Angina Flashcards
1
Q
- discuss the cause, pathophysiology and presentation of angina.
A
- angina is chest pain caused by an imbalance between oxygen supply to/demand of the cardiac tissue.
- an increase in O2 demand can be caused by an increase in:
- HR, contractility, ventricular wall tension
- a decrease in O2 supply can be caused by:
- an increase in coronary artery diameter, perfusion pressure, collateral blood flow
- a decrease in HR
- an increase in O2 demand can be caused by an increase in:
2
Q
how does perfusion pressure effect myocardial oxygen supply?
what cardiac events might effect perfusion pressure?
A
- myocardial O2 supply is contingent upon an adequate perfusion pressure.
- in this case, perfusion pressure = the pressure gradient from the aorta down to the coronary arteries, which branch from it.
- an increase in LV end-diastolic pressure can decrease this gradient, slowing O2 supply to the heart
- (the coronary arteries fill during diastole, and the aorta must overcome the pressure the heart puts on them)
3
Q
how does heart rate effect myocardial O2 supply?
A
- HR is inversely related to myocardial O2 supply.
- the coronary arteries fill during diastole. a faster HR slows down diastole, thus slowing the time for the coronary arteries to fill and perfuse to heart tissue
4
Q
what characterizes stable angina?
A
- stable angina is due a to a fixed atherosclerotic lesion that causes narrowing of the major coronary arteries.
- this plaque does NOT rupture or embolize
- stable angina tends to present during exertion/stress.
5
Q
what characterizes unstable angina?
A
- unstable angina is due to plaque rupture/clot formation in the major coronary arteries. the pain often presents during rest
6
Q
what characterizes variant angina?
A
- variant angina is caused by a transient vasospasm (spasm of coronary vessel muscles) in the large coronary arteries rather than a fixed atherosclerotic lesion.
- it presents during rest
7
Q
what characterizes microvascular angina?
A
- microvascular angina is caused by a transient vasospasm in the small coronary arteries
- like with variant angina, there is no atherosclerotic lesion involved.
- presents during rest
8
Q
what is the general phamaceutical approaches to managing angina?
A
- treat angina be either
- reducing oxygen demand
* lower HR, BP (afterload, preload) and contractility
- reducing oxygen demand
- increasing O2 supply
9
Q
nitrate esters
- MOA
- pharmokinetics
- what drugs are included in this class?
A
- drugs:
- nitroglycerine
- isosorbide dinitrate
- isosorbide mononitrate
- MOA:
- nitrate esters are vasorelaxants.
- they are all prodrugs.
- in the liver, dinitrates are broken down to mononitrates.
- in smooth muscle mitrochondria, mononitrates are converted to NO2 by aldehyde dehyrogenase 2 (ALDH2)
- in the cytosol, NO2 is converted to NO (active drug) by P540 reductase
- NO2 activates guanylyl cyclase –> active guanylyl cyclase cleaves GTP to cGMP –> cGMP phosphorylates an activates MLC phsophotase –> dephosphorylates and inactivates myosin light chain kinase –> relaxation
- they are all prodrugs.
- nitrate esters are vasorelaxants.
10
Q
what is ALDH2*2 and what is its clinical significance?
A
- a mutated version of the aldehyde dehydrogenase 2 enzyme (results from a single nucleotide polymorphism).
- clinical:
- ALDH2*2 is seen in 30-50% of Asians
- results in less NO production from nitrate esters. thus, nitrates are less effective vasorelaxer in these patients.
- ALDH2 is also involved in ethanol metabolism, and patients with this mutation will experience facial flushing when drinking (a way to identify pts with mutation)
11
Q
what are the primary effects of nitrates
A
venous dilation. this ultimately lowers the end diastolic wall pressure (lowering O2 demand) while increasing O2 supply.
12
Q
which nitrate is immediate release? what are its indications and other characteristics?
A
-
nitroglycerine in the form of sublingual/buccal oral spray
- has a rapid onset of action and short duration
- used to treat an acute angina attack (all four types)
13
Q
which nitrates are long-acting? what are their indications and characteristics?
A
- nitroglycerine in transdermal patch/ointment form
- isosorbided mono-nitrate
- isosorbide dinatates
- indications:
- prevention of stable, unstable, and variant angina
-
treatment of stable angina:
- used as an alternative to beta blockers
- or combined w/ a beta blocker or calcium channel blocker
14
Q
what are the acute and chronic adverse effects of nitrates?
A
- acute AEs
- headache
- flushing
- syncope
- orthostatic hypotension
- reflex tachycardia
- chronic AEs
- development of tolerance to nitrates (in long acting nitrates)
- methemoglobinemia - a lack of oxygenation to systemic tissues
- seen only at high doses
15
Q
how do we prevent development of tolerance to nitrates?
A
by mandating a 8-10 hour drug-free period every 24 hrs while using long acting nitrates
16
Q
potential drug drug interactions of nitrates
A
- PDE5 inhibitors (-“fils”: sildenafil, taladafil) - the additive effects can cause extreme vasodilation
- CYP-3A4 inhibitors/inducers
- dapsone - poses a risk of methemobloginemia
17
Q
contraindications of nitrates
A
- hypotension
- PDE inhibitors (- “fls”)
- soluble guanylyl cyclase inhibitors
- elevated intracranial pressure
23
Q
calcium channel blockers (CCPs)
- what are the two subsets within this class?
- what are their MOAs in the treatment of angina?
A
- calcium channel blockers promote smooth muscle relaxation. there are two classes
- DHPs: “-dipines”
- reduce myocardiac O2 demand by relaxing cardiac muscle, which reduces HR and contractility
- non-DHPs: verapamil, diltiazem
- reduce myocardial O2 demand AND increase O2 supply by relaxation vascular muscle. this dilates arteries, which 1. increases coronary blood flow to cardiac tissue and 2. reduces afterload against the heart
- DHPs: “-dipines”
33
Q
what is the late phase sodium current and what is its physiological role in cardiac muscle relaxation?
A
- in cardiac myocytes, the late phase of sodium current is point of the action potential during which intracellular Na+ is low
- this low intracellular Na+ favors creates a favorable gradient for Na+ influx, which will drive the Na-Ca exchanger (NCX) to bring in Na+ in exchange for Ca++
- the consequent decrease in intracellular calcium allows for muscle relaxation
34
Q
how does the late phase sodium channel play a role in cardiac ischemia?
A
- in pathological circumstances, is a higher intracellular [Na+] during the late phase than there should be.
- this high intracellular Na+ reverses the NCX channel, which drives Na+ out and pulls Ca++ in the high intracellular [Ca++] causes myocyte contraction, which will increase workload on the heart
- –> myocardial ischemia
- this high intracellular Na+ reverses the NCX channel, which drives Na+ out and pulls Ca++ in the high intracellular [Ca++] causes myocyte contraction, which will increase workload on the heart
