Therapeutic approach for treatment of angina

1. Dr Monica Jain,
Senior Professor,
Department of Pharmacology,
SMS Medical College , Jaipur.

2. The LAD artery is the most commonly occluded of the
coronary arteries. It provides the major blood supply to the
interventricular septum, and thus bundle branches of the
conducting system.

3. Learning objectives
• Definition
• Types
• Classification of drugs
• Nitrates
• Beta blockers
• Calcium channel blockers

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.

6. Clinical classification
• A. used to abort or terminate attack –GTN iso
sorbide dinitrate
• B.used for chronic prophylaxis all other drugs

13. NITRATES
Classification of nitrates:
1. Rapidly acting nitrates or short acting
* used to terminate acute attack of angina
* e.g.- Nitroglycerin(glyceryl trinitrate) and
isosorbide dinitrate
* usually administered sublingually
2. Long acting nitrates
*used to prevent an attack of angina
*e.g. –Erythrityl tetranitrate, isosorbide
mononitrate, Isosorbide dinitrate,
Pentaerythrytol tetranitrate
* administered orally or topically

15. Mechanism of action Organic nitrates
• are rapidly denitrated enzymatically in the smooth
muscle cell to release nitric oxide (NO) which activates
cytosolic guanylyl cyclase → increased cGMP → causes
dephosphorylation of myosin light chain kinase (MLCK)
through a cGMP dependent protein kinase
• Reduced availability of phosphorylated (active) MLCK
interferes with activation of myosin → it fails to
interact with actin to cause contraction.
• Consequently relaxation occurs. Raised intracellular
cGMP may also reduce Ca2+ entry—contributing to
relaxation.

16. Contd
• Veins have greater amount of mitochondrial
aldehyde dehydrogenase that generates NO
from GTN so prominent venodialation
• Have platelet antiaggregating effect

20. Action
• Preload reduction –dilate vein more-
peripheral pooling of blood-decrease venous
return-preload reduce
• Reduce ventricular radius –reduce tension-less
o2consumption
• Afterload reduction-some arteriloar reduction
–dec t.p.r or afterload on heart BP falls
significantly systolic more than diastolic

21. Redistribution of coronary flow
• Nitrates relax bigger conducting
angiographically visible coronary arteries than
arterioles or resistance vessel
• Ischemic zone coronaries they dialate not the
non ischemic zone blood vessel

22. Tolerance
• Attenuation of heamodynamic and
antischaemic effect of nitrates in dose and
exposure duration manner
• Not with intermittent use of sublingual
• Reason-reactive oxygen derived species
produce during denitration inhibits
mitochondrial aldehyde dehydrogenase so no
further release of NO take place

24. Reason for tolerance continue
• Activation of renin-angiotensin system or
other humoral pathways
• Increase sympathetic
• Increase volume expansion as compensatory
mechanism
• Prevention –most practical way to prevent
nitrate tolerance is provide nitrate free
intervals

25. Dependance
• Sudden withdrawal after prolong exposure
lead to spasm of coronary and peripheral
blood vessel
• Withdrawal – should be gradual

27. ROUTE OFADMINISTRATION
1. Sublingual route – rational and effective for t
h
e
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 o
f
coronary vasospasm and acute ischemic syndrome.
4. Topical route – used to provide gradual absorption
of the drug for prolonged prophylactic purpose.

28. 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
Nitroglycerin slow
released
10 – 25 mg /24hrs (one
patch/day}
transdermal 8 –10 hrs
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

29. EFFECTS
1. Coronary artery dilatation
2. Reduction of peripheral arterial resistance
– decrease after load
3. Reduce venous return – decrease preload

30. 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.

31. • 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.

33. CONTRAINDICATIONS
1. Renal ischemia
2. Acute myocardial infarction
3. Patients receiving other antihypertensive
agent

34. Nitroglycerine
• Volatile liquid adsorbed on the inert matrix of
the tablet and rendered nonexplosive
• Glass containers air tight
• I V USE FOR- unstable angina,coronary
vasospasm LVF,MI,HYPERTENSION DURING
SURGERY

39. Uses of nitrates
• Acute coronary syndrome
• M I-dec preload,after load and reduce
pulmonary congestion antiplatelet action
• CHF AND LVF
• BILIARY COLIC
• ESOPHAGEAL SPASM
• CYANIDE POISONING
• HYPERTENSIVE EMERGENCY

42. Monday blues
• Workers who are exposed to Nitroglycerin or
isosorbide dinitrate , like who work in
construction or demolition industries, mix
concrete, do plaster, etc.
During the week, Monday to Friday, they are
exposed to the vasodilating action, so they build
up a tolerance. If they are off on Saturday and
Sunday the tolerance is lost. So when they go
back to work on Monday the tachycardia,
hypotension, flusing and headache return, but a
tolerance is built up again by the next day.

43. BETA- BLOCKERS
decrease oxygen demands of myocardium by
lowering
the heart rate and contractility (decrease CO)
particularly the increased demand
associated with exercise.
reduce peripheral vascular
resistance by arterial dialation

44. Why do beta blockers still used even if
not dialating coronaries?
• Ischemic subendocardial region flow is not
Effected because of favourable redistribution
and decrease in ventricular wall tension
• Why are selective blockers better?
• Nonselective are prone to worsen variant
angina by unopposed vasoconstrictive alpha
blockers
• Imp point – should be taken on regular basis
withdrawl may cause anginal attack

46. 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

47. HEMODYNAMIC EFFECT
1. Decrease heart rate
2. Reduced blood pressure and cardiac
contractility without appreciable decrease
in cardiac output

48. MECHANISM OFACTION
Decrease heart rate & Contractility
Increase duration of diastole
Decrease workload
Increase coronary blood flow
Decrease
oxy.consumption
Increase oxygen supply

49. CONTRAINDICATIONS
1. Congestive heart failure
2. Asthma
3. Complete heart block

50. CCB
• 1962 –verapamil as coronary dialator
• 1967-fleckenstein showed it interfered with calcium
movement
• Although the blockers currently available for clinical
use in cardiovascular conditions are exclusively L-
type calcium channel blockers.

54. CCB
• They divided into three
chemical classes:
• a. Diphenylalkylamines,
Verapamil
• b. Benzothiazepines,
Diltiazem
• c. Dihydropyridines,
Nifedipine

57. • MECHANISM OF
ACTION
c
k
• Calcium enters muscle cell through special voltage sensitive
calcium channel.
• Normally, L-Type of channels admit Ca+ and causes
depolarization – excitation- contraction coupling through
phosphorylation of myosin light chain – contraction of
vascular smooth muscle – elevation of BPCCBsblockL-Type
• These agents exert their
effect by antagonists
blocking for the inward
movement of calciumby
binding to the L-typechannels
in the heart and peripheral vasculature

60. ORGAN SYSTEM
EFFECTS
• 1
.Smooth muscle:dependent on
transmembrane calcium influx for normal resting tone
and contractile responses.
• Vascular smooth muscles (most sensitive) relaxed by
the calcium channel
blockers.
• reduction in peripheral vascular resistance.
• Reduction of coronary artery spasm.

61. 3.SKELETAL
MUSCLE
• Skeletal muscle is not depressed by the calcium channel
blockers because it uses intracellular pools of calcium to
support excitation-contraction coupling and does not
require as much transmembrane calcium influx.

62. CLINICAL
EFFECTS
• decrease myocardial contractile force.
• reduces myocardial oxygen requirements.
• Decrease peripheral resistance .
• Decreased heart rate with the use of
verapamil or diltiazem causes a further
decrease in myocardial oxygen demand.

64. NIFEDIPINE DILTIAZEM VERAPAMIL
coronary
arteries
dilation
++ ++ ++
peripheral
arteries dilation
++++ ++ +++
negative
inotropic
+ ++ +++
slowing AV
cond
 +++ ++++
heart rate      
↓ blood
pressure
++++ ++ +++
depression of
SA
 ++ ++
increas
e in
cardiac
output
  

65. INDICATIONS
• Angina.
• Hypertension.
• Raynaud's phenomenon. (Nifedipine is the mainstay of
medical treatment).
• Supraventricular tachycardias, including atrial fibrillation.
• Ischaemic neurological deficit after subarachnoid
haemorrhage.
• Delay of preterm labour(prevent premature labour has
been with nifedipine)
• Prophylaxis for cluster headache.

66. USES
• Verapamil and Diltiazem are used in arrhythmias
• because they have negative inotropic and chronotropic effects,
• however are used in patients who have
palpitations/arrhythmias and suffer from HTN since they can
reduce heart rate and blood pressure simultaneously.
• Dihydropyridines: depend on JNC-8, found in first line
theraby espically in black population have a high efficacy of
40 mmHg, regarding that the highest reduction in blood
pressure an orally taken anti-hypertensive drug can cause is 40
mmHg.

68. 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.

69. Nifedipine
• Increase voiding difficulty in elderly ?
• Gasrooesophagal reflux worsen?

70. Felodipine
• Greater vascular selectivity
• Larger tissue distribution
• Longer t1/2
• Dose-5-10mg once a day
• Approved for symptomatic treatment of
Reynaud disease
• Extended release preparation is suitable for
O.D

71. Amlodipine
• Most popular
• No palpitation or flushing headache
• Higher oral bioavailability
• Diurnal fluctuation less t1/2 long
• Dose 5-10 mg Od
• S amlodipine – EFFECTIVE AT HALF DOSES
• LESS ANKLE EDEMA
•

72. Nimodipine
• Short acting
• Highly lipid soluble
• Penetrates BBB
• RELAX cerebral vasculature and used for
prevention and treatment of neurological
deficit due to cerebral vasospasm
• 30-60mg 4-6 hrly

73. NITRENDIPINE
• 10-30%biovailabilty
• Additional mechanism
release NO
Inhibit cAMPphosphodiesterase
Retard atherosclerosis
Ventricular contractility and conduction not
affected
Used in HT and angina

74. Lacidipine 4mg od
• Antihypertensive , highly vasoselective
• Attains higher concentration in membrane of
smooth muscle
Lercanidipine
Longer duration of action t1/2 =5-10 hrs
Benidipine
Only in japan and India
Slow dissociation from DHP receptor

77. Benidipine
• Benidipine is a triple calcium channel inhibitor
by inhibiting L, N and T type calcium channel.
• It very long-lasting activity that can be
explained by its high affinity for cell
membranes
• The additional property of benidipine is the
vascular selectivity towards peripheral blood
vessels.

78. Azelnidipine
• Azelnidipine is a dihydropyridine calcium
channel blocker.
• Unlike nicardipine, it has a gradual onset and
has a long-lasting hypotensive effect, with
minimal increase in heart rate .
• strong anti-arteriosclerotic action in vessels
due to its high affinity for vascular tissue and
antioxidative activity

79. Efonidipine
• Efonidipine exhibits antihypertensive effect
through vasodilatation by blocking L-type and
T-type calcium channels.
• Efonidipine increases coronary blood flow by
blocking L & T-type calcium channels and
attenuates myocardial ischaemia.
• By reducing synthesis and secretion of
aldosterone, Efonidipine prevents hypertrophy
and remodeling of cardiac myocytes.

80. • increases glomerular filtration rate without increasing
intra-glomerular pressure and filtration fraction. This
prevents hypertension induced renal damage.
• Efonidipine suppresses renin secretion from the juxta
glomerular apparatus in the kidneys.
• Efonidipine enhances sodium excretion from the kidneys
by suppressing aldosterone synthesis and secretion from
the adrenal glands. Aldosterone induced renal
parenchymal fibrosis is suppressed
protects against endothelial dysfunction due to its anti-
oxidant activity and by restoring NO bioavailability.
• anti-atherogenic activity and protects the blood vessels
from atherosclerosis.
• lowers blood pressure in cerebral resistance vessels and
prevents hypertension induced brain damage.

81. 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.

82. 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.

83. 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
pharmacokinetics

84. ADVERSE EFFECT
Nausea and vomiting
Dizziness
Flushing of the face
Tachycardia – due to hypotension

85. CONTRAINDICATIONS
Cardiogenic shock
Recent myocardial infarction
Heart failure
Atria-ventricular block

86. 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

87. 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

88. 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

89. TRIPLE DRUGS:-NITRATES+CALCIUM
CHANNEL BLOCKERS+BETABLOCKER
Useful in patients with excertional 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

90. Types of potassium channel
• Voltage dependant
• ATP activated- nicorandil
• Calcium activated
• Receptor operated
• Na activated
• Cell volume sensitive

94. Nicorandil 5-10 mg bd contd
• Arterial and venodialation
• Coronary flow increase
• Protect heart by ischemic preconditioning due
to activation of mitochondrial Katp channel
• Biphasic elimination t1/2 rapid is 1 hr
• Slow is 12 hrs
• Nitrate like tolerance does not occur
• Interact with sildenafil

98. Trimetazidine
• Act by nonhemodynamic mechanism
• Anginal Frequency is reduced ,exercise
capacity increased
• Increases cellular tolerance to ischemia
• Inhibit LC3KETOACYL THIOLASE (LC3-KAT) a
key enzyme in fatty acid oxidation
• Promotes glucose oxidation in myocardium

99. • Limits intracellular acidosis and Na and Ca
accumulation
• Protecting against oxygen free radical induce
membrane damage
• Has been tried in visual
disturbances,tinnitus,meiners disease
• Used as add on therapy in angina and post MI
patient

101. Ranolazine
• Act by inhibiting late Na current in
myocardium which facilitates calcium entry
thru Na/Ca exchanger
• Decrease calcium overload during ischemia
decreases contractility and has
cardioprotective effect
• Also LA ketoacyl THIOLASE INHIBITOR
• No effect on HR and CO but prolong exercise
tolerance in angina

102. Side effects
• Dizziness,weakness,constipation,postural
hypotension, headache and dyspepsia
• It can be given to patient taking sildenafil

104. Ivabradine – dose 5mg B.D
• Found to improve exercise tolerance in stable
angina and reduce angina frequency
• ADR- excessive bradycardia,visual
disturbances,headache ,dizziness and nausea
• Indicated in chronic stable angina in patient with
sinus rhythm and intolerant to beta beta blockers
• Other indication is grade II TO 1V heart failure
due to systolic dysfunction in patient with sinus
rhythm >70/min

105. IVABRADINE
• HEART LOWERING drug
• Blockade of sino-atrial f channel which are funny
cation channel that opens during early part of slow
diastolic phase (phase4)
• Funny channel are expressed in SA and on retinal cell .
The inward current resulting from opening of f channel
determines the slope of phase 4 depolarization
• blocking of this reduces heart rate and o2
consumption reduce and prolongation of diastole
resulting in improve myocardial perfusion
• 5mg BD
• ADR- VISUAL DISTRUBANCES

106. Ivabradine
• No negative inotopic or lusitropic effect
• Increase coronary collateral perfusion and
coronary flow reserve
• It does not unmask alpha adrenergic
vasoconstriction and maintain coronary
dilation during excercise

107. Prescription of patient suffering from
angina
• Praveen 75 yrs male
CAD +TMT BP 150/80mmHg
Rx
Tab METOPROLOL 25mg OD 7AM
TAB ISOSORBIDE MONONITRATE 20mg
TAB ASPIRIN PLUS CLOPIDOGREL
TAB TRIMETAZIDINE M R BD
TAB NICORANDRIL 10 MG OD
TAB RANOLAZINE 500MG BD
TAB ATORVASTATIN 10MG
Advice no alcohol,smoking,less fatty food and low salt , relaxing technique
monica jain

109. Important points
• Monday hues?
• Parkinsonism ?
• Aphthous ulcers?
• Tired for visual disturbances?
• Causes visual disturbance?
• Does not affect HR AND CO only decreases
freq of attacks ?

110. ANGINA
ASSESMENT

111. Define angina pectoris:
Chest pain resulting from a myocardial oxygen
demand that is not met by adequate oxygen
supply; seen in patient with myocardial
ischemia

112. What type of angina is caused by
spontaneous coronary vasospasm?
Prinzmetal (variant) angina

113. What type of angina is caused by
atherosclerosis of coronary vessels
and is precipitated by exertion?
Classic angina

114. What type of angina can be acute in
onset and is caused by platelet
aggregation?
Unstable angina

115. What two mechanistic strategies are
used in the treatment of angina?
Increase oxygen supply to the myocardium
Decrease myocardial oxygen demand

116. What types of drugs can increase oxygen
supply?
Nitrates; calcium channel blockers (CCBs)

117. What types of drugs can decrease
oxygen demand?
Nitrates; CCBs; β-blockers

118. What is the drug of choice for immediate
relief of anginal symptoms?
Sublingual nitroglycerin (NT G)

119. What is the mechanism of action of
nitrates?
Nitrates form nitrites; nitrites form nitric oxide
(NO); NO activates guanylyl cyclase to increase
cGMP; increased cGMP leads to increased
relaxation of vascular smooth muscle

120. How does cGMP lead to relaxation of
vascular smooth muscle?
Causes dephosphorylation of myosin light chains

121. How do nitrates increase oxygen
supply?
Dilation of coronary vessels which leads to
increased blood supply

122. How do nitrates decrease oxygen
demand?
Dilation of large veins which leads to preload
reduction; decreased preload reduces the
amount of work done by the heart; decreased
amount of work results in decreased
myocardial oxygen requirement

123. What are the adverse effects of
nitrates?
Headache; hypotension; reflex tachycardia;
facial flushing; metnemoglobinemia

124. Why must patients have at least a 10- to 12-
hour “nitrate -free” interval every day?
Tolerance (tachyphylaxis) develops to nitrates if
given on a continuous (around-the-clock) basis

125. Nitrates are contraindicated in patients
taking any of what three medications?
Sildenafil
Vardenafil
Tadalafil

126. Methemoglobin formation, specifically by amyl
nitrite, can be used to treat what type of poisoning?
Cyanide

127. What are the common formulations
of nitrates?
NTG; isosorbide mononitrate; isosorbide
dinitrate

128. What is the time to peak effect of
sublingual NTG?
2 minutes

129. What is the dosing frequency of sublingual NTG
during an anginal episode?
Every 5 minutes for a maximum of three doses

130. How do β-blockers work in the treatment of
angina?
Inhibition of α1-adrenoceptors which leads to
decreased CO, HR, and force of contraction,
thereby reducing the workload of the heart
and oxygen demand

131. Do α-blockers increase oxygen
supply?
No

132. New mechanistic approaches
to chronic stable angina
Sinus node inhibition (ivabradine)
Late INa inhibition (ranolazine)
Rho kinase inhibition (fasudil) Metabolic modulation (trimetazidine)
Preconditioning (nicorandil)
O
H3C O
H3C O
N
CH3
O CH3
O CH3
N
O
N
CH3
H
CH3
CH3
O
O H
N
SO2 NH
N
O
O NO2
H
N
O
OH
CH3
CH3
OCH3
H
N N N O
N
N

133. For each of the following CCBs, state
whether their primary effects are on
the myocardium or peripheral
vasculature
Verapamil
Myocardium (greater negative inotropic effects)

134. Dihydropyridines (DHP; nifedipine, amlodipine,
felodipine, isradipine, nicardipine)
Peripheral vasculature (more potent
vasodilators)
Diltiazem
Myocardium

135. For each of the following CCBs, state
whether their primary effects are on
the myocardium or peripheral
vasculature
Verapamil
Myocardium (greater negative inotropic effects)

136. Dihydropyridines (DHP; nifedipine, amlodipine,
felodipine, isradipine, nicardipine)
Peripheral vasculature (more potent
vasodilators)
Diltiazem
Myocardium

137. How do CCBs work in the treatment
of angina?
Block vascular L-type calcium channels which
leads to decreased heart contractility and
increased vasodilation

138. Coronary steal phenomenon is seen
with
Dipyridamole

139. The nitrate which does not undergo
first pass metabolism is
Isosorbide mononitrate

140. You decide not to prescribe sildenafil in a patient
because the patient because the patient told
you that he is taking an antianginal drug.
Organic nitrates

141. The antianginal effects of propanolol may be
attribulated to which of the following?
Block of exercise induced tachycardia

142. Which of the following drugs has been used in
the treatment on angina by inhalation and has a
very rapid onset and brief duration of action?
Amyl nitrite

143. Which of the following is an active
metabolite of another drug and is
available as a separate drug for the
treatment of angina?
Isosorbide mononitrate