Pharma Ch. 21 - Antianginal Drugs

Name the dihydropiridine Ca Channel blockers:

- Amlodipine - Felodipine - Nifedipine

How would we classify a person to have unstable angina?

- Any episode of rest angina longer than 20 minutes - any new-onset angina, - any increasing (crescendo) angina - or even sudden development of shortness of breath

Name the beta adrenergic blockers used to treat angina?

- Atenolo - Bisoprolo - Metoprolol - Propranolo

Ranolazine is metabolized by?

- CYP3A family - CYP2D6 - It is also a substrate of P-glycoprotein

Name the Nondihydropyridine calcium channel blockers?

- Diltiazem - Verapamil

Name the organic nitrates used for angina treatment:

- Nitroglycerin - Isosorbide mononitrat - Isosorbide dinitrate

Amlodipine given orally is used for......?

- arteriolar vasodilation

Name the drug classes used to treat anginas?

- beta blockers - Ca Channel blockers - Nitrates - Na Channel blockers

How do antianginal drugs help to balance the cardiac oxygen supply? (which parameters do they work on)

- blood pressure - venous return - heart rate - contractility

What is a CI of beta blockers?

- bradycardia

Ranolazine indication?

- chronic angina - antiarrythmic

All Ca Channel blockers decrease....?

- peripheral vascular resistance - dec smooth muscle tone

Typical angina pectoris is promptly relieved by......?

- rest or nitroglycerin

Diltiazem is used for trmt of what type of angina?

- variant

Onset of action of nitroglycerin?

1 min

Nitrate MOA:

1) Nitrates convert into NO 2) NO activates GC 3) GC converts GTP into cGMP 4) cGMP activates Myosin LC phosphatase 5) Myosin LC phosphatase desphosphorylates Myosin LC 6) Myosin LC prevents actin-myosin cross bridge formation 7) -> vascular smooth muscle relaxation

The acute coronary syndrome may present as...?

1) ST-segment elevation myocardial infarction 2) non-ST-segment elevation myocardial infarction 3) as unstable angina.

Name the three types of Angina pectoris:

1) stable, effort-induced, classic, or typical angina; 2) unstable angina 3) Prinzmetal, variant, vasospastic, or rest angina.

How long should be the nitrate free interval?

10-12 hours every day

Onset of action of isosorbide mononitrate?

30 min

What is special about all beta blockers at high doses?

All β-blockers are nonselective at high doses and can inhibit β2 receptors.

When should nitrates normally be taken?

At morning, and take off at night EXCEPT - variant angina (is worst in the morning) here interval free should be at afternoon

Why do we give nitroglycerin either sublingually or as patch?

Bec of immense first pass metabolism

How do Ca Channel blockers work? (general)

Calcium influx is increased in ischemia because of the membrane depolarization that hypoxia produces. In turn, this promotes the activity of several ATP-consuming enzymes, thereby depleting energy stores and worsening the ischemia. The calcium channel blockers protect the tissue by inhibiting the entrance of calcium into cardiac and smooth muscle cells of the coronary and systemic arterial beds.

A patient whose angina was previously well controlled with once-daily isosorbide mononitrate states that recently he has been taking isosorbide mononitrate twice a day to control angina symptoms that are occurring more frequently during early morning hours. Which of the following is the best option for this patient? A. Continue once-daily administration of isosorbide mononitrate but advise the patient to take this medication in the evening. B. Advise continuation of isosorbide mononitrate twice daily for full 24-hour coverage of anginal symptoms. C. Switch to isosorbide dinitrate, as this has a longer duration of action than the mononitrate. D. Switch to nitroglycerin patch for consistent drug delivery and advise him to wear the patch around the clock.

Correct answer = A. It is important to maintain a nitrate-free period to prevent the development of tolerance to nitrate therapy. The mononitrate formulation has the longer halflife. The nitroglycerin patch should be taken off for 10 to 12 hours daily to allow for nitrate-free interval.

A 62-year-old patient with a history of asthma and vasospastic angina states that he gets chest pain both with exertion and at rest, about ten times per week. One sublingual nitroglycerin tablet always relieves his symptoms, but this medication gives him an awful headache every time he takes it. Which is the best option for improving his angina? A. Change to sublingual nitroglycerin spray. B. Add amlodipine. C. Add propranolol. D. Replace nitroglycerin with ranolazine

Correct answer = B. Calcium channel blockers are preferred for vasospastic angina. β-Blockers can actually worsen vasospastic angina; furthermore, nonselective β-blockers should be avoided in patients with asthma. The nitroglycerin spray would also be expected to cause headache, so this is not the best choice. Ranolazine is not indicated for immediate relief of an angina attack, nor is it a first-line option.

Which of the following medications would be safe to use in a patient taking ranolazine? A. Carbamazepine. B. Clarithromycin. C. Enalapril. D. Quetiapine

Correct answer = C. All other medications should be avoided due to potential drug-drug interactions.

Which side effect is associated with amlodipine? A. Bradycardia. B. Cough. C. Edema. D. QT prolongation

Correct answer = C. Edema is the correct answer. The other answers are incorrect.

What is the clinical term for angina caused by coronary vasospasm? A. Classic angina. B. Myocardial infarction. C. Prinzmetal angina. D. Unstable angina.

Correct answer = C. Prinzmetal angina is angina caused by vasospasm of the coronary arteries. It is also known as vasospastic or variant angina. The other answers refer to angina (with varying levels of severity) caused by atherosclerosis

A 65-year-old male experiences uncontrolled angina attacks that limit his ability to do household chores. He is adherent to a maximized dose of β-blocker with a low heart rate and low blood pressure. He was unable to tolerate an increase in isosorbide mononitrate due to headache. Which is the most appropriate addition to his antianginal therapy? A. Amlodipine. B. Aspirin. C. Ranolazine. D. Verapamil

Correct answer = C. Ranolazine is the best answer. The patient's blood pressure is low, so verapamil and amlodipine may drop blood pressure further. Verapamil may also decrease heart rate. Ranolazine can be used when other agents are maximized, especially when blood pressure is well controlled. The patient will need a baseline ECG and lab work to ensure safe use of this medication.

Which medication should be prescribed to all anginal patients to treat an acute attack? A. Isosorbide dinitrate. B. Nitroglycerin patch. C. Nitroglycerin sublingual tablet or spray. D. Ranolazine.

Correct answer = C. The other options will not provide prompt relief of angina and should not be used to treat an acute attack.

All of the following medications can be useful for managing stable angina in a patient with coronary artery disease except: A. Amlodipine. B. Atenolol. C. Immediate-release nifedipine. D. Isosorbide dinitrate.

Correct answer = C. The short-acting dihydropyridine calcium channel blocker nifedipine should be avoided in CAD patients as this can worsen angina; however, the extendedrelease formulation can be used.

A 72-year-old male presents to the primary care clinic complaining of chest tightness and pressure that is increasing in severity and frequency. His current medications include atenolol, lisinopril, and nitroglycerin. Which intervention is most appropriate at this time? A. Add amlodipine. B. Initiate isosorbide mononitrate. C. Initiate ranolazine. D. Refer the patient to the nearest emergency room for evaluation.

Correct answer = D. Crescendo angina is indicative of unstable angina that requires further workup

A 68-year-old male with a history of angina had a MI last month, and an echocardiogram reveals heart failure with reduced ejection fraction. He was continued on his previous home medications (diltiazem, enalapril, and nitroglycerin), and atenolol was added at discharge. He has only had a few sporadic episodes of stable angina that are relieved with nitroglycerin or rest. What are eventual goals for optimizing this medication regimen? A. Add isosorbide mononitrate. B. Increase atenolol. C. Stop atenolol and increase diltiazem. D. Stop diltiazem and change atenolol to bisoprolol.

Correct answer = D. Nondihydropyridine calcium channel blockers such as diltiazem should be avoided in patients with heart failure with reduced ejection fraction. Patients should be treated with one of three β-blockers approved for heart failure with reduced ejection fraction (bisoprolol, metoprolol succinate, or carvedilol). It sounds like his angina symptoms are well managed with his current therapy so adding isosorbide mononitrate would not be necessary. These symptoms may become even less frequent as his new β-blocker is titrated

Name the Ca Channel blockers used to treat angina:

Dihydropyridine: Amlodipine, Felodipine, Nifedipine Non-Dihydropyridine: Diltiazem, Verapamil

General MOA of Diltiazem?

Diltiazem also slows AV conduction, decreases the rate of firing of the sinus node pacemaker, and is also a coronary artery vasodilator

Which drug should be avoided in pts with angina and who had MI?

Drugs with ISA - pindolol - bopindolol - Acebutalol

What is the most commone AE of nitrates?

Headache

What is the general believed MOA of nitrates in trtmt of angina?

Nitrates cause dilation of the large veins, which reduces preload (venous return to the heart) and, therefore, reduces the work of the heart

Can you relieve unstable angina by rest or nitroglycerin?

No you can not

CI combination of nitrates is with?

PDE5 inhibitors (bec potentiate it leading to severe hypotension)

Which drugs potentiate the effect of nitrates?

Phosphodiesterase type 5 inhibitors such as sildenafil potentiate the action of the nitrates.

Which angina type is CI to be treated by beta blockers?

Prinzmetal, variant, vasospastic, or rest angina - beta blockers are ineffective could worsen it

Ranolazine prolongs?

QT intervall, dont give with drugs that do this already

Name the sodium channel blocker used for angina treatment?

Ranolazine

Name the MOA of Ranolazine:

Ranolazine inhibits the late phase of the sodium current (late INa), improving the oxygen supply and demand equation. Inhibition of late INa reduces intracellular sodium and calcium overload, thereby improving diastolic function.

Which beta blockers do we prefer in treatment of angina and why?

The selective ones (less AEs) Metoprolol Atenolol Bisoprolol

General description how beta blockers treat angina:

The β-adrenergic blockers decr the oxygen demands of the myocardium by blocking β1 receptors, resulting in decreased heart rate, contractility, cardiac output, and blood pressure. These agents reduce myocardial oxygen demand during exertion and at rest

What is the nitrate-free interval?

Tolerance to the actions of nitrates develops rapidly as the blood vessels become desensitized to vasodilation. Tolerance can be overcome by providing a daily "nitrate-free interval" to restore sensitivity to the drug.

What do you do with a pts, who presents with unstable angina?

Unstable angina is a form of acute coronary syndrome and requires hospital admission and more aggressive therapy to prevent progression to MI and death

Which angina is treated by amlodipine?

Variant

Which one has greater neg inotropic effect, amlodipine or verapamil?

Verapamil

Can you prescribe beta blockers to diabetes, peripheral vascular disease, and chronic obstructive pulmonary disease pts?

YES

Nonselective β-blockers should be avoided in patients with....?

asthma.

Which antianginal drug class will reduce the risk of death and MI in patients who have had a prior MI?

beta blockers

Which antianginal drug do we use for pts with hypertension and heart failure with reduced ejection fraction?

beta blockers

Which drug is recommended as the initial treatment for angina?

beta blockers

All calcium channel blockers lower .....?

blood pressure.

How does stable angina present (symptoms)?

by a short-lasting burning, heavy, or squeezing feeling in the chest

What will induce stable angina?

by physical activity, emotional stress or excitement, or any other cause of increased cardiac workload

Nondihydropyridine Ca Channel blockers should not be used in what type of pts?

can worsen heart failure due to their negative inotropic effect, and their use should be avoided in this population.

Acute treatment of Prinzmetal angina?

coronary vasodilators, such as nitroglycerin and calcium channel blockers.

What does it look like, when stable angina presents atypically?

extreme fatigue, nausea, or diaphoresis

What is Acute coronary syndrome?

is an emergency that commonly results from rupture of an atherosclerotic plaque and partial or complete thrombosis of a coronary artery.

What is Prinzmetal, variant, vasospastic, or rest angina?

is an uncommon pattern of episodic angina that occurs at rest and is due to coronary artery spasm

What causes classical angina?

is caused by the reduction of coronary perfusion due to a fixed obstruction of a coronary artery produced by atherosclerosis.

High doses of nitrates can cause...?

postural hypotension, facial flushing, and tachycardia.

Verapamil is contraindicated in patients with ....?

preexisting depressed cardiac function or AV conduction abnormalities.

nitroglycerin decreases which one, preload or afterload?

preload -> dec venous return -> dec work of heart

Which dihydropyridines should be avoided in CAD because of evidence of increased mortality after an MI and an increase in acute MI in hypertensive patients

short acting

General MOA Verapamil?

slows atrioventricular (AV) conduction directly and decreases heart rate, contractility, blood pressure, and oxygen demand

To which type does silent angina belong to?

stable (effort induced, classical, typical)

Which one is the most common angina type?

stable (effort induced, classical, typical)

Durg of choice for prompt relief of an angina attack precipitated by exercise or emotional stress?

sublingual (or spray form) nitroglycerin is the drug of choice.

Name the MI biomarkers?

troponins and creatine kinase.

When is ranolazine normally prescribed?

when the other antianginals have failed

Atypical presentations are more common in .......?

women, diabetic patients, and the elderly.