ANTI- ANGINAL DRUGS
Anti anginal drugs
 Angina pectoris
 Types
 Classification
 Nitrates
 Calcium channel
blockers
 b blockers
 Combination therapy

CONTENT
ANTI-ANGINAL DRUGS
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Antianginal drugs may relieve attacks of acute myocardial
ischemia by increasing myocardial oxygen supply
or by decreasing myocardial oxygen demand
Three groups of pharmacological agents have
been shown to be effective in reducing the frequency,
severity, or both of primary or secondary angina.
These agents include the nitrates, adrenoceptor antagonists,
and calcium entry blockers.
To understand the beneficial actions of these agents, it is
important
to be familiar with the major factors regulating
the balance between
myocardial oxygen supply and demand.
ANGINA PECTORIS
It is the principal symptoms of patient with
ischemic heart disease.
 Manifested by sudden, severe, pressing
substernal pain that often radiates to the left
shoulder and along the flexor surface of the left
arm.
 Usually precipitated by exercise, excitement or
a heavy meal.

TYPES OF ANGINA PECTORIS
NITRATES
Classification of nitrates:
1. Rapidly acting nitrates
* used to terminate acute attack of angina
* e.g.- Nitroglycerin and Amyl nitrate
* usually administered sublingually
2.
Long acting nitrates
* used to prevent an attack of angina
* e.g. – tetra nitrate, Iso sorbide di nitrate, Penta
erythrytol tetra nitrate
* administered orally or topically
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Organic nitrates & nitrites are
simple nitric & nitrous esters of
glycerol.
These agents cause a rapid
decrease in myocardial oxygen
demand leading to rapid
resolution of symptoms.
Nitrates are effective for all types
of angina.
Activation of guanylate cyclase
increases cGMP activating a
cGMP kinase leading to
dephosphorylation of myosin
light chains decreasing
contractile force.
ORGANIC NITRATES
1ST MECHANISM OF ACTION
Coronary artery dilatation
Decrease coronary bed resistance
(Relieved coronary vasospasm)
Increase coronary blood flow
Increase oxygen supply
2ND MECHANISM OF ACTION
Reduction on peripheral resistance
(Secondary to dilatation of aorta)
Decrease blood pressure
Decrease after load
Decrease workload
Decrease oxygen consumption
3RD MECHANISM OF ACTION
Reduced venous return
(Due to dilatation of the veins)
Decrease left ventricular volume
Decrease preload
Decrease workload
Decrease oxygen consumption
ROUTE OF ADMINISTRATION
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1. Sublingual route – rational and effective for the
treatment of acute attacks of angina pectoris. Half-life
depend only on the rate at which they are delivered to
the liver.
2. Oral route – to provide convenient and prolonged
prophylaxis against attacks of angina
3. Intravenous Route – useful in the treatment of
coronary vasospasm and acute ischemic syndrome.
4. Topical route – used to provide gradual absorption of
the drug for prolonged prophylactic purpose.
Drug
Usual single dose
Route of
administration
Duration of action
Short acting
Nitroglycerin
0.15-1.2 mg
sublingual
10 - 30 min
Isosorbide dinitrate
2.5-5 mg
sublingual
10 – 60 min
Amyl nitrite
0.18 – 3 ml
inhalation
3 – 5 min
Long acting
Nitroglycerin sustained
action
6.5 – 13 mg q 6-8 hrs
oral
6 – 8 hrs
Nitroglycerin 2%
ointment
1 – 1.5 inches q hr
topical
3 – 6 hrs
Niroglycerin slow
released
1 –2 mg per 4 hrs
Buccal mucosa
3 – 6 hrs
transdermal
8 –10 hrs
Nitroglycerin
released
slow 10 – 25 mg /24hrs (one
patch/day}
Isosorbide dinitrate
2.5 – 10 mg per 2 hrs
sublingual
1.5 – 2 hrs
Isosorbide dinitrate
10 –60 mg per 4-6 hrs
oral
4 – 6 hrs
Isosorbide dinitrate
chewable
5 – 10 mg per 2-4 hrs
oral
2 – 3 hrs
Isosorbide mononitrate
20 mg per 12 hrs
oral
6 –10 hrs
EFFECTS
1. Coronary artery dilatation
2. Reduction of peripheral arterial resistance –
decrease after load
3. Reduce venous return – decrease preload
PHARMACOKINETICS
The difference between nitrate preparations is
mainly in time of onset of action.
 Nitroglycerin suffers marked 1st pass metabolism
so administration is sublingual.
 t1/2 ~10 minutes.
 Occasionally as nitroglycerin is metabolized
anginal symptoms will return.
 Transdermal administration either as patch or
paste provides a depot of agent for a steady
availability.
 Nitro-Bid is an oral or topical preparation which
saturates the hepatic catabolic pathways allowing
a prolonged level of nitroglycerine.
 Isosorbide mono nitrate & Isosorbide di nitrate
are long acting nitrates that are relatively
resistant to hepatic catabolism ……t1/2 ~ 1 hour.
ADVERSE EFFECTS
1. Throbbing headache
2. Flushing of the face
3. Dizziness – especially at the beginning of
treatment
4. Postural Hypotension – due to pooling of
blood in the dependent portion of the body
CONTRAINDICATIONS
1. Renal ischemia
2. Acute myocardial infarction
3. Patients receiving other antihypertensive
agent
BETA- BLOCKERS
β-Blockers decrease oxygen demands of the
myocardium by lowering the heart rate and
contractility (decrease CO) particularly the
increased demand associated with exercise.
 They also reduce PVR by direct vasodilatations of
both arterial & venous vessels reducing both preand after load.
 These effects are caused by blocking β1
receptors, selective β1 antagonists (atenolol,
metoprolol ) lose their selectivity at high doses and
at least partially block β2 receptors.
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β1 antagonists reduce the frequency and
severity of anginal episodes particularly when
used in combination with nitrates.
 β1 antagonists have been shown to improve
survival in post MI patients and decrease the
risk of subsequent cardiac events &
complications.
 There are a number of contraindications for β
blockers: asthma, diabetes, bradycardia, PVD &
COPD.
 β-Blockers in combination with nitrates can be
quite effective
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HEMODYNAMIC EFFECT
1. Decrease heart rate
2. Reduced blood pressure and cardiac
contractility without appreciable decrease in
cardiac output
MECHANISM OF ACTION
Decrease heart rate & Contractility
Increase duration of diastole
Decrease workload
Increase coronary blood flow
Decrease oxy.consumption
Increase oxygen supply
CONTRAINDICATIONS
1. Congestive heart failure
2. Asthma
3. Complete heart block
CALCIUM CHANNEL BLOCKERS
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Ca+2 channel blockers
protect tissue by inhibiting the
+2
entrance of Ca into cardiac and smooth muscle cells of the
coronary and systemic arterial beds.
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All Ca+2 channel blockers produce some vasodilation (↓ PVR)
and (-) inotropes.
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Some agents also show cardiac conduction particularly
through the AV node thus serving to control cardiac rhythm.
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Some agents have more effect on cardiac muscle than
others but all serve to lower blood pressure.
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CHF patients may suffer exacerbation of their failure as
these are (-) inotropes.
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They are useful in Prinzmetal angina in conjunction with
nitrates.
AGENTS
Nifedipine:
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This Ca+2 channel blocker works mainly on the arteriolar
vasculature decreasing after load it has minimal effect of
conduction or HR.
It is metabolized in the liver and excreted in both the urine
& the feces.
It causes flushing, headache, hypotension and peripheral
edema.
It also has some slowing effect on the GI musculature
resulting in constipation.
A reflex tachycardia associated with the vasodilatation
may elicit myocardial ischemia in tenuous patients, as
such it is generally avoided in non-hypertensive coronary
artery disease.
VERAPAMIL
The agents has its main effect on cardiac
conduction decreasing HR and thereby O2
demand.
 It also has much more (-) inotropic effect than
other Ca+2 channel blockers
 It is a weak vasodilator.
 Because of its focused myocardial effects it is not
used as an antianginal unless there is a
tachyarrhythmia. It is metabolized in the liver.
 It interferes with digoxin levels causing elevated
plasma levels; caution and monitoring of drug
levels are necessary wit concomitant use.
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DILTIAZEM
This agent function similarly to Verapamil
however it is more effective against Prinzmetal
angina.
 It has less effect on HR.
 It has similar metabolism and side effects as
Verapamil.
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pharmacokinetics
Drugs
Onset of action
Peak of action
Half-life
Nifedipine
20 minutes
1 hour
3-4 hours
Verafamil
1-2 hours
5 hours
8-10 hours
Diltiazem
15 minutes
30 minutes
3-4 hours
Nicardifine
20 minutes
45 minutes
2-4 hours
Felodipine
2-5 hours
6-7 hours
11-16 hour
ADVERSE EFFECT
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Nausea and vomiting
Dizziness
Flushing of the face
Tachycardia – due to hypotension
CONTRAINDICATIONS
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Cardiogenic shock
Recent myocardial infarction
Heart failure
Atria-ventricular block
COMBINATION THERAPY
1. Nitrates and B-blockers
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The additive efficacy is primarily a result of
one drug blocking the adverse effect of the
other agent on net myocardial oxygen
consumption
B-blockers – blocks the reflex tachycardia
associated with nitrates
Nitrates – attenuate the increase in the left
ventricular end diastolic volume associated
with B-lockers by increasing venous
capacitance
CALCIUM CHANNEL BLOCKERS +BETA
BLOCKERS
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Useful in the treatment of exertional angina
that is not controlled adequately with nitrates
and B-blockers
B-blockers – attenuate reflex tachycardia
produce by nifedipine
These two drugs produce decrease blood
pressure
CALCIUM CHANNEL
BLOCKER+NITRATES
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Useful in severe vasospastic or exertional
angina (particularly in patient with exertional
angina with congestive heart failure and sick
sinus syndrome)
Nitrates reduce preload and after load
Ca channels reduces the after load
Net effect is on reduction of oxygen demand
TRIPLE DRUGS:-NITRATES+CALCIUM
CHANNEL BLOCKERS+BETA BLOCKER
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Useful in patients with exertional angina not
controlled by the administration of two types
of anti-anginal agent
Nifidipine – decrease after load
Nitrates – decrease preload
B-blockers – decrease heart rate &
myocardial contractility
Presented by:
ANJALI KOTWAL
5TH SEMESTER
B.PHARMACY
SHOOLINI UNIVERSITY