ISCHEMIC HEART DISEASES: ANGINA

PECTORIS
Halmat M. Jaafar
(MSc. Clinical pharmacy)
Hawler Medical University/ College of Pharmacy
Department of Pharmacology
Halmat.jaafar@pha.hmu.edu.iq
Halmat.jaafar@gmail.com

Definition:
Angina pectoris is a clinical syndrome, usually characterized
by episodes or paroxysms of pain or pressure in the anterior
chest. The cause is causually insufficient coronary blood flow.

• Angina is a common manifestation of CHD.

• patients with aortic stenosis, hypertension, and hypertropic
cardiomyopathy can also have Angina pectoris
 Pathophysiology
• Myocardial ischemia develops when coronary blood flow becomes
inadequate to meet myocardial oxygen demand.

• This causes myocardial cells to switch from aerobic to anaerobic

metabolism, with a progressive impairment of metabolic,
mechanical, and electrical func?ons.

• Stable
• Effort-induced pain from physical activity or
Types of emotional stress
• Relieved by rest
Angina • Predictable and reproducible
• Stable
Unstable
• Pain occurs with increasing frequency
• Unstable • Diminishes patient’s ability to work
• Has decreasing response to therapy
• May signal an oncoming MI
• Variant
Variant
• Pain due to coronary artery spasm
• Pain may occur at certain times of the day,
but is not stress induced
3 Types of
• Microvascular Angina
Angina
Microvascular angina, or Syndrome X, occurs
• Stable
when the pa?ent experiences chest pain but
has no apparent coronary artery blockage.
• Unstable
This condi?on results from poor func?oning
• Variant
•
of the ?ny blood vessels that nourish the
Pain due to coronary artery spasm
heart, arms and legs. Microvascular angina
• Pain may occur at certain times of the day, but is not stress
can occur during exercise or at rest. Reduced
induced
vasodilator capacity of the coronary
microvessels is thought to be a cause of
angina during exercise, but the mechanism of
angina at rest is not known.

Prinzmetal's Angina
-Prinzmetal’s or variant angina is caused by a
vasospasm, a spasm that narrows the coronary
artery and lessens the blood flow to the heart.

-Prinzmetal's Angina usually occurs in arteries

already narrowed by atherolsclerosis, in fact
most people with it have severe coronary
atherosclerosis in at least one major vessel.
stable and unstable angina, Prinzmetal's
Angina usually occurs when a person is at
rest or sleep and not aGer physical exer?on or
emo?onal stress.
 • Microvascular Angina
Microvascular angina, or Syndrome X, occurs
when the pa?ent experiences chest pain but
has no apparent coronary artery blockage.
This condi?on results from poor func?oning
of the ?ny blood vessels that nourish the
heart, arms and legs. Microvascular angina
can occur during exercise or at rest. Reduced
vasodilator capacity of the coronary
microvessels is thought to be a cause of
angina during exercise, but the mechanism of
angina at rest is not known.

Etiology:
1) Physical exertion :
Walking outdoors is the most common form of the
exer?ons, that produce an aMack. Isometric
exer?on of the arms as on raking leaves, pain?ng
of
liGing heavy objects also causes exer?onal angina

2) Strong emotions:
S?mulate the sympathe?cnervous system and
Increase the work of the heart. This result in an
increase in HR, BP and myocardial contrac?lity.
3) Temperature extremes: It may be either hot or cold, increases
the
workload of the heart.
• Blood vessels constricts in Response to cold climate.
• Blood vessel dilate hot s?mulus

Cold weather also cause increased metabolism to

maintain internal temperature regula?on.
4) Cigarette Smoking: causes vasoconstruc?on and
an increased HR because of nico?ne s?mula?ons
of the catecholamine releases. It also diminishes
available oxygen by increasing level of carbon
monoxide

1) Sexual Ac?vity: increase the work load and

sympathe?c s?mula?on. In a person with severe
CAD, the resul?ng extra workload of the heart
may precipitate angina

2) S?mulants: Such as cocaine, cause increased HR

and subsequent myocardial demand. S?mula?on of
catecholamine release is the precipita?ng Factor
Clinical Manifestations:
Characteristics of Angina: Angina is a clinical
syndrome characterized by discomfort in the chest, Jaw,
shoulder, back or arm. Angina pectoris produce transient
paroxysmal aMacks of substernal or precordial pain
with the following characteris?cs.
Onset – Angina can develop quickly or slowly. Loca?on:
Nearly 90% of clients experience the pain as retrosternal or
slightly to the leG of the sternum

Radia?on: The pain usually radiates to the leG

shoulder and upper arm, and may then travel
down the inner aspect of the leG arm to the
elbow, wrist and Fourth and FiGh fingers. The
pain may also radiate to the right shoulder, neck,
Jaw or epigastric region.

Dura?on: Angina usually last less than 5 minutes.

However, aMack precipitated by a heavy meal or
extreme angor may last 15 to 20 minutes.
Sensation: Clients describe the pain of angina
as squeezing, burning, pressing, choking,
aching or bursting pressure. The clients often
says the pain feels like gas, heart burn, or
indigestion.

Severity: The pain of angina is usually mild

or moderate in severity. It is often called
“discomfort”, not “pain”. Rarely is the pain
described as “severe”

Associated characteris?cs: other manifesta?on that

may accompany the pain includes:
• Dyspnea.
• Pallor
• Sweating
• Faintness
• Palpitations.
• Dizziness.
• Digestive disturbances.
 Diagnosis
• A diagnosis of stable angina is based primarily on symptoms, such as chest pain.
• A diagnosis of unstable angina is made when there is
- new onset angina that is severe and/or frequent;
- chronic stable angina who develop more frequent, severe, prolonged, or more
easily triggered episodes;
- angina at rest.

Diagnostic Tests and

Procedures
1- ECG (Electrocardiogram)
It detects and records the electrical ac?vity of the heart. Certain electrical
paMerns that the ECG detects can suggest whether CAD is likely.
However, some people with angina have a normal ECG.
• The ECG is usually normal between aMacks. During an aMack there may be a
transient ST segment depression.
• If the angina is provoked by exer?on, an exercise stress ECG should be
performed.
 ECG for stable
angina
• The one above was taken
when pa?ent was at rest

• The one below was taken aGer

exercise- a typical ST-segment
depression can be seen

Diagnostic Tests and

Procedures
2- Stress ECG Tes?ng
Typically, this test involves taking an electrocardiogram (ECG) before, during, and
aGer exercise on a treadmill or sta?onary bicycle. Pa?ents who are at risk for
a coronary event with exercise are, instead, given a drug to increase the heart
rate.
 Goals of Treatment
• All treatments for people with coronary artery disease have the
same goals:
- to decrease the effects of the disease on the quality of life and
alleviate symptoms.
- to reduce mortality due to CAD progression.

DRUG THERAPY
Improving Oxygen Demand:Supply
a.
Ratio
. Relaxa?on of resistance vessels (small arteries and arterioles)
↓TPR
→ ↓BP → ↓AGerload (Nitrates, calcium channel blockers and beta-
blockers)
b. Relaxa?on of capacitance vessels (veins and venules) ↓Venous
return, ↓heart size, ↓Preload (Nitrates and calcium channel
blockers)
c. Blockade or aMenua?on of sympathe?c influence on the heart
↓Contac?lity, ↓HR, ↓O2 demand (Beta-blockers)
d. Coronary Dila?on, Important mechanism for relieving vasospas?c
angina, ↑O2 supply (Nitrates)
 Drug
Therapy
• Currently, there are three main types of drugs used:
1) Nitrates
2) Beta blockers
3) Calcium channel blockers
4) Ranolazine,Trimetazididne and Ivabradine(read it in details)

• Nitrates or beta blockers are usually preferred for ini?al treatment of

angina, and calcium channel blockers may be added if needed.

NITRATES
• Prodrugs
• Source of Nitric Oxide
• Eg. Nitroglycerin,
Isosorbide-5-
Mononitrate Isosorbide
Dinitrate

oMechanism of ac?on
 Use of nitrates in unstable
angina
• Nitrates are also useful in the treatment of the acute coronary
syndrome of unstable angina, but the precise mechanism for
their beneficial effects is not clear.
• Because both increased coronary vascular tone and increased
myocardial oxygen demand can precipitate rest angina in these
pa?ents, nitrates may exert their beneficial effects both by
dila?ng the epicardial coronary arteries and by simultaneously
reducing myocardial oxygen demand.

Tolerance
• The clinical efficacy of nitrates in maintenance therapy of angina is
limited by tolerance when they are administered over a long period
of ?me. A nitrate-free period of at least 8 hours between doses
should be observed to reduce or prevent tolerance.
• Although the mechanisms of tolerance are not fully understood,
diminished release of NO due to reduced bio-ac?va?on and systemic
compensa?on may play a role.
 Contraindications
• Nitrates are contraindicated if intracranial pressure is raised.
• Rarely, the transdermal patches ignite when external
defibrillator electroshock are applied to the chest of pa?ents
with ventricular fibrilla?on.

early myocardial infarction

severe anemia

TOXICITY OF NITRATES
• Headache
• Increased mortality
• Recurrence of Myocardial
Infrac?on
• Dizziness
• Flushing
• Rapid heart beat
• Restlessness
• Dry mouth
• Skin rash
• Nausea
Nitroglycerin (Minitran, Nitrolingual, Nitrostat)

• Drug of choice for acute attacks

• Spray and tablets taken sublingually
• May also be used as a prophylaxis
• If using a patch, it should not remain on the skin for a full
24 hours, there needs to be free time

nitroglycerin’s Side Effects

• Severe headache
• Orthostatic
hypotension
• Flushing
 Drug Therapy
(cont.)
• 2) Beta blockers
Beta blockers reduce the heart rate, blood pressure, and the force of
contrac?ons, thereby decreasing the amount of oxygen the heart requires to
pump blood.
• Examples: atenolol, metoprolol, nadolol and propranolol.
• Side effects:
Cardiac effects -- worsen heart failure, bradycardia
Noncardiac effects -- constric?on of airways, circulatory problems,
Impotence, hallucina?ons, insomnia, and fa?gue

Drug Therapy
(cont.)
• 3) Calcium channel blockers
Calcium channel blockers dilate arteries and lower blood pressure, which
decreases the force of contrac?ons.
They also dilate veins, reducing the amount of blood returning to the heart,
which reduces the workload of the heart.
• Examples: amlodipine, nifedipine, nicardipine, verapamil and dil?azem.
• Side effects:
flushing, dizziness and lightheadedness, headache, peripheral edema and
depression of cardiac func?on (with non-dihydropyridines)
 CCB
•
(cont)
Disrupt Ca++ through Ca++ channels
• -ve ionotrpic effect
2 types:-
Dihydropyridine
amlodipine, nifedipine, nicardipine
Non-Dihydropyridine
• Phenylalkylamine (verapamil,
gallopamil)
• Benzodiazapenes (dil?azem)
• Non-selec?ve (bepridil, mibefradil)

MECHANISM OF
ACTION
 CCBs
(cont.)
• The main use of calcium-channel antagonists in pa?ents with angina
is for prophylaxis.
• They are par?cularly useful in pa?ents in whom beta-blockers are
contraindicated.
• They may be par?cularly useful in vasospa?c angina (spasm can be
worsened by β-blockers).
• Short-ac?ng dihydropyridines (e.g. nifedipine) should be avoided
because they cause reflex tachycardia.
• Dil?azem or a long-ac?ng dihydropyridine (e.g. amlodipine or a
controlled-release prepara?on of nifedipine) are oGen used.

Antiplatelet and antithrombotic

therapy
• In pa?ents with unstable angina with recurrent ischemic episodes at
rest, recurrent platelet-rich non-occlusive thrombus forma?on is the
principal mechanism. Aggressive an?platelet therapy with a
combina?on of aspirin and clopidogrel is indicated.
• lower doses of aspirin should be used rou?nely for chronic
prophylaxis. At the onset of ACS it is appropriate to use a higher
dose (e.g. 300 mg) to obtain rapid and complete inhibi?on of
platelet cyclo-oxygenase (COX).
• Intravenous heparin or subcutaneous low-molecular-weight heparin
is also indicated in most pa?ents.
• If percutaneous coronary interven?on with sten?ng is required,
glycoprotein IIb/IIIa inhibitors such as abciximab should be added.
• This an?platelet/an?thrombo?c regime approximately halves the
likelihood of myocardial infarc?on, and is the most effec?ve known
treatment for improving outcome in unstable angina.

COMBINATION
• THERAPY
Nitrates + B-blockers :- in stable angina
• Ca++ channel blockers + B-blockers :-in stable angina when the
treatment with nitrates and B-blockers has failed.
• Ca++ channel blockers + Nitrates :- in unstable angina
• All 3 together:- when the combina?ons of 2 drugs has failed,
Where as:-
• Nitrates:- decrease Preload
• Ca++ channel Blockers:- decrease AGerload
• B-blockers:- decrease heart rate and myocardial contrac?ons
 Other Measures in Managing
•
CAD
Treat high blood pressure
• Treat high cholesterol
• Quit smoking
• Lose excess weight
• Reduce stress
• Exercise regularly

Other Treatment
Options
• Percutaneous Coronary Interven?on (previously called Angioplasty or Balloon
Angioplasty)
• CABG (Coronary Artery Bypass GraG Surgery)
• CABG and PCI are both excellent treatments for relieving the symptoms of angina
although they are not a permanent cure and symptoms may recur if there is
• Restenosis the recurrence of abnormal narrowing of an artery or valve after corrective surgery.
• the graG becomes occluded,
• the underlying atheromatous disease progresses.