Transcript Angina pectoris-Block.ppt

Lecture Outcomes:Define angina pectoris
and know the causes
Identify the factors that
control coronary blood
flow
Know the types of angina
Be aware of the drug
therapy of angina pectoris
Angina pectoris
”strangle breast”
Can occur during
exercise or stress
 ischaemia
release of K+,
PGs, Kinins,
nuclotides [pain
factors].
Basic mechanism is an imbalance between
O2 demand & O2 supply.
Coronary
arteriosclerosis.
Transient platelet
aggregation &
coronary thrombosis.
Coronary artery
spasm.
Coronary flow is controlled mainly by :1-Transmural pressure during systole .
Diastolic coronary perfusion pressure
=Diastolic aortic pressure - Diastolic
ventricular pressure.
2-Vasodilator
metabolites,↓pO2
→ adenosine, K+
Coronary
ischaemia is
usually the result
of
atherosclerosis,
and causes
anginal pain.
Sudden
ischaemia is
usually caused
by thrombosis
and may result in
cardiac
infarction .
Cellular Ca++ overload results from
ischaemia and may be responsible
for:1-cell death
2-initiation of dysrhythmias .
Effects of myocardial ischaemia .This leads to cell death by one of
two pathways: necrosis or apoptosis (TNFα, tumour necrosis factor
α; ICE, interleukin-1-converting enzyme; PARP, poly-[ADP-ribose]polymerase
1-Chronic stable
angina caused by
fixed coronary
stenosis
2-Unstable
angina:- occurs
at rest or with
physical
activity.
3-Variant angina
or Prinzmetal’s
occurs at rest &
is caused by
coronary
vasospasm.
Organic nitrates.
-adrenoceptor blockers.
Calcium channel
blockers.
Potassium channel
openners.
Partial fatty acid
oxidation(pFOX)
inhibitors.
Aspirin.
Mechanism
of action:Act by
relaxing
smooth
muscles.
Pharmacodynamic
effects:Nitrates are converted into
nitrites , this requires SH
group which could be
blocked by ethacrynic acid.
Dilate large veins  central venous
pressure CO.
Reduced stroke output is compensated for
by reflex tachycardia.
At high doses arterioles are dilated
arterial blood pressure.
Organic nitrates coronary blood flow
although the mean arterial blood pressure
is reduced  vascular resistance.
 CO + ABP  O2 demand.
1-O2 demand +Blood flow O2
supply.
2-In variant angina
organic nitrates relieve
coronary spasm.
3-Organic nitrates divert
blood from normal to
ischaemic areas of the
myocardium dilatation
of large collateral
arterioles enabling
partially blocked
venules to be bypassed.
Relaxation of smooth muscle of the
bronchi, gastrointestinal tract , biliary
system
Genitourinary tract
Decrease in platelet aggregation
Administration:Glycerytrinitrate ,
formulated as:1-sublingual
tablets,
2-preparation for
transdermal
absorption,
3- 2% in lanolin for
prophylaxis , 4-8h,
occluded into
dressing on the
chest , well
absorbed through
the skin more
sustained effect,
4-Oral sustainedrelease
preparations.
5-Buccal sustainedrelease.
6-IV preparations.
The sublingual tablet of nitroglycerin may
lose potency when stored as a result of
volatilization and adsorption to plastic
surfaces.
GTN metabolized by the liver by removal
of nitrate groups in stepwise fashion from
the parent molecule little dilator effect,
(duration of effect 15-30min)
If swallowed the drug is ineffective
because of first –pass inactivation(10-20%
bioavailability)
Amyl nitrite is available in
fragile glass ampoules
packaged in a protective cloth
covering.
The ampoule is crushed and
the drug is inhaled through the
cloth covering.
Due to unpleasant odour and
short duration of action ,now
little used.
Long- acting organic nitrates isosorbide
dinitrate .
Isosorbide dinitrate is rapidly metabolized
in the liver to mononitrate which is
biologically active t½=4h.
Isosorbide mononitrate is available for
clinical use and has 100% bioavailability.
Isosorbide dinitrate
is administered
orally for
prophylaxis ,
chewed for more
rapid effect
They have slow
onset of action.
ADR:-
Unpleasant
sensation of
flushing &
headache.
Orthostatic
hypotension
Tachycardia
Carcinogenesis???
Formation of
methaemoglobin.
Tolerant is more when long-acting preparations
(oral, transdermal) or continuous intravenous
infusions are used for more than a few hours
without interruption.
May be partly due to diminished release of nitric
oxide or systemic compensation (initial
sympathetic discharge and salt and water
retention after one or two days).
Known sensitivity to organic nitrates.
Glaucoma???
head trauma or cerebral haemorrhage
Increase→ intracranial pressure .
Uncorrected hypovolemia
Concomitant administration of
phosphodiesterase inhibitors for the
treatment of erectile dysfunction.
Antagonizes the
effect of NA from
sympathetic nerve
ending & AD from
adrenal medulla .
Prevent  in
cardiac
activity,O2
demand.
Antihypertensive effect.
Prolongation of diastolic period 
coronary blood flow.
Contraindicated in variant angina , may
allow unopposed -adrenergic coronary
vasoconstriction to occur.
- blockers should not be rapidly
withdrawn from patients a rebound in
the frequency & severity of pain.
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.
Binding of calcium
channel blockers with
the channel reduces
the frequency of
opening in response
to depolarization.
This results in a
marked relaxation in
smooth muscle and in
cardiac muscle in
reduction in
contractility.
Type
Distribution
L
Muscle, neurons
T
Heart, neurons
N
Neurons
P
Cerebellar Purkinje
neurons
Dihydropyridine series:- nifedipine ,
isradepine, amlodepine.
Phenylalkylamines:- verapamil.
Benzthiazepines:- diltiazem.
Mainly affect heart and smooth muscles
inhibiting calcium entry caused by
depolarization.
Selectivity between heart and smooth
muscle varies ,
verapamil→ heart
Nifedipine →smooth muscle
diltaizem→ intermediate
In angina calcium antagonists reduce
cardiac work and oxygen consumption.
Serious cardiac depression,including cardiac
arrest, bradycardia, atrioventricular block, and
heart failure
Immediate-acting nifedipine increased the risk of
myocardial infarction in patients with
hypertension
Patients receiving -adrenoceptor-blocking drugs
are more sensitive to the cardiodepressant
effects of calcium channel blockers
Flushing, dizziness, nausea, constipation, and
peripheral edema
Aspirin reduces the
chance of coronary
thrombosis.
Acetylates  amino
group of the terminal
serine residue of COX
enzyme.
Used for stable &
unstable angina.
ADR:-GIT
bleeding.
Gastric ulceration.
Reduced renal
function.
Occasional
bronchospasm with
high dose.
Potassium channel openers
(Nicorandil )
Relaxes vascular smooth muscles
especially veins by:1-Activation of potassium channels
→stabilize membrane potential near
resting potential.
2-Nitric oxide release.
Used as prophylactic therapy .
May cause : flushing, palpitation,
weakness, headache, mouth and peri-anal
ulcers, nausea and vomiting.
Oxidation of fatty acids
requires more oxygen per
unit of ATP generated than
oxidation of carbohydrates.
Metabolism shifts to oxidation
of fatty acid in ischaemic
myocardium.
Partial fatty acid oxidation
inhibitors (pFOX inhibitors)
shift myocardial metabolism
toward greater use of glucose
and reduce the oxygen
demand without altering
hemodynamics.
e.g. trimetazidine.
Drug treatment of angina
1- Acute attack :Short acting nitrates or nitrites.
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
nitrates.
Calcium channel blockers, βadrenoceptor blockers,
nitrates.
Unstable Angina & Acute
coronary syndrome
Anticoagulant (Heparin) & Antiplatlet
(Aspirin) play a major role in therapy.
Nitroglycerin & β –blockers should be
added,
Calcium channel blockers should be
added in refractory cases.
Balloon catheter
Coronary bypass
surgery