Pharmacology PPT

1. Angina Pectoris:
Pharmacotherapy
Dr Chintan Doshi

2. Introduction
• Angina Pectoris : (angere = to strangulate; pectus =
chest)
• Clinical manifestation of the reversible or transient
myocardial ischemia
• Experienced as suffocating substernal pain in the
chest, over the heart
• On exertion, radiate to left arm, neck or the jaw
• Relieved by rest

3. Cause Of Angina
Transient Myocardial Ischemia
Angina Pectoris
Myocardial Blood Flow
Myocardial O2 Demands

4. Types of Angina
1) Classical or Stable angina:
(Angina of effort or exertional angina)
• About 90%
• Cause : Fixed atheromatous sclerosis of larger
coronary arteries
• Provoked by exercise, emotional stress, meals
• Relieved by taking rest and reducing myocardial
workload

5. Contd...
2) Unstable or Cresendo Angina :
• Recurrent attacks, even with minimal exertion or
even at rest
• Rupture of an atheromatous plaque  attracting
platelets deposition  progressive occlusion of the
lumen
• considered a medical emergency as many cases may
progress to Myocardial Infarction
• Occasionally vasospasm

6. Contd....
3) Variant or Prinzmetal Angina :
• Vasospastic Angina
• Recurrent localized coronary vasospasm
• Occur at rest or during sleep, and is not related to
exertion or exercise and is not relieved by rest
• Superimposed with atheromatous stenosis
• Deteriorate into Unstable Angina

7. Management
• Non- Medical Management:
• Diet
• Smoking cessation
• Physical exercise
• Weight reduction

8. Angina – consequence of myocardial O2
demand exceeding O2 supply

9. Clinical Classification
• Drugs used to abort or terminate attack:
Organic Nitrates:
• Rapid onset, short acting :
Amyl nitrite
Nitroglycerine (glyceryl trinitrate)
• Slow onset, long acting
Isosorbide dinitrate
Isosorbide mononitrate
Erythrityl tetranitrate
Pentaerythritol tetranitrate

10. • Drugs used for chronic prophylaxis
Calcium channel Blockers (CCBs)
• Phenyl alkylamine: Verapamil
• Benzothiazepine : Diltiazem
• Dihydropyridines: Nifedipine
Amlodipine
Nicardipine
Nitrendipine
Benidipine

11. Contd....
Beta-Blockers:
• Propranolol
• Atenolol
• Metoprolol
• Nadolol
• Bisoprolol
• Celiprolol

12. Contd....
• Miscellaneous:
Potassium channel openers:
• Nicorandil
Cytoprotective Drugs:
• Trimetazidine
• Ranolazine
Bradycardiac Drugs :
• Ivabradine

13. Contd...
• Additional Drugs:
Antiplatelet drugs:
• Aspirin, Ticlopidine, clopidogrel
HMG-CoA Reductase Inhibitors:
• Rosuvastatin
• Atorvastatin
• Simvastatin
• Fluvastatin

14. GTN(prototype)

15. Pharmacological Action
Preload reduction :
Nitrates dilate veins more than arteries
peripheral pooling of blood
↓ venous return
↓Preload on heart
↓end diastolic size and pressure
↓cardiac work Load according to Laplace relationship

16. Afterload reduction :
Some arteriolar dilatation
slightly decrease total peripheral
resistance or afterload on heart
BP falls somewhat; systolic more than diastolic
Reduction in cardiac work which is directly
proportional to aortic impedance

17. Redistribution of coronary flow:
Relax bigger conducting coronary arteries
than arterioles or resistance vessels
Ischaemic zone : Dilatation of conducting vessels along
with ischaemia-induced dilatation of
autoregulatory resistance vessels
↑ blood flow to this area
Non-ischaemic zones :
Resistance vessels maintain their tone
flow does not increase, or may decrease to
compensate for increased flow to ischaemic zone

18. Contd...
Heart and peripheral blood flow:
• No direct stimulant or depressant action
• Dilate cutaneous → flushing
• Meningeal vessels → headache
• Splanchnic and renal blood flow decreases to
compensate for vasodilatation in other areas
• Decongest lungs by shifting blood to systemic
circulation

19. Contd....
• Other smooth muscles Bronchi, biliary tract and
esophagus : relaxed
• Intestine, ureter, uterus : variable and insignificant
Platelets :
• NO generated from nitrates  activates cGMP
production in platelets  mild antiaggregatory effect
• Valuable unstable angina

20. USES.
• Classical angina: reduce cardiac work by action on
peripheral vasculature, though increased blood
supply to ischaemic area
• Variant angina: dilator effect on larger coronary
vessels
• Unstable angina : Addition to this antiaggregatory
effect
• Exercise tolerance of angina patients is increased

21. Contd.
Myocardial infarction (MI)
• Given i.v.
• Relieving chest pain
• Pulmonary congestion
• Limiting the area of necrosis by favorably altering O2
balance in the marginal partially ischemic zone
• Not given if
– Systolic BP is < 90 mm Hg
– Heart rate is < 50 or > 100 beats/min
– Right ventricular infarction is suspected
– Patient has taken sildenafil in the past 24
hours.

22. Other uses
• CHF and acute LVF
• Hypertensive emergencies
• Biliary colic
• Esophageal spasm
• Cyanide poisoning

23. Cyanide poisoning
• Haemoglobin
↓ Sod. nitrite (10 ml of 3% solution i.v.)
• Methaemoglobin
↓ Cyanide
• Cyanomethaemoglobin
↓ Sod. thiosulfate (50 ml of 25% solution
i.v.)
• Methaemoglobin + Sod. thiocyanate
↓
• Excreted in urine

24. Adverse eftects
• Headache – Most common
• Flushing, weakness, sweating, palpitation, dizziness
and fainting
• Postural Hypotension
• Syncope
• Rashes are rare (pentaerythritol tetranitrate)
• Tolerance

25. Dependence
• Sudden withdrawal after prolonged exposure has
resulted in spasm of coronary and Peripheral blood
vessels
• Angina threshold may be lowered during nitrate free
interval in some Patients: episodes of angina may
increase
• Drug of another class should be added
• Withdrawal of nitrates should be gradual

26. Interaction
• PDE-5 Inhibitors: e.g. Sildenafil
• Vasodilators

27. Preparations
Nitroglycerin:
• volatile liquid
• stored in a tightly closed glass (not plastic) container
• sublingual route is used: terminating an attack or
aborting imminant one
• sublingual spray
• Acts within 1-2 min
• Peak blood level in 3-6 mins
• Plasma half life - 2min

28. Contd....
Isosorbide Dinitrate :
• Sublingual administration: Peak - 6 minutes, and the
fall in concentration is rapid , t1/2 of ~45 mins
• Enzymatic denitration followed by glucuronide
conjugation

29. Contd....
Erythrityl tetranitrate and pentaerythritol
tetranitrate:
• longer-acting nitrates
• chronic prophylaxis
• Sustained release oral preparations are now available
for 2-3 times a day dosing
Amyl nitrite
• Highly volatile liquids
• unpleasant odor and short duration of action, now
obsolete for angina

30. Calcium channel
blockers

31. Calcium Channel Blockers
Voltage gated Ca2+ channels types – L ,N, T
L type - important for
Vascular smooth
muscle depolarization →
contraction
Heart
– cardiac muscle contraction
- in SA & AV node – Ca 2+
dependent depolarization
CCBs – block L type of Ca2+ channels

32. Mechanism of action

33. Calcium Channel Blockers
Dihydropyridines DHPs ‘dipine’
Nifedipine , Amlodipine , Nitrendipine , Felodipine
Predominant effect on arterioles
relax arterial smooth muscle , ↓TPR , ↓ afterload
↓ O2 demand
Effect on heart at much higher doses
ADR
tachycardia , hypotension , flushing , headache,
ankle edema

34. Amlodipine
• Oral absorption is slow, but complete
• Palpitation, flushing, headache, postural
dizziness are avoided
• Oral bioavailability is higher
• Volume of distribution and t½ are long
• First line drug for Hypertension

35. Calcium channel blockers
USES
Prophylaxis of chronic stable angina
-- ↓O2 demand
Variant angina – prevent arterial spasm
Hypertension – 1st line Rx
PSVT (paroxysmal supraventricular tachycardia)
– Verapamil

36. Other uses
Hypertrophic
cardiomyopathy
Nifedipine is an alternative
drug for premature labour
Verapamil :to suppress nocturnal
leg cramps
Raynaud’s episodes

37. Calcium Channel Blockers
Verapamil , Diltiazem
Heart - ↓ HR , ↓ contractility ,slow AV conduction
Relax arterial smooth muscle -↓ afterload
↓ O2 demand
ADR
Bradycardia , constipation ,hypotension

38. Beta blockers
negative chronotropic effect - ↓HR
negative inotropic effect - ↓contractility
Speed limit
Work limit
Beta 1 receptor – ↑ rate & contraction

39. Beta blockers
negative chronotropic effect - ↓HR
negative inotropic effect - ↓contractility
↓BP
↓ O2 demand in stable angina – used for prophylaxis
Metoprolol
Atenolol
Propranolol
To be avoided in variant angina
- unopposed α action may worsen the condition

40. As K+ ion control Resting membrane potential
IC concentration of K+ ion > EC
Efflux K+ occur
Hyperpolarization
Indirectly oppose opening of voltage-gated Ca+ channel
Fall cytosolic Ca+ concentration
Reduce contraction at myocardial & vascular beds
Potassium channel openers
M/A :

41. Nicorandil
• Activate ATP-sensitive K+ channel
• Reduce pre and afterload
• Coronary dilatation
• Carries nitrate-like moiety-nitrate like effect
• Vasodilator – K+ channel opening
• Venodilator – nitrate- like activity
• No tolerance
• ADR:flushing, palpitation, weakness, headache,
dizziness, nausea

42. β blocker + nitrate / DHP
1.Tachycardia by nitrate / DHP is blocked by β blocker
2.Tendency of β blocker to reduce coronary flow
opposed by nitrate/DHP
Nitrate (↓preload) + CCB (↓afterload)
Rational drug combinations in angina

43. Ranolazine
late Na+ current inhibitor
inhibits late Na+ current ,↓ Ca2+ overload in
myocardium during ischemia → cardiac workload ↓
Used in combinations with other drugs
- particularly in patients who are not responsive to
maximal tolerated doses of other antianginal drugs.

44. Dipyridamole
Coronary dilator , antiplatelet effect
Coronary steal phenomenon
diverts the already ↓blood flow away
from ischemic zone to non ischemic
zone – worsening
Not used nowadays

45. Trimetazidine
pFOX ( partial fatty acid oxidation ) inhibitor
Shifts metabolism in favor of glucose in myocardium during
ischemia
Reduce O2 demand

46. •Ivabradine

47. • ‘Pure’ heart rate lowering antianginal drug
• Mechanism of action
• blockade of cardiac pacemaker (sino-atrial)
cell ‘f’ channels
• open during early part of slow diastolic (phase
4) depolarization
• Resulting inward current (If) determines the
slope of phase 4 depolarization.
• blockade of (If) current by ivabradine results in
heart rate reduction

48. Contd.
• Advantages
– without any other electrophysiological or negative
inotropic or negative lucitropic (slowing of
myocardial relaxation) effect
• Uses
– Stable angina
– Inappropriate sinus tachycardia
– CHF

49. Contd.
• ADR
– Bradycardia
– Extrasystoles
– prolongation of P-R interval
– visual disturbance
– headache, dizziness
– and nausea

50. Antiplatelet therapy – low dose aspirin
Lipid lowering therapy - statins
– HMG Co-A reductase inhibitors

51. Treatment of MI
1. Pain, anxiety and apprehension
– 3 doses of GTN given 5 min
if not relieved
– opioid analgesic or diazepam
• 2. Oxygenation By O2 inhalation
• 3. Maintenance of blood volume, tissue perfusion
and microcirculation:Slow i.v. infusion of
saline/low molecular weight dextran
• 4.Correction of acidosis:i.v. sod. Bicarbonate

52. 5. Prevention and treatment of arrhythmias
– Prophylactic i.v. infusion of a β blocker:reduce the
incidence of arrhythmias and mortality
– Tachyarrhythmias:lidocaine
– Bradycardia and heart block:Atropine
• 6. Pump failure
– Furosemide
– Vasodilators:GTN or sodium nitropruside
– Inotropic agents: dopamine or dobutamine i.v.

53. • 7. Prevention of thrombus extension,
embolism, venous thrombosis
– Aspirin(162-325mg) as chewing
– Heparin/LMW
• 8. Thrombolysis and reperfusion
– Streptokinase/urokinase/altepase
• 9.Prevention of remodeling and subsequent
CHF
– ACE inhibitors/ARBs

54. • 10. Prevention of future attacks
– Platelet inhibitors—aspirin or clopidogrel
– β blockers:reduce risk of reinfarction, CHFand
mortality
– Control of hyperlipidaemia—dietary substitution
with unsaturated fats, statins

55. MCQS
• Angiotensin converting enzyme inhibitors are
useful in congestive heart failure as:
(a) First choice drugs unless contraindicated
(b) An alternative to diuretics
(c) A substitute for digitalis
(d) Adjuncts only in resistant cases

56. • Nitrates are used for all of the following
conditions except?
(a) Congestive heart failure
(b) Cyanide poisoning
(c) Esophageal spasm
(d) Renal colic

57. • The antianginal effect of propanolol may be
attributed to which of the following?
(a) Block of exercise induced tachycardia
(b) Dilation of constricted coronary vessels
(c) Increased cardiac force
(d) Increased resting heart rate

58. Contd.
• Nitroglycerine causes all except
• (a) Hypotension and bradycardia
• (b) Methemoglobinemia
• (c ) Hypotension and tachycardia
• (d) Vasodilation

59. • You decide not to prescribe sildenafil in a
patient because the patient told you that he
is taking an antianginal drug. Which of the
following can it be?
• (a) Calcium channel blockers
• (b) b adrenergic blockers
• (c) Organic nitrates
• (d) Angiotensin converting enzyme inhibitors

60. • Mechanism of action of sodium nitrite in
cyanide poisoning
• (a) Produces methemoglobinemia
• (b) Increased blood flow to liver
• (c) Increased blood flow to heart
• (d) Increased blood flow to kidney

61. • Propanolol is contra-indicated in a patient of
angina pectoris who is already receiving:
• (a) Nifedipine
• (b) Aspirin
• (c) Verapamil
• (d) Isosorbide mononitrate

62. • Nitroglycerine can be administered by all of
the following routes except:
• (a) Oral
• (b) Sublingual
• (c) Intramuscular
• (d) Intravenous

63. • Which of the following is a K+ channel
opener?
• (a) Nifedipine
• (b) Nicorandil
• (c) Enalapril
• (d) Atenolol

64. • Which of the following is not a Ca++ channel
blocker?
• (a) Enalapril
• (b) Nifedipine
• (c) Diltiazem
• (d) Verapamil

65. • Antihypertensive drug of choice in a diabetic
patient is:
• (a) Methyldopa
• (b) Beta blocker
• (c) ACE inhibitor
• (d) Thiazides

66. • Telmisartan lowers blood pressure by:
• (a) Inhibiting formation of angiotensin I to
angiotensin II
• (b) Inhibiting conversion of renin to
angiotensin I
• (c) Blocking AT1 receptors
• (d) Interfering with degradation of bradykinin

67. • The drug of choice in scleroderma induced
hypertensive
• crisis is:
• (a) ACE inhibitors
• (b) Thiazides
• (c) b-blockers
• (d) Sodium nitroprusside

68. • Adverse effect of losartan are all except:
• (a) Fetopathic
• (b) Cough
• (c) Hyperkalemia
• (d) Headache

69. • Anti-hypertensive drug contraindicated in
pregnancy is:
• (a) Enalapril
• (b) Cardio selective beta blockers
• (c) Methyl dopa
• (d) Hydralazin

70. • Which of the following is not a
cardioselective b-blocker?
• (a) Acebutolol
• (b) Atenolol
• (c) Pindolol
• (d) Metoprolol