This document discusses anti-ischemic drugs used to treat angina. It defines ischemia as insufficient blood supply and oxygen delivery to tissues. The main causes of ischemia are discussed as atherosclerosis and blood clots blocking arteries. Different types of angina - stable, unstable, and variant - are also defined. The document then summarizes the mechanisms and uses of several classes of anti-ischemic drugs - nitrates, beta-blockers, calcium channel blockers, and antiplatelet drugs. Specific drugs within each class are mentioned along with their mechanisms of action, indications, contraindications and importance in treating different forms of angina and acute coronary syndromes.
2. • Ischemia is a restriction in
blood supply to tissues,
causing a shortage of oxygen
that is needed for cellular
metabolism.
• Ischemia is generally caused
by problems with blood
vessels, with resultant
damage to or dysfunction of
tissue.
• Ischemia comprises not only
insufficiency of oxygen, but
also reduced availability of
nutrients and inadequate
removal of metabolic wastes
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3. • One of the main causes of ischemia is atherosclerosis. That’s where
plaque collects in the arteries.
• Plaque is a hard, sticky substance that’s made mostly of fat. It builds
up slowly, but over time, it .
• This slows the blood flow because , blood has less space to move
through.
• Ischemia can be also due to blood clot. Plaque itself is a problem. But
sometimes, it can This causes a sudden
and serious stoppage to your blood flow..
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4. What is atherosclerosis?
• Atherosclerosis is a narrowing of the arteries caused by a buildup of
plaque. It’s also called arteriosclerosis or hardening of the arteries.
Arteries are the blood vessels that carry oxygen and nutrients from
your heart to the rest of your body.
• As you get older in your arteries and
form plaque. The buildup of plaque makes it difficult for blood to flow
through your arteries.
• This buildup may occur in any artery in your body and can result in a
shortage of blood and oxygen in various tissues of your body. Pieces
of plaque can also break off, causing a blood clot. Atherosclerosis can
lead to heart attack, stroke, or heart failure if left untreated.
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5. Pathophysiology of atherosclerosis
is considered one of the main triggers of
atherosclerosis. The increase in plasma cholesterol levels results in
that allow the
• Circulating to the endothelial cells that express
adhesion molecules , Once in the sub endothelial space, the monocytes
acquire macrophage characteristics
in the sub endothelial space are oxidised and become strong
These processes only enhance
The end result is a cascade of vascular
modifications .
• Clinical sequelae of atherosclerosis are vessel narrowing with symptoms
due to plaque instability.
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7. ANGINA PECTORIS
• Angina pectoris , is
caused by transient episodes of myocardial ischemia that are due to
an
• Angina pectoris has three patterns:
1) effort-induced, classic, or typical angina;
2) ; and
3) , variant, vasospastic, or rest angina.
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8. STABLE ANGINA
• Classic angina is the form of angina and, therefore, is
also called typical angina pectoris.
• It is usually characterized by a
• Classic angina is caused by the reduction of coronary perfusion due to
a .
• When the pattern of the chest pains and the amount of effort needed
to trigger the chest pains do not vary over time, the angina is named
“stable angina.”
• Typical angina pectoris is promptly
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9. Unstable angina
• Unstable angina is classified In
unstable angina, chest pain occurs
• The symptoms are not relieved by rest or nitroglycerin. Unstable
angina is a and requires hospital
admission and more aggressive therapy to prevent progression to MI
and death.
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10. Prinzmetal, variant, vasospastic, or rest angina
• Prinzmetal angina is an uncommon pattern of episodic angina that
occurs at rest and is Prinzmetal’s
angina almost always occurs when a person is at rest, usually
between These attacks can be very
painful.
• Symptoms are caused by decreased blood flow to the heart muscle
from the spasm of the coronary artery.
• Although individuals with this form of angina may have significant
coronary atherosclerosis, the
• Prinzmetal angina generally responds promptly to coronary
vasodilators, .
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13. 1. Progressive narrowing of
2. Sudden enlargement of ASO plaque.
3. Sudden
by an intracoronary thrombus following rupture or erosion of an
ASO plaque.
4. usually in association with ASO disease e.g.
5. Other causes: coronary embolism, abnormal coronary rheology slow
flow, compression of epicardial coronary artery by myocardial bridge,
coronary ectasia.
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14. 1. Heart rate.
2. Arterial pressure.
3. Myocardial inotropic state (contractility).
4. An increase in LV muscle mass (LVH).
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16. • The main indication of this group is the .
• Myocardial ischemia is the result of imbalance between myocardial
oxygen supply and demand.
• Anti ischemic drugs produce their beneficial effect by either
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17. • Mechanism of Action
• Clinical Indications
• Contraindications
• Uses in Acute Coronary Syndromes
• Nitrate Tolerance
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18. • Three organic nitrates are currently used:
• MECHANISM OF ACTION:
A. Increase coronary blood supply.
B. Decrease myocardial oxygen consumption.
C. Antiplatelet action
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19. Molecular Mechanism of Action
• Nitrates act through endothelial-independent pathway to relax all
types of vascular smooth muscle cells to varying degrees.
• Nitrates are converted to , which then
Guanylate cyclase, in turn, produces cyclic guanosine
monophosphate which leads to increased levels of
intracellular cGMP
• In platelets, increases in cGMP exert an
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21. NITRATE PREPARATIONS
• Nitroglycerin (NTG)
• Available in many formulations, parenteral, sublingual, buccal, ointment and
patch.
• It has a ; Veins take up NTG more avidly
than arteries.
• Dosages
• : 0.3-0.6 mg, onset of action is 2-5 minutes and its duration is 20-
30 minute. The usual tablet dose is 0.3 mg to 0.4 mg repeated every five minutes
for a total of three doses.
• NTG tablets are both They should be stored in atightly
capped dark bottle in the refrigerator. Prescription should be renewed every
three to six months.
• : 0.4-0.8 mg/h, the patch should be applied for only 12-14 hours each
day.
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23. Isosorbide Dinitrate (ISDN)
• The most widely
• Available as short-acting and sustained-release formulation.
• Onset of action is within 15 to 30 minutes and the duration of action is three to six
hours. There is
• Dosage:- 10 to 40 mg three times daily. There is no added benefit with 60 and 120 mg
doses.
• Tolerance has limited the usefulness of ISDN as a chronic antianginal agent.
Development of tolerance occurs despite higher plasma concentrations of ISDN during
maintenance therapy.
• To prevent the development of tolerance, it is recommended to give ISDN at 8 AM, 1 PM
and 6 PM. This regimen can offer antianginal protection for at least six hours.
• Begin with a dose of 10 mg three times daily and advance to 40 mg three times daily as
needed.
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24. Isosorbide Mononitrate (ISMIN)
• Onset of action is within 30 minutes, and the duration of action is six
to eight hours. It is completely bioavailable.
• The usual starting dose is 20 mg twice daily to be increased to 40 mg
twice daily if necessary. Seven hours interval between doses followed
by 17 hours nitrate-free interval.
• Extended (sustained) release preparation is given once daily and lasts
12 hours.
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25. CONTRAINDICATIONS
• Patients who have taken
• Patients even those without a
resting gradient across left ventricular outflow tract.
• Patients with suspected right ventricular infarction because of risk of
hypotension.
• Use cautiously in patients with severe aortic stenosis or with volume
depletion.
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26. USE OF NITRATES IN ACUTE CORONARY SYNDROMES
• IV NTG is preferable because of its short half life and feasibility of rapid
dose titration. Tolerance may develop after 24 hours with recurrence of
chest pain. Such patients respond to dose increases.
• Once the patient has been stabilized, IV NTG can be tapered gradually, and
intermittent therapy with long-acting oral nitrate can be started about 1-2
hours, before discontinuation of the nitrate infusion.
• Recent guidelines recommend the use of nitrates for the first 24 to 48
hours in patients with AMI who have an indication for nitrate therapy such
as: recurrent ischemia, heart failure or hypertension. The infusion of IV
NTG should be initiated at 5 to 10 mcg/min and gradually increased
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27. • . The goal is a 10% reduction in systolic blood pressure for
normotensive subjects and approximately a 30% reduction in systolic
blood pressure in hypertensive patients, avoiding hypotension.
• IV NTG is discontinued within 24 to 48 hours. Long acting oral
nitrates may be indicated in patients with significant residual ischemia
or heart failure.
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28. NITRATE TOLERANCE
• Attenuation and sometimes abolition of hemodynamic and antianginal
effects of nitrates.
1. Increased Superoxide
anions inactivate nitric oxide.
2. necessary for biotransformation of nitrate
to nitric oxide (NO).
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.
• Intermittent therapy with an adequate nitrate-free interval. It is thought
that a nitrate-free interval permits the generation of reduced sulfhydryl
groups
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29. 𝛃-ADRENERGIC BLOCKERS
• The β-adrenergic blockers
, resulting in decreased heart
rate, contractility, cardiac output, and blood pressure.
• These
As such, they can reduce both the frequency and severity of
angina attacks.
• Agents with intrinsic sympathomimetic activity (ISA) such as pindolol
should be avoided in patients with angina and those who have had a
MI.
.
• Thus, other β-blockers, such as are
preferred.
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34. CONTRAINDICATIONS
• In and may actually
worsen symptoms.
• β-Blockers should be .
• Nonselective β-blockers should be avoided in patients with asthma.
• [Note: It is important not to discontinue β-blocker therapy abruptly.
The dose should be gradually tapered off over 2 to 3 weeks to avoid
rebound angina, MI, and hypertension.]
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36. CALCIUM CHANNEL BLOCKERS
• Voltage-sensitive Ca2+ channels (L-type or slow channels)
albeit by different mechanisms.
• Ca2+ channel antagonists, also called
• These drugs also produce
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37. • 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,
• All calcium channel blockers are, therefore,
that cause a .
• In the treatment of effort-induced angina, calcium channel blockers
reduce myocardial oxygen consumption by decreasing vascular
resistance, thereby decreasing afterload.
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38. A. Dihydropyridine calcium channel blockers
• Amlodipine an functions mainly as an arteriolar
vasodilator. This drug has minimal effect on cardiac conduction. The
vasodilatory effect of amlodipine is
.
• Nifedipine is another agent in this class; it is usually administered as
an extended-release oral formulation.
• [Note: Short-acting dihydropyridines should be avoided in CAD
because of evidence of increased mortality after an MI and an
increase in acute MI in hypertensive patients.]
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39. slows atrioventricular (AV) conduction directly
Verapamil has greater negative inotropic effects than
amlodipine, but it is a weaker vasodilator
• Diltiazem also slows AV conduction, decreases the rate of firing of the
sinus node pacemaker, and is also a coronary artery vasodilator.
Diltiazem can relieve coronary artery spasm and is particularly useful
in patients with variant angina.
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43. DRUGS
aspirin small dose (75-325 mg)
epoprostenol but very short half life.
Clopidogrel,ticlopidine,prasugrel,ticagrelor.
abciximab-tirofiban-eptifibatide.
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