Exam 3: CAD and Heart Failure Pharmacotherapy Flashcards
Coronary blood flow at rest:
70 ml/min/100g
% O2 extraction by myocardial tissue beds:
70% (very high!)
Heart gets ____% of CO:
5%
Coronary blood flow increases ____x during intense exercise:
2-4x
Cardiac demand increases _____x during intense exercise:
4-7x
Systolic contraction impedes coronary filling because:
Intramural pressure increases, redistributes blood from subendocardial to subepicardial layers, compresses vessels
Perfusion pressure to LV =
DBP - LVEDP
Tachycardia during anesthesia greatly increases the chance of:
Myocardial ischemia
Factors (4) that ↑ myocardial O2 demand:
Tachycardia*
High afterload (↑ SVR)
High preload
↑ contractility
Factors (6) that ↑ myocardial O2 supply:
Hgb concentration O2 saturation Bradycardia (w/in reason) ↑ DBP Low-normal preload ↓ contractility
Goal HR range and indicated drugs in pts with CAD:
Slow
Indicated: β-blockers, CCBs
Drugs (4) with negative effect on HR in pts with CAD:
Isoproterenol
Dobutamine
Ketamine
Pancuronium
Sympathomimetic/vagolytic
Goal preload and indicated drugs in pts with CAD:
Low-normal
Indicated: NTG, diuretics
Therapy with negative effect on preload in pts with CAD:
Volume loading
Goal afterload and indicated drugs in pts with CAD:
High-normal
Indicated: Phenylephrine
Drugs (2) with negative effect on afterload in pts with CAD:
Nitroprusside
High-dose volatile agents
Goal contractility and indicated drugs in pts with CAD:
Normal-low
Indicated: β-blockers, CCBs, high-dose volatile agents
Drugs (2) with negative effect on contractility in pts with CAD:
Epinephrine
Dopamine
Summary of stable angina treatment (mnemonic):
A: ASA/anti-anginals B: BP control C: cholesterol, cigarettes D: diet, diabetes E: education, exercise
MoA of organic nitrates:
Release NO after metabolism which ↑ NO concentration in smooth muscle cells
Relaxes coronary arteries to increase supply, decrease demand (↓ preload?)
Examples of organic nitrates:
NTG Isosorbide dinitrate (Isordil) Isosorbide mononitrate (Imdur)
Nitrates are not good long-term antihypertensives d/t:
Baroreceptor reflex ↑ HR
Describe the NO signal pathway on the endothelial cell side:
Endothelial cell: bradykinin activates GPCR, which ↑ Ca2+ and triggers calmodulin, which activates eNOS to turn arginine into NO, which diffuses out
Describe the NO signal pathway on the vascular smooth muscle cell side:
NO diffuses in and activates guanylyl cyclase to ↑ cGMP, which leads to decreased Ca2+ and vasodilation
Enzyme that converts (active) cGMP to (inactive) GMP:
Phosphodiesterase inhibitors
Nitrate effects on O2 consumption:
Reduces it via ↓ preload (venodilation) and ↓ afterload (arterial dilation)
Stronger effect of NTG: venodilation or arterial dilation?
Venodilation
NTG provides preferential dilation of:
Collateral vessels serving ischemic areas
Metabolism of nitroglycerin:
90% degraded by liver to inactive metabolites; sublingual/transdermal bypass first pass effect
E1/2t of NTG:
1.5 minutes
Adverse effects of NTG:
Headaches
Postural hypotension/syncope
Methemoglobinemia
Tolerance issues with NTG:
Limits the efficacy, regardless of the route
Must have nitrate-free intervals (usually at night, when O2 demand is lower)
Advantages of oral isosorbide mononitrate:
High bioavailability
Long t1/2
High levels during day, low levels at night
Drug interactions with nitrates:
Phophodisterase inhibitors (sildenafil, tadalafil, vardenafil) - additive effect w/ nitrates
Supply/demand benefit of β-antagonists in CAD:
↓ demand via ↓ CO from ↓ HR
↑ supply via longer diastolic filling time
Specific β-antagonists to use in CAD:
β1-selective agents: metoprolol, atenolol
Don’t want to ↓ flow to peripheral vessels
Benefit of β-antagonists post-MI:
↓ post-MI remodeling
S/E of β-antagonists:
Depression Insomnia Masking hypoglycemia Exercise intolerance Bronchospasm
Discontinuation of β-antagonists:
Do not stop suddenly due to receptor upregulation
MoA of CCBs:
Bind the α1 subunit of the L-type calcium channel in mode “0”, the state where channel will not respond to depolarization
Effect of CCBs at the SA node:
↓ HR (negative chronotropic effect)
Effect of CCBs at the AV node:
↓ conductivity (negative dromotropic effect)
Effect of CCBs at the cardiac muscle:
↓ contractility (negative inotropic effect)
Effect of CCBs at the coronary vasculature:
Vasodilation
Adverse effects of CCBs:
AV block Cardiac failure Headache Constipation Hypotension
All “too much of a good thing”