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2. Angina pectoris pain
• Angina pectoris is the principle symptom of
ischemic heart disease (IHD)
• It is a pain felt right in the middle of the
chest, behind the sternum
• sensation of tightness, yet some people
describe it as only mildly painful discomfort
– can spread towards the neck or the jaw,
the arm and the wrist (and feel like
handcuffs), most often on the left side
– sometimes situated lower down,
towards the pit of the stomach

4. • The ischemic condition results from an imbalance
between myocardial oxygen demand and
myocardial oxygen supply
• This imbalance may be due to a decrease in
myocardial oxygen supply, an increase in myocardial
oxygen demand or both

6. Types of angina pectoris
1. Stable angina
Chest pain on exertion
2. Unstable angina
Angina at rest with increased frequency &
duration of attack
3. Prinzmetal angina/Variant angina
 Occurs at rest due spasm of coronary vessels

7. CLASSIFICATION
1. Nitrates:
I. Rapid onset, short acting :- Nitroglycerine (glycerine trinitrate)
II. Slow onset, long acting :- Isosorbide dinitrate, Isosorbide mononitrate
Erythrityl tetranitrate, Pentaerythritol tetranitrate
2. Beta blockers :-
 Propranolol , Atenolol , Metoprolol , Nadolol , Bisprolol ,Celiprolol
3. Calcium channel blockers (CCBs)
 Verapamil, Diltiazem , Nifedipine , Amlodipine , Nicardipine , Nitrendipine,
Benidipine

8. 4. Potassium channel openers: Nicorandil
5. Miscellaneous :-
a. Cytoprotective drugs: Trimetazidine, Ranolazine
b. Antiplatelet drugs: Aspirin, Ticlopidine, Clopidogrel,
Dipyridamole and Cilostazol
c. Bradycardiac drugs: Ivabradine
d. HMA-CoA reductase inhibitors: Statins
e. Drugs for peripheral vascular disease: Naftidofuryl and
Pentoxiphylline

9. Nitrates
• Rapidly acting nitrates
* used to terminate acute attack of angina
* usually administered sublingually
• Long acting nitrates
* used to prevent repeated attack of angina
* administered orally or topically

10. MOA

11. 1ST MECHANISM OF ACTION
Coronary artery dilatation
Decrease coronary bed resistance
(Relieved coronary vasospasm)
Increase coronary blood flow
Increase oxygen supply

12. 2ND MECHANISM OF ACTION
Reduction on peripheral resistance
(Secondary to dilatation of aorta and arterioles)
Decrease blood pressure
Decrease after load
Decrease workload
Decrease oxygen consumption

13. 3RD MECHANISM OF ACTION
Reduced venous return
(Due to dilatation of the veins)
Decrease left ventricular volume
Decrease preload
Decrease workload
Decrease oxygen consumption

14. Route of administration
1. Sublingual route – rational and effective for the treatment of acute
attacks of angina pectoris.
2. Oral route – to provide convenient and prolonged prophylaxis
against attacks of angina
3. Intravenous Route – useful in the treatment of coronary vasospasm
and acute ischemic syndrome.
4. Topical route – used to provide gradual absorption of the drug for
prolonged prophylactic purpose.
5. Transdermal  administration either as patch or paste provides a
depot of agent for a steady availability.

15. Drug Usual single dose Route of
administration
Duration of action
Short acting
Nitroglycerin
0.15-1.2 mg sublingual 10 - 30 min
Isosorbide dinitrate 2.5-5 mg sublingual 10 – 60 min
Amyl nitrite 0.18 – 3 ml INHALATION 3 – 5 min
Long acting
Nitroglycerin
sustained action
6.5 – 13 mg q 6-8 hrs oral 6 – 8 hrs
Nitroglycerin 2%
ointment
1 – 1.5 inches q hr topical 3 – 6 hrs
Niroglycerin slow
released
1 –2 mg per 4 hrs Buccal mucosa 3 – 6 hrs
Nitroglycerin slow
released
10 – 25 mg /24hrs
(one patch/day}
TRANSDERMAL 8 –10 hrs
Isosorbide dinitrate 2.5 – 10 mg per 2 hrs sublingual 1.5 – 2 hrs
Isosorbide dinitrate 10 –60 mg per 4-6 hrs oral 4 – 6 hrs
Isosorbide dinitrate
chewable
5 – 10 mg per 2-4 hrs oral 2 – 3 hrs
Isosorbide
mononitrate
20 mg per 12 hrs oral 6 –10 hrs

16. Pharmacokinetics
• Nitrates are lipid soluble
• The difference between nitrate preparations is mainly in time of onset of
action.
• Nitroglycerin suffers marked 1st pass metabolism so administration is
sublingual.
• t1/2 =10 minutes.

17. SIDE EFFECTS OF NITRATES
• Pulsating headache
• Flushing, weakness, sweating, palpitation ,
dizziness
• Methemoglobinemia
• Rashes
• Tolerance

18. Uses
1. Angina pectoris : classical and variant angina
2. Acute coronary syndrome: unstable angina & NSTEMI
3. Myocardial infarction: GTN is used
4. Oesophageal spasm : GTN sublingual
5. Biliary colic: GTN sublingual / isosorbide dinitrate
6. CHF and acute LVF
7. Cyanide poisoning

19. Cyanide poisoning

20. β -Adrenergic receptor
antagonists
• Bind to β-adrenergic receptors
• reduce the response caused by the activation
of β-receptors by the sympathetic nervous
system
• inhibiting some of the cardiovascular effects

21. CARDIAC
Site Receptor Effect of Sympathetic
Stimulation
Effect of β
Blocker
muscle β1 ↑ Force ↓ Force
SA node β1 ↑ Rate ↓ Rate
AV node β1 ↑ Conduction ↓ Conduction
His-Purkinje β1 ↑ Cardiac Output ↓ Cardiac Output

22. VASCULAR
Site Receptor Effect of Sympathetic
Stimulation
Effect of β
Blocker
Renin-
angiotensin
system
β1 ↑ Angiotensin

↑ Vasoconstriction
↓ Angiotensin
β1 ↑ Peripheral resistance

↑ Blood Pressure
↓ Blood Pressure

24. • Use and beneficial effects of β blockers in
the treatment of angina pectoris:
– ↓ frequency and severity of anginal attacks
– ↓ nitroglycerin consumption
– ↑ exercise tolerance
– β blockers are used prophylactically to prevent
exertional angina.
• not useful for vasospastic angina.
• most useful in patients whose attacks of angina are
frequent and unpredictable
• Has to be taken regularly

25. DRUG HALF-LIFE RECEPTOR SELECTIVITY
Propranolol 3-4 hr β1, β2
Nadolol 10-20 hr β1, β2
Metoprolol 3-5 hr β1
Atenolol 6-8 hr β1
Acebutolol 3-4 hr β1
Drugs that block both β1 and β2 adrenergic receptors and those that block only
β1-adrenergic receptors are both used to treat angina pectoris. The
maximal effectiveness of these drugs in treating angina pectoris is similar

26. Contraindications
1. Congestive heart failure
2. Asthma
3. Complete heart block
4. Hypotension: BP < 100 mmHg
5. Bradycardia: HR < 50 bpm
6. Chronic bronchitis.
7. Severe chronic renal insufficiency

27. Calcium channel blockers
• Ca+2 channel blockers protect tissue by inhibiting
the entrance of Ca+2 into cardiac and smooth
muscle cells of the coronary and systemic arterial
beds.
• All Ca+2 channel blockers produce some
vasodilation (↓ PVR) and (-) inotropes.
• Some agents also show cardiac conduction
particularly through the AV node thus serving to
control cardiac rhythm.

28. Calcium channel-blocking agents
Mechanism:
– Calcium channel-blocking agents produce a
blockade of L-type (slow) calcium channels, which
decreases contractile force and oxygen
requirements.
Agents cause coronary vasodilation and relief of
spasm
they also dilate peripheral vasculature and decrease
cardiac afterload.

30. Pharmacologic properties
• Calcium channel-blocking  administered orally.
• When administered intravenously, they are effective
within minutes.
• The therapeutic use of these drugs in angina is
generally reserved  nitrates are ineffective or when
β-blockers are contraindicated.
• These drugs produce hypotension.

31. phenylalkylamines
A (verapamil)
dihydropyridines
B (nifedipine)
benzothiazepines
C (diltiazem)
vasodilatation
peripheral ++ +++ +
coronary ++ +++ +++
cerebral + + +
heart rate ↓ ↑** ↓
SA node ↓ -- ↓
AV node ↓↓ -- ↓
contractility ↓ ↑** ↓
**, reflex effect; +, mild effect; ++, moderate effect; +++, pronounced effect; --, no change
Indications:
A angina; hypertension; supraventricular tachyarrhythmias
B angina; hypertension
C angina; hypertension; supraventricular tachyarrhythmias

32. Use of CCBs in angina:
1. Exertional angina: verapamil, diltiazem and DHPs
• therapeutic effects are due to increased coronary blood flow and/or
decreased myocardial oxygen consumption
2. Vasospastic angina: verapamil, diltiazem and DHPs
• benefits of CCBs are primarily due to coronary artery dilation

33. Side Effect
Calcium Antagonist Oral Intravenous
verapamil
constipation (8%)
facial flushing (8%)
dizziness (6%)
headache (8%)
AV block (1%)
worsening of heart
failure
hypotension
bradycardia
nifedipine
ankle edema (10%)
facial flushing (12%)
headache (6%)
nausea (4%)
tachycardia (12%)
dizziness (3%)
N/A
diltiazem
headache (2%)
facial flushing (1%)
nausea (3%)
ankle edema (2%)
hypotension
bradycardia

34. Combination therapy

35. NITRATES + BETA BLOCKERS
• Beta Blockers prevent reflex tachycardia and contractility
produced by nitrate-induced hypotension.
• Nitrates prevent tendency of ventricular dilatation &
reduction of total coronary flow produced by Beta Blockers.
• Nitrates and Beta Blockers both reduce myocardial oxygen
consumption by different mechanisms.
• Nitrates and Beta Blockers both increase subendocardial
blood flow by different mechanisms

36. Calcium channel blockers +beta blockers
• Useful in the treatment of exertional angina that is
not controlled adequately with nitrates and B-
blockers
• B-blockers – attenuate reflex tachycardia produce by
nifedipine
• These two drugs produce decrease blood pressure

37. Calcium channel blocker + nitrates
• Useful in severe vasospastic or exertional angina
• Nitrates reduce preload and after load
• Ca channels reduces the after load + increase coronary blood
flow
• Net effect is on reduction of oxygen demand

38. Triple drugs:-Nitrates + CCBs + beta
blocker
• Useful in patients with exertional angina not controlled by the
administration of two types of anti-anginal agent
• CCBs– decrease after load + increase coronary blood flow
• Nitrates – decrease preload
• Beta-blockers – decrease heart rate & myocardial
contractility

39. Miscellaneous antianginal drugs

40. Potassium channel openers
• K ions control the resting membrane potential.
• Efflux of K causes hyperpolarisation.
• Such effect indirectly opposes the opening of
voltage gated Ca channels.
• This results in fall in cytosolic Ca concentration with
reduction of cellular contractility activity at the
myocardial and vascular level.

41. Types of K channels
1. Voltage gated K channels
2. Calcium activated K channels
3. ATP sensitive K channels
• Drug : Nicorandil

42. Nicorandil
• It’s a newer antianginal drug which activates ATP sensitive K
channels and hyperpolarises vascular smooth muscle.
• It reduce pre and after load and produce coronary
vasodilatation.
• Nicorandil carries a nitrate like moiety.
• Arterial vasodilatation is by K channel open.
• Venodilator effect are due to nitrate like activity.

43. • It increases coronary blood flow without
causing coronary steal phenomenon.
• Used to treat vasospastic and chronic stable
angina .
• Dose : 10-20mg BD orally.

44. Side effects
• Flushing
• Palpitation
• Dizziness
• Headache
• Stomatitis
• Nausea and vomiting
• Contraindicated in cardiogenic shock and LVF

45. Cytoprotective drugs
1. Trimetazidine (pFOX inhibitor)
• It is a new Ca channel blocker belonging to
piperazine group.
• It’ is a cellular anti-ischemic drug that has
cytoprotective effect on myocardial energy
metabolism.
• It prevents degradation of membrane unsaturated
fatty acids by lipid peroxidation (LC3-KAT) there by
increasing glucose metabolism and thus reduce the
myocardial O2 demand.

46. • It also inhibits the superoxide cytotoxicity.
• In presence of ischaemia it maintain LV function
without affecting haemodynamics.
• Frequency of angina is reduced and exercise
tolerance is increased
• Indicated in stable angina, infarction sequelae and
ischaemia of labyrinths as in menieres disease.
• Dose: 20-60mg OD

47. Ranolazine
• It acts by inhibition of inward sodium current (late
Ina) during ischaemia.
• Ca load is reduced indirectly via Na-Ca exchanger.
• It prolongs exercise tolerance to angina.
• Oral BA: 30-50%
• It mainly metabolised by CYP3A4.
• It can be safely combined with CCBs, beta-blockers
or nitrates.

48. • Side effects:
• QTc prolongation
• Quinidine, dofetilide and sotalol should be
avoided.
• It not only relieves angina but reduce incidence
of serious ventricular arrhythmias in patient with
post acute coronary syndrome.
• Dose: 500mg tab

49. Direct bradycardic agents
• Ivabradine: (heart rate lowering agent)
• Introduced in 2006
• Acts by blocking cardiac pacemaker cell f
channels (If) there by reducing the heart rate
• It decreases the myocardial O2 demand by
decreasing the heart rate.

50. • Its antianginal potency is equivalent to beta-blockers
or CCBs.
• There is no negative inotropic effect or reduction in
BP nor rebound on cessation of therapy.
• Improve exercise tolerance in stable angina and
redcuces the frequency of angina
• Oral BA: 40%, undergoes FPM
• Metabolized by CYP3A4
• Excreted in urine

51. • Side effects: Rare except unusual disturbance
in nocturnal vision with flashing lights
• Dose: 5-7.5mg
• Should not be used if HR is < 60bpm

52. Management of MI
1. Pain anxiety and apprehension
2. Oxygenation
3. Maintenance of blood volume, tissue perfusion and
microcircluation
4. Prevention and treatment of aarythmia
5. Pump failure
6. Prevention of thrombus extension, embolis and venous
thrombosis
7. Thrombolysis and reperfusion
8. Prevention of remodelling and subsequent CHF

53. Thank you...