3. ANTI-ANGINAL DRUGS
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
4. 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.
10. 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
11.
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
14. 2ND MECHANISM OF ACTION
Reduction on peripheral resistance
(Secondary to dilatation of aorta)
Decrease blood pressure
Decrease after load
Decrease workload
Decrease oxygen consumption
15. 3RD MECHANISM OF ACTION
Reduced venous return
(Due to dilatation of the veins)
Decrease left ventricular volume
Decrease preload
Decrease workload
Decrease oxygen consumption
16.
17. ROUTE OF ADMINISTRATION
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.
18. 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
20. 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.
21. 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
23. 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
pre- and 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.
24. 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
25. HEMODYNAMIC EFFECT
1. Decrease heart rate
2. Reduced blood pressure and cardiac
contractility without appreciable decrease
in cardiac output
28. CALCIUM CHANNEL BLOCKERS
Ca+2 channel blockers protect tissue by inhibiting the
entrance of Ca+2 into cardiac and smooth muscle cells of
the coronary and systemic arterial beds.
All Ca+2 channel blockers produce some vasodilation (↓
PVR) and (-) inotropes.
Some agents also show cardiac conduction particularly
through the AV node thus serving to control cardiac
rhythm.
Some agents have more effect on cardiac muscle than
others but all serve to lower blood pressure.
CHF patients may suffer exacerbation of their failure as
these are (-) inotropes.
They are useful in Prinzmetal angina in conjunction with
nitrates.
29. AGENTS
Nifedipine:
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.
30. 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.
31. 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.
35. COMBINATION THERAPY
1. Nitrates and B-blockers
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
36. CALCIUM CHANNEL BLOCKERS +BETA
BLOCKERS
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
37. CALCIUM CHANNEL
BLOCKER+NITRATES
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
38. TRIPLE DRUGS:-NITRATES+CALCIUM
CHANNEL BLOCKERS+BETA BLOCKER
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
