Antianginal

1. Dr. Binu Babu
Ph.D., M.Sc. (N), MBA
Mrs. Jincy Ealias
M.Sc. (N)

2.  Anti - anginal drugs are the drugs that
prevent or terminate attacks
of angina pectoris.

3. • Eg: Nitroglycerin (GTN), isosorbide
dinitrate, isosorbide mononitrate,
pentaerythritol tetranitrate.
Nitrates
• Eg:Verapamil, diltiazem, amlodipine,
nifedipine.
Calcium channel
blockers
• Eg: Propranolol, atenolol
β- adrenergic
blockers
• Eg: Nicorandil, pinacidil.
Potassium channel
openers
• Dipyridamole, aspirin, trimetazidine,
ranolazine, ivabradine.
Miscellaneous

5.  Nitrates are vasodilators.
 Nitrates act directly on smooth muscles and
produce relaxation.
 Commonly used nitrate is nitroglycerine
(GTN).

6. Short acting nitrates
Used to terminate acute attack of angina
Eg: Nitroglycerin (GTN)
Long acting nitrates
Used to prevent an attack of angina
Eg: isosorbide dinitrate, isosorbide
mononitrate, pentaerythritol tetranitrate

7.  In the smooth muscles nitrates are converted to
nitric oxide.
 This nitric oxide activates vascular guanylyl
cyclase (GC) which in turn increases the
synthesis of cGMP (Cyclic guanosine
monophosphate).
 This cGMP causes sequestration of Ca2+ , which
is responsible for relaxation of the smooth
muscles.
 Results in vasodilation.

8. Vasodilation
Relax vascular smooth muscle
Relaxation of smooth muscles
cGMP causes sequestration of Ca2+
Increases the synthesis of cGMP
Activates vascular guanylyl cyclase
Nitrates converted to nitric oxide

10. 1. Reduction of preload
2. Reduction of afterload
3. Coronary dilation
4. Other actions
1. Dilation of other vasculature
2. Relaxation of other smooth muscles
3. Effects on platelets.

11. Nitrates are vasodilators.
1. Reduction of preload
Venodilation reduces
venous return to the heart
thereby reduce preload.
2. Reduction of afterload
Arteriolar dilation reduces
vascular resistance thus
decrease afterload
3. Coronary dilation
Nitrates cause coronary vasodilation, thus relieves
vasospasm and increases coronary blood flow.
As both preload and afterload are reduced,
workload of the heart is decreased, thereby
reducing oxygen requirement of the heart.

12. 4. Other actions
Dilation of other vasculature
• Dilation of blood vessels in
skin results in flushing.
• Dilation of meningeal
vessels results in headache.
Relaxation of other smooth
muscles
Nitrates relax the bronchial,
gastrointestinal and
genitourinary smooth muscles
for a short period.
Effects on platelets
Nitric oxide from nitrates inhibits platelet aggregation.

13.  Nitrates are available for oral, Sublingual, spray
parenteral, ointment and transdermal patch.
 Nitrates are well-absorbed orally, but they
undergo extensive first pass metabolism.
 So the oral bioavailability of nitrate is poor.
 Sublingual route is preferred in case of
emergency for rapid absorption and better
bioavailability.
 Sublingual tablets acts within 1-2 minutes
whereas Sublingual spray acts faster than tablets.

14. Sublingual Spray
Transdermal patch

15. Drug Dose Route
Nitroglycerin (GTN) 0.5 mg Sublingual
5 mg Oral
2% Ointment
0.4-0.8 mg Sublingual spray
5-20 μg/min IV
14-16 hrs/day Transdermal patch
Isosorbide dinitrate (Sorbitrate) 5-10 mg Sublingual
10-20 mg Oral
Isosorbide mononitrate (Ismo) 10-20 mg Oral
pentaerythritol tetranitrate 10-40 mg Oral

16.  Headache (common)
 Flushing of face
 Nausea and vomiting
 Sweating
 Tachycardia
 Palpitation
 Weakness
 Postural hypotension
 Rashes
 Contact dermatitis
 Local hypersensitivity reaction
for topical use

17.  Exertional angina
 Acute anginal attacks :
▪ Sublingual nitroglycerin
▪ Drug of choice for acute anginal attacks.
▪ Relieves pain in 2 to 5 minutes.
▪ If the pain is not relieved, the dose is repeated-upto 3 tablets in 15
minutes.
 Prophylaxis of angina
▪ NTG can be used for chronic prophylaxis.
▪ Longer acting nitrates are preferred.
▪ Nitroglycerin ointment orTransdermal patch may be used.

18.  Vasospastic angina
 Unstable angina
 Acute coronary syndrome
 Cardiac failure
 Myocardial infarction
 Cyanide poisoning
 Nitrates are life saving in cyanide poisoning.
 Amylnitrite is given by inhalation and sodium
nitrite by IV injection (10 ml of 3% solution). Then
Sodium thiosulphate is given IV (50 ml of 25%
solution).

19.  Role of nitrates in cyanide poisoning.
 Nitrates (Amylnitrite and sodium nitrite) convert
hemoglobin into methemoglobin, which has high
affinity for cyanide and forms cyano-
methemoglobin.
 Cyano-methemoglobin reacts with Sodium
thiosulphate to form thiocyanate which is easily
excreted by the kidneys.

20.  Relieve esophageal spasm
 Sublingual NTG is taken just before meals to
counter the spasm.
 Relieve biliary colic
 Sublingual NTG is also useful as a spasmolytic.

21.  Monitor BP before and after administration.
 Nitroglycerine is sensitive to light, heat and
moisture, so stored in tightly closed amber
colored glass bottles.
 Give sublingual preparations under the tongue
or in the buccal pouch.
 Nitroglycerine IV preparation is mixed in 5%
Dextrose Injection or 0.9% Sodium Chloride.
 Instruct the patient that a sublingual dose may
be repeated in 5 minutes if pain is not relieved,
for a total of 3 doses.

23.  Calcium channel blockers (CCBs) are the
drugs that disrupt calcium movement by
blocking voltage-dependent Ca2+ channels
used to treat angina and supraventricular
tachydysrhythmias as well as hypertension.
 Also known as calcium antagonists.

24. Calcium
channel
blockers
Dihydropyridines
1st generation Eg: Nifedipine
2nd
generation
Eg: Isradipine,
Nicardipine,
Felodipine
3rd
generation
Eg:
Amlodipine
Phenilalkylamines Eg:Verapamil
Benzothiazepines Eg: Diltiazem

25. Decrease myocardial contraction, Decrease heart rate and AV conduction
velocity, also cause Vascular smooth muscle relaxation
Decrease calcium entry into cardiac and smooth muscle cells
Block L-type calcium channels
Calcium channel blockers

26.  Cardiac and smooth muscle
cell contraction depends
upon the activation of
calcium channels in the
cardiac myocytes. For
depolarization of cardiac and
other smooth muscles cells,
entry of calcium into the cells
occurs through these calcium
channels. This calcium
triggers the release of
intracellular calcium from
sarcoplasmic reticulum.

27.  On vascular smooth muscles and Coronary
circulation
 On other smooth muscles
 On heart

28.  On vascular smooth muscles and Coronary circulation
Vascular smooth muscle relaxation
peripheral Coronary artery
vascular dilation dilation
Decrease peripheral Increase coronary
vascular resistance blood flow
Decrease Decrease Increase myocardial
BP afterload O2 supply
Decrease myocardial
O2 consumption
HTN treatment Angina treatment

29.  Dihydropyridine CCBs have prominent effect
on blood vessels.
 Nimodipine crosses the blood brain barrier
and relaxes the cerebral blood vessels.
On other smooth muscles
 Relax GI and bronchial smooth muscles
 Relax uterus, so used in premature labor.

30.  On heart
Decrease myocardial DecreaseAV
Contraction conduction velocity
Decrease heart Rate Bradycardia
Reduce myocardial workload
Decrease myocardial O2
Consumption
Angina treatment Arrhythmia treatment

31.  Verapamil, bepridil and diltiazem have promi-
nent cardiac effects.

32.  CCBs are well-absorbed orally but undergo
extensive first pass metabolism.
 They are metabolized in the liver.
 Excreted through kidneys.
 Onset of action is in 30-60 minutes after oral
administration while on IV use the action is
quick.

33. 1. Verapamil
 Decrease heart rate (negative chronotropic effect)
 Decrease force of myocardial contraction (negative
ionotropic effect)
 DecreaseAV conduction
 Vasodilator effect of verapamil is less potent.
 Used in arrhythmia and angina.
 Dose: 40-160 mgTDS orally and 5 mg by slow IV
inj.
 Adverse effects
 Nausea
 Constipation
 Bradycardia
 Heart block
 Hypotension
 Skin rashes

34. 2. Diltiazem
 Decrease heart rate (negative chronotropic
effect)
 Decrease force of myocardial contraction
(negative ionotropic effect)
 Vasodilator effect is less potent.
 Dose: 30-60 mgTDS orally.
 Adverse effects –same as verapamil.

35. 3. Nifedipine
 Potent vasodilator and causes a significant fall in
BP and evokes reflex tachycardia.
 Myocardiac depressant effect is weak
 It can be given orally or sublingually. Patches also
 Dose: 5-20 mg BD
 Adverse effects
 Headache
 Flushing
 Palpitation
 Dizziness
 Fatigue
 Hypotension
 Leg cramps
 Ankle edema
 Long-term use : gum hypertrophy

36. 3. Nimodipine
 Crosses the blood brain barrier and relaxes
the cerebral blood vessels.
 Used in haemorrhagic stroke and
subarachnoid haemorrhage.
 Dose: 30-60 mg QID.

37. 4. Amlodipine, felodipine, nitrendipine,
nicardipine
 High vascular effects.
 Long acting CCBs.
 Can be given once daily.
 Useful HTN.

38.  Angina pectoris
 As prophylaxis for exertional angina
▪ Verapamil and diltiazem for prophylaxis
 Variant angina
 Vasospastic angina
▪ Verapamil and amlodipine are preferred
 Unstable angina
▪ Verapamil is used
 Dihydropyridine CCBs like amlodipine with beta
blockers for long term management.

39.  Hypertension
 Chronic hypertension :
▪ Long acting CCBs.
▪ Amlodipine is preferred
 Hypertensive crisis: nifedipine used sublingually
 Arrhythmias
 Supraventricular Arrhythmias : premature atrial
contraction, atrial tachycardia, atrial fluttr, atrial
fibrillation
 Verapamil, diltiazem and bepridil

40.  Peripheral vascular disease
 Nifedipine, felodipine and diltiazem can be used in
Raynaud's disease.
 Migraine
 Prophylaxis- verapamil is useful
 Hypertrophic cardiomyopathy
 Verapamil is useful
 Subarachnoid hemorrhage and haemorrhagic
stroke
 Nimodipine is useful.
 Preterm labor
 Nifedipine is useful.

41.  Verapamil and diltiazem should be avoided
in patients receiving beta-adrenergic blockers
because the myocardiac depressant effects
get added up.
 Verapamil can precipitate digoxin toxicity by
increasing digoxin levels (verapamil reduces
digoxin excretion).

44.  Beta blockers are the drugs that block beta
receptors thereby inhibiting the actions of
sympathetic stimulations (catecholamines).
 Beta antagonist.

45. • Eg: Propranolol, nadolol, timolol,
sotalol
Nonselective
• Eg: Metoprolol, atenolol,
acebutolol, esmolol
Cardioselective (β1)
• Eg:- Pindolol, oxprenolol,
carteolol, bopindolol, penbutotol
Partial agonists
• Eg: Labetalol, carvedilol
With additional alpha
blocking property
• Eg: Celiprolol
β1 blocker β2 agonist

46. 1. Nonselective
 Blocks both β1 and β2 receptors.
2. Cardioselective (β1)
 Blocks cardiac specific β1 receptors. β2 receptor
blockade is weak.
3. Partial agonists
 Have some sympathomimetic action due to partial β
agonist property.
4. With additional alpha blocking property
 Blocks both α and β (β1 and β2) receptors.
5. β1 blocker β2 agonist
 Blocks only cardiac specific β1 receptors.

47. 1st generation
(Non selective)
Eg: Propranolol, timolol, sotalol,
2nd generation
(Cardioselective)
Eg: Metoprolol, atenolol, acebutolol, esmolol
3rd generation
(With additional α blocking property & vasodilator
property)
Eg: Labetalol, carvedilol, Celiprolol

48. Reduce cardiac workload
Reduce myocardial O2 demand
Decrease heart rate, Decrease force of contraction,
Decrease cardiac output, Decrease BP, Delay AV conduction
Inhibit sympathetic (catecholamines) stimulations
Blocks beta receptors

50.  CVS
 Act as cardiac depressant
 Decrease heart rate (negative chronotropic effect)
 Decrease force of contraction (negative ionotropic effect)
 Decrease cardiac output
 Decrease BP
 Delay AV conduction (negative dromotropic effect)
 Reduce myocardial O2 demand
 Reduce cardiac workload.
 Improve exercise tolerance in angina patients.

51.  Respiratory tract
 Blockade of B2 receptors in the bronchial smooth
muscle causes increase in airway resistance.
 May precipitate acute attack in asthmatics.
 Eye
 Reduce intraocular pressure by decreased secretion of
aqueous humor.
 Metabolism
 β-antagonists block lipolysis & glycogenolysis – cause
rise in plasma free fatty acid and triglyceride.Also
interfere with recovery from hypoglycemia in diabetics

52.  Well absorbed orally.
 Given intravenously in emergencies.
 Low oral bioavailability due to extensive first
pass metabolism.
 Highly lipid soluble, so crosses blood brain
barrier.
 Metabolized in the liver.
 Excreted through kidneys.

53.  Bradycardia (common)
 CCF
 Acute pulmonary edema
 Cold extremities (in patients with peripheral vascular
disease)
 Acute asthmatic attack (in asthmatics)
 CNS
 Insomnia
 Depression
 Halluçination (rare)
 Fatigue, weakness
 Decrease exercise capacity
 Rebound hypertension and anginal attacks
 Due to abrupt withdrawal of B-blockers after prolonged use.

54.  Hypertension
 As first line drugs in mild to moderate hypertension
 Used alone or with other antihypertensives.
 Angina pectoris
 Long term prophylaxis of exertional angina and
classical angina.
 Cardioselective drugs are preferred than non
selective drugs.
 Have to take on regular basis.
 Cardiac arrnythmias
 For both supraventricular & ventricular arrhythmias

55.  Myocardial infarction
 Given IV infusion in acute MI to limit the size of
infarct.
 Long-term treatment prolongs survival.
 Congestive cardiac failure
 Obstructive cardiomyopathy
 Pheochromocytoma
 Propranolol is given before surgery to control
hypertension.

56.  Thyrotoxicosis
 Propranolol controls palpitation, tremors and affords
symptomatic relief in thyrotoxicosis.
 Used as adjuvant.
 Also useful in thyrotoxic crisis.
 Glaucoma
 Timolol is used topically in open angle glaucoma.
 Migraine
 As prophylaxis.
 Propranolol is used.
 Anxiety
 Propranolol prevents the acute panic symptoms

57.  Bradycardia
 COPD
 Asthma
 Heart block

58.  Atenolol
 Cardioselective
 Longer acting-given once daily
 Less lipid soluble-does not cross BBB-hence no CNS
side effects
 No side effects on lipid profile. Hence very
commonly used
 Dose: 25-100 mg daily.
 IV (5-10 mg over 5 minutes) reduce short term
mortality in MI and lowers incidence of arrhythmias.

59.  Esmolol
 Cardioselective
 Ultra short acting - t½ - 8 minutes.
 Used IV.
 Safer in critically ill patients and in emergencies.
 Metoprolol
 Cardioselective
 Well-absorbed but undergoes first pass metabolism
 Given twice daily
 Dose: 50-200 mg
 Used in hypertension and angina pectoris.

60.  Acebutolol
 Cardioselective
 Used in hypertension and arrhythmias.
 Celiprolol
 β1 blocker and β2 agonist
 Safer in asthmatics
 Used in hypertension.

61.  Propranolol
 Nonselective
 Dose: oral 10 mg BD to 160 mgTID.
 First line drugs in mild to moderate hypertension
 Used in HTN, angina, arrhythmias, migraine

63.  Potassium-channel openers are drugs that
activate (open) ATP-sensitive K+ channels in
vascular smooth muscle and results vascular
smooth muscle relaxation.

64. Potassium channel openers
Open ATP-sensitive K+ channels in vascular
smooth muscle
Enhance K+ efflux
Membrane Hyperpolarization
↓ Ca 2+ entry
Reduced intracellular calcium
Smooth muscle relaxation

66.  Nicorandil is an arterial and venous dilator.
 MOA
Nicorandil
Open ATP-sensitive Act as nitric oxide
K+ channels donor
Enhance K+ efflux
Membrane Hyperpolarization
↓ Ca 2+ entry
Reduced intracellular calcium
Smooth muscle relaxation
Decrease preload and afterload, increase coronary blood flow

67.  Use
 Resistant angina
 In combination with other drugs
 Dose: 10-20 mg twice daily.
 Adverse effects
 Headache
 Flushing
 Palpitation
 Dizziness
 Hypotension

68.  Similar to nicorandil.
 Uses
 Angina
 Hypertension

70.  Coronary vasodilator
 But it is not used in angina as it diverts blood
from ischemic zone to non ischemic zone.
 It inhibits platelet aggregation for which
it is used in post-MI and post-stroke patients
tor prevention of coronary and cerebral
thrombosis.
 Dose 25-100 mgTID.

71.  Long-term administration of low dose
aspirin is recommended to prevent myocardial
infarction.
 Inhibits platelet aggregation.
 Dose: 75-100mg

72.  Anti-anginal action through inhibition of fatty
acid metabolism, also known as fatty acid
oxidation inhibitor.
 Used in post MI patients.
 Dose: 20 mgTID.

73.  Recently introduced trimetazidine congener.
 MOA
 Prevents calcium overload in the myocardium during
ischemia and reduces myocardial O2 demand.
 Uses
 Prevention of angina as add on therapy.
 Dose : 500 mg sustained release tablets twice daily.
 Adverse effects
 Weakness
 Postural hypotension
 Dizziness
 Headache
 Constipation

74.  Nitrates + β blockers
 Nifedipine + β blockers
 Nitrates + CCB
 Nitrates + β blockers+ CCB
 If not controlled by 2 drug combination.