Angina pectoris is caused by transient episodes of myocardial ischemia due to an imbalance in the myocardial oxygen supply-demand relationship. There are three main types of angina: stable angina, which is triggered by exertion and relieved by rest; unstable angina, which occurs at rest and is a medical emergency; and Prinzmetal angina, which occurs due to coronary artery spasm. Treatment strategies for angina include nitrates like nitroglycerin which relieve symptoms rapidly, calcium channel blockers which prevent calcium entry and relax blood vessels, beta blockers which reduce the heart's oxygen demand, and ranolazine which inhibits sodium channels to reduce the heart's work.

1. Laraib
M.Phil pharamcology

2. Angina pectoris, the primary symptom of
ischemic heart disease, is caused by
transient episodes of myocardial ischemia
It is a characteristic sudden, severe,
crushing chest pain that may radiate to
the neck, jaw, back, and arms
ANGINA

3. Ischemia results due to an imbalance in the myocardial oxygen supply–
demand relationship.
This imbalance may be caused by an increase in myocardial oxygen
demand (which is determined by heart rate,ventricular contractility, and
ventricular wall tension) or by a decrease in myocardial oxygen supply
(primarily determined by coronary blood flow, but occasionally modified
by the oxygen-carrying capacity of the blood) or sometimes by both
PATHOPHYSIOLOGY OF ANGINA

5. Stable angina, effort-induced angina, classic or typical angina
Unstable angina
 Prinzmetal, variant, vasospastic, or rest angina
TYPES OF ANGINA

6. Classic angina reduction of coronary perfusion due to a fixed obstruction
of a coronary artery produced by atherosclerosis.
Fixed obstruction the blood supply cannot increase, and the heart becomes
vulnerable to ischemia whenever there is increased demand, such as that produced by
physical activity, emotional stress or excitement, or any other cause of increased cardiac
workload
A. Stable angina, effort-induced angina, classic or typical
angina

7. Typical angina pectoris is promptly
relieved by rest or nitroglycerin.
When the pattern of chest pain
and effort needed to trigger the chest
pains do not vary over time, the
angina is named “stable angina.”

8. In some patients, anginal
symptoms may occur
without any increase in
Myocardial O2 demand, but
rather as a consequence of
an abrupt reduction in
blood flow, as might result
from coronary thrombosis
B. Unstable angina

9. Any episode of rest angina longer than 20 minutes,
any new-onset angina, any increasing angina, or
even sudden development of shortness of breath
The symptoms are not relieved by rest or nitroglycerin. Unstable angina is a
form of acute coronary syndrome and requires hospital admission and more
aggressive therapy to prevent progression to MI and death

10. uncommon pattern of episodic angina that occurs at rest and is due to coronary
artery spasm ( localized vasospam)
Prinzmetal angina generally responds promptly to coronary vasodilators, such as
nitroglycerin and calcium channel blockers
C. Prinzmetal, variant, vasospastic, or rest angina

11. TREATMENT STRATEGIES

12. These compounds are effective in stable, unstable, and variant angina.
These include:
 Nitroglycerine
 Isosorbide dinitrate
 Isosorbide mononitrate
 Inhaled NO
ORGANIC NITRATES

13. Phosphorylation of the myosin light chain regulates the maintenance of the contractile state
in smooth muscle.
Nitrites, organic nitrates, lead to the formation of the reactive gaseous free radical NO and
related NO-containing compounds
NO can activate guanylyl cyclase, increase the cellular level of cyclic GMP, activate PKG,
and modulate the activities of cyclic nucleotide phosphodiesterases (PDEs 2, 3, and 5) in a
variety of cell types.
In smooth muscle, the net result is reduced phosphorylation of myosin light chain, reduced
Ca2+ concentration in the cytosol, and relaxation
Mechanism of action

15. Nitrates such as nitroglycerin cause dilation of the large veins, which
reduces preload (venous return to the heart) and, therefore, reduces the
work of the heart
Nitrates also dilate the coronary vasculature, providing an increased blood
supply to the heart muscle

16. Because of its rapid onset of action (1–3 minutes), sublingual nitroglycerin is the most
frequently used agent for the immediate treatment of angina.
Because its duration of action is short (not exceeding 20–30 minutes), it is not suitable for
maintenance therapy
Significant first-pass metabolism of nitroglycerin occurs in the liver. Therefore, it is
commonly administered via the sublingual or transdermal route (patch or ointment)
Clinical Use & pharmacokinetics

17. Headache is the most common adverse effect of nitrates.
High doses of nitrates can also cause postural hypotension, facial flushing, and
tachycardia.
Phosphodiesterase type 5 inhibitors such as sildenafil potentiate the action of the
nitrates. To preclude the dangerous hypotension that may occur, this combination is
contraindicated
Adverse effects

18. 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.
This interval of 10 to 12 hours is usually taken at night because demand on the heart is
decreased at that time.
However, variant angina worsens early in the morning, perhaps due to circadian
catecholamine surges. Therefore, the nitrate-free interval in these patients should occur in the
late afternoon
Tolerance

19. Ca2+ CHANNELANTAGONISTS

20. Voltage-sensitive Ca2+ channels (L-type or slow channels) mediate the entry of extracellular Ca2+ into
smooth muscle and cardiac myocytes in response to electrical depolarization.
In both smooth muscle and cardiac myocytes, Ca2+ is a trigger for contraction, albeit by different
mechanisms
Calcium entry into the myocyte first triggers intracellular calcium release; the released calcium then
binds the regulatory protein troponin, resulting in a calcium-troponin complex which allows actin and
myosin to interact and contract.
The sequence of events is the same in vascular smooth muscle cells, except that a calcium-calmodulin
complex instead of calcium-troponin.
The net effect is vasodilatation; the ensuing fall in blood pressure decreases cardiac work and may
contribute to the efficacy of these drugs in the patient with angina.
Mechanism of action

22. Exertional Angina increase in blood flow owing to coronary arterial
dilation, from a decrease in myocardial oxygen demand (secondary to a decrease in
arterial blood pressure, heart rate, or contractility), or both
vasospastic angina due to relaxation of the coronary arteries
Clinical uses

23. • vasodilatory effect of amlodipine is useful in the
treatment of variant angina caused by spontaneous
coronary spasm
• Oral dihydropyridine
amlodipine
• administered as an extended-release oral
formulationnifedipine
A. Dihydropyridine calcium channel blockers

24. verapamil
slows atrioventricular (AV) conduction
directly and decreases heart rate,
contractility, blood pressure, and oxygen
demand
Contraindicated in patients with preexisting
depressed cardiac function
diltiazem
also slows AVconduction, decreases the
rate of firing of the sinus node
pacemaker and is also a coronary artery
vasodilator
can relieve coronary artery spasm and is
particularly useful in patients with variant
angina
B. Nondihydropyridines

25. Most common ADR is constipation
Othes include:
Headache, flushing, peripheral edema, hypotension, rebound tachycardia
Adverse effects

26. BETA-BLOCKING DRUGS
The β-adrenergic blockers decrease the oxygen demands resulting in decreased heart rate,
contractility, cardiac output, and blood pressure.
These agents reduce myocardial oxygen demand during exertion and at rest. As such, they can
reduce both the frequency and severity of angina attacks.
β-Blockers are recommended as initial antianginal therapy in all patients unless
contraindicated.
The exception to this rule is vasospastic angina, in which β-blockers are ineffective and may
actually worsen symptoms

28. Propranolol is the prototype for this class of compounds, but it is not cardioselective Thus,
other β-blockers, such as metoprolol and atenolol, are preferred.
Nonselective β-blockers should be avoided in patients with asthma. All β-blockers are
nonselective at high doses and can inhibit β2 receptors
β-Blockers should be avoided in patients with severe bradycardia.
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

29.  Bradycardia
 Worsen peripheral vascular disease
 Sleep distubances
 Inhibit beta-2 mediated bronchodilation in asthamatics
Adverse effects

30. A decreased efflux or increased influx of sodium may cause cellular sodium overload
The peak sodium current underlies excitability and conduction in heart muscle, but a late
sodium current flowing after the peak contributes to maintaining and prolonging the action
potential plateau, and also to intracellular sodium loading, that in turn increases intracellular
calcium with consequent effects on arrhythmia and diastolic function.
Late sodium current is pathologically increased in both genetic and acquired heart disease,
making it an attractive target for therapy to treat arrhythmia, heart failure, and angina. Late INa
may represent a major source for increased intracellular sodium during ischemia.
Sodium channel blocker

31.  Ranolazine inhibits the late inward sodium current in heart muscle. Inhibiting that
current leads to reductions in elevated intracellular calcium levels. This in turn leads
to reduced tension in the heart wall, leading to reduced oxygen requirements for the
muscle

33. It is indicated for the treatment of chronic angina and may be used alone or in
combination with other traditional therapies.
It is most often used in patients who have failed other antianginal therapies.
Ranolazine is extensively metabolized in the liver, mainly by the CYP3A family and
also by CYP2D6.
It is also a substrate of P-glycoprotein. As such, ranolazine is subject to numerous drug
interactions

34.  Constipation
 Headache
 Edema
 QT interval prolongation
Adverse effects

36. Aspirin reduces the incidence of MI and death in patients with unstable angina.
In addition, low doses of aspirin appear to reduce the incidence of MI in patients with
chronic stable angina.
aspirin inhibits prostaglandin action and therefore avoid clotting followed by
preventing thromboxane A2, the platelet-aggregating substance, formation
ANTI-PLATELET

38. Prevention doses: 81 to 325mg daily or every other day;
Treatment doses: 160 to 325mg once daily
One of the main adverse effects of aspirin is gastric upset. Especially when taken in
high doses the risk of gastrointestinal bleeding increases.
Other side effects include:
Nausea, heartburn, thrombocytopenia, prolonged bleeding time Rey's syndrome,
anaphylaxis and angioedema.

39. Atorvastatin
Fluvastatin
Lovastatin
Pravastatin
Simvastatin
The most effective impact of statins on the patients suffering from anginal attacks is
believed to be through lowering the LDL cholesterol level in plasma
Statins or HMG CoA reductase inhibitors

40. HMG CoA reductase is an enzyme responsible for mevalonate production.
In lipid forming pathway, mevalonate is finally transformed to cholesterol.
Statins which have some structural similarities with this HMG CoA reductase, can
competitively attach to the enzyme and block it.
Therefore, the speed of cholesterol biosynthesis will decline.
Mechanism of action

41. statins

42. Stenting —or "percutaneous coronary intervention" ( PCI)
Is a procedure that uses a flexible plastic catheter with a tiny balloon at the end to dilate
narrowed arteries in the heart.
A metal stent is then placed at the site of a major blockage to hold the artery open.
This procedure (which also used to be called "angioplasty")
Interventional treatments

44. CABG , is a surgery used to treat narrowed or blocked arteries that supply blood to the
heart.
This is accomplished by going around or “bypassing” the blocked artery with a healthy
vessel called a “graft” that is taken from the leg, arm or chest.
The graft will now carry the blood around the blockage to improve the blood flow to the
heart.
Coronary artery bypass grafting

46. The university of chicago chronic angina program considering for alternative methods
to treat chronic ischemic heart disease.
One option currently under investigation involves "angiogenesis," the formation of new
blood-flow pathways.
Physicians are studying the use of gene therapy to trigger the creation or enlargement of
blood vessels to the heart; thereby improving previously impaired blood flow.
These substances are delivered directly into the arteries. If successful, this gene therapy
treatment may either reduce or stop angina, and decrease the severity of heart disease.
Angiogenesis/Gene Therapy

47. Cardiac Center heart surgeons are using lasers to reduce cardiac chest pain.
Transmyocardial laser revascularization (TMR) is an FDA-approved surgical technique
that uses lasers to create small holes in heart muscle.
These laser "channels" may destroy nerve fibers that cause pain or they may stimulate
new blood vessels to grow
Transmyocardial Laser Revascularization

48. Crataegus hawthorn, has acquired the
reputation in modern herbal literature as
an important tonic for the cardiovascular
system that is particularly useful for angina.
Crataegus leaves, flowers, and fruits contain
a number of biologically active substances,
such as oligomeric procyanins, flavonoids,
and catechins.
From current studies, Crataegus extract appears to have antioxidant properties and can inhibit
the formation of thromboxane as well
Medicinal plants

49. Crataegus extract antagonizes the increases in cholesterol, triglyceride, and
phospholipid levels in low-density lipoprotein (LDL) and very low-density lipoprotein
in rats fed a hyperlipidemic diet; thus, it may inhibit the progression of atherosclerosis.

50. In recent decades, research has focused on garlic's
use in preventing atherosclerosis.
Garlic, like many of the other herbal
medicines discussed previously, has
demonstrated multiple beneficial
cardiovascular effects.
A number of studies have demonstrated these effects that include lowering blood
pressure, inhibiting platelet aggregation, enhancing fibrinolytic activity, reducing serum
cholesterol and triglyceride levels
Garlic (Allium sativum)

51. Useful as an antianginal drug because
It has been shown to dilate coronary arteries
S. Miltiorrhiza also inhibits platelet aggregation
Salvia miltiorrhiza