An interesting ppt on antianginal drugs and drug therapy of myocardial infarction with illustrations for better understanding of concepts and grasping facts...

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Subside when the increased energy demand is withdrawn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