Drugs used in Chronic IHD Flashcards Preview

MED233 Cardiovascular > Drugs used in Chronic IHD > Flashcards

Flashcards in Drugs used in Chronic IHD Deck (47):

What are the two approaches to treat angina pectoris?

1) Reduce O2 demand by decreasing cardiac work.
2) Increase oxygen supply by increasing blood flow through coronary arteries.


What are ways to increase coronary blood flow?

1) Surgical or non-surgical revascularization approaches
2) Vasodilators


What type of angina are vasodilators useful for? Not useful for?

Useful - Vasospastic (Prinzmetal) angina.
Not useful for atherosclerotic (classic) angina.


What is the significance of coronary steal phenomenon?

Explains why vasodilators are not useful in atherosclerotic angina. Arteriolar dilation (i.e. Dipyridamole) of normal vessels diverts blood away from ischemic/stenotic areas.


What are the determinants of myocardial oxygen demand that are used to reduce O2 demands of heart in tx of angina?

HR, contractility, preload, afterload


What are three nitrovasodilators?

1) Nitroglycerin
2) Isosorbide dinitrate
3) Isosorbide mononitrate


Where is there high nitrate reductase activity?
What else is special about nitrate reductase activity?

Liver - first pass metabolism.
Nitrate reductase activity is saturable.


What is EDRF?

Nitric Oxide: Endothelium-Derived Relaxing Factor - released by ACh when endothelium is PRESENT. NO] relaxes smooth muscle of blood vessels.


What does endothelial NOS produce? And what is the ultimate result?

Produces endogenous NO, resulting in vasorelaxation (of vascular smooth muscle).


What acts as an extracellular NO donor?

An organic nitrate (i.e. Nitroglycerin) that gets metabolically activated to NO.


What physiologically results from NO inside a vascular smooth muscle cell?

NO activates GC, which turns GTP to cGMP, which then activates PKG, which then causes:
1) hyperpolarization of cell and reduced Ca entry (opens K channel) AND 2) smooth muscle relaxation


Sensitivity of vasculature to nitrate-induced vasodilation.

veins > large arteries > small arteries and arterioles


What two things does nitrate-induced relaxation of vascular smooth muscle result in?
What change in coronary blood flow in atherosclerotic angina?

Dilation of veins (major)
Dilation of arteries (needs higher concentration of nitrates). **No significant increase in coronary blood flow to ischemic area in atherosclerotic angina.**


What effects do nitrates have in angina of effort/atherosclerotic angina (2)?

1) Decreased preload/volume heart has to pump, therefore deceased O2 demand.


What effects do nitrates have in vasospastic angina (2)?

1) Relaxation of coronary artery vascular smooth muscle, relieving coronary artery spasm


Clinical use: short v. long acting nitrovasodilators.
What is the duration of short v. long?

Short acting used to relieve angina attack (10-90min)
Long acting used to prevent attacks (3-10hrs)


Which nitrovasodilators are short acting? Long acting? Formulation?

1) Nitroglycerin - short (subL, spray *shortest duration*) and long (oral, ointment, patch)
2) Isosorbide dinitrate - short (subL, spray) and long (oral)
3) Isosorbide mononitrate - long (oral *longest duration*)


How is NO depleted in tissue?

Increased generation of superoxide radicals deplete tissues of NO.


What occurs in development of nitrate tolerance (4)?

Depletion of thiol compounds, increased oxygen radical generation, REFLEX ACTIVATION of SNS (tachycardia, decreased coronary blood), retention of salt and water


What are the ADVERSE EFFECTS of nitrates?

1) HA (meningeal vasodilation)
2) Orthostatic hypotension
3) Increased sympathetic discharge*


What are the adverse effects of increased sympathetic discharge due to nitrates (and tolerance)?

Tachycardia, increased cardiac contractility, Increased renal salt and water reabsorption.


What is the major class of drug interaction with nitrates (3 drugs) and what is this class used for? What two adverse effects can occur?

Drugs used for ED - sildenafil, vardenafil, tadalafil.
(1) Severe cGMP increased and a dramatic drop in BP and (2) acute MIs have been reported.


What two classes of CCBs are used in angina, and what drugs in each class?

1) Non-cardiactive (DHPs) - amlodipine, nifedipine, nicardipine.
2) Cardioactive (non-DHPs) - diltiazem, verapamil


What two tissues have L-type calcium channels that CCBs interact with and what does intracellular calcium do?

Vascular smooth muscle (L-type) and Cardiac muscle (L-type). Calcium mediates smooth muscle contraction


What do CCBs do for anti-angina (A, B)?

A. Decrease myocardial O2 demand (vasodilation of arterioles)
B. Increased blood supply - via dilation of coronary arteries (for VASOSPASTIC ANGINA only)


How do CCBs decrease myocardial O2 demand (2)?

(1) Dilation of peripheral arterioles (dec. afterload and PVR)
(2) Decreased cardiac contractility and HR (cardioactive DHPs)


What type of angina can CCB-induced increased blood supply be used for (B)? What is it not used for?

Vasospastic (Prinzmetal) angina - dilation of coronary arteries relieves local spasms. NOT used for atherosclerotic angina.


Are DHPs or non-DHPs more potent vasodilators (of arterioles?

DHPs (non-cardioactive CCBs)


MAJOR adverse effects of CCBs (4)

1) Cardioactive CCBs - cardiac depression, cardiace arrest, AcuteHF
2) Cardioactive CCBs - bradyarrhyth, AV block
3) Short active DHPs - vasodilation triggers reflex sympathetic activation
4) Nifedipine (immediate release) - increases risk of MI in people with HTN.


What is better tolerated for tx of angina than Nifedipine, that will not increase risk of MI in patients with HTN?

Slow release and long acting DHPs.


MINOR adverse effects of CCBs

Flushing, HA, anorexia, dizziness
Peripheral edema


What four beta-blockers are indicated in angina?



MOA of b-blockers in angina.

Decrease myocardial O2 demand: (1) Dec. HR leading to better perfusion and dec. O2 demand at rest+excercise. (2) Dec. contractility. (3) Dec. afterload


Adverse effects of b-blockers

Reduced CO, Bronchoconstriction, Impaired liver glucose mobilization, Inc. VLDL/dec. HDL, Sedation and depression, Withdrawl.


Contraindications of b-blockers

ASTHMA, PVD, Type1 DM on insulin, bradyarrhythmias, AV abnormalities, severe depression of cardiac function


AE of admin of Nitrates alone for angina.

Reflex increase in HR and contractility.


AE of Nitrates + b-blocker or CCBs for angina.

Increased end-diastolic volume and increased ejection time.


Physiological action of Ranolazine

Inhibits late Na+ current in cardiomyocytes


MOA of ranolazine in angina.

Normalizes the repolarization of myocytes and reduces mechanical dysfunction (it inhibits the Na+ current that is enhanced in ischemic myocardium, which results in Ca overload and repol abnormalities)


What four things does ranolazine NOT affect?

HR, inotropic state of myocardium, coronary blood flow, peripheral hemodynamics.


What is the clinical use of ranolazine? (When is it used and what does it do?

Use for stable angina that is refactory to standard meds.
It decreases angina episodes and improves excercise tolerance in people taking NITRATES, AMLODIPINE, OR ATENOLOL.


Adverse effects of ranolazine.

QT prolongation (may trigger vent arrhythmias)
Constipation, nausea, dizziness, HA.


What two types of drugs should not be used with ranolazine?

Do not use with CYP3A inhibitors (bc its metab by CYP3A4/5).
Do not use with drugs that prolong QT interval (Quinidine=antiarrhythmic or antipsychotic=thioridazine). Triggers vent arrhythmias.


What CYP does ranolazine inhibit (and consequently, should not be used with what drugs)?

Inhibits CYP2D6, which increase half life of amitriptyline, fluoxetine, metoprolol, and opioid drugs


What two things do nitrates alone increase?

Reflex increase in contractility
Reflex increase in HR


What do BB or CCB alonge increase?

Increase EDV and Ejection time.


Combined, what do nitrates and BB/CCB cause?

Decreased HR and Decreased arterial pressure.