This document discusses several classes of drugs used to treat angina pectoris, including nitrates, beta blockers, and calcium channel blockers. Nitrates such as nitroglycerin are used to relieve acute anginal attacks and can be used long-term in combination with other drugs to prevent attacks. Beta blockers work by blocking beta receptors to reduce the effects of epinephrine and norepinephrine. Calcium channel blockers inhibit the entry of calcium into cardiac and smooth muscle cells to reduce contraction and dilation of blood vessels. Each drug class is described in terms of examples, mechanisms of action, indications, administration routes, side effects and contraindications.

1. ANTIANGINAL DRUGS
By Dr. Dinesh Kumar G
Pharm. D

2. CLASSIFICATION
1. Nitrates
(a) Short acting: Glyceryl trinitrate (GTN, Nitroglycerine)
(b) Long acting: Isosorbide dinitrate (short acting by sublingual route), Isosorbide
mononitrate, Erythrityl tetranitrate, Pentaerythritol tetranitrate
2. β Blockers: Propranolol, Metoprolol, Atenolol and others.
3. Calcium channel blockers
(a) Phenyl alkylamine: Verapamil
(b) Benzothiazepine: Diltiazem
(c) Dihydropyridines: Nifedipine, Felodipine, Amlodipine, Nimodipine
4. Potassium channel opener: Nicorandil
5. Others: Dipyridamole, Trimetazidine, Ranolazine, Ivabradine, Oxyphedrine

3. NITRATES

6. • Nitrate therapy may be used to terminate an acute anginal attack, to prevent effort- or stress-
induced attacks, or for long-term prophylaxis, usually in combination with β-blockers or
calcium channel antagonists. Sublingual, buccal, or spray nitroglycerin products are preferred
for alleviation of anginal attacks because of rapid absorption. Symptoms may be prevented by
prophylactic oral or transdermal products (usually in combination with β-blockers or calcium
channel antagonists), but development of tolerance may be problematic.
• Sublingual nitroglycerin, 0.3 to 0.4 mg, relieves pain in about 75% of patients within 3
minutes, with another 15% becoming pain-free in 5 to 15 minutes. Pain persisting beyond 20 to
30 minutes after use of two to three nitroglycerin tablets suggests ACS, and the patient should
be instructed to seek emergency aid.
• Because both the onset and offset of tolerance to nitrates occur quickly, one strategy to
circumvent it is to provide a daily nitrate-free interval of 8 to 12 hours. For example, ISDN
should not be used more often than three times a day to avoid tolerance.
• Nitrates may be combined with other drugs with complementary mechanisms of action for
chronic prophylactic therapy. Combination therapy is generally used in patients with more
frequent symptoms or symptoms that do not respond to β-blockers alone (nitrates plus β-
blockers or calcium channel antagonists), in patients intolerant of β-blockers or calcium
channel antagonists, and in patients having an element of vasospasm leading to decreased
supply (nitrates plus calcium channel antagonists).

8. NITRATES
DRUG NAME nitroglycerin; isosorbide dinitrate; isosorbide mononitrate
CLASS Nitrates
MECHANISM OF
ACTION
Relax vascular smooth muscle cells, thereby causing venous and arterial vasodilation;
decrease both preload and afterload; relax coronary arteries
INDICATIONS Angina pectoris, hypertension, heart failure, anal fissure
ROA
Nitroglycerin - S/L, PO, PO spray, IV, Transdermal patch, Topical ointment.
Isosorbide dinitrate, isosorbide mononitrate – PO
SIDE EFFECTS
Headache, dizziness, flushing, nausea and vomiting, orthostatic hypotension, reflex
tachycardia, tolerance
CONTRA
INDICATIONS
AND CAUTIONS
•Hypotension, hypovolemia, severe anemia, cardiomyopathy
•Use carefully during pregnancy, breastfeeding, children or elderly, increased intracranial
pressure, cerebral hemorrhage, renal or hepatic disease, and syncope
•Drug interactions: other vasodilators (i.e., alcohol or erectile dysfunction medication like
sildenafil, tadalafil, or vardenafil)

9. NITRATES
ASSESSMENT
AND
MONITORING
•Prior to administration – Frequency and severity of angina pain, Baseline vital signs,
Health history
•Laboratory report: CBC, lipid profile renal and hepatic function
Continued monitoring – Side effects, Worsening symptoms, Therapeutic response
CLIENT
EDUCATION
•Correct self-administration procedures
Angina with activity: take prior to precipitating activities or situations
•Acute angina: call emergency services if pain unresolved within five minutes after first
dose; while awaiting emergency care to arrive, may take a second and third dose five minutes
apart if needed
•Managing side effects
Headache: acetaminophen
Orthostatic hypotension: make position changes slowly
• Proper storage – Store in original container at room temperature, Protect from light and
moisture
• Prevention of nitrate tolerance with patches or extended-release forms
At least 12 hours of nitrate free time / 24 hours
• Avoid substances that cause excessive hypotension
E.g., alcohol, erectile dysfunction medications

10. β ADRENERGIC BLOCKING DRUGS
CLASSIFICATION
• Nonselective (β1 and β2)
a. Without intrinsic sympathomimetic activity Propranolol, Sotalol,
Timolol.
b. With intrinsic sympathomimetic activity Pindolol
c. With additional α blocking property Labetalol, Carvedilol
• Cardioselective (β1) Metoprolol, Atenolol, Acebutolol, Bisoprolol,
Esmolol, Betaxolol, Celiprolol, Nebivolol

11. Beta blockers, also known as beta-adrenergic blocking agents, are drugs that block
norepinephrine and epinephrine (adrenaline) from binding to beta receptors on
nerves. Norepinephrine and epinephrine are produced by nerves throughout the
body as well as by the adrenal gland. They serve as neuro-transmitters (chemicals
that nerves use to communicate with one another) that may be active locally where
they are produced, or elsewhere in the body, when they are released into the blood.
There are both alpha and beta receptors in the body. There are three types of beta
receptors, and they control several different functions based on their location in the
body.
1. beta-1 (β1) receptors are located in the heart, eye, and kidneys.
2. beta (β2) receptors are found in the lungs, gastrointestinal tract, liver, uterus,
blood vessels, and skeletal muscle.
3. beta (β3) receptors are located in fat cells.
Beta blockers primarily block β1 and β2 receptors and thereby the effects of
norepinephrine and epinephrine. By blocking the effects of norepinephrine and
epinephrine, beta blockers reduce heart rate; reduce blood pressure by dilating blood
vessels; and may constrict air passages by stimulating the muscles that surround the
air passages to contract considered an adverse side effect).

14. BETA-ADRENERGIC BLOCKERS
DRUG NAME nadolol, propranolol, pindolol, sotalol atenolol, metoprolol, carvedilol, nebivolol
CLASS Nonselective β-blockers Selective β-blockers
MECHANISM
OF ACTION
Block β receptors → prevent catecholamines (norepinephrine and epinephrine) from binding and activating them
→ decrease cardiac contractility, decrease conduction velocity through AV node, decrease heart rate, cardiac
output, and blood pressure
INDICATIONS
•Hypertension
•Coronary artery disease; angina pectoris, myocardial infarction
•Arrhythmias
•Heart failure
•Essential tremor
•Glaucoma
•Migraine prophylaxis
ROA
•PO
•IV
•Opth
SIDE
EFFECTS
•Bradycardia
•Hypotension
•Fatigue, Dizziness
•Bronchospasm and dyspnea
•Headache, Depression, Hallucination, Insomnia and nightmares
•Erectile dysfunction, Decreased libido
•Hyperglycemia, Hypertriglyceridemia, Hyperkalemia.

15. CONTRAINDICATIONS
AND CAUTIONS
•Bradycardia, Hypotension
•Decompensated heart failure
•Asthma, COPD
•Diabetes
•Raynaud phenomenon
•Severe hepatic or renal disease
ASSESSMENT AND
MONITORING
•Baseline assessment
• Vital signs
• Orthostatic hypotension
• Frequency and duration of angina attacks
• Weight, lung sounds; presence of edema, dyspnea
•Laboratory test results: renal and hepatic function tests, electrolytes, glucose, lipid panel.
•Monitor - Heart rate, blood pressure, ECG
• Evaluate therapeutic response; e.g., normalized blood pressure, decreased anginal pain,
absence of heart failure symptoms
CLIENT EDUCATION
•Change positions slowly
•Do not abruptly discontinue medication
•Self-monitoring of pulse, blood pressure
•Lifestyle modifications
• Dietary modifications; e.g., low sodium diet
• Weight control and Regular activity as tolerated
• Alcohol and Smoking cessation
•Clients with diabetes: recognize signs of hypoglycemia; e.g., fatigue, hunger and difficulty
concentrating
•Report symptoms such as bradycardia, hypotension, hypertension, dyspnea, edema

16. Calcium Channel Blockers
Calcium influx occurs during the contraction of cardiac and smooth muscle
cells.
Calcium channels types
1. Voltage gated channels
1. L- type: Long lasting channel – cardiac, smooth muscle and neurons
2. T- type: Fast channel – neurons and endocrine cells
3. N- type: neural channel – neurons
2. Receptor operated channels
3. Stretch operated channels
4. Sodium calcium exchange channels

17. CCBs
Block L type Ca++ channels
Decreased frequency of Ca++ channel opening
Decreased Ca current and Ca++ entry into
cardiac and smooth muscle cells
1. Decreased cardiac contractility, heart rate
2. Vascular smooth muscle relaxation
• Benzothiazepines (diltiazem);
• Phenylalkylamines (verapamil);
• Dihydropyridines
o Amlodipine
o Felodipine
o Isradipine
o Nicardipine
o Nifedipine
o Nimodipine
o Nisoldipine
Classification

20. CALCIUM-CHANNEL BLOCKERS
DRUG NAME
Dihydropyridines: nifedipine, amlodipine, nicardipine, felodipine, nimodipine
Non-dihydropyridines: diltiazem, verapamil.
CLASS Calcium Channel Blockers (CCB)
MECHANISM OF
ACTION
•Block the entry of calcium into the cells
•Reduce the contraction of vascular smooth muscle and cardiac muscle
• Dilate arterioles, and reduce blood pressure and peripheral vascular resistance
• Dilate coronary vessels and increase oxygen supply to the heart
• Reduce force of contraction of cardiac muscles and reduce oxygen demand of the
heart
•Reduce the firing and conduction of impulse through the SA and AV nodes in the heart
INDICATIONS
•Cardiac arrhythmia, hypertension, angina pectoris, tocolysis in preterm labor, Raynaud’s
phenomenon, migraine prophylaxis; Nimodipine: subarachnoid hemorrhage
ROA PO, IV
SIDE EFFECTS
•General: headache, dizziness, flushing of the skin, peripheral edema, hypotension
•Dihydropyridines: reflex tachycardia, gingival hyperplasia
•Non-dihydropyridines: bradycardia, constipation and hyperprolactinemia
CONTRAINDICATIONS
AND CAUTIONS
•Pre-existing bradycardia
•Heart block and Heart failure
•Use with caution: hepatic and renal disease
•Interactions: digoxin, grapefruit

21. CALCIUM-CHANNEL BLOCKERS
ASSESSMENT AND
MONITORING
•Vital signs, CBC, sodium, potassium, creatinine, BUN, liver function tests, and
urinalysis, ECG
•For angina: frequency and severity of symptoms
•Monitor for side effects and therapeutic response
CLIENT EDUCATION
•Purpose of medication
•Self-administration
• Take exactly as prescribed, do not stop abruptly
• Swallow whole; do not divide, crush, or chew
• Avoid grapefruit juice and limit caffeine
•Side effects
• Hypotension and reflex tachycardia: change positions slowly
• Peripheral edema: elevate legs
• Constipation: increase fiber and fluids
• Gingival hyperplasia: good dental hygiene
•Lifestyle modifications for cardiovascular health
•Heart rate and blood pressure self-monitoring
•Report persistent side effects, hypotension, bradycardia; seek medical attention
if angina not relieved by rest or medication

22. POTASSIUM CHANNEL OPENERS
Multiple types of K+ channels, viz:
• Voltage dependent K+ channel
• ATP activated K+ channel
• Ca2+ activated K+ channel
• Receptor operated K+ channel
• Na+ activated K+ channel
• Cell volume sensitive K+ channel
Nicorandil
Nicorandil
Opens ATP sensitive K+ channels
Opens ATP sensitive K+ channels
Hyperpolarization
Hyperpolarization
Relaxes vascular smooth mucsle
Relaxes vascular smooth mucsle
↓Preload, ↓Afterload,
Coronary vasodilation
↓Preload, ↓Afterload,
Coronary vasodilation

23. Nicorandil
• Nicorandil is well absorbed orally, nearly completely metabolized in liver and is
excreted in urine.
• Side effects of nicorandil are flushing, palpitation, weakness, headache, dizziness,
nausea, and vomiting.
• Large painful aphthous ulcers in the mouth, which heal on stopping nicorandil
have been reported.
• Nitrate like tolerance does not occur with nicorandil, but it has the potential to
interact with sildenafil.
• Dose: 5–20 mg BD
• Though nicorandil is an alternative antianginal drug, its efficacy and long term
effects are less well established. It has failed to acquire wide acceptance but may
be useful in resistant angina when combined with other drugs. Administered i.v.
during angioplasty for acute MI, it is believed to improve outcome.

24. OTHER ANTIANGINAL DRUGS
• Dipyridamole It is a powerful coronary dilator; increases total coronary flow by
preventing uptake and degradation of adenosine which is a local mediator involved
in autoregulation of coronary flow in response to ischemia. It dilates resistance vessels
and abolishes autoregulation but has no effect on larger conducting coronary vessels.
Cardiac work is not decreased because venous return is not reduced. BP is minimally
altered. Accordingly, it fails to relieve anginal symptoms or avert ECG changes.
The pharmacological success but therapeutic failure of dipyridamole has been explained
based on ‘coronary steal’ phenomenon. By dilating resistance vessels in nonischemic
zone as well, it diverts the already reduced blood flow away from the ischemic zone.
Dipyridamole inhibits platelet aggregation. By potentiating PGI2 and increasing cAMP
in platelets, it enhances antiaggregatory influences. Though not useful as an antianginal
drug, it is being employed for prophylaxis of coronary and cerebral thrombosis in post-
MI and poststroke patients, as well as to prevent thrombosis in patients with prosthetic
heart valves.
Dose: 25–100 mg TDS

26. Trimetazidine
• Protective effect on the ischemic myocardium and to maintain left ventricular function.
• MOA: pFOX inhibitor (Partial inhibitor of fatty acid oxidation)
• Also inhibits the superoxide induced cytotoxicity to the myocardial cells - protecting
the myocardium from ischemic damage.
• Side effects are—gastric burning, dizziness, fatigue and muscle cramps. Reversible
parkinsonism has been reported in the elderly. Trimetazidine has also been advocated
for visual disturbances, tinnitus, Méniére’s disease, dizziness, etc., but conclusive
evidence of efficacy in these conditions is lacking. For ischaemic heart disease, it has
been widely used in France, Spain, some other European countries and India, but not in
the UK or USA. It is mostly an add on medication to conventional therapy in angina and
post-MI patients.
Dose: 20 mg TDS.

27. Ranolazine
• Reduction in Ca2+ overload in the
myocardium during ischemia decreases
contractility and has a cardioprotective effect.
Sparing of fatty acid oxidation during
ischemia in favor of more O2 efficient
carbohydrate oxidation by inhibiting LC3KAT
(long chain 3-ketoacyl-CoAthiolase) has also
been demonstrated. This was earlier believed
to be the main mechanism of antianginal
action of ranolazine but is now considered
secondary. Ranolazine has no effect on HR
and BP but prolongs exercise duration in
angina patient.
• Side effects reported are dizziness, weakness,
constipation, postural hypotension, headache
and dyspepsia.
• Dose: 0.5–1.0 g BD as SR tab

28. Ivabradine - an alternative to β blockers
• Blocks the sodium channels in the SA node and decreases the heart rate (direct
bradycardiac).
• Heart rate reduction decreases cardiac O2 demand and prolongation of diastole tends to
improve myocardial perfusion (O2 supply).
• Ivabradine is indicated in chronic stable angina in patients with sinus rhythm who are
intolerant to β blockers or when the latter are contraindicated. It can also be used in
inappropriate sinus tachycardia.
• Side effects: excess bradycardia, visual disturbance, headache, dizziness and nausea.
• Dose: Initially 5 mg BD, increase if needed to 7.5 mg BD, Elderly 2.5 mg BD.

29. Oxyphedrine
• This drug is claimed to improve myocardial metabolism so that heart can sustain
hypoxia better. Though used in angina and MI for over 3 decades, its efficacy and
status in coronary artery disease is not defined.
It can diminish or alter taste sensation.
• Dose: 8–24 mg TDS oral, 4–8 mg i.v. OD-BD;