2. Over-View of Angina
▪ Angina pectoris refers to a strangling or
pressure-like pain caused by cardiac ischemia.
▪ The pain is usually located substernally but
sometimes perceived in the neck, shoulder
and arm, or epigastrium.
3. Pathophysiology of Angina
1. Atherosclerotic Angina
▪ Atherosclerotic angina is also known as angina of effort or classic
angina.
▪ It is associated with atheromatous plaques that partially occlude
one or more coronary arteries.
▪ It is usually characterized by a short-lasting burning, heavy or
squeezing feeling in the chest.
▪ Atherosclerotic angina constitutes about 90% of angina cases.
4. Pathophysiology of Angina
2. Vasospastic Angina
▪ Vasospastic angina, also known as rest angina, variant angina, or
Prinzmetal’s angina, is responsible for 10% of cases.
▪ It involves reversible spasm of coronaries, usually at the site of an
atherosclerotic plaque.
▪ Spasm may occur at anytime, even during sleep.
5. Pathophysiology of Angina
3. Unstable Angina
▪ Unstable or crescendo angina, also known as acute coronary
syndrome, is characterized by increased frequency and severity of
attacks that result from a combination of atherosclerotic plaque,
platelet aggregation at fractured plaques, and vasospasm.
▪ Unstable angina is thought to be the immediate precursor of a
myocardial infarction, and is treated as medical emergency.
6. Therapeutic Strategies
▪ The defect that causes anginal pain is inadequate myocardial
oxygen delivery to meet the myocardial oxygen requirement.
▪ The major therapeutic aims in the treatment of angina are direct
at:
• Increasing myocardial oxygen delivery (coronary vasodilation)
to ischemic areas
• Reducing overall myocardial oxygen demand (reduce heart rate,
contractility, preload and afterload).
7. Treatment Strategies
Pharmacological Therapies
▪ Traditional pharmacologic therapies include:
1. The nitrates
2. The calcium channel blockers
3. The b-adrenergic blockers
The nitrates, calcium channel blockers and b blockers all reduce
the oxygen requirement in atherosclerotic angina.
9. The Nitrates
Mechanism of Action
▪ Nitrates release nitric oxide (NO) within smooth muscle cells,
probably through the action of the mitochondrial enzyme
aldehyde dehydrogenase-2 (ALD2).
▪ Nitric oxide stimulates guanylyl cyclase and cause an increase of
the second messenger cGMP (cyclic guanosine monophosphate).
▪ Elevated cGMP leads to smooth muscle relaxation by
dephosphorylation of myosin light-chain phosphate.
10. The Nitrates
Pharmacokinetic Features
▪ Nitroglycerine is available in the forms that provide a range of
durations of action from 10-20 min (sublingual for relief of acute
attacks) to 8-10 h (transdermal for prophylaxis).
▪ Nitroglycerin is rapidly denitrated in the liver and in smooth
muscles – first to dinitrate (glyceryl dinitrate), which retains a
significant vasodilating effect; and more slowly to the
mononitrate, which is less active.
11. The Nitrates
Pharmacokinetic Features
▪ Isosorbide dinitrate is another commonly used nitrate which is
available in sublingual and oral forms.
▪ Isosorbide dinitrate is rapidly denitrated in the liver and smooth
muscles to isosorbide mononitrate, which is also active.
▪ Isosorbide mononitrate is available as a separate drug for oral use.
12. The Nitrates
Toxicity of Nitrates
▪ The most common toxic effects of nitrates are the responses
evoked by vasodilation.
▪ These include:
• Tachycardia (from the baroreceptor reflex)
• Orthostatic hypotension (a direct extension of venodilator effect)
• Throbbing headache (from meningeal artery vasodilation)
14. The Calcium Channel-Blockers
Classification
▪ Several types of calcium channel
blockers are approved for use in
angina.
a) Dihydropyridine calcium channel
blockers
▪ Amlodipine
▪ Felodipine
▪ Nicardipine
▪ Nifedipine
▪ Nisoldipine
b) Non-Dihydropyridine calcium
channel blockers
▪ Diltiazem
▪ Verapamil
15. The Calcium Channel-Blockers
Mechanism of Action
▪ Calcium channel blockers block voltage-gated L-type calcium
channels in cardiac and smooth muscles, and reduce intracellular
calcium concentration and muscle contractility.
▪ None of these channel blockers interfere with calcium-dependent
neurotransmission or hormone release because these processes
use different type of calcium channels that not blocked by these
agents.
16. The Calcium Channel-Blockers
Mechanism of Action
▪ Calcium channel blockers block voltage-gated L-type calcium
channels in cardiac and smooth muscles, and reduce intracellular
calcium concentration and muscle contractility.
▪ None of these channel blockers interfere with calcium-dependent
neurotransmission or hormone release because these processes
use different type of calcium channels that not blocked by these
agents.
17. The Calcium Channel-Blockers
Pharmacokinetic Features
▪ Most of these agents have low and variable oral bioavailability because all are
subject to extensive first-pass metabolism.
▪ The exception is amlodipine which has substantially longer half-life (more
than 40h), although it is extensively metabolized.
18. The Calcium Channel-Blockers
Toxicity
▪ The calcium channel blockers
cause:
▪ Constipation
▪ Pretibial edema
▪ Nausea
▪ Flushing
▪ Dizziness.
▪ Most serious adverse effects
include:
▪ Heart failure
▪ AV blockade
▪ Sinus node depression
▪ These are most common with
verapamil and least common with
dihydropyridines.
20. The b-Adrenergic Blockers
Effects and Clinical Use
▪ The role of beta blockers in angina depends mainly on decreasing myocardial
oxygen consumption by:
▪ Limiting the increased heart rate associated with exercise and anxiety.
▪ Limiting the increased force of contraction associated with the same
stimuli.
▪ Increasing the length of diastole, the period during which coronary blood
flow occurs.
▪ Beta blockers are used only for prophylactic therapy of angina; they are of no
value in acute attacks.
▪ They are effective in preventing exercise-induced angina but are ineffective
against the vasospastic form.
21. The b-Adrenergic Blockers
Toxicity
▪ The common side effects are:
▪ Lethargy
▪ Fatigue
▪ Bradycardia
▪ Bronchospasm.
▪ Rebound worsening of angina, myocardial infarction or tachycardia has been
reported when beta-blockers are suddenly withdrawn.
22. Newer Drugs
▪ Ranolazine appears to act mainly by reducing a late, prolonged
sodium current in myocardial cells.
▪ The decrease in intracellular sodium cause an increase in calcium
expulsion via the Na/Ca transporter and a reduction in cardiac
force and work.
▪ Ivabradine, an investigational drug, inhibits the If sodium current
in the sinoatrial node.
▪ The reduction in this hyperpolarization-induced inward pacemaker
current results in decreased heart rate and consequently
decreased cardiac work.
