CAD drugs Flashcards
Oxygen saturation of blood as it returns to the heart
MVO2
SVO2
Myocardial O2 supply determined by these factors:
1) perfusion pressure
2) intrinsic vascular resistance
Myocardial O2 demand determined by:
1) heart rate
2) contractility
3) wall stress
4) MVO2 = HR x SBP
First line drugs in CAD
Nitrates
Primary effect of nitroglycerin and related drugs:
venous dilation (relaxes all types of smooth muscle)
Secondary effects if nitroglycerin
Coronary artery dilation increases supply
Arterial dilation decreases afterload
Disadvantage for chronic use of nitrates?
Drug tolerance
Effect of venous dilation on CO?
Venodilation increases venous capacitance –> decrease venous return –> decreasing preload and thus decreasing CO
How does the consumption of sulfhydryl groups contribute to nitrate tolerance?
Sulfhydryl groups on cell membrane are needed for nitrates to enter cell.
No nitrates will enter the cell if nitrates are constantly given.
How does continuous nitrate use cause receptor down-regulation?
vasodilation –> larger blood volume –> sympathetic receptors downregulated
MoA of nitrates:
Enter cell membrane –> Nitrification process
NO activates guanylyl cyclase –> increase in cGMP –> Ca release is INHIBITED –> smooth muscle relaxation –> venous dilation
venous dilation –> decreased preload –> decreased CO –> decrease O2 demand
Nitrate drug interactions:
Nitrates cannot be taken with other drugs that use cGMP pathway like PDE-5 inhibitors –> severe hypotension
sildenafil, vardenafil, tadalafil
Type of beta blocker for CAD treatment?
beta 1 blocker
Decreases oxygen demand by decreasing heart rate.
How do beta blockers enhance coronary blood flow?
B1 blockage –> Dereased HR –> Increased diastolic perfusion –> increased filling time
Negative effect of increased filling time?
preload inreased –> more force required –> hypertrophy
How do beta blockers reduce MVO2
B1 blockage –> Decreased HR and contractility
Why are B blockers without ISA preferred?
ISA = partial agonist at receptor
Therefore they will show less decrease in HR.
Why are non-selective 3rd gen BBs unwanted in CAD patients?
3rd gen BB (mostly non-selectives) can have alpha antagonistic effect or stimulate NO release –> increase vasodilation –> profound hypotension –> REFLEX TACHYCARDIA –> higher O2 demand for heart
CAD + asthma: what drugs could be used
Cardio-selective 3rd gen with partial B2 agonism
Celiprolol
A patient with CAD is on BBs. What drugs should be avoided?
CCBs (verapamil, diltiazem)
Anti-arrhythmics (amiodarone)
They have cardiosuppressive effects leading to profound decrease in HR and CO.
BB with highest lipid solubility?
propanolol
This is why it can cause lethargy, mental depression, hallucinations
BBs used for early administration after ischemic episodes:
IV esmolol
IV metoprolo or atenolol followed by oral metoprolol/atenolol
BBs used for late administration after ischemic episode:
BBs without ISA
Two mechanisms of CCBs
- Block L-type voltage operated channels (VOCs) and receptor operated channels at membrane
- Bind to calcium channel protein
CCB group with more vasodilatory effect, less HR effect
dihydropyridines
Benzothiazepine
Diltiazem
Phenylalkylamine
Verapamil
Second Gen CCB are all this type
dihydropyridines
Second Gen CCB compared to First Gen?
More vasoselective than 1st
Examples of 2nd Gen CCB
amlodipine
felodipine
nicardipine
isradipine
Examples of 1st Gen CCB
nefidipine
All CCB are metabolized solely by the liver except?
diltiazem
Drugs that increase BA of CCB
Cimetidine
phenytoin
carbamezapine
diltiazem and verapmil increase BA of what drugs?
cyclosporine
Verapimil effect on digoxin?
increased serum levels
Lithium levels increase due to which CCB?
diltiazem
CCB that blocks K channel in smooth muscle inhibiting vasodilation
verapamil
Effects calcium channel blockers on cardiac muscles
Because of the blocked transmembrane calcium current:
1) decreased contractility
2) decrease SA conduction velocity
3) decreased AV conduction velocity
Myocardial selectivity of CCB (ranking):
verapamil > diltiazem > nifedipine (DHPs)
verapamil has less vasodilation properties
CCB that can more likely cause reflex tachycardia
DHPs –> nifedipine
CCB causing decreased HR
verapamil, diltiazem
CCB with most sympathetic antagonism
diltiazem
less: verapamil, NONE with nifedipine
Preferred CCB with AV conduction abnormalities
nifedipine
least effect on AV node
Preferred CCB with overt heart failure
All CCB WORSEN (negative inotropic effects) more commonly with non-DHP
Amlodipine can be used
Preferred CCB for hypotension
non-DHP
diltiezam, verapamil
Preferred CCB with tachycardia, flutter, fibrilliation
diltiezam and verapamil
antiarrhythmic effects
Preferred CCB with unstable angina
NOT nifedipine
in combination with nitrates
Preferred CCB with non q-wave myocardial infarction
diltiazem can decrease frequency of postinfarction angina
Combination of DHP with B-blockers can cause what?
AV block
Ventricular depression
Action of angiotensin II
1) vasoconstriction
2) aldosterone stimulation –> Na and H20 reabsorption
How do ACE-I’s decrease remodelling
decrease wall stress (load), prevent LV dilatation.
Angiotensin II contributes to remodelling through stimulation of the proto-oncogens c-fos, c-jun, c-myc, transforming growth factor beta (TGF-B), through fibrogenesis and apoptosis
Why are ACE-I’s safe to use in patients with ischemic heart disease?
they do NOT cause reflex sympathetic activation
Adverse effects of ACE-I’s:
cough
angioedema
ACE-Inhibitors increase bradykinin which cause cough and angioedema
Angiotensin II contributes to remodelling through stimulation of:
Pproto-oncogens c-fos, c-jun, c-myc, transforming growth factor beta (TGF-B), through fibrogenesis and apoptosis
ACE inhibitors mechanism:
Vasodilation
Decrease aldosterone
Increase bradykinin
Why do ARBs have more potential for angiotensin block?
ARBs block the receptor AT1.
ACE block ACE from forming angiotensin II but other enzymes form angiotensin II.
What was the first peptide ARB? Why is it no longer used?
Saralasin
Low absorption and short half-life
Adverse effects of ARBs
cough, hyperkalemia, LBP, dizziness, headache
abnormal taste
New drug therapy for myocardial ischemia; rho kinase inhibtor
Fasudil
New drug therapy for myocardial ischemia; metabolic modulator
Trimetazidine
New drug therapy for myocardial ischemia; Preconditioning
Nicorandil
New drug therapy for myocardial ischemia; sinus node inhibition
Ivabradine
New drug therapy for myocardial ischemia; Late sodium current inhibition
Ranolazine
New CAD prevent ischemic effects by:
targeting metabolic pathways not hemodynamics
