Angina …a heart

ache
Angina Episode
Angina Pectoris

When myocardial

oxygen demand

exceed myocardial

oxygen supply
Prevalence

Coronary Heart Disease is prevalent

amongst South Asians. South Asian
people born in India, Bangladesh,
Pakistan or Sri Lanka are approximately
50% more likely to die from coronary
heart disease.
Causes of Angina

 Atherosclerotic plaque buildup

which causes critical blockage

of the coronary artery.

 Coronary artery spasm

 Angina Symptoms

Chest & Throat Pain Neck & Shoulder Pain Pain spread through Arms
& whole body
Symptoms of Angina
An uncomfortable pressure, fullness, squeezing, or pain in the center of the chest
It may also feel like tightness, burning, or a heavy weight.
The pain may spread to the shoulders, neck, or arms.
It may be located in the upper abdomen, back, or jaw.
The pain may be of any intensity from mild to severe.
Shortness of breath
Lightheadedness
Anxiety or nervousness
Sweating or cold, sweaty skin
Nausea
Rapid or irregular heart beat
Risk factors of Angina

 Smoking
 Hypertension
 Diabetes.
 Men are at higher risk than women.
 A family history of atherosclerosis.
 High levels of ldl cholesterol in the blood./
Hypercholesterolemia
 Obesity.
 Lack of regular exercise.
If untreated following may happen

Coronary heart disease (CHD)

•MI (Heart attack)

•Heart failure
•Sudden death
• Free Fatty Acid (FFA) requires more oxygen to produce same unit ATP
than Glucose;

• Glucose metabolism requires less oxygen to produce same unit ATP than
FFA
Types of Angina

1. Chronic stable angina (also called classic or effort angina)

2. Unstable angina (also called preinfarction or crescendo angina)

3. Vasospastic angina (also called Prinzmetal’s or variant angina)

Chronic stable angina

• Pain is commonly induced by exercise, excitement or a heavy meal

• Secondary to advanced atherosclerosis of the coronary vessels

• Associated with ST-segment depression on ECG

Unstable angina

• Pain is induced while at rest

• Associated with ST-segment elevation on ECG

• Secondary to vasospasm of the coronary vessels

Vasospastic angina

• May involve coronary spasm and may also have the component of
atherosclerosis

• The duration of manifestation is longer than the first two and has
the manifestation of Myocardial infarction
Angina Drug Therapy …Treatment
Goal of Therapy

 The goal of therapy with antianginal agents is to restore the

balance between oxygen supply and demand in the ischemic
region of the myocardium.
Classification

1. Nitrates
Short acting: Nitroglycerine (also known as Glyceryl trinitrate )
Long acting: Isosorbide dinitrate (short acting by S.L route), Isosorbide
mononitrate, Erythrityl tetranitrate, Pentaerythritol
tetranitrate
2. β-Blockers
• Propranolol, Metoprolol, Atenolol and others
Classification

3.Calcium channel blockers

 Phenyl alkylamine : Verapamil
 Benzothiazepine : Diltiazem
 Dihydropyridines : Nifedipine, Felodipine, Amlodipine, Nitrendipine,
Nimodipine, Lacidipine, Benidipine

4. Potassium channel opener

Nicorandil, Pinacidil
Classification

5. Metabolic Agent: Dipyridamole, Trimetazidine, Oxyphedrine,

Ranolazine
Therapeutic Objectives

 Increase blood flow to ischemic heart muscle and/or

 Decrease myocardial oxygen demand

 Minimize the frequency of attacks and decrease the duration and
intensity of anginal pain
 Improve the patient’s functional capacity with as few side effects as
possible

 Prevent or delay the worst possible outcome, MI

1. Nitrates

Available forms:
• Sublingual Ointments
• Buccal Transdermal patches
• Chewable tablets Inhalable sprays
• Capsules Intravenous solutions

Short acting: Glyceryl trinitrate (GTN or Nitroglycerine)

Long acting: Isosorbide dinitrate (short acting by S.L route), Isosorbide
mononitrate, Erythrityl tetranitrate, Pentaerythritol tetranitrate
 Short Acting Nitrates

i) Nitroglycerin
• Prototypical nitrate
• Large first-pass effect with PO forms
• Used for symptomatic treatment of ischemic heart conditions
(angina)
• I.V form used for BP control in perioperative hypertension, treatment
of CHF, ischemic pain, and pulmonary edema associated with acute
MI
Long Acting Nitrates

i) Isosorbide dinitrate : Isordil, Sorbitrate, Dilatrate SR

ii) Isosorbide mononitrate : Imdur, Monoket, ISMO
iii) Erythrityl tetranitrate : Not available
iv) Pentaerythritol tetranitrate : Not available
 Mechanism of Nitrates

Nitrates
Denitrated in the smooth muscle cell

Release Nitric Oxide

Deposphorylation of myosin light chain (reduced ca2+ in
the cytosol)
Stimulate Guanylyl
Cyclase
Relaxation of vascular smooth
muscle fibres
Increased cGMP

Dilation of coronary
Mainly Vasodilation Arterial dilation
vessels
Comparison
Route of Duration of
Drug Usual single dose
administration action
Nitroglycerin 0.15-1.2 mg sublingual 10 - 30 min
Amyl nitrite 0.18 – 3 ml inhalation 3 – 5 min
Nitroglycerin sustained action 6.5 – 13 mg oral 6 – 8 hrs
Nitroglycerin 2% ointment 1 – 1.5 inches topical 3 – 6 hrs
Niroglycerin slow released 1 –2 mg per 4 hrs Buccal mucosa 3 – 6 hrs
Nitroglycerin slow released 10 – 25 mg per 24 hrs Transdermal 8 –10 hrs
Isosorbide dinitrate 2.5-5 mg once sublingual 10 – 60 min
Isosorbide dinitrate 2.5 – 10 mg per 2 hrs sublingual 1.5 – 2 hrs
Isosorbide dinitrate 10 –60 mg per 4-6 hrs oral 4 – 6 hrs
Isosorbide dinitrate chewable 5 – 10 mg per 2-4 hrs oral 2 – 3 hrs
Isosorbide mononitrate 20 mg per 12 hrs oral 6 –10 hrs
2. Beta Blockers

Available Forms: Tablet & Injection

Example:

• Atenolol (Tenormin)

• Metoprolol (Lopressor)

• Propranolol (Inderal)

• Nadolol (Corgard)
Mechanism of Beta Blockers

Decrease Heart Rate & Contractility

Increase duration of diastole Decrease workload

Increase coronary blood flow Decrease O2 consumption

Increase oxygen supply

 Effects , Uses & Side Effects Beta Blockers
Effects Uses Side Effects
• Hemodynamics Effects • Bradycardia,
(Negative) • Antihypertensive hypotension
• Decrease heart rate • Antianginal • Second- or third-
• Reduced blood • Cardioprotective degree heart block
pressure and cardiac Effects. Specially MI • Heart failure,
contractility Dizziness, Fatigue,
• Mental depression,
Lethargy, Drowsiness,
Unusual dreams,
impotence
3. Calcium Channel Blockers (CCB’s)

Available Forms: Tablets & Injectables

Example:
• Phenyl alkylamine: Verapamil
• Benzothiazepine: Diltiazem
• Dihydropyridines:Nifedipine,Felodipine,Amlodipine,Nitrendipine,
Nimodipine, Lacidipine
Mechanism of CCB’s

Coronary artery dilatation

Decrease coronary bed resistance

(Relieved coronary vasospasm)

Increase coronary blood flow

Increase oxygen supply

Mechanism of CCB’s

Reduction on peripheral resistance

(Secondary to dilatation of aorta)

Decrease blood pressure

Decrease after load & thus

Decrease workload

Decrease oxygen consumption

 Effects , Uses & Side Effects CCB’s

Effects Uses Side Effects

• Coronary artery • Hypertension • Nausea and vomiting

dilatation • Anti aginals • Dizzyness
• Reduction on • Flushing of the face
peripheral arterial • Tachycardia – due to
resistance – decrease hypotension
after load
Comparison

Onset of Peak of
Drugs Half-life
action action
Nifedipine 20 minutes 1 hour 3-4 hours

Verafamil 1-2 hours 5 hours 8-10 hours

Diltiazem 15 minutes 30 minutes 3-4 hours

Nicardifine 20 minutes 45 minutes 2-4 hours

Felodipine 2-5 hours 6-7 hours 11-16 hour

4. Potassium channel opener

• Their efficacy is similar to nitrates, beta & blockers, CCBs

• Main advantages of Nicorandil, it has longer duration of action and

does not cause tolerance

• Administered orally

• Ex: Nicorandil, Pinacidil

4. Mechanism of Potassium Channel Openers

Nicorandil & Pinacidil

Open ATP-dependent K+ channels

K+ efflux

Hyperpolarization of the membrane

Venodilators Arterial Dilators

Preload Afterload
5. Metabolic Agents: Trimetazidine

Indication: It is indicated in prophylactic treatment of

ANGINA & Heart Failure

Example: Trimetazidine
Trimetazidine: Mechanism

Fatty acids Glucose

Glycolysis
Trimetazidine

β-oxidation Pyruvate
3-KAT

Acetyl CoA Acetyl CoA

TCA cycle

ATP ATP
Dosage & Administration

Angivas MR Tablet:

1 tablet in the morning & 1 tablet in the evening

(1+0+1)
Side Effects

Trimetazidine is safe and well tolerated. The most commonly encountered side
effects are gastric discomfort, nausea, headache and vertigo. However, the side
effects are mild and non-specific.

Excellent Safety Profile

Advantage

Ensures sustained anti-anginal efficacy;

Longer duration of action;

Convenient twice daily dosing;

Increased patients’ compliance.

Unique benefits

 Significantly increases work capacity of Heart

 Significantly increases Left Ventricular Ejection Fraction

 Delays the appearance of angina episodes during exercise

 No effects on heart rate and blood pressure

 Significantly lowers the consumption of nitrates

Multiple benefits

Trimetazidine is a highly effective agent in coronary diabetic patients.

Trimetazidine protects the myocardium from ischemic reperfusion damage in

patients undergoing CABG (Coronary Artery Bypass Graft).

Excellent safety profile

5. Metabolic Agents: Ranolazine

Ranolazine represents a newer class of antianginal drugs. It is a compound

with a structure similar to trimetazidine. It is a partial inhibitor of fatty acid
oxidation (pFOX).

Indication: It is indicated in treatment of ANGINA & MI

Example: Ranolazine
Mechanism: Ranolazine

• Inhibit late inward Na+ entry in

ischaemic myocardium thus-
• Decrease calcium overload from Na+
& Ca2+ exchanger thus
• reduce diastolic stiffness /impaired
relaxation thus

• Improve myocardial perfusion

Dose:

• Ranolazine 500 mg

1+0+1
May be increased to (Maximum Dose)-
Ranolazine 1000 mg

1+0+1