Ch 24 - Antianginal Drugs - DONE Flashcards
What is the definition of angina pectoris?
Sudden substernal chest pain caused by coronary blood flow that is insufficient to meet the oxygen demands of the myocardium
Identify the three types of angina:
- Classic (stable) angina
- Unstable angina
- Prinzmetal´s (variant) angina
Classic (stable) angina:
chest pain occuring upon exertion that is usually due to an atheromatous lesion
Unstable angina:
angina that suddenly becomes worse or that occurs at rest
Prinzmetal´s (variant) angina:
a form of angina that results form coronary vasospasm
Which type accounts for most angina cases?
Classical angina accounts for ca. 90% of cases
What percentage of patients who have unstable angina progress to an MI?
10%-20%
What is the treatment strategy for angina?
Because angina is caused by O2 demand, greater than O2 supply, there are two treatment options:
- Increase oxygen delivery
- Decrease cardiac oxygen demand
What does myocardial oxygen demand depend on?
- Preload: diastolic filling pressure
- Afterload: PVR
- Heart rate
- Wall tention
PVR =
Peripheral Vascular Resistance
Name four major classes of drugs used to treat angina:
- Nitrates
- Calcium channel blockers
- β-blockers
- Aspirin
Why is Aspirin useful in treating angina?
Because of its ability to inhibit platelet aggregation, aspirin has been shown to reduce mortality in patients who have unstable angina
How do Nitrates relieve angina?
Nitrates relax vascular smooth muscle through conversion into nitric oxide (NO) and subsequent elevation of intracellular cyclic guanosine monophosphate (cGMP).
The increased activity of cGMP ultimately leads to dephosphorylation of myosin light chains and smooth muscle relaxation.
What is the principal physiology effect of low doses of nitroglycerin?
Dilation of the VEINS, which causes a diminished preload and reduced cardiac workload
What happens at higher doses of nitrates?
Arterioles become dilated, which leads to decrease in peripheral resistance and blood pressure
Give three examples of nitrates and their route of administration:
- Nitroglycerine: sublingual, transdermal, and IV
- Isosorbide dinitrate: oral
- Amyl nitrate: inhaled, rarely used
What is the pharmacokinetics of Nitroglycerine?
An extensive first-pass metabolism of nitroglycerin (90%) occurs in the liver.
Therefore it is common to give the drug sublingually or through the use of a transdermal patch
What are the therapeutic uses of Nitroglycerine?
- Acute anginal attack: use the sublingual form of Nitroglycerine because its onset of action is seconds to minutes
- Prevention of attacks: use the oral or transdermal form of Nitroglycerine
Does tolerance develop to Nitrates?
Yes; therefore it is important to have nitrate-free periods during long-term use
What are the toxicities of Nitrates due to vasodilation?
- Postural hypotension
- Reflex tachycardia
- Dizziness
- Throbbing headaches due to meningeal artery dilation
- Hot flushes
When are Nitrates contraindicated?
Nitrates should not be used in conjunction with drugs used to treat erectile dysfunction, such as SILDENAFIL (viagra).
The combination can cause extreme hypotension.
Name another important use of Nitrates other than angina:
They are used in treatment of cyanide poisoning.
Give three examples of calcium channel blockers:
- Nifedipine
- Verapamil
- Diltiazem
What is the mechanism of action of calcium channel blockers?
All three drugs inhibit the influx of Ca2+ into cardiac and smooth muscle cells by blocking voltage-dependent “L-type” calcium channels, thereby reducing smooth muscle and cardiac contractility.
The degree of blockade is proportional to the degree of stimulation of these calcium channels.
