Angina

contents
• Definition
• Classification
• Signs and symptoms
• Causes
• Pathophysiology
• Diagnosis
• Treatment
• Drug therapy
ANGINA
Angina pectoris is a clinical syndrome of IHD resulting from
• transient myocardial ischemia.
• It is characterized by paroxysmal pain in the substernal or
• precordial region of the chest which is aggravated by an increase in the
demand of the heart and relieved by a decrease in the work of the heart.
• Often, the pain radiates to the left arm, neck, jaw or right arm.
• It is more common in men past 5th decade of life.
Types of angina
• Stable -chest pain precipitated by
exertion or stress. Myocardial oxygen
demands increased.
• Unstable (preinfarction) chest pain
occurring at rest.
• Intractable - severe
• Silent ischaemia - diabetics
• Prinzmetal Angina (varient)
vasospasm
Stable angina
• Stable angina is the most common type of angina.
• It occurs when the heart is working harder than usual.
• Stable angina has a regular pattern. ("Pattern" refers to how often the
angina occurs, how severe it is, and what factors trigger it.)
• The pain usually goes away a few minutes after you rest or take your
angina medicine.
• Stable angina isn't a heart attack, but it suggests that a heart attack is
more likely to happen in the future.
Unstable Angina
• Unstable angina doesn't follow a pattern.
• It may occur more often and be more severe than stable angina.
• Unstable angina also can occur with or without physical exertion, and
rest or medicine may not relieve the pain.
• Unstable angina is very dangerous and requires emergency
treatment.
• This type of angina is a sign that a heart attack may happen soon.
Variant (Prinzmetal's) Angina
• Variant angina is rare.
• A spasm in a coronary artery causes this type of angina.
• Variant angina usually occurs while you're at rest, and the pain can be
severe.
• It usually happens between midnight and early morning.
• Medicine can relieve this type of angina.
SIGNS AND SYMPTOMS
• Chest discomfort rather than actual pain:
• The discomfort is usually described as a
- pressure,
- heaviness,
- tightness,
- squeezing,
-burning,
- choking sensation.
• Apart from chest discomfort, anginal
pains may also be experienced in
• the epigastrium (upper central abdomen),
back, neck area, jaw, or shoulders.
• It is exacerbated by having a full stomach
• and by cold temperatures.
• Pain may be accompanied by
breathlessness, sweating, and nausea in
some cases.
2) Other medical problems
• Hyperthyroidism
• Hypoxemia
• Profound anemia
• Uncontrolled hypertension
Pathophysiology
• Angina results when there is an imbalance between the heart's
oxygen demand and supply.
• This imbalance can result from an increase in demand (e.g., during
exercise) without a proportional increase in supply (e.g., due to
obstruction or atherosclerosis of the coronary arteries).
• However, the pathophysiology of angina in females varies significantly
as compared to males Non-obstructive coronary disease is more
common in females
Classification of Antianginal Agents
1. Nitrates:
a) Short acting (10 minutes): Glyceryl trinitrate (GTN and Nitroglycerine) – EMERGENCY
b) Long acting (1 Hour): Isosorbide dinitrate, Isosorbide mononitrate, Erythrityl tetranitrate,
Pentaerythritol tetranitrate
2. Calcium Channel Blockers:
c) Phenyl alkylamine: Verapamil Benzothiazepin: Diltiazem
d) Dihydropyridines: Nifedipine, Felodipine, Amlodipine, Nitrendipine and Nimodipine
e) Beta-adrenergic Blockers: Propranolol, Metoprolol, Atenolol and others
f) Potassium Channel openers: Nicorandil
g) Others: Dipyridamole, Trimetazidine, Ranolazine and oxyphedrine
Organic nitrates
• Organic nitrates are prodrugs and they release nitric oxide.
• Nitrates are mainly venodilators also cause arteriolar dilation and as a
result reduces both preload and afterload.
• These compounds cause a rapid reduction in myocardial oxygen
demand, followed by rapid relief of symptoms.
pharmacokinetics
• The nitrates are inactivated in liver by
glutathione organic nitrate reductase.
• Therefore their oral bioavailability is
considerably less due to their first-pass
metabolism.
• The sublingual route, which avoids first pass
effect, is therefore preferred.
• Duration of action lasts for about 25-30min
Pharmacological actions of nitrates:
• On other smooth muscles:
• Smooth muscles of bronchi, oesophagus, biliary tract, etc are relaxed
by nitrates.
Adverse drug reactions
• The most common adverse effect of nitroglycerin, as well as of the
other nitrates, is headache.
• High doses of organic nitrates can also cause postural
• hypotension, facial flushing, and tachycardia. Sildenafil potentiates
the action of the nitrates.
• Over doses may cause methaemoglobinaemia.
Tolerance
• Continuous exposure to nitrates in the chemical industry results in
development of tolerance.
• Workers may experience headache and dizziness on starting work
during first few days.
• As there is no exposure to chemicals over the weekend, tolerance
disappears.
• Symptoms disappear when they start work on Monday- “ Monday
disease".
Drug interactions
• Sildenafil and other vasodilators potentiate the hypotensive action of
nitrates
• MI and sudden death have occurred.
Nifedipine
• Functions mainly as an arteriolar vasodilator.
• This drug has minimal effect on cardiac conduction or heart rate.
• Nifedipine is administered orally, usually as extended-release tablets.
It undergoes hepatic metabolism to products that are eliminated in
both urine and the feces.
•  The vasodilation effect of nifedipine is useful in the treatment of
variant angina caused by spontaneous coronary spasm.
• Nifedipine can cause flushing, headache, hypotension, and peripheral
edema
Verapamil
• The diphenylalkylamine verapamil slows cardiac atrioventricular (AV)
conduction directly, and decreases heart rate, contractility, blood
pressure, and oxygen demand.
• Verapamil causes greater negative inotropic effects than nifedipine,
but it is a weaker vasodilator.
• The drug is extensively metabolized by the liver; therefore, care must
be taken to adjust the dose in patients with liver dysfunction.
• Verapamil is contraindicated in patients with preexisting depressed
cardiac function or AV conduction abnormalities.
• It also causes constipation.
• Verapamil should be used with caution in patients taking digoxin,
because verapamil increases digoxin levels.
Diltiazem
• It dilates peripheral and coronary arteries but its dilating property is
less marked than DHPs.
• It also causes negative inotropic, chronotropic and dromotropic
effects.
• It is used in the treatment of angina, hypertension and
supraventricular arrhythmias.
DRUG INTERACTIONS
• Verapamil or diltiazem should not be given with beta blockers as
• SA nodal depression, conduction defects or asystole may occur
• or be aggravated.
• These should not be used with other cardiac depressants drugs like
quinidine or disopyramide.
• These drugs increase plasma digoxin levels by decreasing its
excretion.
Pharmacokinetics
• All CCBs are well absorbed through GI tract but they undergo varying
degree of first pass metabolism.
• All are highly bound to plasma proteins, metabolized in the liver and
excreted in urine.
Uses of CCBs
• Angina pectoris
• Variant angina
• Unstable angina
• Supraventricular arrhythmias
• Hypertension
• Hypertropic cardiomyopathy
• Migraine
• Raynaud's phenomenon
• They are, however, contraindicated in patients with asthma, diabetes, severe
bradycardia, peripheral vascular disease, or chronic obstructive pulmonary disease.

Adverse effects:
• Bradycardia
• Heart block
• Bronchospasm
• hypoglycaemia
Combination therapy
• Nitrates x beta blockers
• Nifedipine x B-blockers
• B-blockers x verapamil/diltiazem
• Calcium channel blockers x nitrates
• Nitrates + B-blockers + CCBs
Potassium channels
• Voltage gated K channels: These channels open when the cell is
depolarized and therefore help in the process of repolarization. These are
• present mainly in vascular and other smooth muscles
• Calcium activated K channels: An increase in intracellular ca+2
concentration causes opening of these channels, causes repolarization.
• ATP sensitive K channels: These are present in cardiac muscle and beta
cells of islets of Langerhans of pancreas
PHARMACOTHERAPY OF ANGINA
AND MYOCARDIAL INFARCTION
1. Angina Pectoris
• Acute anginal attack: Nitroglycerin (NTG) 0.5 mg sublingually. If the pain is not relieved within 5 minutes, repeat the dose but not
more than three tablets in 15 minutes.
• Prevention of further attacks (prophylaxis):
• (i) Nitrates (long acting)-Isosorbide mononitrate, transdermal NTG patch. (ii) B-Blockers-Propranolol, metoprolol, atenolol.
• (iii) Calcium channel blockers-Amlodipine, verapamil SR, diltiazem SR.
2. Variant angina (Prinzmetal's angina)
a. Nitroglycerin s.1. or intravenous, to abolish the episodes.
b. Long-acting nitrates (isosorbide mononitrate) to prevent recurrence.
c. Calcium channel blockers: Amlodipine, diltiazem SR.
d. Potassium channel openers: Nicorandil, pinacidil.
3. Unstable angina
a. Nitroglycerin s... if the pain persists or recurs even after three tablets, i.v. nitroglycerin should be given.
b. Antiplatelet agents:
• (i) Aspirin 300 mg stat followed by 75-325 mg daily for long term. (ii) Clopidogrel 300 mg stat followed by 75 mg daily for 1 year.
• c. B-Blocker: Atenolol or metoprolol.
d. CCBs: Amlodipine or nifedipine SR.
e. LMW heparin.
4. Myocardial infarction
a. Analgesic: Inj. morphine sulphate 10 mg i.v./Inj. pethidine 75 mg.
b. Antiemetics: H,-blocker (promethazine).
c. Aspirin low dose (50-325 mg daily), clopidogrel (75 mg daily).
d. Fibrinolytics: Streptokinase/urokinase/alteplase.
e. Anticoagulants: LMW heparin.
f. B-Blockers: Atenolol or metoprolol to prevent/treat arrhythmias and decrease the size of infarct. Wituales
g. ACE-Inhibitor (should be given within 24 hours).
h. Statins: Usually started within 24 hours or prior to discharge (e.g. atorvastatin).