CHAPTER 12 VASODILATORS IN ANGINA Flashcards
Which structure as the highest vascular tone?
Arteriolar tone- major areas of smooth muscle contraction
Venous tone - some but less tone.
What keeps veins flow since they have lower tone?
Series of one way valves keeps blood flowing the correct direction.
Muscle pumps
What percentage of the blood is in the venous system?
70%
What is the pathway of blood vessel contraction?
How does it contract?
- Ca2+ comes causes CICR.
- Ca2+ is released from SR and binds to Calmoudulin.
- Ca2+ Calmouldulin complex activates MLCK
- MLCK adds phosphate group to myosin causing an interaction with actin resulting in contraction.
cAMP will inhibit MLCK, relaxing SM
What are the 3 AHA Angina Classification
Causes and Precipitating Factors?
Stable (Angina of Effort): Caused by plaque, precipitating factor: exercise/stress, can be relieved with rest.
Unstable (Acute coronary syndrome): Caused by plaque, precipitating factor: resting, this is an emergency.
Variant (Prinzmetal): Caused by hyperreactive vessels, precipitating factor: resting, rare: 2% of angina
What is oxygen debt?
Balance of oxygen availability and the oxygen requirement of the heart.
What affects O2 availability?
Arterial O2 concentration (Hgb concentration): Anemic patients will have less O2 carry capacity in the blood.
Coronary Flow and Distribution: Plaque and Shunts
O2 extraction and coronary circulation: Small amount of plaques elsewhere
What contributes to O2 requirement?
HR- Increase HR, Increase O2
Wall Tension- amount of pressure b/w heart and walls of the heart, blood in the heart at any given time.
Contractile State- Increase in systole
How is coronary blood flow related to perfusion pressure, duration of diastole, and to coronary vascular bed resistance?
Directly related to perfusion pressure
Directly related to duration of diastole (coronary blood flow is perfused during diastole)
Inversely proportional to coronary vascular bed resistance (more plaque, less coronary blood flow)
What are the targets to relax vascular tone?
Blocking Ca2+ Channels
Increasing cGMP (removes the phosphate group from MLC causing relaxation)
Target Beta-2 agonist (increase in cAMP to phosphorylate MLCK, inactivating the enzyme), but can have systemic effects.
Actions of NO, Nitrates, Nitrites
Activates GC
Increase cGMP
Relaxation
Actions of Beta-2 Agonist
GPCR
cAMP
Relaxation (mainly respiratory)
Actions of Beta Blockers
Decrease demand by decrease HR
Actions of CCB
Less Ca2+ influx
Relaxation
Actions of Sidenafil
Blocks PDE5
increase cGMP
Relaxation
Describe the pathway of Nitric Oxide
- Nitrates will activate guanylyl cyclase in the vascular smooth muscle
- Cyclates GTP to cGMP
- cGMP directly dephosphorylates myosin light chain.
- When myosin loses its phosphate group, it can longer interact with actin, causing relaxation.
How do PDE inhibitors like Milrinone work?
PDE3 inhibitors like Milrinone prevent the break down of cAMP and cGMP.
cAMP in the cardiac muscle will cause contraction (inotropic).
cGMP in the smooth muscle will cause relaxation (vasodilation).
What is the half life of nitroglycerin?
What nitrate is more efficacious with a half life?
2-8 minutes
Dinitroglycerin
What are the pros and cons of nitrates/nitrites?
Pro:
Increase venous capacitance, decrease preload, decrease heart size, decrease CO
Cons:
Orthostatic hypotension, syncope, HA, reflex tachycardia, hemoglobin interactions
What are the clinical use of nitrates/nitrates?
Do you need an off period with nitrate/nitrates
Sub Lingual: immediate onset, 10-30 minute effect
IV Nitroglycerin: for severe non-effort angina
Tachyphylaxis- need off period of at least 8 hours
What are the 3 CCB used for angina?
Verapamil - more cardiac affect
Dihyropyridines (nicardipine) - peripheral effects
Diltiazem- both cardiac and peripheral
How to CCB work?
Blocks L-type Ca2+ channels and produce long lasting smooth muscle relaxation and decrease BP.
Heart: decrease contractility, decrease SA node pacemaker rate, decrease AV node conduction velocity
Are beta blockers vasodilators? What are beneficial effects of beta blockers?
Beta Blockers are not vasodilators!
Beneficial effects of beta blockers is decrease in O2 demand.
Decrease BP
Decrease HR
Decrease Contractility
Where are the micro-arteries located? What receptors do they have?
Micro-arteries are in the walls of the heart!
They have alpha2 and beta2 receptors.
What do the epicardial arteries include? What receptors do they have?
Epicardial arteries are your coronary and circumflex arteries on the surface of the heart.
They have alpha1 and beta1 receptors.
What happens when you give a nonselective beta blocker to micro-arteries and epicardial arteries?
Non-selective beta blockers will block Beta1 in the epicardial artery and Beta2 in micro-arteries. Overall, this will cause constriction. Bad in angina patients.
What happens when you give a selective beta-1 blocker (atenolol, metorprolo) to micro-arteries and epicardial arteries?
Only blocking beta1 in epicardial artery. Still have beta2 dilatory effects in micro-arteries.
What happens when you give a third generation nonselective beta blocker (labetalol) to micro-arteries and epicardial arteries?
Will block both alpha and beta receptors in epicardial arteries, but will have overall relaxation effect.
What happens when you give a third generation selective beta-1 selective blocker (Nebivolol) to micro-arteries and epicardial arteries?
Will block everything besides Beta2 in the micro-arteries, with Beta 1 blocked in there it will also decrease HR. This drug will have the best effects.
What does heart prefer when it comes to energy metabolism?
Heart prefers fatty acids.
How do pFOX inhibitors work?
Partial inhibitors of Fatty Acid Oxidation. This will increase glucose utilization in the heart and decrease O2 demand.
Not approved in the USA
What are therapies for Angina
Modify Risk Factors
Use CCB and Beta Blockers
Long Acting Nitrates
Why is it better to use dual therapy of nitrates with CCB or BB?
There will be reflex compensatory mechanism if taken alone.
Nitrates will decrease arterial pressure, EDV, and Ejection Time, but will increase HR and Contractility.
BB and CCB will decrease HR, Arterial pressure, Contractility, but increase EDV and Ejection Time.
The dual therapy will just have and Decrease in HR, Arterial Pressure, and Decrease EDV. No effects on Contractility or Ejection Time.
What are Non-pharmacological Intervention for Angina
Surgical revascularization (CABG)
Cardiac Catheter
Stent
