The document provides detailed information about the human heart, including its function, statistics, and various types of angina pectoris. It outlines antianginal drugs, their classifications, mechanisms, and side effects, alongside the roles of other medications in managing heart conditions. It also discusses the importance of gradual withdrawal of certain drugs and implications of combining treatments for effective cardiovascular care.

5. HEART FACTS
 The average adult heart beats
 72 times a minute;
 100,000 times a day;
 3,600,000 times a year;
 and 2.5 billion times during a lifetime.

6. HEART FACTS
 Though weighing only 11 ounces on average,
 a healthy heart pumps
 2,000 gallons of blood through
 60,000 miles of blood vessels
 each day.

7. HEART FACTS
 5% of blood supplies the heart,
 15-20% goes to the brain and central nervous system,
 and 22% goes to the kidneys.

8. ANGINA PECTORIS
 Is a pain syndrome due to an adverse
oxygen supply/demand situation in a
portion of myocardium

11. ANTIANGINAL DRUGS
DR. V.SATHYANARAYANAN M.D
PROFESSOR OF PHARMACOLOGY
SRM MCH & RC
CHENNAI, INDIA

16. TYPES OF ANGINA
Classical angina
common form
due to fixed coronary obstruction
Ischemic pain is felt
Subside when the increased energy demand is withdrawn
attacks are provoked by
 exercise,
emotion,
 eating or
coitus

21. Variant angina
 Prinzmetal’s angina
 Attacks occur at rest or during sleep
 Unpredictable
 Due to localized coronary vasospasm

23. Unstable angina

Rapid increase in duration and
severity of attacks
Due to rupture of an atheromatous plaque
 platelet deposition
 progressive occlusion of coronary artery

27. HEART FACTS
 The human heart begins to beat as
early as
four weeks after conception

28. HEART FACTS
 Grab a tennis ball and squeeze it tightly:
 that’s how hard the beating heart works to pump blood.
 A woman’s heart typically beats faster than a man’s.

29. HEART FACTS
Every day, the heart creates enough energy to
drive a truck 20 miles.
 In a lifetime, that is equivalent to
driving to the moon and back.

30. HEART FACTS
 During an average lifetime,
 the heart will pump nearly 1.5 million gallons of blood—
 enough to fill 200 train tank cars.

32. ANTIANGINAL DRUGS
 Prevent, abort or terminate
attacks of angina pectoris
Do not alter the
course of coronary artery
pathology

33. CLASSIFICATION
1.NITRATES – SHORT ACTING –Glyceryl trinitrate
LONG ACTING – Isosorbide dinitrate, Isosorbide mononitrate
2.BETABLOCKERS – Propranolol, metoprolol, Atenolol
3.CALCIUM CHANNEL BLOCKERS – Verapamil, Diltiazem,
Nifedipine, Amlodipine, Nitrendipine
4.POTASSIUM CHANNEL OPENER – Nicorandil
5.OTHERS – Trimetazidine, Dipyridamole, Oxyfedrine

34. NITRATES- GLYCERYL TRINITRATE-
(PROTOTYPE)
 ACTIONS

1. PRELOAD REDUCTION
 Dilate veins
  peripheral pooling of blood
  decrease venous return
  decrease preload
  decrease cardiac work according to Laplace
relationship
  decrease oxygen consumption, decrease in the
cardiac output

36. ACTIONS
decrease afterload
Some arteriolar dilatation
 slightly decrease total peripheral resistance
decrease afterload
 decrease in cardiac work

39. ACTIONS
Dilate larger coronary vessels

 increase blood flow to
ischemic areas

43. ACTIONS

Dilate cutaneous blood vessels  flushing

Dilate meningeal vessels  headache
 Shift blood from pulmonary circuit to systemic circuit 
decongest lungs

47. ACTIONS
Relax bronchi
Relax biliary tract
Relax esophagus

50. MECHANISM OF ACTION
Denitrated in smooth muscle
 release Nitric Oxide
 activates cytosolic guanylyl cyclase
 increase cGMP
 dephosphorylation of MLCK
 reduced availability of active MLCK
interferes with the activation of Myosin

 fails to interact with actin  relaxation

cGMP  decrease ca entry  relaxation

54. PHARMACOKINETICS
Well absorbed from buccal mucosa, skin,
intestine
Lipid soluble
Undergo extensive 1st
pass metabolism
except isosorbide mononitrate
Rapidly denitrated  produce less active
metabolites with longer t1/2

57. ADR
 Headache, fullness in head
 Flushing,
 weakness
 Palpitation,
 sweating,
 dizziness, fainting
 Methemoglobinemia – a problem in severe
anemia
 Rashes – particularly with pentaerythritol
tetranitrate

65. TOLERANCE
 Decreased effectiveness of nitrates on repeated
administration
 Seen with GTN used orally, i.v, transdermally
 With long acting agents
 Cross tolerance also seen

Prevented by keeping nitrate free
interval everyday

66. DEPENDENCE
Seen after sudden withdrawal after
prolonged exposure
Myocardial infarction,
sudden deaths,
increase episodes of angina on record
Add a drug of another class
Withdrawal must be gradual

69. Sex and cardiovascular system
 CHANGES DURING ORGASM……
 Tachycardia  upto 180 beats/ minute
 BP  230/130 mmHg even in
normotensives
 ECG abnormalities may occur
 RESPIRATORY RATE  60 / min
 SUDDEN DEATHS
 CAUTION – older patients with CAD

71. INTERACTIONS
Potentiation of action by
sildenafil  severe hypotension
 MI, deaths
With other vasodilators
 additive hypotension

74. GLYCERYL TRINITRATE
Volatile liquid
Stored in tight glass container
Taken sublingually terminate an anginal
attack
Acts within 1-2 minutes
Also administered as
sublingual spray,
S.R. capsule,
transdermal patch,
i.v infusion,
transmucosal dosage form
Given as i.v infusion in unstable angina, LVF in MI, during
cardiac surgeries

84. DOCTOR….. DOCTOR…..
Patient: It's been one month since my last visit
and I still feel miserable.
Doctor: Did you follow the instructions on the
medicine I gave you?
Patient: I sure did - the bottle said 'keep
tightly closed.'

85. ISOSORBIDE DINITRATE
 Solid
 S/L – Slower acting than GTN
 Orally given for chronic prophylaxis
 High 1st pass effect
 t1/2 - 4O min
 Leave 6-10 hr nitrate free interval

86. ISOSORBIDE MONO NITRATE
 Active metabolite of ISDN
Little 1st
pass effect  high BA
 Long acting
 SR tablet given once daily in morning

87. OTHER NITRATES
• Erythrityl tetranitrate,
Pentaerythritol tetranitrate
are longer acting
• Used for chronic prophylaxis

89. HEART FACTS
 When the body is at rest,
 it takes only 6 seconds for the blood
 to go from the heart to the lungs and back,
 only 8 seconds for it
 to go the brain and back, and
 only 16 seconds for it
 to reach the toes and travel all the way
back to the heart.

102. USES
 Angina pectoris –effective in classical
angina, variant angina increase exercise tolerance,
given as “as and when required” basis
 Acute coronary syndromes
 Congestive heart failure
 Acute left ventricular failure
 Myocardial infarction – of marginal benefit
 Interventional cardiac procedures
 Biliary colic
 Esophageal spasm
 Cyanide poisoning
 Venipuncture

114. BETABLOCKERS IN ANGINA
Decrease cardiac work, oxygen consumption during
exercise, anxiety
All are Equally effective in preventing angina
Cardio selective beta blockers are preferred
To be taken on regular schedule
Dosage to be individualized
Tolerance does not develop
DO NOT DILATE CORONARY VESSELS

118. BETABLOCKERS IN ANGINA - CAUTION
Sudden withdrawal
precipitates angina, even MI
 beta-blockers are Contraindicated in
variant angina

126. SUMMARY
 Angina pectoris is a symptom of myocardial ischaemia
 Acute attack is treated with GTN 0.5mg sublingually
 Affords only symptomatic relief
 Nitrates act by reducing pre-load, afterload, dilates
coronary arteries
 Cause headache, flushing, palpitation as side effects
 Betablockers are useful in the prophylaxis
 Withdrawal of these drugs must be gradual
 Sildenafil usage during nitrates therapy may be
fatal

129. CALCIUM CHANNEL BLOCKERS
 Verapamil
 Nifedipine
 Diltiazem

131. PHARMACOLOGICAL ACTIONS
 Smooth muscle relaxation –
 arterioles, bronchi, biliary, intestinal, bladder,
uterine relaxation-
 Marked with DHP group ( nifedipine)
 Heart –
 negative inotropic, chronotropic, dromotropic
action –
 marked with verapamil, lesser extent with
diltiazem, not with DHP group

134. VERAPAMIL
 Decreases heart rate, A-V conduction,
dilates arterioles, decreases t.p.r
 ADR- nausea, constipation, bradycardia
 C/I – A-V block, CHF
 D/I – Should not be given with
betablockers, quinidine, increases digoxin
level

141. DILTIAZEM
 Cause consistent fall in BP, dilate
coronaries
 Less potent vasodilator than nifedipine &
verapamil
 Modest negative inotropic action
 ADR – similar as verapamil

145. NIFEDIPINE
 Prototype of DHP
 Arteriolar dilatation  t.p.r decreases 
fall in BP
 ADR – palpitation, flushing, ankle edema,
hypotension, headache
 ADR can be minimized by low starting
dose, using retard formulation

151. FELODIPINE
 Greater vascular selectivity
 Larger tissue distribution
 Long t ½

152. AMLODIPINE
 Slow oral absorption
 Devoid of vasodilator side effects like
flushing, palpitation, headache, postural
dizziness
 Long t1/2
 Diurnal fluctuation is small
 Action extends over next morning

159. NITRENDIPINE
 Release nitric oxide  additional
mechanism For vasodilatation
 Retard atherosclerosis
 Indicated in hypertension, angina
pectoris

162. LACIDIPINE
 Highly vasoselective newer DHP
 Once daily dose
 Used only in hypertension

164. NIMODIPINE
 Short acting DHP
 Selectively relaxes cerebral blood vessels
 Used in treating neurological deficit due
to cerebral vasospasm following
subarachnoid hemorrhage

168. USES OF CALCIUM CHANNEL
BLOCKERS
•
Can be safely given where beta blockers are
contraindicated ( COPD, PVD )
• Angina pectoris – in both classical angina & variant angina
• reduce afterload, long acting DHP are preferred
• Myocardial Infarction - verapamil/diltiazem given in secondary prophylaxis
where beta blockers are contraindicated
• Hypertension
• Cardiac arrhythmias

176. OTHER USES OF CALCIUM CHANNEL BLOCKERS
 Hypertrophic cardiomyopathy – verapamil
 Premature labour – nifedipine
 Migraine – verapamil
 Raynaud’s phenomenon – DHP’s
 Nocturnal leg cramps

184. RATIONAL DRUG COMBINATIONS
• When mono therapy fails to give relief
• Beta blockers + long-acting nitrates –
• tachycardia due to nitrates is blocked,
• ventricular dilatation, reduced coronary blood flow due to
B –blocker is blocked
• Slow acting DHP Ca channel blocker + B-blocker
• Nitrates + CCB  Valuable in severe vasospastic angina
• Nitrates + B-blocker + CCB in resistant cases
• (VERAPAMIL/DILTIAZEM should be avoided in such
combinations)

187. POTASSIUM CHANNEL
OPENERS
 Minoxidil, diazoxide
 Nicorandil
 Pinacidil
 cromokalim

188. MECHANISM OF ACTION
 Activates ATP sensitive K+ Channels
  increase outflow of K+ ions
  hyperpolarisation
  decrease Ca++ entry
  smooth muscle relaxation

190. NICORANDIL
 Novel antianginal drug
 Cause arteriolar, venodilatation
 Increase coronary blood flow
 Beneficial effects similar to nitrates,
CCB’s, B-blockers
 Decrease myocardial stunning, infarct
size, arrhythmias in MI
 Dose – 5-20 mg bd

194. Side effects
 headache,
 flushing,
 palpitation,
 dizziness,
 painful apthous ulcers

201. POTENTIAL CLINICAL
APPLICATIONS
 Angina pectoris when tolerance is a
problem, when others are
contraindicated
 Hypertension
 CHF
 Myocardial salvage in MI

206. POTENTIAL CLINICAL
APPLICATIONS
 Bronchial asthma
 Peripheral vascular disease
 Premature labour
 Urinary urge incontinence
 Penile erection disorder

212. DIPYRIDAMOLE
 Powerful coronary dilator
 Can cause coronary steal phenomenon
 Inhibits platelet aggregation
 Not useful as an antianginal drug
 Used in the prophylaxis in post MI, post
stroke to prevent thrombosis

217. TRIMETAZIDINE
 Novel antianginal drug
 Improve cellular tolerance to ischemia by
inhibiting LC3CAT
 Reduce anginal attacks in patients not
responding to other drugs
 ADR- gastric burning, dizziness, fatigue,
parkinsonism
 Useful as an add on medication to
conventional therapy in angina, post MI

219. RANOLAZINE
 Trimetazidine congener
 Spares fatty acid oxidation and shifts ATP
production to more O2 efficient
carbohydrate oxidation
 Torsades de pointes is a risk
 Recommended only in combination

221. IVABRADINE
 Pure hear rate lowering antianginal drug
 Recently introduced as an alternative to betablockers
 Blocks cardiac pacemaker cell “f” channels 
decreases heart rate  decreases oxygen demand,
 prolongs diastole  improves myocardial blood flow
 increased oxygen supply
 ADR  VISUAL DISTURBANCES, headache, dizziness,
nausea
 USES  chronic stable angina pectoris alternate to
betablockers, inappropriate sinus tachycardia

223. DRUGS FOR PERIPHERAL
VASCULAR DISEASES
 CYCLANDELATE
 XANTHINOL NICOTINATE
 PENTOXIPHYLLINE
 CILOSTAZOLE
 CCBs
 ALPHABLOCKERS
 PGI2  severe cases with rest pain

224. PENTOXIPHYLLINE
 Analogue of theophylline
 Weak PDE inhibitor
 Increases blood flow in ischemic areas by
reducing whole blood viscosity,
 And by improving flexibility of RBCs
 ADR  nausea, vomiting, dyspepsia,
bloating
 USES  intermittent claudication, Trophic
leg ulcers, TIAs

227. CILOSTAZOLE
 PDE-3 inhibitor
 Increases cyclic AMP  vasodilatation, antiplatelet
aggregating activity
 More effective than pentoxiphylline for claudication
pain
 Not to be used in heart failure
 ADR  HEADACHE, nausea, dizziness, palpitation,
weakness
 USES  intermittent claudication with no rest pain or
heart failure

230. MYOCARDIAL INFARCTION
 Ischaemic necrosis of a portion of the
myocardium due to sudden occlusion of a
branch of coronary artery
 Acute thrombus is the cause
 25% die before therapy
 Has to be treated in I.C.C.U’S

241. DRUG THERAPY OF
MYOCARDIAL INFARCTION
 Parenteral
Morphine/pethidine,
 diazepam for pain, anxiety,
fear
 Oxygenation
 Streptokinase/ urokinase/
alteplase for thrombolysis

249. DRUG THERAPY OF MYOCARDIAL INFARCTION
• Low dose aspirin for the
prevention of thrombi
extension
• Heparin/oral anticoagulants
to prevent DVT
• Dopamine/ dobutamine for
increasing pumping action of
heart

253. DRUG THERAPY OF
MYOCARDIAL INFARCTION
 GTN i.v/nitroprusside for vasodilatation
 Frusemide I.V if pulmonary edema present
 i.v beta blocker to prevent arrhythmias
 Lidocaine/procainamide for tachyarrhythmias
 Atropine for heart block

263. DRUG THERAPY OF
MYOCARDIAL INFARCTION
• Sodium bicarbonate i.v to correct acidosis
• Slow i.v infusion of saline/LMW dextran
• to maintain blood volume,
• tissue perfusion,
• Microcirculation
• ACE inhibitors/ARB’s to prevent
remodeling, CHF

268. PREVENTION OF FUTURE
ATTACKS
 Aspirin low dose/clopidogrel given on
long-term basis
 Betablockers to reduce
 risk of reinfarction,
 CHF,
 death
 Statins to control hyperlipidaemias

297. Any intelligent fool can make things
bigger, more complex, and more violent.
It takes a touch of genius -- and a lot of
courage -- to move in the opposite
direction."
Albert Einstein

300. THANK YOU