Pharmacologic agents for Coronary Artery disease Flashcards
How much coronary blood flow per minute?
With intense exercise?
How much O2 extracted?
- Coronary blood flow is 70 ml/min/100g at rest
- 5% of the CO
- Coronary blood flow increases 2-4x with intense exercise
- 70% of the oxygen is extracted from the blood
What are the physiological factors that regulate coronary flow?
- Physical factors
- Vascular control by metabolites
- adenosine is released by myocardial cells in response to decreased PO2, causing coronary vasodilation
- Neural and humoral control
- sympathetic innervation
- large vessels- Alpha; vasoconstriction effects
- smaller vessels- Beta 2; dilator effects
What is the perfusion pressure to the left ventricle?
perfusion pressure to the left ventricle = DBP - LVEDP
Left ventricle only receives blood flow during diastole b/c systolic squeezing pressure closes arterioles and capillaries. This is not as much of an issue on the R side b/c the muscle mass is not as large
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What factors increase myocardial demand?
- tachycardia
- high afterload
- high preload
- increased contractility
What factors increase myocardial supply?
- hgb concentration
- O2 saturation
- bradycardia (within reason)
- increased diastolic blood pressure
- low-normal preload
- decreased contractility
What is the treatment summary for stable angina?
(ABCDE)
- A: ASA, antianginals (nitrates, CCB, BB)
- B: Blood pressure (controlled)
- C: Cholesterol (statin), Cigarettes (stop)
- D: diet, diabetes
- E: education, exercise
How do nitrates help with CAD?
- Increase concentration of NO in smooth muscle cells
- Relax venous capacitance vessels and large coronary arteries to decrease preload and ventricular wall tension
- decrease demand and increase supply
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Nitrate MOA?
- Nitrates release NO after they are metabolized
- NO activates soluble guanylate cyclase, increasing cGMP, which increases PKG
- This prevents Ca from entering the cell and the smooth muscle relaxes
What are the organic nitrate drugs?
- Nitroglycerin
- Isosorbide dinitrate
- DOA 6 hours
- Isosorbide mononitrate
What are the different ways nitroglycerin can be delivered?
- Sublingual- tablets or spray
- Oral- has a huge first pass liver metab, not often used
- Topical- ointment, patches
- Intravenous
Nitroglycerin
E1/2t
SE
- 90% degrated by the liver to inactive metabolites
- E1/2t of IV = 1.5 minutes
- SE
- HA
- postural hypotension
- methemoglobinemia- usually only with high doses or liver disease
Whats the deal with Nitrate tolerance?
- Nitrate-free intervals are necessary to prevent tolerance and/or adverse effects
- Usually nitrate-free intervals are done at night when the person is at rest
- removal of patch at night
- Oral Isosorbide mononitrate has a long E1/2t so it can provide high levels followed by low levels and can be administered once/day
How are Beta antagonists helpful in treating CAD?
- provide a more favorable O2 supply vs demand balance
- used to prevent stable or unstable angina
- decreases O2 demand by decreasing CO (more dramatic during activity than at rest)
- decrease HR, decrease contractility
- increase diastolic filling time (supply)
What kind of Beta antagonists are most used?
What should be avoided?
SE?
- Use primarily beta-1 selective agents
- metoprolol
- atenolol
- Improve survival in CAD
- Avoid:
- sudden d/c
- in variant angina- can worsen shoch symptoms after MI if given within 8 hours of STEMI
- SE
- depression
- insomnia
- mask hypoglycemic warning signs in DM
- exercise intolerance
- bronchospasms
What is the MOA of CCB?
Where do they have their effect?
- All bind to the alpha-1 subunit of the L-type calcium channel (at distinct sites)
- Dihydropyridines are more selective for Ca channels in vasculature (arterial)
- may cause reflex tachycardia
- Non-Dihydropyridines are more selective for Ca channels on the SA & AV nodes
- more at risk for heart block
- avoid with BBs
- Dihydropyridines are more selective for Ca channels in vasculature (arterial)
What are the dihydropyridines CCBs?
What are the non-dihydropyridines?
- Dihydropyridines:
- Nifedipine
- Amlodipine
- Nicardipine
- Non-dihydropyridine
- Verapamil
- Diltiazem
How is ASA used to treat CAD?
- Antiplatelet activity of ASA prevents thrombus formation
- Irreversible cox inhibition- lasts duration of platelet life (8-10 days)
- 80 mg