ANTI ANGINA

INTRODUCTION
Atherosclerotic disease of the coronary arteries
Coronary artery disease (CAD)
Ischemic heart disease (IHD)
Most common cause of mortality worldwide
CAUSES:
1. Atherosclerotic lesions in coronary arteries
obstruction of blood flow, imbalance in
myocardial oxygen supply and demand
stable angina or an acute coronary syndrome
(myocardial infarction [MI] or unstable angina)
2. Vascular smooth muscle spasm impede
cardiac blood flow reduced perfusion
ischemia anginal pain
 ANGINA PECTORIS
Typical angina pectoris
Sudden, severe, crushing chest pain
Radiate to the neck, jaw, back, and arms
Dyspnea
Atypical symptoms: indigestion, nausea,
vomiting, or diaphoresis
Stable angina: Transient, self-limited
episodes of myocardial ischemia; do not
result in cellular death
Acute coronary syndromes and chronic
ischemia deterioration of cardiac function,
heart failure, arrhythmias, and sudden death
 TREATMENT
All patients with IHD and angina should
receive guideline-directed medical therapy
Emphasis on lifestyle modifications to
reduce cardiovascular morbidity and
mortality:
Smoking cessation
Physical activity
Weight management
Management of modifiable risk factors
(hypertension, diabetes, dyslipidemia)
OVERVIEW OF ANTI-
ANGINALS
 TYPES OF ANGINA
1) Stable, effort-induced, classic, or
typical angina
2) Unstable angina and
3) Prinzmetal, variant, vasospastic,
or rest angina.
) Caused by increased myocardial
demand and decreased myocardial
perfusion
 STABLE ANGINA
Most common form of angina
Typical angina pectoris
Usually characterized by a short-lasting
burning, heavy, or squeezing feeling in the
chest
Atypical: extreme fatigue, nausea, or
diaphoresis
Silent angina: may not be associated with
any symptoms
Atypical presentations are more common
in women, diabetic patients, and the
elderly
 CLASSIC ANGINA
Caused by the reduction of coronary
perfusion: Fixed obstruction of a coronary
artery (atherosclerosis) Blood supply
cannot increase vulnerable to ischemia
Increased demand:
Physical activity, emotional stress or excitement,
or any other cause of increased cardiac workload
Relieved by rest or nitroglycerin
Stable angina: When the pattern of the chest
pains and the amount of effort needed to
trigger the chest pains do not vary over time
 PRINZMETAL ANGINA
Uncommon pattern of episodic angina
Occurs at rest
Due to coronary artery spasm
Caused by decreased blood flow to the heart
muscle from the spasm of the coronary artery
May have significant coronary atherosclerosis
Angina attacks are unrelated to physical
activity, heart rate, or blood pressure
Responds promptly to coronary vasodilators:
nitroglycerin and calcium channel blockers
 UNSTABLE ANGINA
Classified between stable angina and MI
Chest pain occurs with increased frequency,
duration, and intensity and can be precipitated by
progressively less effort
Any episode of rest angina longer than 20 minutes
New-onset angina
Increasing (crescendo) angina
Sudden development of shortness of breath
Not relieved by rest or nitroglycerin.
Form of acute coronary syndrome and requires
hospital admission and more aggressive therapy
to prevent progression to MI and death.
BLOOD FLOW IN CORONARY
ARTERIES
BLOOD FLOW IN CORONARY
ARTERIES
 ACUTE CORONARY
SYNDROMES
Emergency
Results from rupture of an atherosclerotic plaque
and partial or complete thrombosis of a coronary
artery
Disruption of an atherosclerotic lesion (mc)
platelet activation of the coagulation cascade and
vasoconstriction intraluminal thrombosis and
vascular occlusion necrosis of the cardiac muscle
MI (necrosis) is typified by increases in the serum
levels of biomarkers such as troponin I/T and
creatine kinase-MB
May present as ST-segment elevation myocardial
infarction, nonST-segment elevation myocardial
 TREATMENT STRATEGIES
Four types of drugs: used either alone or
in combination:
1. -blockers
2. Calcium channel blockers
3. Organic nitrates
4. Sodium channelblocking drug:
ranolazine
. Balance the cardiac oxygen supply and
demand: by affecting blood pressure,
venous return, heart rate, and contractility
TREATMENT OF ANGINA WITH
COMORBIDITIES
TREATMENT ALGORITHM FOR
ANGINA
1. BETA-BLOCKERS
 1. BETA-BLOCKERS
Decrease the oxygen demands of the myocardium by
blocking 1 receptors decreased heart rate,
contractility, cardiac output, and blood pressure
Reduce myocardial oxygen demand during exertion and
at rest reduce both the frequency and severity of
angina attacks
Increase exercise duration and tolerance in patients with
effort-induced angina
Recommended initial antianginal therapy in all patients
unless contraindicated. [EXCEPTION: vasospastic angina
-ineffective and may actually worsen symptoms]
Reduce the risk of death and MI in patients with prior MI
Improve mortality in patients with hypertension and
heart failure with reduced ejection fraction
 1. BETA-BLOCKERS
Agents with intrinsic sympathomimetic activity (ISA):
Pindolol: avoided in patients with angina and those with prior MI
Propranolol: prototype (non-cardioselective)
Metoprolol and Atenolol: are preferred
All -blockers are nonselective at high doses and can
inhibit 2 receptors
Avoided in patients with severe bradycardia
Used in patients with diabetes, peripheral vascular
disease, and chronic obstructive pulmonary disease
Nonselective -blockers: Avoided in patients with asthma
DO NOT discontinue -blocker therapy abruptly.
Dose should be gradually tapered off over 2 to 3 weeks to avoid
rebound angina, MI, and hypertension
2. CALCIUM CHANNEL
BLOCKERS
 2. CALCIUM CHANNEL
BLOCKERS
Calcium is essential for muscular contraction
Hypoxia membrane depolarization
calcium influx in ischemia promotes the
activity of several ATP-consuming enzymes
depletion of energy stores and worsening the
ischemia
MOA: Inhibit entry of calcium into cardiac and
smooth muscle cells of the coronary and
systemic arterial bed arteriolar
vasodilatation decrease in smooth muscle
tone and vascular resistance
Primarily affect the resistance of peripheral
and coronary arteriolar smooth muscle
 2. CALCIUM CHANNEL
BLOCKERS
Treatment of effort-induced angina:
vascular resistance myocardial oxygen
consumption afterload
Treatment in vasospastic angina:
Relaxation of the coronary arteries
Verapamil: mainly affects the myocardium
Amlodipine: greater effect on smooth
muscle in the peripheral vasculature
Diltiazem: intermediate in its actions
All calcium channel blockers lower blood
pressure
2. CCB: DIHYDROPYRIDINES
1. Amlodipine:
oral dihydropyridine
arteriolar vasodilator
minimal effect on cardiac conduction
vasodilatory effect: useful in the treatment of
variant angina caused by spontaneous coronary
spasm
2. Nifedipine:
extended-release oral formulation
. Short-acting dihydropyridines: AVOIDED in
CAD
evidence of increased mortality after an MI and
an increase in acute MI in hypertensive patients
 2. CCB:
NON-DIHYDROPYRIDINES
1. Verapamil:
slows atrioventricular (AV) conduction directly
decreases heart rate, contractility, blood pressure, and
oxygen demand
greater negative inotropic effects than amlodipine
weaker vasodilator
Contraindications: preexisting depressed cardiac function or
AV conduction abnormalities
2. Diltiazem:
slows AV conduction, decreases the rate of firing of the sinus
node pacemaker
coronary artery vasodilator
variant angina: relieve coronary artery spasm
AVOID: heart failure: negative inotropic effect aggravate HF
 3. ORGANIC NITRATES
Reduction in myocardial oxygen demand relief
of symptoms.
Effective in stable, unstable, and variant angina.
Mechanism of action
Intracellular conversion to nitrite ions nitric oxide
activation of guanylate cyclase cellular cyclic
guanosine monophosphate (cGMP)
dephosphorylation of the myosin light chain vascular
smooth muscle relaxation
Nitroglycerin:
Dilation of the large veins preload (venous return
to the heart) work of the heart
Main mechanism of action in the treatment of angina
Dilate the coronary vasculature blood supply
to the heart muscle
3. ORGANIC NITRATES: MOA
 3. ORGANIC NITRATES:
PHARMACOKINETICS
Differ in their onset of action (1 min for NTG to
30 min for ISMN) and rate of elimination
1. NITROGLYCERINE:
Prompt relief of an angina attack precipitated by
exercise or emotional stress
DOC: Sublingual (or spray form) nitroglycerin
Commonly administered via the sublingual or
transdermal route (patch or ointment) (avoid
significant hepatic first-pass effect)
2. ISOSORBIDE MONONITRATE:
improved bioavailability and long duration of action
(stability against hepatic breakdown)
3. ORAL ISOSORBIDE DINITRATE:
Denitration to two mononitrates (both with
antianginal activity
ORGANIC NITRATES:
PHARMACOKINETICS
 3. ORGANIC HITRATES:
ADVERSE EFFECTS
1. Headache:
most common adverse effect of nitrates

High doses postural hypotension,

facial flushing, and tachycardia

Phosphodiesterase type 5 inhibitors

(sildenafil) potentiation of action of
nitrates dangerous hypotension
 3. ORGANIC HITRATES:
ADVERSE EFFECTS
2. Tolerance:
Develops rapidly as the blood vessels become
desensitized to vasodilation
Overcome by providing a daily nitrate-free
interval to restore sensitivity to the drug (interval
of 10 to 12 hours) at night (demand on the heart)
Nitroglycerin patches: worn for 12 hours and then
removed for 12 hours
Variant angina worsens early in the morning
(circadian catecholamine surges) nitrate-free
interval in late afternoon
 4. SODIUM CHANNEL
Eg: Ranolazine
BLOCKERS
Inhibits the late phase of the sodium current (late I Na),
improving the oxygen supply and demand
Inhibition of late INa reduces intracellular sodium and
calcium overload improving diastolic function
Anti-anginal AND antiarrhythmic properties
Treatment of chronic angina (alone or in combination)
Used in patients who have failed other antianginal
therapies.
Extensive hepatic metabolism: mainly by the CYP3A
and CYP2D6 and is a substrate of P-glycoprotein
Drug interactions
Prolong the QT interval avoided with other drugs
that cause QT prolongation
SUMMARY OF ANTI-
ANGINALS
SUMMARY OF ANTI-
ANGINALS
SUMMARY OF ANTI-
ANGINALS