Download Angina pectoris

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
Exertional angina,
Stable,Atherosclerotic,Classic,
Due to obstruction of coronaries by
atheroma.
2. Variant, Vasospastic angina
due to Spasm of coronaries.
3- Unstable angina.
Due to spasm and partial obstruction of
coronaries.
1.
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
2- Long acting
Nitroglycerine, Isosorbide dinitrate,
Isosorbide mononitrate,Erythrityl –
Tetranitrate.

Action of all start withen hours and
continue for hours .
They are given :
Orally,Ointment,Buccal,Transdermal
patch,Parenteral.
Absorption
Well absorbed according to the route:
GIT for the long acting
short acting Sublingual
Transdermal for long acting
inhaLation
Metabolism
Through first pass hepatic metabolism .
Short acting have a low oral bioavailability
(10-20%),so not given orally to avoid first
pass metabolism.
Nitroglycerine metabolites( two dinitro And
two mononitro forms).
The dinitro forms are active metabolites
and have significant vasodilator effect.
Metabolism
Isosorbide dinitrate metabolite (5mononitrate) is an active metabolite
used clinically.
Excretion
As metabolites through kidney.
Mechanism of action
Glutathione S-transferase
Nitroglycerine ————————
No.
guanylyl cyclase and NO activates
increase c GMP
c GMP dephosphorelate myosin light
chain (Myosin-LC-po4 ) to myosin- LC
Causing muscle relaxation.
Pharmacological actions
Nitrates relax all types of smooth muscles
vascular or non vascular .
Relax both arteries and veins but more
effective on veins.
They have no direct effect on cardiac or
skeletal muscles.
NO released stimulate guanylyl cyclase
In platelets causing increase cGMP that
decrease platelet aggregation.
Clinical uses
Short acting for acute attacks
Long acting for prophylactic.
Treatment of all types of angina .
1- Angina of effort
A) Decrease venous return
B) Decrease ABP
Both A&B decrease myocardial
oxygen requirement.
2-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
Throbbing headache
Tachycardia
Facial or cutaneous flushing
Tolerance (Tachyphylaxis)
Salt and water retention
Carcinogenicity
Methaemoglobinemia only with nitrities
Contraindication
Nitrates are contraindicated in
increase intracranial pressure.
Nitrates can be used safely in
increase of intraocular pressure
(Glucoma).
Calcium channel blockers
1- They block calcium entry in
myocardium causing ;
 A) decrease myocardium
contractility & myocardium
oxygen requirement.
B) decrease heart rate causing
decrease in myocardium oxygen
requirement.
2-Block calcium entry in vascular
smooth muscles (arterioles) causing
a)decrease in peripheral resistance(
after load)------ decrease in oxygen
requirement.
• b)Relief of coronary spasm.
Clinical uses
In all types of angina but very
effective in variant angina .
Used mainly in prophylactic therapy.
β-Adrenoceptor blocking
drugs
They are not vasodilators
They are used in treatment of angina
:
They decrease both heart rate &
myocardial contractility that
decrease in myocardial oxygen
requirement at rest & in exercise so
improve exercise tolerance.
Clinical uses
They are effective in the prophylactic
treatment of classic & unstable angina.
They are not used in variant angina.
They are effective in treatment of silent or
ambulatory angina (no pain ).
Decrease mortality of patients with recent
myocardial infarction.
Potassium channel openers
(Nicorandil )
 Activation
of potassium channels.
Nitric oxide release.
Arterio & venodilators.
Used as prophylactic therapy .
May cause :
Headache,flushing,dizziness.
Drug treatment of angina
1- Acute attack :
Short acting nitrates or nitritis.
2- Prophylactic therapy ;
Long –acting nitrates.
Calcium channel blockers.
β- adrenoceptors blockers.
Potassium channel openers.
Combination therapy
Nitrates and β-adrenoceptors
blockers.
Calcium channel blockers and βadrenoceptor blockers .? ?
Calcium channel blockers and
nitrates.
Calcium channel blockers, βadrenoceptor blockers, nitrates.
Surgical therapy
Ballon
Coronary by pass.