Drugs used for the treatment of

myocardial ischemia
 Presented by
Sk.yasmeen I/II M.Pharmacy
Department of pharmacology
Hindu college of pharmacy
Guntur

Under the Guidance of

Mrs.G. Sumalatha,M.Pharm(PhD)
Department of pharmacology
Hindu college of pharmacy
Guntur
myocardial ischemia
 Myocardial ischemia:
o Myocardial ischemia also known angina is a heart
condition caused by a temporary lack of oxygen-rich
blood to the heart.
o The sudden severe, pressing chest pain occurs, starting
from substernal and radiate to left arm.
o The inadequate blood flow is caused by narrowed
coronary arteries, which are the vessels that supply
blood to the heart
Myocardial ischemia
Myocardial infraction
Understanding the heart and coronary arteries
 Like any muscle, the heart needs a constant supply of
oxygen and nutrients
 Which are carried to it by the blood in the coronary
arteries similar to other muscle.
 The harder the heart is working the more oxygen
&nutrients it needs
 The coronary arteries can become narrowed or
clogged, which can decrease the amount of blood that
goes to the heart muscle
Types of myocardial ischemia
Stable (typical angina)
Unstable (crescendo angina)
Varient (prinzmetal’s angina)

Stable MI
 It is a most common type
 Occurs when heart is working harder than usual
 Regular pattern to this condition
 After several episodes, patient learns to recognize &predict
 Pain goes away in a few min by taking rest & medicine
 variant MI
• It is rare and occurs at rest
• Pain associated with this can be severe and usually
occurs between midnight and early morning
• Pain relieved by medicines
 unstable MI
• it is dangerous condition & requires emergency
treatment
• it is a sign that heart attack could occur soon
• it does not follow a pattern
• occurs without physical exertion & not relieved by rest
& medicine
Conditions that increases o2 supply
1. Stress
2. Exercise
3. During increased heart rate
Conditions that decrease o2 supply
1. Coronary arteries diseases
 Accumulation of plaques
 Platelets aggregation
 Stenosis or spasm or constriction or narrowing
2. Reduction in blood flow to heart
 Due to constriction of blood vessels
3. Reduction in o2carrying capacity of blood
 Decrease Hb levels (in anemic conditions)
 Normal blood flow and supply but decrease in o2 carrying
capacity
Symptoms
 Some people have “silent ischemia”
 MI with sign & symptoms include
1. Chest pain (left side)
2. Neck or jaw pain
3. Shoulder or arm pain
4. Clammy skin
5. Nausea &vomiting
Causes
1. Coronary artery diseases
2. Blood clot
3. Coronary spasm
4. Sever illness
Risk factors
1. Tobacco
2. Diabetis
3. High B.P
4. High blood cholesterol or triglyceride levels
5. Lack of physical activity
6. Obesity
7. Family history
Complications
 Irregular heart rhythms (arrhythmia)
 Heart attack (myocardial infarction)
Classification
 coronary vasodilators
1. Nitrites & nitrates
according to duration of action
 Shot acting (3 to 60 min)
Amyl nitrite, nitroglycerin(sublingual), isosorbide
dinitrate
 Intermediate acting(3 to 6hrs)
Isosorbide dinitrate ,nitroglycerin(ointment)
 Long acting(6 to 10 hrs)
Erythirtyl tetranitrate, nitroglycerin (trans-cutaneous
Beta adrenergic blocking agents
Atenolol
Propranolol
Nadolol

Calcium Channel Blockers

Amlodipine , Bepridil
Diltiazem , Felodipine
Isradipine, Nicardipine, Nifedipine
Nimodipine, Verapamil
Potassium Channel Activators:
Nicorandil, Pinacidil
Antiplatelet Drugs :
Aspirin Clopidogrel
Angiotensin-Converting enzyem Inhibitor:
captopril, enalapril, lisinopril

Cholesterol Lowering Medication :

Atorvastatin, Fenofivrate
Further treatment
 surgical procedures for MI
1. Angioplasty and stenting
2. Coronary artery bypass surgery
stenting Angioplasty
Organic nitrates
Biochemical role of nitrates
Release of Nitric oxide radical

Activation of Guanylate cyclase

Accumulation of cGMP

Activation of cGMP dependent Kinases

Dephosphorylation of myosin light chain

Vasodilatation of Venules and Arterioles
1. Hemodynamic role of nitrates
1. Venodilatation   Preload
2 . Arteriolar dilatation  After load
3. Redistribution of blood in myocardinm
4. Increase PGE1, PGI2
Decrease in platelet aggregation
 •Pharmacokinetics
-Extensive first pass metabolism.
- Metabolized by denitration & conjugation
-Low bioavailability only 20%
-Unchanged nitrate has half life of 2-8min
-Excretion : renal route.

Clinical uses of Nitrates:

For treatment & prophylaxis of classical angina
pectoris
Treatment of Variant Angina
Treatment of Unstable Angina
Adverse effects of Nitrates
 In therapeutic doses:-
1. Throbbing Headache
2. Flushing
3. Syncope
 In high doses:-
4. Drug rash
1. Reflex sympathetic over activity
5. Tolerance leading to tachycardia which
6. Constipation. increases work load on heart.
2. Fall in blood pressure
3. Methemoglobinemia
Ca+2 Channel Blockers
Ca+2 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
vasodilatation (↓ PVR)
 Some agents also slow cardiac conduction
particularly through the AV node thus serving to
control cardiac rhythm.
 Some agents have more effect on cardiac muscle
than others but all serve to lower blood pressure.
 They are useful in Prinzmetal angina in
conjunction with nitrates.
pharmacokinetics
•Administration: orally well absorbed
•Undergoes first pass metabolism
•Half life : 3 to 5 hrs

Side effects
•Swelling of legs
•Excess lowering of heart rate and blood pressure
•Depressing heart muscle function
 β-Blockers
 These decrease O2 demands by lowering the heart rate &
contractility (decrease CO) particularly the increased
demand associated with exercise.
 They also reduce PVR by direct vasodilation of both
arterial & venous vessels reducing both pre- and after load.
 These effects are caused by blocking β1 receptors, selective
β1 antagonists
o atenolol,
o metoprolol and
o acebutolol
 lose their selectivity at high doses and at least partially
block β2 receptors (a concern for bronchospastic disease).
 β1 antagonists reduce the frequency and severity of anginal
episodes particularly when used in combination with
nitrates.
β-Blockers
• There are a number of contraindications for β blockers:
asthma, diabetes, bradycardia.

Pharmacokinetics:
• GI
• 30-50% metabolized in the first-pass in liver.
• T1/2: 3-5 hours,

Side effects
•Worsening of asthma
•Depression, fatigue
•Impotence
•Increased cholesterol levels
•Shortness of breath due to diminished heart muscle function
Potassium channel opener’s mechanism
Potassium channel openers

Activate potassium channel

increase potassium permeability in cell

l
Hyperpolarisation occurs

Closer of L-type calcium channels

Reduced intracellular free calcium

Leads to vasodilatation
Nicorandil
•Administration : orally
•Bioavailability : 75 to 80%
•Protein binding : 25%
•Metabolism : hepatic
•Half life : 1hr
•Excretion : renal Adverse effect
•Headaches
•Nausea
•Vasodilatation
•Vomiting
•Decrease B.P
•Stomach pain
 Antiplatelet drugs
Mechanism of action
• prostacyclin (PGI2) & thromboxane (TXA2) are derived from archedonic
acid.
•PGI2 is formed from vascular endothelium
•TXA2 is generated by platelets is a vasoconstrictor
•PGI2 is important for natural resistance to arterial thrombosis
•TXA2 and vascular PGI2regulates the the platelet aggreability
•Collagen form sub endothelial matrix of damaged vessel initiates the
attachment
•TXA2 inhibits the adenylyl cyclase and lowers the cAMP concentration
•Low concentration of cAMP accelerates platelets aggregation
-Aspirin inhibits cyclo-oxygenase

-Inhibits the TXA2 synthesis

-Prevention of platelet aggregations

Pharmacokinetics
•Administration : orally
•Bioavailability : rapidly and completely absorbed
•Protein binding : 99.6%
•Metabolism : hepatic
•Half life : 5-9hr
•Excretion : renal

•Adverse effects
•Nausea
•Rashes and diarrohea
•Peptic ulceration
Angiotensin converting enzyme inhibitors
Mechanism:
inhibit ACE

low circulating Ang II

decreased PVR
Pharmacokinetics
Bioavailability : 60% (oral)
Metabolism : hepatic
Half life : 11 hrs
Excretion : renal
Main effects: decreased PVR  decreased BP
Adverse effects: skin rash, taste, cough, hyperkalemia
Cholesterol lowering drugs
Mechanism of action
•Competitively inhibiting HMG-CoA reductase first
enzyme of HMG-CoA reductase pathway
•Statins are similar to HMG-CoA
•They take the place of HMG-CoA in the enzyme
and reduce the rate by which it is able to produce
mevalonate which is used in production of
cholesterol

•Reduce LDL levels by 30% to40%

•Reduce HDL levels by 2% to 15%
•Reduce triglycerides by 10% to30%
Atrovastatin
•absorption :rapid oral absorption
•T max 1 to 2 hours
•High intestinal clearance &first pass metabolism
•Protein binding >98%
•Excretion: hepatic biliary excretion
Fenofivrate
•absorbtion : oral absorbtion
•Half life :20 hrs
•Protein binding >99%
Adverse effects •Excretion: renalexcretion
•Mild transient GI disturbances
•Rash headache
•Myopathy (muscle pain)
•Elevation of liver diseases
Contraindication

•Interaction with anti arrhythmic drugs Antidepressants

o Failure of sublingual tablets of nitrates to dissolve
•Interactions with corticosteroids NSAIDS
o Hypotensive action is antagonized
•Interaction with beta blockers and calcium channel blockers
oThey can cause the excessive hypotension
Additional MI treatment
 Stop smoking
 Eliminate alcohol
 Manage any underlying disorders, such as, high B.P
high levels of serum cholesterol,
Newer antianginal drugs
Because of high prevalence of angina ,new drugs are actively
sought for its treatment
Some of the drugs or groups currently under investigation are listed
Drugs
•Potassium channel activators : nicorandil
•Metabolic modulators : trimetazidine, ronolazine
•Direct bradycardic agents : ivabradine
•Protein kinase Gfacilitators : detanonoate
•Sulfonyl ureas : glybenclamide
•Nitric oxide donors : L-arginine
•Capsaicin
•amiloride
•Thiazolidinediones
•Vasopepdidase inhibitors
 REFERENCE
•RANG &DALE’S pharmacology 6th edition
•BERTRAM G.KATZUNG BASIC AND CLINICAL
PHARMACOLOGY
•ROBBIN AND COTRON PATHOLOGIC BASIS OF DISEASE
•PRINCIPLES OF PHARMACOLOGY HL.SHARMA
KK.SHARMA
•PHARMACOLOGY AND PHARMACOKINETICS
R.S.Satoskar S.D.Bhandarkar
Thank you