDEMA AS FUROSEMIDE

Question 38

Other vasodilators

Answer 38

Hydralazine, minoxidil

Question 39

Hydralazine: clinical indications and important note

Answer 39

Hypertension; in combination with isosorbide dinitrate decreased mortality in African American CHF patients

Question 40

Hydralazine: SEs, including one rare one

Answer 40

Hypotension, reflex tackycardia, edema (from increased aldosterone), rare: drug-induced lupus erythematosus

Question 41

Minoxidil: mechanism

Answer 41

Opens ATP-dependent K+ channels in arterioles --> K+ exits cell --> inhibition of VG Ca2+ channel --> decreased Ca2+ --> relaxation

Question 42

Minoxidil affects what vessels?

Answer 42

Arterioles but NOT veins

Question 43

Clinical indication of minoxidil and important note

Answer 43

Hypertension, but not 1st line due to SEs

Question 44

Minoxidil: SEs

Answer 44

Hypotension, reflex tachycardia, edema (increased aldosterone), hypertrichosis

Question 45

Because of tachycardia/edema, what do you use minoxidil in combination with? (2)

Answer 45

Beta-blocker and diuretic