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clinical syndrome of chest discomfort caused by reversible myocardial ischemia

angina pectoris

Angina pectoris produces changes in?

Myocardial function without causing myocardial necrosis

Myocardial ischemia is a result of?

Increased myocardial work and/or decreased myocardial oxygen supply

Types of Angina

*chronic stable angina
*variant or Prinzmetal's angina
*unstable angina

Angina pectoris is usually a manifestation of?

atherosclerotic coronary artery disease

Acute coronary syndrome is an umbrella term which covers clinical conditions such as:

*unstable angina
*non-Q wave MI (NSTEMI)
*Q-wave MI (STEMI)

Angina pectoris is usually associated with:

Large single to multivesel atherosclerotic CAD, coronary artery vasopasm, or both

Risk factors for developing atherosclerosis

*family history of premature MI or sudden death
*cigarette smoking
*Physical Inactivity
*Males older than 45yo

Prognosis of anginal symptoms is mainly determined by what?

*Extent/severity of underlying CAD
*Extent of LV systolic dysfunction
*Presence/severity of ischemia during exercise

When does myocardial ischemia occur?

When myocardial oxygen demand exceeds myocardial oxygen supply

What are the major determinants of myocardial oxygen demand?

*heart rate
*left ventricular systolic wall tension

What is the most important determinant of myocardial oxygen demand?

Heart rate

Rate of rise in the intraventricular pressure during isovolumetric contraction

Myocardial Contractility

What is myocardial contractility influenced by?

*Autonomic nervous system
*Heart rate
*Blood cacium level

Systolic wall tension is directly related to?

ventricular systolic pressure and ventricular wall radius

Systolic wall tension is inversely related to?

wall thickness

Reducing systolic blood pressure does what to the afterload, decreasing oxygen demand?

reduces the afterload

Reductions in preload reduces what to reduce oxgyen demand?

left ventricular dimension

What is myocardial oxygen supply determined by?

*coronary blood fow
*oxygen carrying capacity of the blood

What is the most important determinant of myocardial oxygen supply?

coronary blood flow

When does myocardial ischemia develop?

When narrowing of the epicardial vessels by vasopasm or atherosclerosis results in high enough resistance to restrict coronary blood flow

What are the factors that affect coronary blood flow?

*Duration of systole
*Coronary vascular resistance

What is coronary vascular resistance determined by?

*metabolic control
*extravascular compressive forces
*humoral and neural factors

Angina in which the frequency, severity, duration of symptoms, and time of day have not changed over the previous 2 months

Chronic stable angina

How does angina classically present?

*substernal discomfort that radiates to the neck and left arm
*pressure, heaviness, fullness, squeezing, burning, aching, gas, anxiety
*gradual onset
*lasts a few minutes
*relieved by rest or nitroglycerin

A long duration of anginal discomfort implies what?

*severe ischemia
*coronary spasm
*unstable angina
*impending MI

Functional classification of angina pectoris

*Class I - symptoms occur with unusual activity with minimal or no functional impairment
*Class II - symptoms occur with prolonged activity with mild functional impairment
*Class III - symptoms occur with usual ADL's with moderate functional impairment
*Class IV - symptoms occur at rest with severe functional impairment

Myocardial ischemia in the absence of an objective signs of angina

Silent myocardial ischemia

How is silent myocardial ischemia detected?

exercise ECG testing (asymptomatic St-segment depression)

The incidence of MI, sudden cardiac death, Prinzmetal's angina, and myocardial ischemia associated with stable angina is higher at what time of day?


What are some factors that may provoke angina episodes?

*physical exercise
*emotions (anger, excitement, anxiety)
*exposure to cold, heat, or humidity

Abnormal ECG findings in patients with chronic stable angina

*ST-segment depression
*T-wave inversion
*ST-segment elevation in patients with Prinzmetal's angina

When can be used when aspirin is absolutely contraindicated?

Clopidogrel (Plavix)

What is the initial therapy in the absence of contraindications in patients with chronic stable angina with or without prior MI?


What should be used in all patients with chronic stable angina with CAD who also have diabetes and/or LV systolic dysfunction?


What is used for immediate relief of angina?

Sublingual nitroglycerin or nitroglycerin spray

What can be used when beta-blockers are contraindicated for initial therapy?

Long-acting calcium antagonists or long-acting nitrates
*can also be combined with beta-blockers when initial treatment with beta-blockers alone is not successful

Goal of treatment of chronic stable angina

Preventing MI and death while reducing anginal symptoms

Antiplatelet Agents

*Ticlopidine (Ticlid)
*Clopidogrel (Plavix)
*Prasugrel (Effient)
*Dipyridamole (Persantine)

MOA of aspirin

*Inhibits cyclo-oxygenase preventing synthesis of thromboxane A-2
*decreased platelet release and aggregation

In patients with unstable angina, what does aspirin do?

Decreases the short and long-term risks of fatal and nonfatal MI

What should be used in all patients with acute or chronic ischemic heart disease with or without symptoms in the absence of contraindications?


MOA of Ticlopidine (Ticlid)

*inhibits platelet aggregation induced by ADP and low concentrations of thrombin, collagen, thromboxane A2, and platelet activating factor

What has ticlopidine (ticlid) been used for?

secondary prevention of stroke and MI and prevention of stent closure and graft occlusion

What limits the use of ticlopidine (ticlid)?

The potential for neutropenia and thrombotic thrombocytopenia purpura (TTP)

MOA of Clopidogrel (Plavix)

*Prevents ADP-mediated activation of platelets by blocking the activation of the glycoprotein IIb/IIIa complex

In a trial in patients with previous MI, stroke, or symptomatic peripheral disease, was clopidogrel or aspirin more effective?


MOA of Prasugrel (Effient)

*Prevents ADP mediated activation of platelets by blocking the activation of the glycoprotein IIb/IIIa complex

What is Prasugrel (Effient) indicated for?

reduction of thrombolic events in patients with acute coronary syndrome (ACS) who are managed with percutaneous coronary intervention

MOA of Dipyridamole (Persnatine)

*has vasodilatory effects on coronary resistance vessels and antithrombotic effects
*causes vasodilation via increased plasma adenosine

Why is it recommened that dipyridamole not be used as an antiplatelet agent in patients with stable angina?

Can enhance exercise induced myocardial ischemia

Beta Blockers (Examples)

Propanolol, metoprolol, atenolol, acebutolol, pindolol, nadolol, timolol, betaxolol, bisoprolol, carteolol, penbutolol, esmolol (IV)
*carvedilol and labetolol

MOA of beta blockers

*competitively inhibit the binding of catecholamines to the beta-adrenergic receptors

Two types of beta receptors

*Beta 1 - myocardium
*Beta 2 - pulmonary and vascular tissue

What does stimulation of Beta 1 receptors cause?

increased heart rate, accelerated AV nodal conduction, increased myocardial contractility

What does stimulation of beta 2 receptors cause?

bronchodilation and vasodilation

What are the beneficial effects of beta blockers in angina?

*reduction in heart rate which reduces cardiac work and decreases oxygen demand
*slowing of heart rate also prolongs diastolic filling leading to improved oxygen supply
*reduction of myocardial contractility and arterial blood pressure which reduces oxygen demand
*reduce frequency of angina episodes, improve exercise tolerance, and decrease need for NTG

What are the cardioselective beta blockers?

Metoprolol, Atenolol, Acebutolol

Nonselective beta blockers should be avoided in patients with?

obstructive lung disease, asthma, poor circulation, and diabetes

Beta blockers with partial agonist activity

Pindolol, carteolol, penbutolol, acebutolol

Beta blockers with partial agonist activity may be detrimental in what patients?

Patients with rest angina or post MI
*may not decrease heart rate and blood pressure at rest

Why are beta blockers frequently combined with nitrates?

To attenuate the potential for reflex tachycardia caused by increased sympathetic tone from nitrates

In patients with vasospastic angina, what might beta blockers do?

precipitate an anginal episode

Adverse effects of beta blockers

*sinus bradycardia and sinus arrest
*AV block
*Reduced LV function
*Sexual dysfunction
*Intensification of insulin-induced hypoglycemia

Patients with what should avoid using beta blockers?

*AV conduction disturbances
*asthma, COPD, CHF, DM
*peripheral vascular disease

How should beta blocker use be discontinued?

Taper off over 2-3 weeks

Lipid lowering agents are recommened in patients with what?

CAD and LDL cholesterol over 130mg/dl

ACE Inhibitors (Examples)

Benazepril, Captopril, Enalapril, Fosinopril, Lisinopril, Moexipril, Perindopril, Quinapril, Ramipril, Trandolapril

All CAD patients who also have diabetes and/or LV systolic dysfunction should receive what?

ACE inhibitor

MOA of Ace-Inhibitors

*Suppress renin-angiotensin aldosterone system
*decrease the formation for angiotensin II and decrease the degredation of bradykinin

Why are ACE-inhibitors less effective in blacks?

Low renin levels

Adverse Effects of ACE-Inhibitors

*Dry cough, angioedema, dizziness, hypotension, rash
*Hyperkalemia, neutropenia, proteinuria, renal function impairment

Contraindications to ACE-Inhibitors

Angioedema, bilateral renal artery stenosis, and pregnancy

Angiotensin II Receptor Antagonists (ARBs)

Candesartan, Eprosartan, Irbesartan, Losartan, Telmisartan, Valsartan

MOA of Angiotensin II Receptor Antagonists

*Block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues

Adverse reactions of angiotensin II receptor antagonists

*much lower incidence of cough, angioedema, and dizziness
*higher incidence of URTI, hypotension, renal function impairment, hyperkalemia
*fetal and neonatal morbidity and death when administered to pregnant women

What is nitrate tolerance?

A decreased pharmacologic response in the presence of continuously or frequently administered nitrates

How is nitrate tolerance prevented?

Provide a 10-12 hour daily nitrate-free interval with chronic dosing (usually at night except in patients with nocturnal angina)

Adverse effects of nitrates

Headache, lightheadedness, dizziness, facial flushing, hypotension, reflex tachycardia

Drug Interactions with Nitroglycerin

*Viagara use within 24 hours
*Cialis use within 48 hours
*Levitra use within 48 hours
*These drugs exaggerate and prolong NTG mediated vasodilation

What is sublingual nitroglycerin used for?

Management of acute episodes of angina and prophylaxis of an expected anginal episode

What is nitoglycerin sensitive to?

Heat, air, moisture and light

Why does sublingual aerosol spray nitroglycerin have some benefits over sublingual tablet nitroglycerin?

Shelf life of 3 years and no rigid storage conditions

Where are buccal tablets of NTG placed?

between the upper teeth and inner lip

What can increase the absorption of nitroglycerin transdermal patches?

Exercise and high temperatures

How long should nitroglycerin transdermal patches be worn?

12-14 hours/day

When should the last dose of ISDN be given?

with the evening meal

MOA of calcium channel blockers

*inhibit movement of calcium ions across the cell membrane decreasing the contraction of cardiac and vascular smooth muscle cells and depresses impulse formation and conduction velocity

Diphenylaklylamine calcium channel blocker


Benzothiazepine calcium channel blocker


Dihydropyridine calcium channel blockers

Nifedipine, Nimodipine, Amlodipine, Felodipine, Isradapine, Nicardipine, Nisoldipine

What calcium channel blockers are most cardioselective?

Verapamil and Diltiazem

Effects of calcium channel blockers

*Decrease coronary vascular resistance
*Increase epicardial coronary artery size
*decrease systemic vascular resistance
*decrease myocardial contractility
*slow sinus and AV nodal conduction

Adverse efects of DHP calcium channel blockers

Flushing, headache, dizziness, and peripheral edema

What may occur with nifedipine?

Reflex tachycardia

What adverse reactions occur commonly in patients treated with verapamil and diltiazem?

Depression of myocardial contractility, bradycardia, and AV block

Verapamil and Diltiazem should be used with caution in what patients?

Patients with CHF or in combination with beta-blockers

Nausea and constipation are most common with what CCB?


What is Ranolazine (Ranexa) used for?

Treatment of chronic angina pectoris

What effect does Ranolazine have on heart rate and blood pressure?

It has antianginal effects without reducing heart rate or blood pressure

Ranolazine is contraindicated in patients with what conditions?

QT prolonging conditions

Ranolazine is contraindicated with what medications?

*CYP3A inducers (Rifampin, rifabutin, rifapentine, phenoarbital, phenytoin, carbamezapine, St.John's Wort)
*CYP3A inhibitors (ketoconazole, itraconazole, clarithromycin, nefazadone, ritonavir, indinavir)

Adverse reactions of Ranolazine

Bradyarrhythmia, hypotension, peripheral edema, prolonged QT interval, N/V,constipation, dizziness, headache

Four areas in the management of chronic stable angina pectoris

*Correction/treatment of all modifiable cardiovascular risk factors
*Alteration in lifestyle
*Drug therapy
*Revascularization therapy (PTCA or CABG) in patients where medical therapy is not effective in reducing the number of anginal attacks or with underlying severe CAD

What drug is recommended in stable angina and has been shown to reduce the risk of first MI?


What medication should be used in patients with chronic stable angina who cannot take beta blockers?

Calcium channel blocker

What medications are often used with nitrates to prevent angina during the nitrate-free interval?

Beta Blockers and Calcium channel blockers

Why should diltiazem and verapamil be used with caution with beta blockers?

slowing of the AV nodal conduction and decreasing contractility

What is the preferred drug for sinus bradycardia?

Nitrate, long acting DHP CCB

What drugs should be avoided in sinus bradycardia?

Diltiazem, verapamil, beta blocker

Preferred drugs for sinus tachycardia

Beta bocker, verapamil, diltiazem

Drugs to avoid with sinus tachycardia

Nifedipine, nitrates

Preferred drugs for SVT

Verapamil, diltiazem, beta blocker

Preferred drugs for AV block

Long acting CCB, nitrates

Drugs to avoid with AV block

Beta blocker, diltiazem, verapamil

Preferred drugs for A.fib

Beta blocker, verapamil, diltiazem

Preferred drugs for ventricular arrhythmias

Beta blocker

Preferred drugs for LV dysfunction

Low dose beta blocker, nitrates DHP CCB

Drugs to avoid with LV dysfunction

Diltiazem and verapamil

Preferred drugs for post-MI

non-ISA beta blocker

Drugs to avoid with post-MI

ISA beta blocker

Preferred drugs for systemic hypertension

Beta blocker, CCB

Preferred drugs for migraine

Beta blocker, verapamil, diltiazem

Drugs to avoid with migraines

Nitrates, DHP CCBs

Preferred drugs for COPD/asthma

Nitrates, CCBs

Drugs to avoid with COPD/asthma

beta blockers

Preferred drugs for hyperthyroidism

Beta blockers

Preferred drugs for Raynaud's

Nitrates, CCBs

Drugs to avoid with Raynauds

Beta blockers

Preferred drugs for Claudication

Nitrates, CCBs

Drugs to avoid with claudication

Beta blockers

Preferred drugs for depression

Nitrates, CCBs

Drugs to avoid with depression

Beta blockers

Preferred drugs for diabetes

Beta 1 selective beta blockers, Nitrates, CCBs

Myocardial ischemia associated with coronary artery vasospasm and not necessarily associated with atheroscleoritic CAD

Variant Angina or Prinzmetal's angina

Decreased myocardial oxygen supply in variant angina is due to?

narrowing of a large coronary vessel

When does variant angina pain usually occur?

Between midnight and 8am

What is used for acute episodes of variant angina?

Sublingual nitroglycerin

What is used for chronic prophylaxis of variant angina?

Calcium channel blockers or long acting nitrates with nitrate free period during the day

Combination therapy with what 2 CCBs have shown effective in variant angina but with increased adverse drug effects?

Diltiazem and Nifedipine

Why should beta blockers be avoided in patients with variant angina?

exacerbation of coronary artery vasospasm

How does unstable angina usually present?

*rest angina over 20 minutes in duration
*new onset angina which occurs with minimal exertion
*angina with increasing frequency/duration

What does an ECG of a patient with unstable angina usually show?

ST Segment changes
*elevation with STEMI
*depression with UA/NSTEMI

What 3 processes contribute to the decreased myocardial oxygen supply with unstable angina?

*progression of atherosclerosis
*platelet aggregation
*thrombus formation

What is acute myocardial infarction usually asociated with?

total occlusion of the coronary artery

What is the primary goal in unstable angina?

Prevent MI by inhibiting extension of the thrombus

When a patient is admitted to the hospital for acute coronary syndrome, what does standard medical therapy usually consist of?

*Beta blocker
*Anticoagulant therapy
*GP IIb/IIIa inhibitor
*Thienopyridine (Clopidogrel)

What medication is recommended immediately for patients with unstable angina?

Aspirin (chew or swallow)

What is the preferred alternative to aspirin in unstable angina?


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