Lecture 31: Angina and Hypertension Drugs Flashcards
Drugs used to treat angina (classes, 4)
Nitrates, Ca2+ channel blockers, beta blockers, late Na+ channel blocker
Drugs used to treat HT (classes, 7)
Diuretics, ACEis etc, Ca2+ channel blockers, beta blockers, alpha blockers, combo beta and alpha blockers, alpha agonists, other vasodilators
What is the primary goal of pharmacological treatment of angina. What three things determines this?
Decrease mycoardial oxygen demand (ventricular wall stress, heart rate, contractility)
What determines ventricular wall stress?
Afterload (AS/HTN), preload (volume), ventricular wall thickness
Three key nitrates
Nitrogylcerin, isosorbide dinitrate, nitroprusside
Nitrates: mechanism
Nitrates release NO –> cGMP –> dephosphorylation of myoslin light chain phosphate –> relaxation
What vessels do nitrates dilate? And what does this all do?
Veins (decrease preload) > arteries (decrease afterload, may help increase coronary flow) > arterioles (decrease afterload)
How can nitrates affect the HR?
Reflex tachycardia
Primary clinical indication for nitrates
Angina
What nitrate can be used in hypertensive emergency
Nitroprusside
Besides tachycardia, what other SEs do you get with nitrates?
Orthostatic hypotension, headache (vasodilationof meningeal artery)
Do not use nitrates with…why? Mechanism?
PDE-5 inhibitor (sildenafil) because they will cause PROFOUND hypotension; PDE inhibits cGMP –> GMP, so you get more cGMP –> MORE RELAXATION
Nitroprusside: PKs. What does this mean?
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
Prolonged nitrate use causes…How to avoid this?
Tolerance (tachyphylaxis); discontinue nitrate use for 8-12 hours/day
Two classes of Ca2+ channel blockers and associated drugs
Dihydropyridines (nifedipine, amlodipine); Non-dihydropyridines (dilitiazem, verapamil)
Ca2+ channel blockers: mechanism
Blocks VG L-type CA2+ channel –> less phosphorylated myosin light chain –> relaxation of SM
What vessels are dilated with Ca2+ channel blockers?
Aterioles and arteries (afterload reduction)
Do Ca2+ channel blockers affect preload?
Not really
Where else do Ca2+ channel blockers work?
Uterus, bronchi, gut
What’s important about non-dihydropyridines
More potent on cardiac L-type Ca2+ channels –> decrease cardiac contractility AND decrease HR (via affect on AV/SA node)
So, what are non-dihydropyridines heart affects?
Negative inotrope, dromotrope, chronotrope
What’s important about dihydropyridines?
Does not decrease cardiac contractility, but does cause greater vasodilation –> reflex tachycardia
Which dihydropyridines causes greater reflex tachycardia?
Nifedipine > amlodipine
Order HR affects of Ca2+ channel blockers
Fast –> slow: nifedipine –> amlodipine –> verapamil, diltiazem
Clinical indications of Ca2+ channel blockers
Angia, HTN, supraventricular tachycardia (for non-dihydropyridines)
Ca2+ channel blockers: SEs
Hypotension, edema (decreased renal perfusion –> aldosterone), constipation (gut relaxation)
Verapamil and diltiazem: SEs
Exacerbates CHF (decreae contractility), bradycardia
Nifedipine: SEs
Reflex tachycardia
Ranolazine: mechanism
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
Summarize the mechanism of Ranolazine and point out a cool effect
Keeps Ca2+ in cell NORMAL –> improves O2 consumption in ischemic cell; only effects ischemic cells!
Primary clinical indication for ranolazine
Stable angina
T/F: Does ranolazine affect BP?
Nope
Ranolazine: SEs
Prolongs QT interval (blocks IKr)
T/F: Ranolazine can cause torsades de pointes
Low risk due to balanced effect of IKr and late sodium current inhibition
Thiazides: mechanism
Inhibit NaCl symporter in distal convoluted tubule
Thiazides: SEs
Hypokalemia (same mechanism as furosemide), volme depletion, hypotension
Thiazides: clinical indications (2) and one note
Hypertension, edema (CHF, cirrhosis, renal failure/proteinuria); note: NOT AS GOOD AT EDEMA AS FUROSEMIDE
Other vasodilators
Hydralazine, minoxidil
Hydralazine: clinical indications and important note
Hypertension; in combination with isosorbide dinitrate decreased mortality in African American CHF patients
Hydralazine: SEs, including one rare one
Hypotension, reflex tackycardia, edema (from increased aldosterone), rare: drug-induced lupus erythematosus
Minoxidil: mechanism
Opens ATP-dependent K+ channels in arterioles –> K+ exits cell –> inhibition of VG Ca2+ channel –> decreased Ca2+ –> relaxation
Minoxidil affects what vessels?
Arterioles but NOT veins
Clinical indication of minoxidil and important note
Hypertension, but not 1st line due to SEs
Minoxidil: SEs
Hypotension, reflex tachycardia, edema (increased aldosterone), hypertrichosis
Because of tachycardia/edema, what do you use minoxidil in combination with? (2)
Beta-blocker and diuretic
