This document provides information on drugs used for the treatment of myocardial ischemia. It discusses the types of myocardial ischemia including stable, unstable, and variant angina. It then describes the heart and coronary arteries and risk factors for myocardial ischemia. The main drug classes used for treatment are discussed in detail, including nitrates, calcium channel blockers, beta blockers, potassium channel activators, antiplatelet drugs, ACE inhibitors, and cholesterol lowering medications. Adverse effects, pharmacokinetics and contraindications are summarized for each drug class. Additional treatments beyond medications are also mentioned.
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Drugs used for the treatment of myocardial ischemia
1. 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
2. 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
5. 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
6. 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
7. 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
8. 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
9. 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
10. 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)
11. 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
17. 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
18. 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
19. •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
20. 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
22. 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.
23. 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
24. 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.
26. • 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
27. 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
29. 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
31. 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
32. 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%
34. 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
35. Additional MI treatment
Stop smoking
Eliminate alcohol
Manage any underlying disorders, such as, high B.P
high levels of serum cholesterol,
36. 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
37. 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