zafgdzgfgegezgezzzzzzzfdghhhhhhhhhhhhhhhhhhhhhhvvvvvvvvvvvvvvddddddddddddddddddddddtttttttttttttttttttttttttttttttttttttttttttttttttttttttttttttttttthhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhxxx

1. 1

2. – Refers to CVS disorder characterized by sever aching pain
of the heart
– Often starts as crushing pain of chest which usually
radiates to Left arm, shoulder, jaw and neck
– Angina occurs as result of an imbalance b/n myocardial O2
demand and supply
– O2 Demand: determined by HR, myocardial contractility
and intra-myocardial wall tension
• preload: amount of tension or stretch applied to the
muscle before contraction. Determined by ventricular
filling pressure
• After load: arterial pressure that the left ventricle must
overcome to eject the blood
– O2 Supply: Determined by myocardial blood flow
2

3. Angina is caused by an imbalance
between O2 supply and demand
3
No anginal symptoms
Angina
A
B
O2 supply O2 demand

4. • There are three types of angina
Stable angina(angina of effort)
– Also called angina of effort, typical angina
– Is the most common type
– Usually triggered by physical activity
– Also emotional excitement, large meal, cold exposure can
precipitate this type of angina
– Caused by atherosclerosis blockade of blood vessels
Variant angina
– Also called Prinzmetal’s or vasospastic angina
– Occurs due to spasm of coronary arteries
– Associated with pain at rest
– May occur with stable angina
4

5.  Unstable angina
– Also c/d crescendo or preinfarction angina
– It is a medical emergency
– Associated with pain at rest
– Occurs as result of high degree of atherosclerosis in the
coronary arteries
– It is the worst of all types of angina
– It has high risk for Myocardial infarction and Death
– Caused by severe stenosis with probable plaque rupture leading
to platelet aggregation, thrombosis and/or vasoconstriction
Therapeutic Objectives of angina treatment
– Increase blood flow to ischemic heart muscle and/or decrease
myocardial oxygen demand
5

7.  Goals of angina treatment
 Terminate acute angina pain
 Reduce the frequency (recurrence) of angina attacks
• Reducing myocardial oxygen demand
• Increasing oxygen supply to the myocardium
 Prevention of myocardial infarction & death
• This can be achieved by:
– Slowing heart-rate
– Reducing the preload by dilating veins
– Causing heart to contract with less force
– Lowering blood pressure – less resistance in heart to
pushing blood from chambers (reduce after-load)
– Preventing (reducing) lipid & platelet accumulation
in the blood vessels 7

8. • Classes of Drugs available for angina
treatment
Nitrates
Calcium channel blockers
Beta blockers
Antiplatelet agents
8

9. – Includes: nitroglycerin, isosorbide mononitrate, isosorbide
dinitrate, pentaerythritol tetranitrate
– Except nitroglycerin which volatile liquid, these drugs are solid
at room temperature
– MOA: nitrates are thought to work by interacting with nitrate
receptors found on vascular smooth muscles
• Nitrate receptors contain sulfohydryl (SH) groups which
reduces nitrates to nitric oxide (NO)
• NO stimulates guanylyl cyclase which synthesizes cGMP
• cGMP causes smooth muscle relaxation which leads to
vasodilation
– Nitrates produce more pronounced dilation on the veins than the
arteries

10. • Nitrates relieve the symptoms of angina by restoring the
balance b/n myocardial O2 demand & supply
• O2 demand is lowered as result of:
– Reduction in cardiac preload (as result of venous pooling of
blood)
– Reduction in cardiac afterload (as result of arteriolar dilation)
• O2 supply is increased as result of:
– Increased blood flow to ischemic areas as result of direct
vasodilatory effects of nitrates on coronary arteries
– Nitrates were also found to prevent platelet aggregation

11. • Preparations: based on their duration of action
nitrates can be divided into three groups:
– Short acting (several minutes)
• Amyl nitrate: inhalant, very rapid absorption
• Sublingual: Nitroglycerin, isosorbide dinitrate
• Avoid hepatic first pass metabolism, very short duration of
action
– Intermediate-acting (several hours)
• Oral Erythrityl tetranitrate and pentaerythritol tetranitrate
• Oral Isosorbide dinitrate, Buccal nitroglycerin slow-release
• Oral isosorbide mononitrate
– Long-acting
• Transdermal, nitroglycerin slow–release (8-10 hours)
11

13. • Tolerance & dependence
– Repeated & frequent exposure to organic nitrates is
accompanied by dev’t of tissue tolerance to the drugs
vasodilatory effects
– The mechanism for tolerance to nitrates is not well
understood but could be due to:
• Depletion of SH group
• Decrease in sensitivity of guanylyl cyclase to NO
• Activation of RAAS
– To reduce/prevent nitrate tolerance, clinicians should
employ the smallest effective dose & administer the
drugs infrequently
– A daily nitrate free period is also recommended

14. • Side effects
– Headache
– Postural hypotension
– Reflex tachycardia are common side effects

15. – Since an increase in SNS activity is a common feature of anginal
attacks, the use of β-antagonists is rational
– β-antagonists approved for secondary angina in USA includes:
• Propranolol & nadolol(non selective β1 &2 antagonists)
• Metoprolol & atenolol (β1 selective antagonists)
– MOA:
• Antagonize the actions of catecholamines on the heart &
reduce HR, FC
• β-antagonists also increase blood supply to ischemic areas
– By decreasing HR, they increase diastolic perfusion time
• There is also evidence that β-antagonists can inhibit platelet
aggregation

16. • β-antagonists have also been found to reduce arterial blood
pressure (afterload)
• Mechanism not well known but expected to be due to:
– Reduced HR & FC produces reduced cardiac output
– Reduce plasma renin activity
– An action on the central nervous system
• So, β-antagonists reduce myocardial O2 demand by reducing 3
of the major determinants of myocardial O2 demand
– HR, FC, arterial wall tension (afterload)
• Generally, β-antagonists produce their antianginal effects by:
– Decreasing O2 demand (by decreasing HR, FC & after load)
– Increasing O2 supply (increasing diastolic perfusion time)
– Preventing platelet aggregation

17. • β-antagonists are particularly indicated in the management of
patients whose anginal attack are frequent & unpredictable
– They can be combined with nitroglycerin
• Side effects
– Abrupt interruption of β-antagonists can lead to
• Reappearance of angina
• Acute myocardial infarction
• death

18. – Are orally active group of drugs approved for
treatment of vasospastic & effort angina
– Are particularly effective in the prophylaxis of
coronary vasospasm or variant angina
– MOA: bock L-type calcium channels in vascular
smooth muscles & heart producing:
• Decreased HR & FC (decrease demand)
• Decrease PVR (decrease demand)
• Dilate coronary arteries (increase supply)
• Also inhibit platelet aggregation

19. • Different classes of CCBs are available
– Phenyalkylamines: verapamil, with T1/2 3-6 hours
– Benzothiazepines: Diltiazem; T1/2 3-6 hours
– Both verapamil & diltiazem are cardioselective CCBs
– Dihydropyridines:
• Nimodipine-: T1/2 1-2 hours
• Nifedipine- T1/2 2-6 hours
• Nifedipine sustained-release, Isradipine - T1/2 8-12 hours
• Amlodipine – very long acting – T1/230-50 hours
19

20. Side effects
• Serious side effects
• Cardiac depression (non-DHPs)
– Cardiac arrest
– Bradycardia
– Atrio-ventricular block
– Heart failure
• Minor side effects
– Headache, flushing, dizziness, nausea, constipation,
coughing, wheezing
– Peripheral edema due to greater arteriolar than venous
dilation
20

21. – Aspirin
• Inhibits TXA2 synthesis & produces its antiplatelet activity
• Reduces incidence of myocardial infarction & death in
patients with unstable angina
• Low doses of aspirin also reduces the incidence of
myocardial infarction in patients with chronic stable angina
– Clopidogrel
• Is another antiplatelet agent which is added to aspirin to
reduce mortality in patients with coronary syndromes
– Heparin
• Is antithrombin agent given intravenously
• Reduces & prevents infarction in patients with unstable
angina

22. • Abciximab, tirofiban, eptifibatide
– Inhibit platelet aggregation by inhibiting GpIIb/IIIa
receptor
– Are effective in preventing complications of unstable
angina