Angina

1. Anti-anginal Drugs
Sreenu Thalla
Associate Professor
Department of Pharmacology

2. Definition
 Angina pectoris is a primary symptom of myocardial ischemia, which is the
severe chest pain that occurs when coronary blood flow is inadequate to
supply the oxygen required by the heart.

3. Clinical Symptoms
• Patient history is a˝golden standard˝
• Retrosternal pain
• Dyspnea
• Nausea
• Arrhythmia
• Restlessness
• Pain eased after taking nitrates

4. Clinical Classifications of angina
 Stable angina pectoris
 Unstable angina pectoris
 Prinzmetal’s Variant angina pectoris

5. Physical examination
• Hypertension
• Obesity
• Hyperglycemia
• Hyperlipidemia

6. 1.Stable angina
• Is caused by narrowed arteries due to atherosclerosis
• Occurs when the heart works harder
• Episodes of pain tend to be alike
• Usually lasts a short time
• Is relieved by a rest or angina medicine
2. Unstable angina
• Often occurs at rest
• Is more severe and lasts longer than stable angina
• Episodes of pain tend to be changing in the character, frequency, duration
as well as precipitating factors
• Is caused by episodes of increased coronary artery tone or small platelet
clots occurring in the vicinity of an atherosclerotic plaque.
• Is associated with a high risk of myocardial infarction and death.

7. 3. Variant angina
• Usually occurs at rest
• Tend to be severe
• Is relieved by angina medicine (vasodilators)
• Is caused by a transient spasm in a coronary artery

15. The difference of
Arteriovenous
oxygen pressure
O2
demand
O2
supply
Wall tension
Heart rate
Contractility
Coronary blood flow
Angina
Aortic
Diastolic
pressure
Coronary
Vascular
resistance
Ventricular
Pressure
Ventricular
Volume
>
the duration
of diastole
Pathophysiology

20. Treatment of angina
Lifestyle changes
Nitrates
Medication β-blockers
Calcium channel blockers
Surgery : CABG ( coronary artery bypass graft)
PTCA (percutaneous transluminal coronary angioplasty)

22. Organic nitrates
Key structure: -O-NO2
• Nitroglycerin
• Isosorbide dinitrate
• Isosorbide mononitrate

23. Pharmacological actions
1. Dilate vascular smooth muscle, decrease myocardiac oxygen consumption
– dilate veins
– dilate arteries
2. at minimal effective dose:
dilate veins blood returning to heart
preload Ventricular volume wall tension
3. at higher dose:
dilate arteries peripheral resistance
afterload wall tension myocardial
oxygen
consumption.

24. • Increase blood supply to ischemic area
• Increase sub-endocardium blood flow
• Redistribution of coronary blood flow
• Increase embranchment cycle in ischemic area
blood flows from epicardium to endocardium
dilate veins blood returning to heart
dilate arteries ventricular wall tension

25.  Protect the ischemic myocytes
 Inhibit platelet aggregation and adhesion
 Decrease ischemic damage

26. Mechanisms of action
cGMP
Nitrates NO cGMP platelet
PGI2 ; CGRP
CGRP：calcitonin gene-related peptide
smooth muscle
relaxation

27. Nitrates
NO
Guanylyl cyclase* Guanylyl cyclase
GTP cGMP
PDE
GMP
Ca2+ (intracellular)
MLCK*
MLC MLC-PO4 MLC
Actin
Contraction Relaxation
Mechanisms of action
(MLCK-myosin light chain kinase

28. Pharmakinetics
• Absorption oral bioavailability 10-20%
sublingual route: t1/2 2~4min
• Metabolism liver
• Excretion kidney
Clinical uses
 All types of angina sublingual
 Acute myocardial infarction iv
 Congestive heart failure (CHF) load
Adverse reactions
 Respond to vasodilation
 Flushed appearance
 Throbbing headache
 Orthostatic hypotension
 Tachycardia

29. Beta-adrenoceptor Blocking Drugs
 Nonselective β-blokers - Propranolol, Pindolol, Timolol
 Selective β1-blokers - Atenolol, Metoprolol, Acebutolol
1. Decrease myocardial oxygen consumption
 β - blocker decrease heart rate, contractility, and blood pressure
decrease myocardial oxygen consumption
 β- blocker increase in end-diastolic volume, ejection time
 increase myocardial oxygen consumption total effect: decrease

30. 2. Improve blood supply to the ischemic area
 Decrease myocardial oxygen consumption
 Promote the blood supply to the compensative dilating ischemic area
 Decrease heart rate
 Increase diastolic perfusion time
 Blood flow from epicardium to endocardium
 Increase embranchment cycle in ischemic area
3. Decrease myocardial free fatty acid, improve myocardial metabolism
4. Promote oxygen to dissociate from oxygenated hemoglobin (HbO2)

31. β-blockers combines with nitrates
Nitrates β-blokers
alone alone
Heart rate reflex increase decrease
Arterial pressure decrease decrease
End-diastolic volume decrease increase
Contractility reflex increase decrease
Ejection time decrease increase
synergism

32. Calcium channel-blocking drugs
 Decrease myocardial oxygen consumption
 Heart rate and contractility;
 Vasodilation
 Antisympathetic action
 Improve the blood supply to the ischemia
 Dilate coronary artery
 Decrease the platelet aggregation
 Protect ischemic cardiac myocytes
 Antiatherosclerosis

33. Clinical uses
 Antianginal effect is similar to β-blokers, but have many virtues
 Suit for the anginal patient with asthma
 Variant angina first choice
 Suit for the anginal patient with surrounding blood vessel spasm
Nifedipine
 Variant angina - strongest action
 Stable angina - Combined with β-blokers

34. Verapamil
 Weaker for dilating peripheral vessels
 Inhibit the heart
 Used for stable angina and variant angina combined with other drugs
 Contraindications:
 heart failure
 atrioventricular blockade
Diltiazem
• Moderate , used for all types of angina
• Anginal patient with heart failure
• Atrioventricular blockade caution

35. Other Antianginal Drugs
• Dipyridamole
• Nicorandil
• Molsidomine
• ACEI

37. Angina of Effort (stable angina)
 Nitrates, calcium channel blockers, and β-blockers are all useful in prophylaxis in
patients with angina of effort.
 For maintenance therapy of chronic stable angina, long-acting nitrates, calcium
channel-blocking agents, or β-blockers may be chosen.
 The combination of a β-blocker with a Nitrates or a β-blocker with a calcium
channel blocker or two different calcium channel blockers has been shown to be
more effective than individual drug used alone.
 If response to a single drug is inadequate, a drug from a different class should be
added to maximize the beneficial reduction of cardiac work while minimizing
undesirable effects.

38. Vasospastic Angina
• Nitrates and the calcium channel blockers are effective drugs for relieving and
preventing ischemic episodes in patients with variant angina.
Unstable Angina
 In patients with unstable angina，anticoagulant and antiplatelet drugs play a major
role in therapy.
 Aggressive therapy with antilipid drugs, heparin, and antiplatelet agents is
recommended.
 In addition, therapy with nitroglycerin and β-blockers should be considered; calcium
channel blockers should be added in refractory cases.

41. NEWER DRUGS
• RANOLAZINE - a drug that has been in development for 20 years. It is a
Sodium Channel Blocker.
• NICORANDIL - a potassium channel activator, and also has a Nitrogen
Donating Moeity.
• IVABRADINE - inhibits the If channel in the sinus node and thereby causes
bradycardia without any negative inotropic effects.