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Transcript
Angina pectoris
Sudden,severe,pressing chest pain
starting substernal &radiate to left
arm.
Due to imbalance between
myocardium oxygen requirement and
oxygen supply.
Risk Factors
Age
Sex
Obesity
Smoking
Diabetes
Classification of angina
1.
Exertional angina,
Stable, Atherosclerotic or Classic,
Due to obstruction of coronaries by
atheroma.
2.
Prinzmetal(Variant or vasospastic )
Due to Spasm of coronaries.
Continue
3- Unstable angina
Due to spasm and partial obstruction of
coronaries
4- Silent angina
Nitrates & Nitrites
Preparations :
1- Short acting:
Start within few minutes and total
duration of action 15-30 minutes.
A) Nitroglycerine (Glyceryl trinitrate)
Used as sublingual tablets.
B) Isosorbide dinitrate
As sublingual spray.
C) Amyl nitrite
 Inhalation
Continue
2- long acting
Nitroglycerine, Isosorbide
dinitrate,Isosorbide mononitrate.
Delayed onset of action and continue
for hours .
 Given : Orally,Ointment,Transdermal
patch, Intravenous.

Pharmacokinetics
Absorption
Well absorbed according to the
route of administration
Continue
Metabolism
Through first pass hepatic metabolism.
Short acting not given orally to avoid first
pass metabolism.
Nitroglycerine & Isosorbide dinitrate have
active metabolites.
Continue
Excretion
Through the kidney.
Mechanism of action
Glutathione S-transferase
Nitroglycerine ————————
Nitric oxide ( NO).
NO activates guanylyl cyclase and
increase c GMP
c GMP dephosphorylate myosin light
chain
Causing smooth muscle relaxation.
Pharmacological actions
Nitrates relax all types of smooth muscles
vascular or non vascular .
Potent venodilator.
Have no effect on cardiac or skeletal
muscles.
NO released stimulate guanylyl cyclase
in platelets causing increase cGMP that
decrease platelet aggregation.
Clinical uses
Effective in all types of angina:
Short acting for acute attacks
Long acting for prophylactic.
Severe heart failure.
Angina of effort
Decrease preload ( increase venous
capacitance )
Decrease afterload
decrease myocardial oxygen
requirement.
Redistribution of coronary blood
flow.
Prevent platelet aggregation
Variant angina
Relax smooth muscle of epicardial
coronary artery and relief coronary
spasm.
Unstable angina
Decrease myocardial oxygen
requirement.
 Relief coronary spasm.
 Decrease platelet aggregation.

Adverse effects
Orthostatic hypotension & syncope
Palpitation & Tachycardia
Salt & water retention
Throbbing headache
Facial flushing
Tolerance
Carcinogenicity
Methemoglobinemia only with nitrites
Contraindication
Nitrates are contraindicated in
increase intracranial pressure.
Notice:
Nitrates can be used safely in
increase of intraocular pressure
(Glucoma).
Calcium channel blockers
Block calcium entry in myocardium
causing :
 decrease in myocardium
contractility & heart rate
Causing decrease in
myocardium oxygen
requirement.
Continue
Block calcium entry in vascular
smooth muscles ( arteries &
arterioles) causing :
Decrease in peripheral resistance
(after load)------ decrease in oxygen
requirement.
Relief of coronary spasm.
Classification of calcium channel
blockers
Dihydropyridine
Nifedipine
More selective as vasodilator
Verapamil & Diltiazem
More selective as cardiac depressant
Pharmacokinetics
Given orally
Verapamil & Diltiazem can be given
intravenously
Excreted in urine
Clinical uses
In all types of angina but very
effective in variant angina .
Used in prophylactic therapy.
Hypertension
Supraventricular tachycardia
Peripheral vascular disease
Adverse effects
 Cardiac
arrest, bradycardia
( verapamil & diltiazem )
 Reflex tachycardia
( nifedipine)
 Fatigue & headche
 Ankle edema
 Constipation ( verapamil)
Drug interaction
Verapamil or diltiazem with β-blockers
causing bradycardia or cardiac arrest
β-Adrenoceptor blocking drugs
Not vasodilators
Used in prophylactic treatment of
angina through :
Decrease in both heart rate &
myocardial contractility that
decrease myocardial oxygen
requirement at rest & in exercise so
improve exercise tolerance.
Continue
Effective in the prophylactic treatment of
all types of angina Except in
variant angina.
Decrease mortality of patients with recent
myocardial infarction, heart failure &
hypertension.
Potassium channel openers
Nicorandil
Activation of potassium channels.
Nitric oxide release.
Arterio & venodilator.
Used as prophylactic therapy .
Side effects : Headache, flushing,
dizziness.
Fatty Acid Oxidase Inhibitors
Oxidation of fatty acids as a source of energy
needs more oxygen than oxidation of
carbohydrate.
Drugs that shift myocardial metabolism
toward use of glucose (fatty acid oxidase
inhibitors) have the potential of reducing the
oxygen demand without change
hemodynamics , e.g. trimetazidine
Anticoagulants & Antiplatelets
Aspirin & Heparin decreasing the risk in
unstable angina & acute coronary
syndrome.
Drug treatment of angina
Acute attack :
Short acting nitrates or nitrites.
Prophylactic therapy ;
•
•
•
•
•
Long –acting nitrates.
Calcium channel blockers.
β- adrenoceptor blockers.
Potassium channel openers.
Fatty acid oxidase inhibitors
Combination therapy
Nitrates and β-adrenoceptor blockers.
Calcium channel blockers(
dihydropyridine) and β-adrenoceptor
blockers .
Calcium channel blockers and nitrates.
Calcium channel blockers, β-adrenoceptor
blockers, nitrates , antiplateles or
anticoagulants.
Surgical therapy
Ballon
Coronary by pass.