Explain the pharmacology of Angina Pectoris.

1. ANTIANGINAL DRUGS
PRESENTED BY:
Mr. Jithin Mathew, M.Pharm.,
Assistant Professor
Department Of Pharmacology
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2. .ANGINA PECTORIS:
Is a pain syndrome due to induction of an
adverse oxygen supply / demand situation in a
portion of the myocardium.
ANTI ANGINAL DRUGS:
Anti anginal drugs are those that prevent ,
abort or terminate attacks of angina pectoris
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3. Myocardial oxygen demand is chiefly
determined by:
• Myocardial Contractility
• Heart rate
• Wall tension
• Preload (venous return )
• Afterload (arteriolar resistance)
• HEART SIZE
• SYSTEMIC BLOOD PRESSURE
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4. Myocardial oxygen demand is
diminished by:
• Reducing contractility
• Reducing heart rate
• Reducing the preload-wall tension
• Reducing the afterload-Wall tension 
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5. Classification of angina pectoris:
1. Exertional angina
Stable angina
2. Spontaneous angina
Variant angina or prinzmetal
3. Mixed angina
Unstable angina
4.Cardiac metabolic syndrome x 5

6. Chronic Stable Angina: The most common anginal
syndrome.
• Character: More often described as a discomfort, pressure, or
squeezing sensation.
• Less commonly as burning, sticking, or sharp.
• Location: Most often in the substernal area, precardium, or
epigastrium with radiation to the left arm, jaw, or neck.
• Less commonly felt only in radiation areas and not in the
chest.
• Precipitation: Often provoked by exertion, emotion, exposure
to cold, eating or smoking, and relieved by rest, removal of
provoking factors, or sublingual nitrates.
• Duration: Usually lasts a few minutes, rarely over 20-30
minutes.
• The frequency and severity of the symptoms change little with
daily activities, and pain does not usually occur at rest 6

7. • Unstable Angina Pectoris
• Unstable angina pectoris is a combination of syndromes
also called as preinfarction angina, impending myocardial
infarction, progressive, coronary insufficiency, new onset
angina, etc.
• Unstable angina pectoris usually presents in one of three patterns:
 angina pectoris of recent onset (less than 1 month)
 chest pain occurring more frequently, with greater severity and duration, with less provocation, and requiring larger doses of nitroglycerine to abort attacks.
 prolonged chest pain at rest, clinically indistinguishable from acute MI at the time of presentation.
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8. • Variant Angina Pectoris (Prinzmetal's Angina)
• This type of angina results from myocardial
ischemia caused by coronary artery spasm and
may occur in patients with or without
coronary atherosclerosis.
• Pain occurs principally at rest, usually
unprovoked
• The pain may occur in a circadian manner,
often in the early morning hours.
• Often subclinical (painless) episodes occur
often associated with arrhythmias
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9. CARDIAC METABOLIC SYNDROME X:
• Common in women
• Angina or angina like chest pain on exercise
• “sensitive heart” is believed to the mechanism
of pain
• Response to physical training and beta
blockers ,and less satisfactory response to
nitrates and CCB .aid in its diagnosis.
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10. Classification:
1. NITRATES:
a. Short acting :GTN, nitroglycerin
b. Long acting : isosorbide dinitrate(short acting
by sublingual route),isosorbide
mononitrate,erithrityl
tetranitrate,pentaerythritol tetranitrate
2. B BLOCKERS:
propanolol,metoprolol,atenolol,and others.
3. CALCIUM CHANNEL BLOCKERS
a. Phenylalkylamine: verapamil
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11. b. Benzothiazipene: diltiazem
c. Dihydropyridines:nifidipine,felodipine,amlodi
pine,nitredipine,nimodipine,lacidiline,lercani
dipine,benidipine
4. POTASSIUM CHANNEL OPENER:nicorandil
5.OTHERS: dipyridamole,
trimetazidine,ranolazine,oxyphedrine
CLINICAL CLASSIFICATION:
A.Used to abort or terminnate attack:
GTN,isosorbide dinitrate,(sublingually),
b. Used for chronic prophylaxis: all other drugs
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12. • 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.
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13. Mechanism of action of nitrates:
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14. 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
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15. 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, BLURRING OF VISION
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
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16. BETA BLOCKERS
MODE OF ACTION: LOWERS MYOCARDIAL OXYGEN DEMAND BY
A. REDUCING HEART RATE
B. REDUCING BLOOD PRESSURE
C. REDUCING MYOCARDIAL CONTRACTILITY
Can exaccerbate symptoms of peripheral vascular disease
May provoke bronchospasm in patients with obstructive airway
disease
e.g asthma
Advice: use a once daily cardio-selective preparation e.g atenolol
50-200mg daily
slow release metoprolol 50-200mg daily
bisoprolol 5-10 mg daily
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17. CALCIUM ANTAGONISTS
MODE OF ACTION
1. 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
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 PRECIPITATE
HEART FAILURE
UNWANTED EFFECTS
 PERIPHERAL OEDEMA
 FLUSHING
 HEADACHE
 DIZZINESS
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18. POTASSIUM CHANNEL ACTIVATORS
MODE OF ACTION: DILATES ARTERIES AND VEINS
DOES NOT EXHIBIT TOLERANCE SEEN WITH NITRATES
NICORANDIL- 10-30 mg 12 hourly
Side effects:
a. Headache
b. Flushing
c. Dizziness
d. Weakness
e. May cause a dose dependent increase in heart rate
f. Angioedema
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19. ANTIPLATELET DRUGS
ASPIRIN
CLOPIDOGREL
THROMBOLYTIC AGENTS
STREPTOKINASE
ALTEPLASE
RETEPLASE-
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20. ASPIRIN
ANTIPLATELE T EFFECT BY INHIBITION OF THROMBOXANE A 2
NSAID, INHIBITS COX-1 AND COX -2 WHICH LEADS TO DECREASED PROSTAGLANDIN
SYNTHESIS
USES
ISCHAEMIC HEART DISEASE-PROPHYLAXIS (75MG/DAY) AND ACUTE TREAMENT (300
MG)
CONTRAINDICATIONS
1. THOSE UNDER AGE OF 16Y-CAN INCREASE INCIDENCE OF 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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21. CLOPIDOGREL
ANTIPLATELET AGENT- ADP RECEPTOR ANTAGONIST
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)
ISCHAEMIC CEREBROVASCULAR ACCIDENT- WITHIN 7 DAYS TO 6 MONTHS
PERIPHERAL ARTERIAL DISEASE
CONTRAINDICATION: ACTIVE BLEEDING
NOT RECOMMENDED WITH WARFARIN
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22. 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
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23. ALTEPLASE
(RECOMBINANT) TISSUE-TYPE PLASMINOGEN ACTIVATOR.
RECOMBINANT FIBRINOLYTIC
USE
ACUTE MYOCARDIAL INFARCTION (TOTAL DOSE 100MG-REGIMEN DEPENDS ON TIME SINCE
ONSET OF PAIN
0-6 HOURS: 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
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24. Newer drugs for angina pectoris
• The antianginal effectivity of niludipine , a new
calcium antagonistic drug, was investigated in
angina pectoris patients, selected for admission to
the trials by pre-determined strict criteria.
• Oral administration of from 60--120 mg niludipine
daily for 4--8 weeks, resulted in the following:
• 1. Number of anginal attacks significantly reduced.
• 2. Nitrate consumption markedly lowered.
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25. • BRILINTA, a new oral antiplatelet medicine, is
indicated to reduce the rate of thrombotic
cardiovascular events in patients with ACS (unstable
angina [UA] non-ST-elevation myocardial infarction
or ST-elevation myocardial infarction .
• The FDA approved the thienopyridine prasugrel for
use in patients with unstable angina or myocardial
infarction who undergo percutaneous coronary
intervention.
• PLAVIX 300mg tablet of the antiplatelet PLAVIX®
(clopidogrel bisulfate) will facilitate the use of the
FDA approved loading dose for appropriate acute
coronary syndrome (ACS) patients as soon as
possible after hospital admission
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26. • Angiomax (bivalirudin) is indicated as a
thrombin-specific anticoagulant to be used in
conjunction with aspirin in patients with
unstable angina undergoing percutaneous
transluminal coronary angioplasty (PTCA).
• It is available by prescription only in a 250mg
injectable formulation.
• The drug has been studied only in patients
receiving concomitant aspirin.
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27. REFERENCE
• K.D.Tripathi.,Essentials of medical
pharmacology,6th edition(2010),page no:335-
410
• Roger Walker,Clinical pharmacology and
therapeautics
• H.P Rang etal,Rang and Dale’s pharmacology,
pg 286-290
• Dipiro J.T et al ;Pharmacotherapy: A
Pathophysiologic Approach,2008, 7 th edition
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28. SESSION
FOR
DISSCUSSION
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29. THANK YOU
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