Topic which is prepared for pharmacotherapeutics aspect and help for Pharm D students.

1. ANGINA
PECTORIS
Dr. Sivasakthi K Pharm D
(PB )
Assistant Professor

2. ANGINA PECTORIS
 Angina is a clinical syndrome characterized by discomfort in the
chest, jaw, shoulder, back, and arms, which is usually aggravated by
exertion or stress and relieved by nitroglycerin.
 Angina pectoris is the most common form of IHD

3. Types
 Stable (classic) angina
exertion, emotional stress, or a heavy meal,
relieved by rest, nitroglycerin,or both.
 Unstable angina
Rest angina, which usually is prolonged 20 mins
Decreased response to rest or nitroglycerin
 Variant angina
Coronary artery spasm that reduces blood flow precipitates this
angina.
 Nocturnal angina
 This angina occurs in the recumbent position
 Gravitational forces shift fluids within the body with a
resultant increase in ventricular volume, which increases
oxygen needs and produces nocturnal angina

4. ETIOLOGY
ANGIN
A
O
2
S
U
P
P
L
y
O
2
D
E
M
A
N
D
CORONARY
BLOOD FLOW
BLOOD
OXYGENATION
HEART RATE
CONTRACTION
PRELOAD
AFTERLOAD

5. Etiology
Decreased blood flow to the myocardium
 Atherosclerosis
 Coronary artery spasm
 Traumatic injury
 Embolic events

6. Atherosclerosis
 When plaque (fatty deposits) clogs
arteries, that’s called atherosclerosis.
 These deposits are made up of
cholesterol, fatty substances, cellular
waste products, calcium and fibrin
 As plaque builds up, the wall of the
blood vessel thickens. This narrows
the channel within the artery, which
reduces blood flow. That, in turn,
lessens the amount of oxygen and
other nutrients reaching the body.

7. Coronary artery spasm
 sustained contraction of one or more coronary arteries, can occur
spontaneously or be induced by irritation (e.g., by coronary catheter
or intimal hemorrhage), exposure to the cold, and ergot-derivative
drugs.
 These spasms can cause Prinzmetal angina and even MI.

8. Traumatic injury
 Traumatic injury, whether blunt or
penetrating, can interfere with myocardial
blood supply
 (e.g., the impact of a steering wheel on the
chest causing a myocardial contusion in which
the capillaries hemorrhage).

9. Embolic events
 Embolic events can abruptly restrict the
oxygen supply to the myocardium.
 Emboli: Something that travels through the
bloodstream, lodges in a blood vessel and
blocks it. Examples of emboli are a detached
blood clot, a clump of bacteria, and foreign
material such as air

10. Increased oxygen demand
 Increased oxygen demand usually can occur
with exertion (e.g., exercise, shoveling snow)
and emotional stress as well as increases
sympathetic stimulation and heart rate.

11. Risk factor
 Advance age
 Hypertension
 Increased serum glucose level
 Increased lipoprotein level
 Obesity
 Smoking

12. Initiating factor of an attack
 Cold whether
 Smoking
 heavy meals
 Hypoglycemia
 Pain
 emotions

13. Clinical presentation
 patient’s history
 risk factors
 full description of attacks—precipitation
pattern, intensity, duration, relieving factors—
usually prove diagnostic.

14. DIAGNOSISTIC TEST
 EKG/ECG is normal in 50% or more of patients with stable angina
pectoris, and a normal resting EKG/ECG does not exclude severe IHD.
 However, an EKG/ECG with evidence of left ventricular hypertrophy or ST-
T-wave changes consistent with myocardial ischemia favors the diagnosis
of angina pectoris
 An EKG/ECG obtained during chest pain is abnormal in 50% of patients
with angina who have a normal resting EKG/ECG. The ST segment can be
either elevated or depressed.

15. Exercise EKG/ECG
 Stress testing (exercise EKG/ECG)
is a well-established procedure,
which aids the diagnosis in patients
who have normal resting
EKGs/ECGs. The most commonly
used definition for a positive test is a
1-mm ST-segment depression or
elevation for 60 to 80 m sec either
during or after exercise.

16. Pharmacological stress
testing
 Pharmacological stress testing is performed in suspected IHD
patients when they are not able to perform more than moderate
exercise due to various reasons (i.e., severe arthritis, prior injury,
reduced exercise tolerance as a result of debilitating illnesses, etc.),
or in patients who are unable to increase the heart rate.
 Intravenous dipyridamole
 high-dose dobutamine

17.  Coronary arteriography and cardiac catheterization are very specific
and sensitive but are also invasive, expensive, and risky (the
mortality rate is 1% to 2%)

19. Treatment goals
1. To prevent MI and death, thereby increasing a patient’s quality of life
2. To reduce symptoms of angina and occurrence of ischemia, which should
improve a patient’s quality of life
3. To remove or reduce risk factors
4. The management of angina pectoris includes therapies aimed at reversing
cardiac risk factors.
 Hyperlipidemia
 Hypertension
 Smoking
 Obesity

20. Nitrates
(e.g., nitroglycerin)
a. Mechanism of action
 Nitrates are a vasodilator. Vasodilators widen (dilate) the
blood vessels, improving blood flow and allowing more
oxygen-rich blood to reach the heart muscle.
 By reducing pressure in cardiac tissues, nitrates also
facilitate collateral circulation, which increases blood
distribution to ischemic areas.

22. Indications
 Acute attacks of angina pectoris can be managed with sublingual,
transmucosal (Nitrolingual® spray or Nitrostat® sublingual tablets), or
intravenous delivery.
 Nitrates are used in treatment of stable angina. They may not be effective
as a single agent for treatment of Prinzmetal angina,
 Intravenous nitroglycerin is used in the immediate treatment of unstable
angina.
 Nitrates used in combination with Beta-adrenergic blockers have been
shown to be more effective than nitrates or beta-adrenergic blockers used
alone.

23. d. Precautions and monitoring
effects
 Blood pressure and heart rate should be monitored because all nitrates can
increase heart rate while lowering blood pressure.
 Preload reduction can be assessed through reduction of pulmonary symptoms such
as shortness of breath, paroxysmal nocturnal dyspnea, or dyspnea.
 Nitrate-induced headaches are the most common side effect.
(a) Patients should be warned of the nature, suddenness, and potential strength of these
headaches to minimize the anxiety that might otherwise occur.
(b) Compliance can be enhanced if the patient understands that the effect is
transientand that the headaches usually disappear with continued therapy.
(c) Acetaminophen ingested 15 to 30 mins before nitrate administration may prevent the
headache.

24.  Nitrate tolerance is a major problem with the long-term use of nitroglycerin
and long-acting nitrates.
Management
 8 to 12 hrs of nitrate-free intervals

25. Beta-Adrenergic blockers
Mechanism of action
Beta -Blockers reduce oxygen demand, both at rest and during
exertion, by decreasing the heart rate and myocardial contractility,
which also decreases arterial blood pressure.

26. Indications
(1) These agents reduce the frequency and severity of exertional
angina that is not controlled by nitrates.
(2) Nitrates have been combined with calcium antagonists, when slow-
release dihydropyridines (e.g., felodipine , amlodipine) are preferred
over diltiazem or verapamil. If patients need to receive a beta-
adrenergic blocker along with verapamil or diltiazem owing to the
added effects, they have the potential to induce bradycardia, AV
heart block, and fatigue.

27. Precautions and monitoring
effects
(1) Doses should be increased until the anginal episodes have been reduced
or until unacceptable side effects occur.
(2) Beta -Blockers should be avoided in Prinzmetal angina (caused by
coronary vasospasm) because they increase coronary resistance and may
induce vasospasm.
(3) Asthma is a relative contraindication because all b-blockers increase
airway resistance and have the potential to induce bronchospasm in
susceptible patients.

28. (4) Patients with diabetes should be warned that Beta -blockers mask
tachycardia, which is a key sign of developing hypoglycemia.
(5) Patients should be monitored for excessive negative inotropic eff
ects. Findings such as fatigue, shortness of breath, edema, and
paroxysmal nocturnal dyspnea may signal developing cardiac
decompensation, which also increases the metabolic demands of
the heart.
(6) Sudden cessation of B-blocker therapy may trigger a withdrawal
syndrome that can exacerbate anginal attacks (especially in
patients with IHD) or cause MI.

29. Calcium-channel blockers
 Mechanism of action
(1) These agents prevent and reverse coronary spasm by inhibiting calcium
influx into vascular smooth muscle and myocardial muscle. This results in
increased blood flow, which enhances myocardial oxygen supply.
2) Calcium-channel blockers decrease coronary vascular resistance and
increase coronary blood flow, resulting in increased oxygen supply.
(3) Calcium-channel blockers decrease systemic vascular resistance and
arterial pressure; in addition, they decrease inotropic effects, resulting in
decreased myocardial oxygen demand.

30. Indications
(1)Calcium-channel blockers are used in stable (exertional) angina that
is not controlled by nitrates and B-blockers and in patients for
whom
B-blocker therapy is inadvisable. Combination therapy—with nitrates,
Beta-blockers, or both—may be most effective.
(2) These agents, alone or with a nitrate, are particularly valuable in
the treatment of Prinzmetal angina.
They are considered the drug of choice in treatment of angina at rest.

31. Individual agents
Diltiazem and verapamil
(a) These drugs produce negative inotropic effects, and patients must
be monitored closely for signs of developing cardiac
decompensation (i.e., fatigue, shortness of breath, edema,
paroxysmal nocturnal dyspnea).

32. (b) Patients should be monitored for signs of developing bradyarrhythmias and
heart block because these agents have negative chronotropic effects.
(c) Verapamil frequently causes constipation that must be treated as needed to
prevent straining at stool, which could cause an increased oxygen demand
(Valsalva maneuver).
Verapamil is not recommended in patients with sick sinus syndromes, AV
nodal disease, or heart failure (HF).

33. Nifedipine
 This calcium-channel blocker is believed to possess the greatest
degree of negative inotropic effects compared to the newer second-
generation members of this group, amlodipine and felodipine.
 Nifedipine 10 mg (chewed or swallowed) has been used to treat
Prinzmetal angina

34. (c) Its potent peripheral dilatory effects can decrease coronary perfusion and
produce excessive hypotension, which can aggravate myocardial ischemia.
(d) Dizziness, light-headedness, and lower extremity edema are the most
common adverse effects, but these tend to disappear with time or dose
adjustment.

35.  Amlodipine, clevidipine, felodipine, isradipine , nicardipine, and nisoldipine
are second-generation dihydropyridine derivative, calcium-channel
blockers. They have been used effectively as once- or twice-a-day agents
owing to their long activity.
 Because of the potent negative inotropic effects of these agents, they are
not recommended in patients with HF (amlodipine has been shown to have
less negative potential in HF than other members of the class).

36. Antiplatelet agents
Aspirin
 Based on the 2007 Focused Guidelines for Patients With Chronic Stable
Angina, a class I a recommendation states that aspirin should be started at
75 to 162 mg/day and continued indefinitely in all patients unless
contraindicated

37. Clopidogrel
 Clopidogrel is also a thienopyridine derivative related to ticlopidine,
but it possesses antithrombotic effects that are greater than those of
ticlopidine.
 Clopidogrel is a therapeutic option in those angina patients who cannot
take aspirin because of contraindications.
 Doses of 75 mg daily are recommended to prevent the development of
acute coronary syndromes.

38. ACE Inhibitors and Angiotensin
Receptor Blockers
ACE inhibitors should be initiated in all patients to reduce mortality, and prevent
the development of heart failure.
 Captopril: 6.25 to 12.5 mg initially; target dose 50 mg two or three times
 daily.
 Enalapril: 2.5 to 5 mg initially; target dose 10 mg twice daily.
 Lisinopril: 2.5 to 5 mg initially; target dose 10 to 20 mg once daily.
 Ramipril: 1.25 to 2.5 mg initially; target dose 5 mg twice daily or 10 mg once
daily.
 Candesartan: 4 to 8 mg initially; target dose 32 mg once daily.
 Valsartan: 40 mg initially; target dose 160 mg twice daily.

39. Ranolazine
 It may be related to reduction in calcium overload in ischemic myocytes through
inhibition of the late sodium current
 Based on controlled trials, the improvement in exercise time is a modest increase of
15 to about 45 seconds compared with placebo.
 It should be used in combination with amlodipine, β-blockers, or nitrates.
 The most common adverse effects are dizziness, headache, constipation, and nausea.
 Ranolazine should be started at 500 mg twice daily and increased to 1,000 mg twice
daily if needed based on symptoms.
 Baseline and follow up ECGs should be obtained to evaluate effects on the QT
interval.

40. Ivabradine
 Ivabradine acts by reducing the heart rate via
specific inhibition of the pacemaker current.
Contraindication
 Ivabradine is contraindicated in sick sinus
syndrome.
 It should also not be used concomitantly with
potent inhibitors of CYP3A4, including azole
antifungals (such
as ketoconazole), macrolide antibiotics, nefazodo
ne and the antiretroviral drugs
 Use of ivabradine with verapamil or diltiazem is
contraindicated.

41. Non pharmacological treatment
 PCI
 CABG

42. Reference
• Comprehensive Pharmacy Review- Leon Shargel
• Text Book Of Pharmacotherapy- T.Dipiro

43. Thank you