DRUGS USED FOR
ANGINA PECTORIS

Angina is chest pain or discomfort caused when your heart
muscle doesn't get enough oxygen-rich blood.
Angina is not a disease. It is a symptom of an underlying
heart problem, usually coronary heart disease (CHD).
Angina happens when one or more of the coronary arteries is
narrowed or blocked, also called ischemia.

Mechanism include:
Atherosclerosis (plaque-related epicardial coronary
obstruction)
focal or diffuse spasm of normal or atheromatous
arteries
microvascular dysfunction
left ventricular dysfunction secondary to previous
acute myocardial necrosis/hibernation (ischaemic
cardiomyopathy)
left ventricular hypertrophy (hypertension, aortic
stenosis, hypertrophic cardiomyopathy).

•Four types of Angina
Stable angina
Unstable angina
Microvascular angina
Prinzmetal’s angina

 Mechanisms of atherosclerosis
 The pathophysiology of atherosclerosis, development of
symptomatic angina and subsequent acute coronary
syndrome (ACS) is well characterised.2,3 The microscopic
development of atherosclerotic plaque involves:
 endothelial dysfunction
 sub-endothelial accumulation and oxidation of low-density
lipoprotein (LDL)
 increased expression of adhesion molecules and chemokine
secretion
 immune cell infiltration and development of foam cells
 development of fibroatheromatous plaque involving
positive remodelling, neovascularisation, and development
of necrotic core with overlying fibrous cap formation and
calcification.

 Endothelial dysfunction and nitric oxide
 The endothelium is a single layer of cells lining blood
vessels and performs multiple functions, including:
 the regulation of coronary blood flow
 a barrier to toxic substrates
 regulation of thrombosis and inflammation
 control of angiogenesis.

 Endothelial dysfunction is characterised by a reduction in the bioavailability of
vasodilators, such as NO, as a result of reduced production and increased
consumption of NO, and an increase in endothelium-derived contracting factors,
such as endothelin and angiotensin II (AII) (figure 1). This is seen as the blood
vessel being unable to dilate. In addition, endothelial dysfunction promotes
platelet and leukocyte activation and the release of cytokines, which increase
vessel permeability. This enables the sub-endothelial infiltration of oxidised
lipoproteins and inflammatory cells.

Endothelial dysfunction has been referred to as “the risk of the risk factors”,4 since it has been
shown to occur in the presence of conventional, modifiable risk factors (e.g. cigarette smoking,
high blood pressure, hyperlipidaemia and diabetes). These risk factors are, in turn, associated
with a state of increased oxidative stress and the overproduction of reactive oxygen species. This
all contributes to the complex interplay of endothelial dysfunction since reactive oxygen species
can themselves lead to abnormal NO metabolism (figure 2).

Fatty streaks: A fatty streak marks the earliest macroscopic
atherosclerotic lesion. Beginning in early life, these fatty streaks
comprise a focal build-up of various substrates e.g. lipid-rich
macrophages (foam cells), extracellular matrix, smooth muscle cells,
intracellular and extracellular lipid deposits, and T lymphocytes, to
form a minor thickening of the intimal surface.

Plaque formation

Unstable angina:
•Also called “Crescendo angina”
•Acute coronary syndrome in which angina worsens
•Occurs at rest
•Severe and of acute onset
•Crescendo pain- pain increases every time

Unstable angina:
•Increased frequency , severity or duration of pain
in a apatient of stable angina.
•Pain occurs with less exertion or at rest.
•Myocardial contraction may occur in 10-20%
patients

Microvascular angina:
•Also called Syndrome X
•Cause unknown
•Probably due to poor functioning of the small blood
vessels of the heart, arms and legs
•No arterial blockage
•Difficult to diagnose because it does not have arterial
blockage
•Good prognosis

Prinzmetal’s angina or variant angina
•Prinzmetal’s angina is a variant form of angina with
normal coronary vessels or minimal atherosclerosis
•It is probably caused by spasm of coronary artery

 Immediate pre exertional prophylaxis of angina:
Sublingual Nitroglycerine 0.5mg or Isosorbide
dinitrate 5mg should be taken within 5 minutes.
 For long term prophylaxis:
Long acting nitrates, calcium channel blockers,
beta blockers or combination of these drugs.
 Antiplatelet therapy:
Aspirin small dose 75mg – 150mg once daily orally
or Dipyridimole 75mg orally.

 CORONARY ARTERY REVASCULARIZATION
 For patients not responding to medical
therapy
Percutaneous Transluminar Coronary
Angioplasty (PTCA).
Coronary Artery bypass grafting (CABG)

Pharmacologic management of acute coronary syndromes

Classification
1. Nitrates
a)Short acting: Glyceryl trinitrate (GNT, Nitogycerine)
b)Long acting: Isosorbide dinitrate, Isosorbide mononitrate,
Erythrityl tetranitrate
2.β- blockers: Propranolol, Metoprolol, Atenolol
3.Calcium channel blockers
a)Phenyl alkylamine: Verapamil
b)Benzothiazepine: Diltiazem
c)Dihyropyridines: Nifedipine, Nimodipine, Lacidipine,
Lercanidipine, Benidipine
4.Potassium channel opener: Nicorandil
5.Others: Dipyridamole, Trimetazidine, Ranolazine, Ivabradine,
Oxyphendrine

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)

Mode of action of organic nitrates

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
INTRAVENOUS INFUSION, TITRATING TO CLINICAL RESPONSE
AND BLOOD PRESSURE.

DURATION OF ACTION OF SOME NITRTATE PREPARATIONS
PEAK ACTION
DURATION OF
ACTION
Sublingual GTN(Tablet 300-
500µg or metered dose
aerosol 400µg/spray)
4-8 minutes 10-30 minutes
Buccal GTN (1-5 mg tablet 6
hourly)
4-10 minutes 30-300 minutes
Transdermal. GTN (5-10
daily)
1-3 hours Up to 24 hours
Oral isosorbidedinitrate.(10-
20 mg 8 hourly)
45-120 hours 2-6 hours
Oral isosorbide mononitrate
( 20-60 mg once or twice a
day)
45-120 hours 6-10 hours

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
NOT HABIT FORMING
TEACH PATIENTS TO USE PROPHYLACTICALLY e.g. Before exerting
VIRTUALLY INEFFECTIVE IF SWALLOWED DUE TO EXTENSIVE FIRST PASS
METABOLISM IN THE LIVER
CONTINUOUS USE CAUSES PHARMACOLOGICAL TOLERANCE
THERFORE ATTEMPT TO INCLUDE A ‘NITRATE-FREE’ PERIOD OF 6-8 HOURS
A DAY

 Beta Blockers are effective in Stable and Unstable
Angina.
 In contrast they are not useful in variant angina may
worsen the condition. This deleterious effect is likely
due to the increase in the coronary resistance caused by
the unopposed effects of catecholamines acting at alpha
adrenoreceptors.

• Heart rate
• Contractility
• Preload
• Afterload
• Coronary flow
• Regional
myocardial blood
flow

O2
D
e
m
a
n
d

O2
S
u
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p
l
y
-Blockers/Ca2+ channel
blockers
Nitrates/Ca2+ channel
blockers
Nitrates/Ca2+ channel
blockers/antithrombotics/
statins
HEART

Adverse Drug reactions:
Bronchospasm
Hypotension
Bradycardia
Increase in Lipid profile test
Mask signs of Hypoglycemia
Contraindications:
Asthma, Diabetes, Hypotension

CALCIUM CHANNEL BLOCKERS
MODE OF ACTION
1.DECREASES MYOCARDIAL OXYGEN DEMAND BY REDUCING BLOOD
PRESSURE AND MYOCARDIAL CONTRACTILITY
Mechanism of Action
1.Calcium channel blockers block voltage-gated L-type calcium channels, the calcium
channels most important in cardiac and smooth muscle.
By decreasing calcium influx during action potentials in a frequency and voltage
dependent manner, these agents reduce intercellular calcium concentration and muscle
contractility.
USED IN ALL TYPES OF ANGINA
Verpamil 80-160mg/8hr
Diltiazem 60-120mg/8hr
Nifedipine 10-40mg/8hr
Amlodipine 5mg/day

 VERAPAMIL AND DILITIAZEM-SUITABLE FOR PATIENTS
WHO ARE NOT RECEIVING BETA BLOCKERS AS THEY
DECREASE THE HEART RATE ( DANGEROUS ADDITIVE
EFFECT
 Adverse Drug reactions:
Facial puffiness
Pedal edema
Flushing
Headache
Contraindications: Heart failure, Bradycardia

POTASSIUM CHANNEL ACTIVATORS
MODE OF ACTION: DILATES ARTERIES AND VEINS
DOES NOT EXHIBIT TOLERANCE SEEN WITH NITRATES
NICORANDIL- 10-30 mg 12 hourly
Caution in:
hypovolaemic patients
Patients with pulmonary oedema
Side effects:
a.Headache
b.Flushing
c.Dizziness
d.Weakness
e.May cause a dose dependent increase in heart rate
f.Myalgia
g.Angioedema

 Potassium channel openers:
 Types of potassium channels: Voltage gated, calcium
activated, ATP acyivated
 Nicorandil is a newer agent activates ATP sensitive
potassium channel and hyperpolarises vascular
smooth muscles.
 Decreases pre and after load and produce coronary
dilation

Ranolazine
Reserve agent for chronic, resistant angina
Inhibits cardiac late Na Current influx ,
there by reducing calcium flow into the cells
thus help the heart to relax improve the
blood flow
Decreases cardiac contractility
No change in Heart rate and BP
Prolongs QT interval so it is containdicated
with drugs that prolong QT interval.
Dose: 500mg, 1000mg

IVABRADINE
Direct Bradycardic agent or pure HR lowreing agent
Blocks hyperpolarazation activated if current through Na
channel present in SA node which get activated during early part
of slow diastolic depolarization durring ischemic episodes.
Heart rate decreased and Oxygen demand decreased
No fall in BP
Dose: 5mg

ANTIPLATELET DRUGS
ASPIRIN
CLOPIDOGREL
THROMBOLYTIC AGENTS
STREPTOKINASE
ALTEPLASE
RETEPLASE-

ASPIRIN
ANTIPLATELE T EFFECT BY INHIBITION OF THROMBOXANE A 2
NSAID, INHIBITS COX-1 AND COX -2 WHICH LEADS TO
DECREASED PROSTAGLANDIN SYNTHESIS
USES
THROMBO-EMBOLIC CVA, ISCHAEMIC HEART DISEASE-
PROPHYLAXIS (75MG/DAY) AND ACUTE TREAMENT (375 MG)
CONTRAINDICATIONS
1.THOSE UNDER AGE OF 16Y-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

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 HPOURLY –MAXIMUM DOSE4G/DAY
STOP 7 DAYS BEFORE SURGERY IF SIGNIFICANT BLEEDING IS EXPECTED
IF CARDIAC SURGERY OR PATIENT HAS ACUTE CORONARY SYNDROME-
CONSIDER CONTINUING

CLOPIDOGREL
ANTIPLATELET AGENT- The active metabolite of clopidogrel
selectively inhibits the binding of adenosine diphosphate (ADP) to
its platelet P2Y12 receptor and the subsequent ADP- mediated
activation of the glycoprotein GPIIb/IIIa complex, thereby
inhibiting platelet aggregation. This action is irreversible
USE
PROPHYLAXIS OF ANTI-THROMBOTIC EVENTS IN NON—ST
ELEVATIONMYOCARDIAL INFARCTION AND IN ST ELEVATION
MYOCARDIAL INFARCTION-IN COMBINATION WITH ASPIRIN
MYOCARDIAL INFARCTION (WITHIN A ‘FEW’ TO35 DAYS)
ISCHAEMICCEREBROVASCULAR ACCIDENT- WITHIN 7 DAYS TO 6
MONTHS
PERIPHERAL ARTERIAL DISEASE
CONTRAINDICATION
ACTIVE BLEEDING
NOT RECOMMENDED WITH WARFARIN

CLOPIDOGREL
SIDE EFFECTS
 HAEMORRHAGE (ESPECIALLY GASTRO-INTESTINAL OR
INTRA-CRANIAL
 GASTRO-INTESTINAL UPSET
 PEPTIC ULCER
 PANCREATITIS
 HEADACHE
 FATIGUE
 DIZZINESS
 PARAESTHESIA
 RASH/PRURITUS
MONITOR FULL BLOOD AND FOR SIGNS OF OCCULT BLEEDING

STREPTOKINASE
THROMBOLYTIC AGENT
INCREASES PLASMINOGEN CONVERSION TO PLASMIN WHICH
INCREASES FIBRIN BREAKDOWN
USES
1.ACUTE MYOCARDIAL INFARCTION -1.5 MILLION UNITS
INTRAVENOUS INFUSION OVER 60 MIN
2.THROMBOEMBOLISM OF ARTERIES
3.PULMONARY EMBOLISM
4.CENTRAL RETINAL ARTERY THROMBOSIS
5.DEEP VEIN THROMBOSIS
OTHER DOSES-250,000 UNITS INTRAVENOUS INFUSION OVER
30 MIN, THEN 100,000 UNITS EVERYHOUR FOR UPTO12-72
HOURS

ALTEPLASE
(RECOMBINANT) TISSUE-TYPE PLASMINOGEN ACTIVATOR.
RECOMBINANT FIBRINOLYTIC
USE
ACUTE MYOCARDIAL INFARCTION (TOTAL DOSE 100MG-
REGIMEN DEPENDS ON TIME SINCE ONSET OF PAIN
0-6HOURS: 15 MG INTRAVENOUS BOLUS,FOLLOWED BY 50 MG
INTRAVENOUS INFUSION OVER 30 MINUTES AND 35 MG INTRAVENOUS
INFUSION OVER 60 MINUTES
6-12 HOURS-10 MG INTRAVENOUS BOLUS FOLLOWED BY 50 MG
INTRAVENOUS INFUSION OVER 60 MIN, AND FOUR FURTHER 10 MG
INTRAVENOUS INFUSIONS, EACH OVER 30 MIN)
DECREASE DOSE IF PATIENT WEIGHS LESS THAN 65 KG
RETEPLASE
RECOMBINANT PLASMINOGEN ACTIVATOR; THROMBOLYTIC
USED ONLY FOR MYOCARDIAL INFARCTION
DOSE-10 UNITS AS SLOW INTRAVENOUS INJECTION OVER 2 MINUTES,
REPEAT AFTER 30 MIN

Newer Drugs
A) Ranolazine appears to act mainly by reducing a late,
prolonged sodium current in myocardial cells.
1.The decrease in intracellular sodium causes an increase in
calcium expulsion via the Na/Ca transporter and a reduction in
cardiac force and work.
2.Ranolazine is moderately effective in angina prophylaxis.
B) Dipyridamole
1.It is a powerful coronary dilator;
increases total coronary flow by preventing
uptake and degradation of adenosine.
2.It dilates resistance vessels and abolishes autoregulation.
3.Inhibit platelet aggregation.
4.Not useful as an anti-anginal drug but used for prophylaxis of
Coronary and cerebral thrombosis in post-MI and post stoke
patients.