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 INTRODUCTION

• Angina pectoris is a “clinical syndrome characterized by discomfort in the

chest, jaw, shoulder, back, or arm.”

• At one extreme, angina occurs predictably with strenuous exercise; at the

other, angina can develop unexpectedly with little or no exertion.

• Angina is of two types

• Typical angina/classic angina
• Atypical angina/prinzmetal angina

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• Patients who have a reproducible pattern of angina that is associated with
a certain level of physical activity have chronic stable angina or exertional
angina.

• In contrast, patients with unstable angina experience new-onset angina or

a change in their angina intensity, frequency, or duration.

• Both chronic stable angina and unstable angina often reflect underlying
atherosclerotic narrowing of coronary arteries.

• Classic Prinzmetal's variant angina, or vasospastic angina, occurs in

patients without CHD; it is caused by a spasm of the coronary artery that
decreases myocardial blood flow. When coronary vasospasm occurs at the
site of a fixed atherosclerotic plaque, mixed angina can result.

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• Typical angina, the imbalance of oxygen supply and demand occurs when the
myocardial oxygen requirements are more as occurs during exercise, and the
coronary blood is adequate. Hence, it is also called angina of effort.

• Atypical angina is presented with a decrease in coronary blood supply due to

vasospastic condition of coronary blood vessels.

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 FEATURES OF ANGINA
TYPICAL ANGINA ATYPICAL ANGINA

Pain in the substernal region or heavy, Pain in the substernal region, or heavy,
pressing substernal discomfort with pressing discomfort, often radiating to left
radiation to shoulders, left arm, left jaw. shoulder, arm and jaw.

Pain or discomfort occurring on exertion or Pain occurring at rest

emotion.

Pain relieved by taking rest or Pain relieved by taking nitroglycerine

nitroglycerine

Atherosclerotic narrowing of the Spasm of the coronaries is the main cause

coronaries is the main cause for ischemia of ischemia

ST segment depression and downward Elevation of T wave

deflection of T wave

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October 1, 2021 10
 PATHOPHYSIOLOGY OF ANGINA

• Angina pectoris typically occurs when myocardial oxygen demand exceeds

myocardial oxygen supply (perfusion). The underlying pathologic
condition of this mismatch invariably is the presence of atherosclerosis in
one or more of the epicardial coronary arteries

• The oxygen demand of the heart is determined by its work load. The
factors that determine the myocardial oxygen requirements are mainly
wall stress, intraventricular pressure (end diastolic filling pressure),
ventricular volume (radius), heart rate and contractile force.

• Other factors like the prevailing metabolism in the coronaries also play a
role. As the heart is under continuous activity, its oxygen needs are also
high and nearly 75% of available oxygen is utilized even in normal
conditions.

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• Myocardial oxygen requirements are increased when there is an increase
in heart rate, contractility, arterial pressure or ventricular volume. The
oxygen requirements are more so in physical activity and increased
sympathetic discharge which often precipitate angina in patients with
obstructive coronary vascular disease.

• The pain in angina is also due to accumulation of metabolic products like

lactic acid.

• The heart depends on fatty acids for energy production. However,

oxidation of fatty acids requires more oxygen per unit of ATP generated
than oxidation of carbohydrates. If it is possible to inhibit fatty acid
oxidation and make better use of glucose for myocardial metabolism,
myocardial oxygen demands may be reduced.

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 ISCHEMIA
• Ischemia in the myocardium develops when there is a mismatch between
myocardial oxygen supply and demand. This imbalance is often caused by
a reduction in blood flow as a result of increased coronary arterial tone or
thrombus formation.

• This condition is known as supply ischemia or low-flow ischemia and

typically is present during acute coronary syndromes (ACS) such as
unstable angina or MI.

• Under different conditions, ischemia can result from increased myocardial

oxygen demand in the presence of a fixed supply. This condition is known
as demand ischemia or high-flow ischemia and typically exists in the
setting of chronic stable angina where patients have a fixed supply to the
myocardium and undergo exercise or experience stress.

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 RISK FACTORS/ PRECIPITATING FACTORS

• IHD is usually associated with one or many risk factors like HTN, DM,
hyperlipidemia, obesity, occupational factors which may cause stress,
tensions and anxiety, familial hyperlipidemia, sedentary lifestyle and
tobacco smoking.

• Traditional risk factors, such as smoking, hypertension, hyperlipidemia,

diabetes, and obesity, are linked to the process of atherosclerosis through
their ability to produce oxidative stress within the vasculature.

• Increased oxidative stress leads to progressive decreases in NO levels and

endothelial dysfunction, providing the substrate for atherosclerosis to
develop.

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 SYMPTOMS
• Sensation of pressure or burning over the sternum or near it, often but not always
radiating to the left jaw, shoulder and arm; also chest tightness, shortness of
breath
• Pain usually lasts from 0.5 to 30 minutes, often with a visceral quality (deep
location)
• Precipitating factors include exercise, cold environment, walking after a meal,
emotional upset, fright, anger, and coitus
• Relief occurs with rest and nitroglycerin

SIGNS
• Abnormal pericardial (over the heart) systolic bulge
• Abnormal heart sounds

(While signs are what a doctor sees, symptoms are what a patient experiences)

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 LABORATORY TESTS

• Typically, no laboratory tests are abnormal; however, if the patient has

intermediate to high-risk features for unstable
angina,electrocardiographic changes and serum troponin, or creatine
kinase may become abnormal.

• Patients are likely to have laboratory test abnormalities for the risk factors
for IHD such as elevated total and low-density lipoprotein cholesterol, low
high-density lipoprotein cholesterol, impaired fasting glucose or elevated
glucose, high blood pressure, elevated C-reactive protein, and abnormal
renal function.

• Hemoglobin should be checked to make sure the patient is not anemic.

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 PHYSICAL EXAMINATION

• Hypertension
• Obesity
• Hyperglycemia
• Hyperlipidemia
• Auscultation*

* listening to the internal sounds of the body,

usually using a stethoscope

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 INVESTIGATIONS

• Laboratory tests (leukocytes, hemoglobin, thyroid hormones, troponin I and T, MB-CPK)

• Resting ECG

• Excercise ECG

• Cardiac scintigraphy

• Echocardiography

• Coronary angiography

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October 1, 2021 19
 ANTI ANGINAL DRUGS

Nitrates and nitrites

Short acting Glyceryl trinitrate (GTN, Nitroglycerine),
Long acting Isosorbide mono and dinitrate (S/L), Erthrityl
tetranitrate, Penta erythritol tetranitrate

Beta blockers Metoprolol, atenolol, propranolol and others

Calcium channel blockers Verapamil, Amlodipine, diltiazem, nifedipine,

felodipine, nitrendipine, lacidipine, benidipine

K+ channel openers Nicorandil

Others Ranolazine, dipyridamole, trimetazidine, ivabradine,

oxyphedrine

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 DRUG DOSE

GTN, Nitroglycerine 0.5mg S/L, transdermal patch 5 or 10 mg patch

Isosorbide dinitrate 5-10mg S/L, 10-20mg oral, 20—40mg sustained

release oral

Isosorbide -5-mononitrate 20-40mg oral

Erythrityl tetranitrate 15-60mg oral

Nicorandil 5-20mg BD

Ranolazine 0.5-1.0g BD as SR tab

Ivabradine 5-7.5mg BD

Oxyphedrine 8-24mg TDS oral, 4-8 mg i.v. OD-BD

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 DRUGS USED TO RELIEVE OR PREVENT THE SYMPTOMS OF
ANGINA
1. NITRATES
2. BETA BLOCKERS
3. CALCIUM ANTAGONISTS
4. POTASSIUM CHANEL ACTIVATORS

As the fundamental cause of angina pectoris is insufficient oxygen supply to

heart muscle, it is logical to attempt to increase the oxygen supply by
administering oxygen- that is by increasing the inspired oxygen concentration
similarly, patients with angina may suffer from severe pain and pain relief with
a potent opiate

e.g. Morphine needs to be considered to make the patient more comfortable, less
anxious.

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 NITRATES
MODE OF ACTION :

Acts directly on vascular smooth muscle to produce arterial and

venous dilatation

EFFECT DURING ANGINA

1. Reduces myocardial oxygen demand (lowers pre-load and

after load)

2. Increases myocardial oxygen supply (coronary vasodilatation)

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 NITRATE PREPARATIONS

1.Sublingual glyceryl trinitrate (GTN)

2.Buccal glyceryl trinitrate
3.Transdermal glyceryl trinitrate
4.Oral isosorbide dinitrate
5.Oral isosorbide mononitrate
6.Intravenous GTN- for acute myocardial infarction/left ventricular failure
-10 -200 µg /min i.v. infusion, titrating to clinical response and blood
pressure.

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 DURATION OF ACTION OF SOME NITRATE PREPARATIONS

PEAK ACTION DURATION OF ACTION

Sublingual GTN(Tablet 300-500µg or metered 4-8 min 10-30 min

dose aerosol 400µg/spray)

Buccal GTN (1-5 mg tablet 6 hourly) 4-10 min 30-300 min

Transdermal GTN (5-10 daily) 1-3 hrs Up to 24 hrs

Oral isosorbide dinitrate (10-20 mg 8 hourly) 45-120 min 2-6 hrs

Oral isosorbide mononitrate 45-120 min 6-10 hrs

( 20-60 mg once or twice a day)

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 SUBLINGUAL GTN- Administered
a.As a tablet – 300-500 µg to disolve under the tongue
b.As metered-dose aerosol (400 µg per spray)

RELIEVES AN ATTACK OF ANGINA IN 2-3 MINUTES

UNWANTED EFFECTS
Headache
Symptomatic hypotension –dizziness, postural giddiness, blurring of vision
Rarely syncope – fainting

ASK PATIENT TO SPIT TABLET IF ABOVE EFFECTS OCCUR

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 CALCIUM ANTAGONISTS
MODE OF ACTION
Decreases myocardial oxygen demand by reducing blood pressure and
myocardial contractility

TYPES
A.Dihydropyridine calcium antagonists-nifedipine, nicardipine often cause
reflex tachycardia-best used in combination with beta blocker-not used or
caution when using
B.Verapamil and dilitiazem-suitable for patients who are not receiving beta
blockers as they decrease the heart rate ( dangerous additive effect)

Calcium channel antagonists may reduce myocardial contractility to a degree

that can aggravate or precipitate heart failure

UNWANTED EFFECTS
Peripheral edema
Flushing
Headache
October
Dizziness
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 POTASSIUM CHANNEL ACTIVATORS
MODE OF ACTION: Dilates arteries and veins

NICORANDIL- 10-30 mg 12 hourly

CAUTION IN:
 Hypovolaemic patients
 Patients with pulmonary edema

SIDE EFFECTS:
a.Headache
b.Flushing
c.Dizziness
d.Weakness
e.May cause a dose dependent increase in heart rate
f.Myalgia
g.Angioedema (swelling of the deeper layers of the skin, caused by a build-up of fluid)

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 ANTIPLATELET DRUGS
 ASPIRIN
 CLOPIDOGREL

THROMBOLYTIC AGENTS
 STREPTOKINASE
 ALTEPLASE
 RETEPLASE

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 ASPIRIN
Antiplatelet effect by inhibition of thromboxane (it induces platelet aggregation
and arterial constriction)
NSAID, inhibits COX-1 and COX -2 which leads to decreased prostaglandin
synthesis

USES
Thrombo-embolic CVA, IHD-prophylaxis (75mg/day) and acute treatment (300 mg)

CONTRAINDICATIONS
1.Those under age of 16yr can increase incidence of Reye’s syndrome, liver/brain
damage
2.Gastro-intestinal ulcers
3.Bleeding disorders
4.Gout
5.Hypersensitivity to any NSAID
6.GFR <10ml/min
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 ASPIRIN
CAUTION
1.Asthma
2.Uncontrolled hypertension
3.Any allergic disease
4.G6PD deficiency
5.Dehydration

OTOTOXIC IN OVERDOSE

• May increase effects of sulphonyl ureas and of methotrexate

• For analgesia 300-900 mg 4-6 hourly – max dose 4g/day

• Stop 7 days before surgery if significant bleeding is expected

• If cardiac surgery or patient has Acute Coronary Syndrome-consider continuing

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 CLOPIDOGREL
ANTIPLATELET AGENT

USES:
 Prophylaxis of anti-thrombotic events in NSTEMI and in STEMI-in combination

with aspirin
 Myocardial infarction (within a ‘few’ to35 days)
 Ischemic cerebrovascular accident- within 7 days to 6 months
 Peripheral Arterial Disease
 Active bleeding

NOT RECOMMENDED WITH WARFARIN

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 CLOPIDOGREL
SIDE EFFECTS

 Hemorrhage (especially gastro-intestinal or intra-cranial)

 Gastro-intestinal upset
 Peptic ulcer
 Pancreatitis
 Headache
 Fatigue
 Dizziness
 Paraesthesia (an abnormal sensation)
 Rash/pruritus

Monitor Complete Blood Count and for signs of occult bleeding

(escape
of blood in such small quantity that it can be detected only by chemical tests or by microscopic
examination)

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 STREPTOKINASE

THROMBOLYTIC AGENT

Increases plasminogen conversion to plasmin which increases fibrin breakdown

USES
1.Acute MI -1.5 million units i.v. infusion over 60 min
2.Thromboembolism of arteries
3.Pulmonary embolism
4.Central Retinal Artery Thrombosis
5.Deep Vein Thrombosis

Other doses-2,50,000 units i.v. infusion over 30 min, then 1,00,000 units every
hour for upto12-72 hours

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ALTEPLASE
(Recombinant) tissue-type plasminogen activator. Recombinant fibrinolytic

USE
Acute MI (total dose 100mg)
Regimen depends on time since onset of pain
0-6 hrs: 15 mg i.v. bolus, followed by 50 mg i.v. infusion over 30 min and
35 mg i.v. infusion over 60 min
6-12 hrs: 10 mg i.v. bolus followed by 50 mg iv. infusion over 60 min, and
further 10 mg i.v. infusions, each over 30 min)

Decrease dose if patient weighs less than 65 kg

RETEPLASE
• Recombinant plasminogen activator; thrombolytic
• Used only for MI
• Dose: 10 units as slow i.v. injection over 2 min, repeat after 30 min

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 NON PHARMACOLOGICAL THERAPY

• Percutaneous Coronary Intervention (PCI)

• Coronary Artery Bypass Grafting (CABG)

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 TIPS
• Medications and surgery can help to reduce the build-up of the dangerous
plaque that has formed in your arteries. But you also need to manage the
risk factors that helped contribute to the plaque, and make some lifestyle
changes so that the plaque does not come back and clog your arteries
again.

• If you smoke, stop Ask your doctor or pharmacist about a smoking

cessation program. Quitting smoking is hard. But it is one of the most
important things you can do to improve your heart health and your overall
health. Studies show that there are many potential health benefits to
quitting smoking for you and those around you. For example, 1 year after
quitting excess risk of coronary heart disease is half that of a smoker’s.

• Exercise regularly Ask your doctor about an exercise program that is right
for you. Exercise can actually help your body grow new blood vessels.

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• Watch your alcohol intake Everything in moderation, and that includes
alcohol. Men should not drink more than 14 drinks a week, and women
should drink no more than nine.

• Watch what you eat You should try to stop eating unhealthy fats and
sugars as much as you can, and instead eat more fresh fruits and
vegetables, grains and grain products, lean poultry, beef or fish. (For more
information about eating healthy, consult the list of resources at the end
of this document).

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• Limit your salt intake The added salt in processed foods is not healthy to
our hearts.

• Eat snacks that are low in salt, like unsalted popcorn.

• Most processed or prepared foods have a lot of salt in them. These types of
foods include canned vegetables and frozen dinners. Other foods and
sauces that have a lot of salt are:
• Lunch meat
• Soya sauce
• Ketchup
• Cheese
• Pickles
• Salad dressing

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• Watch your weight Being overweight is a risk factor for angina and other
types of heart disease. One way to determine if you may be overweight is
to calculate your Body Mass Index, or BMI for short. If your BMI score is
25 or more, you may be at higher risk.

• Control high blood pressure through the use of lifestyle modifications

and/or medications. High blood pressure is one of the biggest risk factors
for heart disease. If your high blood pressure is properly taken care of,
you can significantly reduce your risk of heart disease.

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• Define angina pectoris, outline different types of angina

• Mention the role of Nitro-glycerine in angina

• Mention the role of calcium channel blockers in angina

• Mention diagnostic tests for angina pectoris

• Write the differential diagnosis between angina and myocardial infraction

• Define nitrate tolerance. How it can be prevented

• Write the mechanism of action of nitrates and list out its adverse effects

• Define variant angina

• Mention adverse effects of nitrates

• Differentiate between ISMN & ISDN

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