Angina Flashcards
What are the major determinants of myocardial oxygen consumption?
- Ventricular wall stress
- both preload (end diastolic pressure) and afterload (end-systolic pressure) affect ventricular wall stress - Heart Rate
- Inotropic state (contractility)
- Myocardial metabolism (glucose vs fatty acids)
Coronary blood flow is essentially negligible during systole and is therefore determined by:
- perfusion pressure during diastole (aortic diastolic pressure)
- Duration of diastole
- Coronary vascular resistance
- atherosclerosis
- intracoronary thrombi
- metabolic produducts that vasodilate coronary arterioles
- autonomic activity
- extravascular compression
what is the commonly used non-invasive index of myocardial oxygen demand
“double product”
- Heart rate X systolic blood pressure
- also known as the rate pressure product
How do organic nitrate treat angina?
end results!
vasodilate coronary arteries
reduce preload and afterload
How do calcium channel blockers treat angina
vasodilate coronary arteries
reduce afterload
the non-dydropyridines (verapamil and diltiazem) also decrease heart rate and contractility
how do beta blockers treat angina
decrease heart rate and contractility
decrease afterload secondary to a decrease in cardiac output
improve myocardial perfusion secondary to a decrease in heart rate
describe in detail the mechanism of nitrates in vasodilation:
NO activates a ________ form of _______ in smooth muscle.
cytosolic form of guanylate cyclase in smooth muscle
NO:
activated guanylate cyclase catalyzes ____.
formation of cGMP
NO:
cGMP activates _____
cGMP-dependent protein kinase
NO:
Activaiton of the cGMP-dependent protein Kinase results in _______ that reduce _____ and ____ the plasma membrane causing ____.
phosphorylation of several proteins* that reduce the intracellular calcium and hyperpolarize the plasma membrane causing relaxation
The 3 major effects of Nitrovasodilators are 1. Peripheral Vasodilation 2. Increased Coronary Blood Flow 3. Inhibition of platelet function Descibe each of the three in detail.
- dilation of veins predominates over that of arterioles
- decreased preload improves subendocardial perfusion
- little or no effect on total coronary blood flow in patients with typical angina due to atherosclerosis - this is why it is so good at treating unstable angina
What is coronary steal phenomenon?
Effect of nitrovasodilators due to increased coronary blood flow - dilation of coronary arteries can paradoxically result in aggravation of angina
which nitrates can hepatic blood flow and disease affect their pharmacokinetics?
GTN & ISDN
which nitrate is a gas?
onset and duration?
Amyl Nitrate
inhalation
rapid onset, duration 3-5 min
which nitrate is not suitable for maintenance therapy and is metabolized by first pass?
onset?
duration?
GTN & ISDN
rapid onset of action 1-3 min sublingually
duration 20-30 min
not suitable for maintence therapy
which nitrate can be used to treat SEVERE RECURRENT UNSTABLE ANGINA?
IV nitrogylcerin
Which nitrates can be used to provide prolonged prophylaxis?
nitrovasodilators
oral, buccal, transdermal
3-10 hours
but can lead to tolerance (tachyphylaxis)
vasodilators can develop complete tolerance. what is recommended to prevent this?
transdermal GTN may provide therapeutic levels of drug for 24 hours, but efficacy only lasts 8-10 hours
–Nitrate free periods of at least 8 hours (overnight) are recommended to avoid or reduce TACHYPHYLAXIS
industrial (occupational) exposure to organic nitrates has been associated with ______
monday disease & physical dependence manifested by variant angina occuring 1-2 days after withdrawl
**has resulted in myocardial infarction in some patients
what are the 6 major acute diverse effects due to excessive vasodilation?
- orthostatic hypotension
- tachycardia
- severe throbbing headache
- dizziness
- flushing
- syncompe
what patients are organic nitrates contraindicted in?
patients w/ elevated intracranial pressure
which drugs can potentiate teh actions of nitrovasodilators?
Sildenafil (Viagra) and other PDE-5 Inhibitors used for erectile dysfunction can potentiate the actions of vasodilators b/c they inhibit the breakdown of cGMP
***THEY SHOULD NOT BE TAKEN W/IN 6 HOURS of taking a NITROVASODILATOR
THe 2 desired effects in treating angina w/ calcium channel blockers is what? describe each
- improve oxygen delivery to ischemic myocardium
- vasodilate coronary arteries (not veins!)
- may inhibit aggregation
- particularly useful in treating vasospastic angina - Reduce myocardial oxygen consumption
- decrease AFTERLOAD (NOT preload)
- non-dihydropyridines also lower heart rate and decrease contractility
- 9*Dihydropyridines may aggravate angina in some patients due to reflex increases in heart rate and contractility
Which patients should not be treated with verapamil or diltiazem?
pt’s with ventricular dysfunction, SA node or AV conduction disturbances, WPW syndrome, and systolic blood pressures below 90 mmHg
Which Ca Channel blockers may increase mortality in pt’s w/ myocardial ischemia?
immediate release forms of dihydropyridines
which Ca Channel Blocker drug interaction causes
Bradycardia, AV Block, depression of inotropic state
Beta Blockers with Verapamil or Diltiazem
Which calcium Channel Blocker drugs can causes an increase in plasma digoxin levels?
Verapamil and Diltiazem
Which calcium channel blocker drug interaction can cause AV Block with concurrent treatment?
calcium channel blockers and digitalis
Which CCB drug interaction results in decreased clearance of both and an increased risk of brandycardia and AV nodal block?
Quinidine
What are the 2 large desired effects of beta-blockers in the treatment of angina?
- reduce myocardial oxygen consumption by reducing contractility and heart rate
- reducing cardiac output also reduces AFTERLOAD
- some B-blockers can cause vasodilation directly or by acting as alpha blockers - improve myocardial perfusion by slowing heart rate (more time spent in diastole)
Which drug used in treatment of angina can exacerbate heart failure and is contraindicated in pt’s with asthma?
beta blockers
In which patients should Beta-Blockers be used with caution when treating angina?
diabetics since hypoglycemia-induced tachycardia can be blunted or blocked
Which drug interaction with Beta Blockers may depress contractility & heart rate and produce AV block?
non-dyhydropyridine calcium channel blockers
- Verapamil
- Diltiazem
What are the effects of Nitrates alone ; Beta blockers or CCB alone; and nitrates w/ Beta Blockers or CCB in relation to each of the following: Heart Rate Arterial Pressure EDV Contractility Ejection Time
Nitrates: degreases all EXCEPT HR & Contractility in which it has a reflex increase
BB or CCB alone: decreases all except EDV & Ejection time in which they have a reflex increase
Together: Decrease HR, AP,
-none or decrease in EDV
none in contractility & Ejection time
What is used in the treatment of Chronic Angina?
Ranolazine (Ranexa)
What is the MOA of Ranolazine (Ranexa)?
unknown
- at therapeutic levels can inhibit the cardiac late sodium current
however, the relationship of this inhibition to angina symptoms is uncertain
What are the drugs that are contradictations with Ranolazine
CYP 3A inhibitors (Ketoconazole, clarithromycin, nelfinavir)
CYP 3A inducers (rifampin, phenobarbital, St. John’s wort)
Liver Cirrhosis
T/F Ranolazine can cause dizinness, headache, constipation, nausea
true
