Regional Ischemia Flashcards
why does coronary ischemia occur?
- Angina is the result of decreased blood supply to meet the metabolic demands of the heart:
- Reduced oxygen supply and increased oxygen demands - Coronary ischemia – Angina – Chest Pain Ensues. Atheroscerosis, thrombus plug, coronary vasospasm contribute to Angina. Goal of Therapy is: (2)
A) Reduce Oxygen Demand and decrease work load on Heart: by Decreasing cardiac contractility, heart rate, decreased venous return – decrease Work Load
So Give: Nitrates, beta Blockers or Ca2+ Channel Blockers
B) Increase Oxygen Supply to the Heart:
via promoting Vasodilatation: This is however minimal.
Nitrates & Ca2+ Channel Blockers (CCBs) could promote increased oxygen supply by coronary vasodilatation.
beta Blockers: decrease the O2 demand of the heart, decrease heart rate, contractility, best for long term chronic management of Typical - stable/exertional/exercise induced angina. Contraindicated in Atypical - Variant – Vasospastic angina.
Ca2+ channel Blockers (CCBs): Inhibit Ca2+ influx via L-type Ca2+ channels in both heart & Vessels - Diltiazem and verapamil are the best choice. Lowers load on the heart and also promotes coronary vasodilatation. Effective in both typical and atypical angina
what is characteristics of typical/stable angina?
Typical/Stable Angina Double Product (DP) remains at same level before and after Rx
Exertional/Exercise-induced Angina Also known as Stable Angina Depression of S-T Segment -1. Nitrates (for acute attacks) 2. b Blockers as well as 3. Calcium Channel Blocker (diltiazem) work well in the management of Stable/ Typical Angina.
what is characteristic of variant/vasospastic angina ?
Variant/Vasospastic Angina DP (HR x SBP)
Occurs at a Different Level following Rx
Vasospastic/Variant Angina Occurring at Rest - Atypical Elevation in S-T Segment (EKG) b blockers are not recommended but Nitrates for acute management and Diltiazem (CCB) for long term chronic management. They work well.
so what are the two types of angina? what are the causes and the symptoms?
exertional, and variant
- Exertional Pain on exertion Depression of ST Segment (on EKG) Cause— Fixed obstruction Occurs at the Same Double product
- variant Pain at rest Elevation of ST Segment (EKG) Cause—coronary vasospasm? Occurs at Variable Double products
what is the double product and what does this have to do with the two major types of angina?
The “Double Product” (heart rate * systolic pressure) is an easily measured clinical index of myocardial oxygen demand.
Typical/Stable or Exertional/Exercise-Induced Angina: (usually due to a fixed obstruction) an attack occurs with exertion/exercise or emotional excitement, and it occurs at the same double product (shown in Graph A)
Atypical Variant angina or Vasospastic Angina (usually due to a sudden onset of coronary vasospasm) can occur under resting conditions and it occurs at variable double products (shown in Graph B).
While beta blockers is the main stay for long term chronic treatment of stable angina, it is not used for Variant or Vasospastic Angina - Do not give beta blockers.
what is the importance for nitroglycerine and other nitrates for angina? what are their limitations?
NO Donors(cGMP)
VENO- and arterial dilator
Headache, Tolerance!
Nitrates (given for angina),
Sodium nitroprusside (given for hypertensive crisis),
Minoxidil, Hydralazine (antihypertensives) are
other nitro vasodilators. They enhance cGMP mediated vasodilatation. Tolerance & Headache
are its limitations.
what is the mechanism of action of nitrates?
Nitrates, mimic nitric oxide (NO) effect as a NO donor, dilate both the resistance and capacitance vessels but the effect on the capacitance side is more dramatic. By dilating capacitance vessels (Venodilatation), the nitrates decrease venous return and the filling pressures in the heart (ie they decrease the preload), and thereby decrease myocardial wall tension and oxygen demand. The rapid relief of angina or ischemia is due to decrease Preload due to decrease Venous Return due to Venodilatation of the Capacitance Vessels.
Note: Coronary vessels are already dilated to compensate during ischemia and the effect of nitrates on coronary arterial side is minimal although nitrates are indeed powerful vasodilator of all arterioles and arteries.
what is the effect flow of nitrates?
nitrates –> venodilatation –> decrease venous return –> decrease filling pressure (preload) –> decrease intramyocardial tension –> decrease oxygen consumption
Rapid Relief of acute angina by Nitrates is is due to increase Venodilatation
Causing decrease Venous Return to the heart - decrease Preload, decrease work load on the
Heart resulting in decreased oxygen consumption.
what is the route of administration of nitrates of short acting and long acting?
short acting
nitroglycerin, sublingual (10-30 minutes)
long acting
nitroglycerin, 2% ointment (3-6 hours)
nitroglycerin, slow release, transdermal (8-10 hours)
isosorbide dinitrate, oral (6-10 hours)
what is the nutshell for nitrates?
Although nitrates may increase oxygen supply by dilating collateral vessels in the heart, the dominant action of the nitrates appears to be a decrease in oxygen demand by decreasing PRELOAD since the coronary vessels are already dilated maximally to compensate.
The nitrates are rapidly inactivated through first pass metabolism in the liver. Accordingly, nitroglycerin is often administered sublingually or transdermally via a patch. Some nitrates are administered orally in huge doses to achieve therapeutic plasma concentrations.
Tolerance and cross tolerance among the nitrates is a major problem with chronic administration of the nitrates, particularly the orally administered ones. The incidence of tolerance may be reduced by intermittent administration of nitrates (e.g. patch can be worn - 12 hours on and 12 hours off).
Nitrates is one best example of a drug causing Tolerance and the need to give “Drug Holidays” –” Nitrate Free Interval” to maintain its advantage in overcoming acute ischemia.
what are the beta adrenergic antagonists “B1 blockers”? what is their effect?
Beta adrenergic antagonists XX“b1 blockers”: Metoprolol, Atenolol
- Compete with Epi, Norepi at b receptors
- No effect of their own (except Sotalol, see antiarrhythmics)
- Reduce HR (Sinus node: inhibit sympathetic action)
- Reduce Contractility (myocardium: sympathetic)
- Reduce Renin Release in the kidney RAS.
- Reduce afterload (reduce BP)
- Reduce workload on the Heart HR, CO.
- Save lives!
- AE: Lots. Reduced max exercise tolerance; asthma, PAD worsens; cold hands and feet; bad dreams; depression (?)
Erectile dysfunction, Insulin resistance, alters plasma lipids
for calcium channel blockers (CCBs) what are three of them and what do they do?
- Block L-type Ca channels (sinus, AV node, myocardium, peripheral vessels)
- Reduce HR, Afterload
- Negative Inotropic effect
- ‘DHPs (Amlodipine, Nifedipine) have higher affinity for smooth muscle than cardiac muscle (hence they are useful in HTN management)
- Expect AE in other smooth muscle
- constipation, urinary retention, headache
what are the effects of calcium channel antagonists comparatively?
dihydropyridines - e.g. nifedipine
increase peripheral vasodilation, heart rate, decrease myocardial contractility, increase nodal conduction
benzothiazepines - e.g. dilitiazem
increase vasodilation, decrease heart rate, myocardial contractility, nodal conduction
phenylalkylamine - e.g. verapamil
increase vasodilation, decrease heart rate, myocardial contractility, and nodal conduction
Diltiazem & Verapmai are more useful in Angina/CAD decrease HR & Contractility
DHPs -Amlodipine useful as Antihypertensive: Causes Tachycardia & Constipation
what are the salient features of CCBs?
They inhibit Ca2+ entry into Blood Vessels and heart by blocking L-Type Ca2+ Channels. Decrease work load on the heart and also cause vasodilatation.
Adverse effects may include cardiac depression, ankle edema, constipation.
DILTIAZEM and verapamil are preferred in the management of both types of angina.
Nifedipine and amlodipine are more effective as peripheral vasodilators and they are useful as Antihypertensive agents. Not used for angina because they cause a reflex increase in heart rate. Constipation and flushing are its side effects.
what is the nutshell of beta blockers vs. nitrates?
ß-blockers - effective in stable angina because they reduce myocardial oxygen demand by decreasing heart rate (HR) and contractility.
ß-blockers are contraindicated in variant angina because unopposed a-mediated coronary vasoconstriction would be further augmented.
ß-blockers exert a much longer duration of action than nitroglycerin, and tolerance is less problematic with ß-blockers. Thus the ß-blockers are more suited for the long term chronic prophylaxis of stable angina.
