Pharmacology - Ischemic Heart Disease (IHD) Flashcards
angina pectoris meaning
how can it be divided?
chest pain bc of accumulation of metabolites due to ischemia of the heart
classic/effort
unstable/ACS
vasospastic/prinzmetal
acute coronary syndrome (ACS) can also be called ___ angina
unstable angina (pain at rest)
what is preload and afterload
preload - the left ventricular end diastolic volume (how much blood in left ventricle after filling)
afterload - systemic vascular resistance
if O2 demand is greater than O2 supply, what condition is this?
ischemia
name 4 factors contributing to O2 demand
heart rate
contractility
preload
afterload
name 2 factors contributing to O2 supply
the coronary blood flow and regional myocardial blood flow
name drug agents that decrease oxygen demand
name 2 that work on decreasing HR and contractility and 2 others
beta blockers and SOME calcium channel blockers (verapamil and diltiazem) work on the HR and contractility
others are organic nitrates and calcium channel blockers (dihydropyridines)
name 3 agents that increase oxygen supply and improve coronary flow
vasodilators (esp ca channel blockers)
statins
antithrombotics
non-medication option for CAD (coronary artery disease)
bypass surger/angioplasty/stent
name 4 classes of drugs that can be used for CAD (ischemic heart disease)
antianginals
antiplatelets
statins
antihypertensives
can diet and smoking cessation help with CAD/IHD
yes
name 3 particular kinds of antihypertensives that can be used to treat CAD/IHD
ace inhibitors/ARBS
beta blockers
name 2 new drugs (not part of a class) that can sometimes be used for CAD
ranolazine
ivabradine
name 4 nitrate/nitrite drugs that can be used for CAD
amyl nitrite
isosorbide dinitrate
isosorbide mononitrate
nitroglycerin
explain the MOA of anti anginals in CAD/IHD
they decrease the myocardial oxygen requirement by decreasing the major determinants of O2 demand (ie - heart size/HR/BP/contractility)
in some patients, nitrates and calcium channel blockers have what additional benefit
they not only decrease the O2 demand, but in some pts they cause a redistribution of coronary flow and increase O2 DELIVERY to ischemic tissue
ALSO they can be used in variant angina to increase O2 delivery by reversing coronary artery spasm!
name the 2 types of drugs that can be used in variant angina by increasing myocardial O2 delivery by reversing coronary artery spasm
nitrates and calcium channel blockers
3 MOLECULAR mechanisms of antianginals
increased cAMP
decreased intracellular calcium
stabilize/prevent depolarization of smooth muscle membrane
NOTE - ONLY WORK ON SMOOTH MUSCLE !! NOT HEART
How are nitrates stored
in tightly closed glass containers
TRUE OR FALSE
all nitrates are prodrugs
true!!!
they all must be metabolized (reduced) to produce gaseous NO
which 2 nitrates have very high first pass metabolism and thus their oral bioavailability is low
nitroglycerin and isosorbide dinitrate
bc the liver inactivates the drug with its high-capacity organic nitrate reductase
true or false
nitroglycerin given sublingually bypasses its extensive first pass metabolism
TRUE
will go to heart before the liver
true or false
nitroglycerin is not available in an ointment
false - it is
true or false
sublingual nitroglycerin has a long peak plasma time and a short half life
FALSE – has a very fast peak plasma time of 5 mins and a short hald life of 3 mins
true or false
sublingual nitroglycerin has very fast action, but the effects do not last long
true
is the metabolite of nitroglycerin active
yes - but not nearly as active as original molecule
which is only used for prevention and why - isosorbide mononitrate or isosorbide dinitrate
isosorbide mononitrate
has too slow of an onset to be used acutely.
true or false
isosorbide mononitrate has no significant first pass metabolism and has a pretty long half life
TRUE
5-6 hour half life
true or false
isosorbide dinitrate takes a long time to work
FALSE - only takes 6 mins
metabolites give sustained action
true or false
isosorbide dinitrate has high first pass metabolism
true
why is amyl nitrite not really used
smalls bad - and its vapor form to sniff it in
also, short duration of action
how is amyl nitrite excreted
glucuronidation
explain the molecular MOA of nitrates
produced from arginine. through endothelial NO synthase enzyme
NO is a gas and easily diffuses through the endothelial membrane and into SMOOTH MUSCLE CELLS (NOT CARDIAC)
NO activates guanylyl cyclase. guanylyl cyclase makes cGMP
cGMP is a secondary messenger which activates protein kinase G
protein kinase G DEPHOSPHORYLATES myosin-light chain
the dephosphorylated myosin light chain allows for RELAXATION OF SMOOTH MUSCLE CELLS
explain why PDE inhibitors cannot be taken with nitrates
both of them increase cGMP which relaxes smooth muscle WAY TOO MUCH — hypotension liability
true or false
phosphorylated myosin light chain causes smooth muscle contraction
TRUE
what enzyme converts nitroglycerin into nitrate + NO gas
aldehyde dehydrogenase
true or false
nitrates ACTIVATE myosin light chain phosphatase
true - causes smooth muscle relaxation
true or false
nitrates have NO EFFECT on cardiac and skeletal muscles
TRUE - ONLY SMOOTH
true or false
nitrates relax the ENTIRE vascular system - both arteries and veins
true
but have less effect on arterioles and precapillary sphincters
do nitrates have any effect on the heart?
they dont act directly on the heart, but they decrease preload by relaxing veins and increasing capacitance (ability to hold blood without increasing BP)
how do nitrates help ischemic regions
they redistribute coronary flow to ischemic regions
name the NEGATIVE EFFECTS of nitrates
the body’s reflex responses are not very good
cause reflex tachycardia and increased heart contraction – also salt and water retention - to account for the decreased blood pressure
effect of nitrates at TOXIC doses
what is the cure
methemoglobinemia
methylene blue – replaces cyanide from hemoglobin - can reverse
effect of nitrates on platelets
is this good or bad
the increase in cGMP decreases platelet aggregation
this is good in ischemic heart disease patients!
how are nitrates beneficial in each type of angina
classic - reduced oxygen demand reliefs symptoms
unstable - decreased oxygen demand and dilates the coronary arteries
prinzmetal/variant - relieves coronary artery spasm and relaxes coronary arteries
true or false
nitrates can only be used in classic angina
false - all types
which form of nitroglycerin has the fastest onset, but lowest duration
sublingual nitroglycerin
name some side effects of nitroglycerin
headache
hypotension–potential syncope
reflex tachycardia
tolerance!!
“monday disease”
which dosage form of nitroglycerin has the slowest onset
transdermal
true or false
nitroglycerin has high first pass metabolism
true
true or false
isosorbide dinitrate has the same MOA as nitroglycerin
true
true or false
the metabolite of isosorbide dinitrate is inactive
FALSE - active!!
1 of the metabolites is the mononitrate
true or false
isosorbide dinitrate is rarely used today
true - except for sublingual dosage form. bc high tolerance
rank the following according to their tolerance
isosorbide dinitrate
isosorbide mononitrate
nitroglycerin
highest tolerance - nitroglycerin
isosorbide dinitrate
lowest tolerance - isosorbide mononitrate
true or false
isosorbide dinitrate has longer sublingual coverage than nitroglycerin
true
true or false
isosorbide mononitrate has high tolerance liability
FALSE - low tolerance liability
bypasses 1st pass metabolism
true or false
isosorbide mononitrate bypasses 1st pass metabolism
true
___ is a metabolite of ___
isosorbide mononitrate is a metabolite of isosorbide dinitrate
is isosorbide mononitrate used acutely?
NO
as a prophylactic - not during an angina attack
**caution for all nitrates
do not use with sildenafil!!!!!! (or others in category)
can cause severe hypotension, fantining, or myocardial ischemia
too much vasodilation!!!
some SE of isosorbide mononitrate
similar to nitroglycerin - flushing, reflex tachycardia, fainting
also some respiratory effects like bronchitis, pneumonia
true or false
sublingual nitroglycerin is for acute attack and prevention ONLY
true
which dosage forms of nitroglycerin are used prophylactically
long acting dosage forms - ie - po, patch
when should nitrates be discarded after opening
6 months
what is the phenylalkyl amine calcium channel blocker?
what is the benzothiazepine calcium channel blocker?
phenylalkyl amine - verapamil
benzothiazepine - diltiazem
Explain the MOA of calcium channel blockers
NORMALLY - calcium gets into the cell through a channel.
calcium forms a complex with calmodulin.
myosin light chain kinase is activated
myosin light chain is phosphorylated
this allows for contraction
CALCIUM CHANNEL BLOCKERS BLOCK THIS PROCESS BY PREVENTING CALCIUM FROM GETTING INTO THE CELL THROUGH THE CHANNEL
which has more effect on decreasing cardiac contractility and decreasing SA and AV node conduction - verapamil or diltiazem
verapamil
BOTH have much more effect on the heart than dihydropyridines
true or false
nondihydropyridines increase cardiac contractility
FALSE - decrease
true or false
nondihydropyridines AND dihydropyridines all cause vasodilation
TRUE - dihydropyridines just cause the most
are calcium channel blockers indicated for angina
yes
what type of calcium channels do CCB’s block
in which muscle are they found
L-type voltage gated
found in cardiac, skeletal, and smooth muscle
(DHP only act on smooth muscle and non DHP act on cardiac and smooth)
true or false
calcium is a trigger for contraction in BOTH cardiac and smooth muscle
true
true or false
calcium channel blockers inhibit calcium influx
true
calcium channel blockers have negative ____ effects on the heart
inotropic
***what region of the calcium channel do calcium channel blockers bind at
a1 subunit
***explain HOW calcium channel blockers bind to the channel
block FROM THE INSIDE, and only in OPEN and INACTIVATED states
does NOT block when the channel is closed or gated
effect of calcium channel blockers (in general) on:
-smooth muscle
-the heart
smooth muscle - long-lasting relaxation
heart - negative chronotropic, ionotropic, and dromotropic effects
which is more sensitive to relaxation by calcium channel blockers - arterioles or veins
arterioles are more sensitive - relax more
**true or false
dihydropyridines have greater vascular effects than cardiac
true
**true or false
verapamil/diltiazem have a similar effect on both vessels AND the heart
true
action on heart is major tho
true or false
dihydropyridines directly inhibit SNS activation of the heart
false - nondihydropyridines
true or false
both dihydropyridines and nondihydropyridines increase cardiac output
true
