Transcript drug therapy of angina pectoris

Cardiovascular
Pharmacology
Professor Doctor:
Abd Al Rahman Abd Al Fattah
Yassin
Professor and head of clinical pharmacology
department
Mansura university
DRUG THERAPY
OF
ANGINA PECTORIS
Definition
• It is a clinical syndrome characterized
by sudden severe pressing sub
sternal pain that often radiate to the
left shoulder and along the flexor
surface of the left arm that occurs
when coronary blood flow is
inadequate to supply the oxygen
required by the heart.
• Angina occurs when the
myocardial oxygen demands
exceed the oxygen requirement.
Types of Angina
• Stable angina: (Effort, typical angina): The
pain is commonly induced by exercise,
emotion or heavy meals.
• Variant angina: (Prinzmetal's angina, receptor–mediated vasoconstriction): Patient
develope pain even at rest.
• Unstable angina: (accelerated angina): There
is a change in pattern, increase in frequency,
severity and/or duration of pain.
Treatment of Angina Pectoris Includes:
• A. General Measures
• Alteration of life style: avoid intolerable
effort, stress, heavy meals, and smoking.
• Correct obesity and reduce fat intake.
• Treatment of predisposing factors e.g.
hyperlipidemia, hypertension, heart failure,
arrhythmias, anemia and diabetes mellitus.
B. Drugs
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Drugs used during the acute attack:
nitrites or nitrates.
Sedative, analgesics and tranquilizers .
Drugs used in between the attacks:
Long acting nitrates.
Beta adrenoceptor blockers.
Calcium channel blockers.
Cytoprotective drugs(trimetazidine,ranolazine)
Antiplatelets:aspirin,clopidogril.
statins.
C. Surgical Treatment: (Myocardial revascularization)
NITRITES AND NITRATES
Organic nitrates are ester of nitric acid whereas
organic nitrites are esters of nitrous acid.They
are potent vasodilators.
Pharmacologic Characteristics of Currently
Available Nitrates
Pharmacokineticsa
• It is absorbed through mucous membrane,
gastrointestinal tract, skin and from
tracheobronchial tree by inhalation.
• Sublingual administration produces rapid
onset (2-5 minutes) and short duration (less
than 30 minutes)
• It is metabolized by the liver.
• Oral preparations provide more prolonged
prophylaxis.
• Excretion of nitrates is largely via the kidney.
Mechanism of action
 Nitrates converted to NO(nitric oxide) which increase
cGMP,which cause
V.D of vein more than artery.
 SH group is required for this conversion.
Pharmacological Effects
• Cardiovascular system
• Blood vessels
• Nitrites are dilators of venous and to less extent arterial
smooth muscle.
• They increase coronary blood flow due to coronary
vasodilatation
• Arteriolar dilatation of the face and neck lead to flushing
• Vasodilatation of the meningeal arteries leads to throbbing
headache.
• Heart
• The effects on the heart are secondary to the peripheral
effects. They produce tachycardia, decreased venous return
and so the cardiac output (COP) and cardiac work are
decreased.
Blood pressure
• Rapid administration of high doses decreases
systolic and diastolic blood pressure and COP
resulting in palpitations, weakness, dizziness
and tachycardia.
• Systemic venous capacity is increased due to
venular dilatation and this reduces both the
venous return and the pulmonary pressure.
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Pharmacolgical effect
Action on smooth muscle: They relax biliary,
G.I.T,bronchial and uterine smooth muscles.
• Action on respiration
• Reflex increase in the respiratory rate through
the carotid body or secondary to hypotension.
• Smooth muscle relaxation in bronchospastic
disorders.
• Action on blood: Nitrate ions readily oxidize
to methaemoglobin.
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Therapeutic Uses
• 1. Angina pectoris
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Nitrates are effective in the different types of angina:
[A] Reduction of myocardial oxygen demand via:
Venodilatation leading to decreased preload.
Arteriodilatation leading to decreased afterload.
[B] Enhancement of myocardial perfusion
Through:
Coronary vasodilatation
Redistribution of coronary flow to the ischaemic subendocardium
• 2. Congestive heart failure: Due to: mainly
reduction of pre-load.
• And reduction of afterload.
• 3. Acute myocardial infarction: Nitroglycerine
(NG) may reduce the area of myocardial
damage and may preserve viable tissues.
• 4. Other uses
• Biliary colic.
• Management of constriction ring of uterus.
• Treatment of cyanide.poisoning.
Adverse Reactions
• Throbbing headache.
• Postural hypotension, dizziness and even syncope.
• Tachycardia and palpitations.
• Flushing in the face.
• Methaemoglobinaemia.
• Tolerance especially during chronic exposure.
Precautions
• Start with the smallest possible dose in order to
minimise side effects.
• Nitrate therapy should not abruptly stop to avoid
withdrawal symptoms.
• The patient should consult his doctor when more
than 3 tablets sublingually taken over 15 minutes
without improvement for fear of MI.
• Nitroglycerine tablets should not be put in sunlight,
or with cotton.
• The expiry date should be checked (active tablets
have burning taste).
CALCIUM CHANNEL BLOCKERS
(CCBs)
• pharmacologyThe of (CCBs) was
discussed before. They are effective
in the management of variant
angina, chronic stable angina and in
some subsets of unstable angina.
What
are
the
underlying
mechanisms of CCBs in angina?
BETA BLOCKERS
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Beta-blockers are useful in the
management of stable and unstable
angina. However, they may worsen
variant angina due coronary spasm.
Sudden cessation of -blockers may
worse the angina due to up regulation
of -receptors. The beneficial effects of
beta-blockers in angina are:
Mechanism of action of beta blockers as an
anti ischemic:
• They slow the heart rate.
• .They decrease force of cardiac contraction.
• Beta blockers may exert cytoprotective effect.
• Combined use of beta-blockers and nitrates are very effective
in the treatment of typical angina.why
• Because some of the negative aspects of the effects of each
drug are reduced.
• For example, the reflex tachycardia and increased contractility
induced by nitrates are blocked by B-blockers.
Effects of - blockers, nitrates and their
combinations in therapy of angina
CYTOPROTECTIVE AGENTS
• This cytoprotection is obtained by providing enough
energy to maintain an efficient myocardial contraction
during ischemia e.g. TRIMETAZIDINE:
• It produces a metabolic switch via inhibition of fatty
acid oxidation toward activation of glucose oxidation
during ischemia
• It preserves contractile function and limit cytolysis.
• It limits membrane damage induced by oxygen free
radical
Anti-platelete drugs:
• Aspirin small dose.
 Ticlopidine-clopidogre.
 Abciximab-tirofiban
Other antianginal drugs:
Nicorandil
ranolazine
Selection of Anti anginal drugs for patients with
angina pectoris and concomitant diseases
Beneficial anti anginal
combinations
• Nitrate plus beta blockers
• Nitrate plus verapamil
• Unfavorable antianginal combinations
• Nitrate plus nifidipine.
• Beta blocker plus verapamil.
DRUG THERAPY OF ACUTE MYOCARDIAL
INFARCTION (AMI)
• Myocardial infarction is coagulative necrosis
of a part of the cardiac muscles as a result of
sudden and persistent cessation of its blood
supply.
• All patients should be admitted to the
coronary care unit..
DRUG THERAPY OF A. M.I
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Oxygen: To increase PO2.
Relief of pain: Morphine sulfate or Mepridine.
Sedation: by diazepam
Measures to limit the size of infarction: Betablockers, NG or CCBs
DRUG THERPY OF A.M.I.
• Fibrinolytic therapy: e.g. Streptokinase
• Anticoagulants
• Treatment of arrhythmias, heart failure and
cardiogenic shock:
• Control of risk factors: Stop smoking; physical
activity, control hypertension, obesity, diabetes
mellitus and correction of plasma lipids.