Exam 1 - Wendt (Ischemia) Flashcards
Angina Pain occurs when there is decreased ________ or increased _________
decreased coronary blood flow
increased oxygen consumption
what things my lead to decrease coronary blood flow
blockages (vasospasm, fixed stenosis, thrombus)
what things may lead to increased oxygen consumption
increased heart rate
increase contractility
increased afterload
increased preload
what are the risk factors for angina pectoris
- age (> 55 - men; > 65 - women)
- cigarette smoking
- diabetes
- HTN
- Kidney disease
- obesity
- sedentary lifestyle
Preload is seen as a _______ vs Afterload is _______
Preload - volume
afterload - pressure/force
Preload _______ when veins are dilated
decreased
Afterload is _______ when arteries are dilated
decreased
preload decreases when _____ are dilated
veins
afterload decreases when ______ are dilated
arteries
Pre-Load or After-Load: Which one (when decreased) will cause an increase in myocardial perfusion
Preload
What are the 3 hemodynamic factors that influence the O2 supply/demand ratio
Preload
afterload
Heart rate
Chronotropic or Inotropic?
will change heart rate or rhythm
chronotropic
Chronotropic or Inotropic?
will change the strength of contractility
Inotropic
3 types of angina?
- Printzmetal;s/Variant Angina (Vasospasm)
- Chronic Stable Angina (fixed stenosis)
- Unstable Angina (thrombus)
which angina is known as vasospasm
Printzmetal/Variant Angina
when does printzmetal usually occur
night/at rest
which angina is known as fixed stenosis
chronic stable angina
which angina is known as thrombus
unstable angina
which angina is known as supply ischemia
vasospasm/printzmetal/variant
AND
unstable/thrombus
which angina is known as demand ischemia
chronic stable ischemia
which angina is an emergency
unstable/thrombus… (possible MI on the way)
which angina is normally occurring during exertion/after eating/due to heightened emotional states
chronic/stable
2 main causes of Stable/Classic Angina
- Atherosclerosis
- Chronic yet stable obstruction of coronary arteries
With Stable/Classic Angina - the ____ demand exceeds supply due to inadequate _______
O2; perfusion
What commonly triggers vasospasm/printzmetal/variant angina
atherosclerotic damage to endothelium
What agents are used to increase O2 Supply (general terms/drug classes)
vasodilators (CCBs and nitrodilators)
statins
antithrombotics (antiplatelets and anticoagulants)
What agents are used to decrease O2 demand (general terms/drug classes)
Beta adrenergic antagonists
Ca2+ entry blockers
Organic nitrates
HCN channel inhibitor
Treatment Goals for Angina:
Dilate coronary arteries
decrease O2 demand
decrease preload and afterload
MOA for Organic Nitrates:
the nitrates become NO (nitric oxide)
Activation of guanylate cyclase
Organic Nitrates:
dilate (arteries or veins?)
VEINS
very very very minor artery dilation…
Organic Nitrates:
decrease (preload or afterload)
preload (because they dilate veins)
How does NO lead to relaxation/dilation?
NO –> activates soluble GC –> GTP to cGMP –> increase activity of PKG (protein kinase G) –> activates MLCP (myosin light chain phosphotase) –> dephosphorylation of MLC/detachment of myosin from actin
NO has short or long half life – and why?
SHORT(bc high affinity for hemoglobin)
what are the nitrate compounds mentioned in lecture?
glyceryl trinitrate (GTN)
Isosorbide Mononitrate
Isosorbide Dinitrate
which nitrate is used strictly for attacks
GTN (glyceryl trinitrate)
which nitrate has the shortest half life?
GTN (~ 5 mins)
Bioactivation of organic nitrates occurs mainly by ______ in the ______ of target cells
ALDH2; mitochondria
why does tolerance occur for organic nitrates?
ALDH2 is needed to convert nitrates to NO — ALDH2 needs time to regenerate
CCBs dilate (arteries or veins)
arteries
CCBs have a greater effect on (preload or afterload)
AFTERLOAD (bc does artery dilation)
CCBs MOA:
Decrease influx of _______
and
decrease ________ in nodal cells
Ca2+ (duh…); chronotropy
Why does decreasing Ca2+ influx work on causing relaxation?
Because normally….
Ca2+ comes in through ____ Ca2+ channels and Ca2+ binds to ________ for its secondary effects and it also binds to _______ on _______ and all this crap leads to contraction
through L-type; binds to Calmodulin (CM) for secondary; binds to troponin on actin
Beta Blockers:
Block what?
block epinephrine stimulatin of myocardium
Beta blockers _______ inotropic and _____ chronotropic effects
decrease; decrease
Beta Blockers _____ heart rate which ______ coronary perfusion
LOWER HR: INCREASE coronary perfusion
Beta blockers have negative inotropic and chronotropic effects by block _______ in myocytes and nodal cells (respectively)
block cAMP signaling
Coronary perfusion increases with beta blockers because why?
decrease HR = more filling time aka more time in diastole (diastole is only time myocardium can be perfused)
Beta Adrenergic Receptors when stimulated in VSM do what? and via what pathway?
cause RELAXATION (relax arteries and bronchioles)
pathway: G(alpha)S - cAMP - PKA - inhibit MLCK = relaxation
Beta Adrenergic Receptors when stimulated in cardiocytes do what? and via what pathway?
cause contraction! (why we use beta blockers….)
pathway: cAMP - PKA - phosphorylate Ca2+ channels = contraction
what are the cardioselective beta blockers
atenolol
metoprolol
acebutolol
what are the non-selective beta blockers
propranolol
carvedilol
pindolol
labetalol
which drug classes used for angina can cause reflex tachycardia?
Nitrates and CCBs( mainly DHPs)
which CCB is benzothiazopine
diltiazem
which CCB is phenylalkylamine
Verapamil
how do we compensate for the reflex tachycardia for nitrates and CCBs?
beta blockers
beta blockers increase ____load
pre
beta blockers increase preload which can be problematic because why?
too much filling can stress the heart tf out
how do compensate for beta blockers increasing preload
nitrates!
why do nitrates work to compensate for beta blockers increasing preload
nitrates dilate veins aka return reduce venous return and preload!
what is the most common combo for angina
nitrates and beta blockers
what two drug combos are NEVER used for stable angina due to codepression of pacemaker cells
Verapamil and Beta blockers
why is verapamil and beta blockers NOT used together for stable angina
they cause codepression of pacemaker cells
step wise process for Angina (what drug combos do we do in what order
1 - always nitrates and beta blockers
2 - CCB + beta blockers OR nitrates + CCBs
3- last line = all 3 (nitrates, CCBs, beta blockers)
Side Effects of Beta blockers
- bronchoconstrictor
- Bradycardia/AV block
- LV dysfunction
- minor GI distress
Side effects of Nitrates
- Hypotension/Flushing/headaches (v common)
Side effects of Diltiazem
All “minor”
- hypotension/flushing/HAs
- LV dysfunction
- Bradycardia/AV block
Side effects of DHPs
- Hypotension/Flushing/headaches (v common)
Side effects of Verapamil
Lots of GI distress and Bradycardia/AV block
- LV dysfuntion (medium)
- Hypotension/Flushing/headaches (minor)
HCN Channels are regulators of _______
heart rate
HCN channels are regulated by ______ and are sensitive to _______
cAMP; transmembrane voltage
for HCN channels are more open when they are _______
hyperpolarized/negative
HCN is sensitive to cAMP and thus is regulated by _______
catecholamines (NE, E, dopamine)
HCN channels are only found in ______ cells in cardiac cels
Nodal cells (AV and SA)
you can slow heart rate down by slowing down ______ when it comes to HCN channels
the rate of action potential generation
HCN channels usually flux what things?
Na+ and Ca2+ (shocker)
what drug is a HCN channel inhibitor
Ivabrandine
Ivabrandine is a ________ inhibitor
HCN channel
Ivabradine reduces ______ _______ current
diastolic depolarization
Ivabradine _______ heart rate
slows
Ivabradine ______ diastole and thus _______ ventricular filling
prolongs diastole; improves filling
T or F: Ivabradine has NO hemodynamic or conduction abnormalities
TRUE!
what channel has importance during the ischemia cycle? (Wendt mentioned a “vicious cycle of ischemia”)
NCX channel
“Vicious” Cycle of Ischemia:
Normally the NCX channel ______ Ca2+ but during ischemia Ca2+ ______ instead (this happens because Na+ levels get out of wack)
normally Ca2+ gets kicked out of cell; Ca2+ starts to come in during ischemia to make everything worse..
what drug blocks the NCX channel
Ranolazine (Ranexa)
how does Ranolazine work
it blocks NCXS channel — aka will help prevent ischemia
side effects of Ranolazine
Dizziness; QT prolongation
what statins are prodrugs
lovastatin and simvastatin
treatment goals for unstable angina
- block thrombus formation
- dissolve existing thrombi
drugs used for unstable angina
aspirin; heparin; P2Y12 antagonists
Aspirin inhibits what?
platelet activation
P2Y12 antagonists inhibit what?
platelet activation
GPIIb/IIIa antagonists block what?
platelet aggregation
Heparin inhibits what?
thrombin formation
what is aspirins MOA?
it irreversibly acetylates COX-1 platelets –> reduces TXA2 production (TXA2 is major for platelet aggregation)
what drugs are P2Y12 inhbitors
clopidogrel prasugrel (effient) ticagrelor (Brlinta)
Heparin binds to _______ which ends up inactivating what things?
AT-III (antithrombin)
inactivates thrombin; factor Xa
which drugs are LMW heparins (low molecular weight)
enoxaparin
dalteparin
tinzaparin
T or F: Warfarin and direct Xa inhibitors are not indicated for angina
truueee
what drugs are GPIIa/GPIIIa inhibitors
tirofiban
abciximab
eptifibatide
