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PHARMACOLOGICAL TREATMENT OF ISCHAEMIC HEART DISEASE
1. Definition of myocardial ischaemia
"The blood supply to the myocardium is inadequate" (Opie)
"The absence of arterial blood flow" (Jennings)
"Supply-demand imbalance" (Schelbert)
"Ischo" = "to hold back" "haima" = "blood"
The fundmental concept:
Imbalance between blood supply and blood demand of the myocardium (the oxygen
supply is not able to keep up with the oxygen demand of the myocardium)
"Reversible" phase - when it is sufficiently severe to cause characteristic metabolic,
mechanical, electrocardiographic changes that are diminished
when the ischaemia ceases
"Irreversible" phase - as ischaemia progresses
 infarction (= stuffed in)
 cell death (= necrosis; "necro" = death)
Reperfusion (eg. thrombolysis) as early as possible - benefit for cells that are
reversibly damaged
Clinical manifestations
I. Conventional ischaemic syndromes
- Angina pectoris
- effort angina (classical)
- angina at rest (vasospastic)
- unstable angina
- An myocardial infarction
- Ischaemic cardiomyopathy
II. New ischaemic syndromes
- Silent ischaemia (1974)
- Myocardial stunning (1975)
(acute, chronic, maimed)
- Hibernating myocardium (1984)
- Ischaemic peconditioning (1986)
CAD
(stenosis, spasm)
Blood supply 
(oxygen supply)
Impaired perfusion
Exercise, emotional stress,
exertion, increased sympathetic tone
Blood demand 
(oxygen demand)
CHEST PAIN
Metabolic changes
aerobic  anaerobic
(lactate , inorganic P , H+, adenosine,
ATP , CP , “osmotic load”)
Impaired contractility
“Litle blood, little work”
Electrophysiological changes
K+
 ST-deviations, peaked T Arrhythmias
PATHOPHYSIOLOGY OF ISCHAEMIC HEART DISEASE
I. Conventional ischaemic syndromes
1.) Angina of effort (classic angina)
•Coronary stenosis is the sine qua non of classical angina pectoris
• Usually fixed coronary stenosis due to atherosclerosis (atherosclerotic plaques in
the arterial trunks - morphologically, excentric or concentric).
•Myocardium distal from a fix occlusion is potentially ischaemic (fall in CPP).
Factors increase O2 demand (exercise, emotional stress, etc.), result coronary
insufficiency (the fixed stenosis prevents coronary dilatation) and manifest
clinically as myocardial ischaemia or anginal attack.
2.) Variant angina (angina at rest or vasospastic angina)
• Vasospasm of coronary arteries (conductance vessels) may be responsible, which
reduce CBF. Blood supply is inadequate even in resting heart.
• Morphologic picture - normal or stenosed
• Cyclic recurrent chest pain (ST-elevation), prolonged anginal attacks occur at the
same time each day (eg. morning - "warm up" phenomenon), may culminate in
myocardial infarction and sudden cardiac death.
3.) Unstable angina
• Vasospasm superimposed upon more or less pronounced coronary stenosis.
• Functional link between fixed stenosis (usually excentric) which restrict any
increase in flow and the pure spasm (dynamic stenosis).
• Mixed pathophysiological picture with changing intensity of the attacks (ST-
4. Acute myocardial infarction
Sudden and complete occlusion of a coronary artery. "No flow ischaemia".
5. Ischaemic cardiomyopathy
II. New ischaemic syndromes
1. Silent ischaemia (1974; Stern and Tzivoni)
• Episodes of silent ischaemia can cause temporary heart failure (reduced perfusion 
LV dysfunction).
• The mechanism of silent ischaemia is poorly understood. Possible explanations may
include an increased threshold for pain, and increased release of pain modifiers such
as beta-endorphins.
2. Myocardial stunning
1975 Heyndrickx and colleagues (experimental), 1982 Braunwald and Kloner (clinical
A stunned myocardium is defined as viable myocardium salvaged by coronary
reperfusion that exhibit prolonged postischaemic dysfunction after reperfusion.
• Stunning can be characterised by delayed mechanical recovery despite full
reperfusion after ischaemia „perfusion-contraction mismatch”
• Acute stunning: mechanical function recovers minutes and hours
• Chronic stunning: recovery is measured in weeks or months.
• Maimed myocardium: incomplete recovery
• Myocardial stunning may occur: in MI patients follwing thrombolysis or angioplasty
unstable angina patients, exercise-induced angina, coronary artery spasm, platelet
aggregation or transient thrombosis of a coronary artery, angioplasty for chronic
myocardial ischaemia, and immediately following coronary bypass surgery.
• The concept is that ischaemia does something that impairs mechanical function or
activity even after the actual ischaemic event is over.
3. Hibernating myocardium (1984 Rahimtoola)
• Clinical observation: to describe a state of persistently impaired myocardial and left
ventricular function at rest due to reduced coronary blood flow that can be partially
or completely restored to normal if the myocardial oxygen supply-demand
relationship is favourably altered either by improving blood flow and\or by
reducing demand.
•Hibernating myocardium is defined as ischaemic myocardium supplied by a
narrowed coronary artery in which ischaemic cells remain viable but contraction is
chronically depressed.
•The current sine qua non concept for hibernating myocardium would be threefold:
(1) impaired contractile activity
(2) the presence of severe coronary artery disease
(3) recovery of myocardial function after revascularisation
•Hibernating myocardium is found in patients with severe coronary artery stenosis,
even in asymptomatic patients at rest.
4. Mixed postinfarct ischaemic syndrome
•This includes LV dysfunction and LV remodelling, postischaemic diastolic and
systolic failure
5. Ischaemic preconditioning (1986; Murry, Jennnings, Reimer)
• "Multiple brief ischaemic episodes might actually protect the myocardium during a
subsequent sustained ischaemic insult, so that, in effect, we could exploit
ischaemia to protect the heart from ischaemic injury"
Major determinants of myocardial oxygen supply and demand
1.) Factors influencing myocardial oxygen demand
• Heart rate
• Wall tension - preload and afterload
• Myocardial contractility
• Heart size
2.) Factors influencing myocardial oxygen supply
• Hematologic factors - haemoglobin, free oxygen (pO2)
• Myocardial extraction of oxygen from blood
• Coronary blood flow (CBF)
• coronary vascular resistance
• autoregulation
• compression of the deep arteries during
diastole
• fixed resistance (eg. atherosclerotic
plaque)
• coronary perfusion pressure (CPP)
• distribution of the blood (endo/epi)
OBJECTIVE OF THE THERAPY
1.) Reduction of the frequency and severity of attacks of chest pain
2.) Remove of any underlying cause if possible
3.) Promotion of growth of collateral vessels
4.) Prevention of sudden cardiac death
There are two ways to achieve these:
1. To improve coronary blood flow (?)
2. To reduce myocardial oxygen requirements
- decrease preload
- decrease afterload
- decrease contractility
- decrease heart rate
- decrease sympathetic tone
CLASSIC ANGINA
NITRATES
VASOSPASTIC ANGINA UNSTABLE ANGINA
Ca++ ANTAGONISTS
 BLOCKERS
Drugs used in the treatment of angina pectoris
-Blockers
propranolol
Reduced
afterload
Systemic
circulation
CalciumCa2+
antagonists
Ca2+
Ca2+ calmodulin complex
nifedipine
diltiazem
verapamil
Ca2+ -channels
Heart rate
Contractility
Calmodulin
Dilate
Oxygen
demand
Dilate
Arterial
resistance vessels
Tissue thiols
gliceril-trinitrát
izosorbide-dinitrate
izosorbide-5mononitrate
Dilate
Ischaemic
area
MLCKa
MLCK
RELAXATION
+
MLC- P
MLC
Actin
Nitrates
REDUCED
PRELOAD
Stored
Ca2+
Miosin
light chain
(MLC)
Dilate
Dilate
+
Venous
capacitance vessels
cGMP
GTP
Contraction
Guanilatecyclase
+
RSNO
RSH
Reduced venous
return
NO-3
RSH
NO
NO-2
BASIC PHARMACOLOGY OF VASODILATORS
A: ORGANIC NITRITES AND NITRATES
1.) Chemistry
Nitric and nitrous acid esters of polyalcohols
(nitroglycerin = griceryl trinitrate)
CH2 - O - NO2
CH - O - NO2
CH2 - O - NO2
All therapeutically active agents are capable of release nitric oxide (NO) in vascular
smooth muscle cells.
2.) Pharmacological actions
2.1. Mechanism of action
R - O - NO2
ENZYMATIC
NON - ENZYMATIC
R - O - NO2
NO’
NO2
R - OH
+
NO2
guanylate cyclase
cGMP
GTP
NO3
NO3
PROTEIN P KINASE
PROTEIN KINASE
PMLC
SMOOTH MUSCLE CELL
CONTRACTION
Ca++
MLC
RELAXATION
2.2. Organ system effects
Nitroglycerin relaxes all types of smooth muscle resulting in general vasodilatation
a.) Effects on coronary blood vessels
• Dilates large coronary vessels (conductance vessels) but the total coronary
blood flow is unchanged
• Improves collateral circulation to the ischaemic area
• Favoured perfusion to the subendocardium (explained by simple
haemodynamic changes)
b.) Effects on myocardial oxygen demand
(1) Effects which reduce O2 demand
• decreased preload (due to increased venous capacitance)
• decreased afterload (due to reduced peripheral resistance)
• decreased wall tension (decreased heart size and LVEDP/V)
(2) Effects which increase O2 demand
• increased heart rate (due to fall in blood pressure)
• increased contractility (due to compensation)
c.) Direct effect on the myocardium
• niric oxide by stimulating guanylate cyclase increases cGMP
• cGMP modulates L-type Ca2+ channels  reduced Ca2+ influx
• cGMP activates cGMP-dependent cAMP-phosphodiesterase, and
results in a reduced Ca2+ influx
Both effects reduce myocardial contractility and O2 consumption
NITROGLYCERIN
1. VENOUS DILATIION
(pooling)
extracardial
factors
PRELOAD
{LVEDP, LVEDP, PCWP}
WALL TENSION 
intracardial
factors
O2 demand 
endocardial perfusion 
2. ARTERIAL DILATATION
afterload   CO
3. DILATATION OF LARGE
CORONARY ARTERIES
02 supply 
4. COLLATERAL CIRCULATION 
3. Toxicity and tachyphylaxis
Extension of therapeutic vasodilatation
• orthostatic hypotension
• tachycardia
• throbbing headache
Tolerance develops with continuous exposure (eg. chemical industry, explosives,
Monday disease - headache, dizziness)
Dependence: withdrawal symptoms - exacerbated myocardial ischaemia
4. Mechanism of clinical effect
Potential beneficial effects
Decreased ventricular volume
Decreased arterial pressure
Decreased ejection time
Vasodilation of epicardial
coronary arteries
Increased collateral flow
Decreased LVEDP
RESULTS
Decreased myocardial
oxygen requirements
Relief of coronary
artery spasm
Improved perfusion to
the ischaemic area
Increased endocardial
perfusion
Potential deleterious effects
Reflex tachycardia
Increased myocardial
Reflex increase in contractility
oxygen requirements
Decreased diastolic perfusion time
Decreased myocardial
due to tachycardia
perfusion
a.) Nitrate effects in angina of effort
Reduced venous return  reduces intracardiac volume  reduces wall tension 
reduces O2 demand
Decreased O2 demand during exercise is the primary effect (increased
exercise tolerance)
b.) Nitrate effects in angina at rest
Vasodilatation of large epicardial coronary arteries  relief of spasm
c.) Nitrate effects in unstable angina
Reduction of O2 demand + dilation of epicardial coronary arteries
Relieve anginal attack and decrease the incidence of ischaemic episodes
5. Route of administration
(1) To achieve an acute effect (to relief anginal pain)
For this purpose: Sublingual or buccal tablets or spray - (rapid absorption)
NITROGLYCERIN (Tabl. 0.5 mg) onset: 10-20 sec, duration 20 min
ISOSORBIDE DINITRATE (ISORDIL) (Tabl. 2.5, 5 and 10 mg)
AMYL NITRITE for inhalation, onset: 10 sec, duration 5-10 min
Side effects: warmth, flushing, throbbing headache, dizziness, syncope, postural
hypotension
(2) For long term treatment (to prevent anginal attacks)
For this purpose: oral tablets, transdermal patches, oinments
- high degree of "first pass" hepatic biotransformation
NITROGLYCERIN (NITRONG, SUSTAC) (Tabl: 0.5 mg),
onset: 15 min, duration: several hours
PENTAERYTHRYL TETRANITRATE, ERYTRYL TETRANITRATE,
ISOSORBID MONONITRATE (ISMN), ISOSORBID DINITRATE (ISDN)
NITRO-BID (NTG) for iv. infusion
Topical administration - longer duration (6-24 h)
NITRO-BID (2 % ointment)
Transdermal patches: DEPONIT (NTG 5 mg/24h),
NITRODUR (NTG 2.5 and 5 mg/24h)
NITRODISC (NTG 5 mg/24h)
MOLSIDOMINE
New vasodilator with novel structure for oral administration. Improves exercise
tolerance. No tachycardiac effect (less pronounced reduction in afterload)
6. Therapeutic uses
Acute and chronic angina pectoris (stenotic, vasospastic), acute myocardial
infarction, postinfarction angina, acute left ventricular failure (adjuvant therapy)
B: CALCIUM ANTAGONISTS (CALCIUM CHANNEL BLOCKERS, SLOW
CHANNEL BLOCKERS)
1.) Chemistry
Different structures with similar actions
a.) Monophenylalkilamines:
VERAPAMIL, BENCYCLAN,
PERHEXILIN
b.) Diphenylalkilamines:
FENDILINE, PRENYLAMINE,
BEPRIDIL
c.) Dihydropyridines:
NIFEDIPINE, NISOLDIPINE,
AMLODIPINE, FELODIPINE,
NICARDIPINE, NITRENDIPINE
d.) Benzothiazepine:
DILTIAZEM
e.) Diphenylpiperazines:
FLUNARIZINE, CINARIZINE,
LIDOFLAZIME
2.) Pharmacological actions
All inhibit or block the influx of calcium through the voltage activated calcium
channels.
Voltage dependent calcium channels: • L-type (cardiac and vascular)
• N-type (mostly neuronal)
• T-type (neuronal and gland)
Receptorial binding sites for nifedipine, diltiazem and verapamil are different.
Voltage operated calcium channels open at -45 to -25 mV membrane potential 
inward calcium current (trigger calcium)  promotes release of calcium from the
sarcoplasmic reticulum (SR). (Na channels open at -90 to -50 mV, the Na+ inward
current releases Ca2+ from the mithocondrium).
Ca - ANTAGONIST
RECEPTOR OPERATED
VOLTAGE OPERATED

Ca-pump
+
Ca2
+
Ca2
Ca2
+
+
CALMODULIN
ATP-ase
Ca2+ - CALMODULIN COMPLEX
cAMP
+
MLCK(a)
MLCK(a)
MLCK(PO4)2 (i)
+
MYOSIN
MYOSIN PO4
+
+
CONTRACTION
ACTIN
ACTIN
}
MLCK = MYOSIN LIGHT CHAIN KINASE
cAMP regulates:
Na+-K+-ATP-ase
Ca2+ channel phosphorylation (PKC) Ca2+ influx
SR Ca-ATPase  Ca2+ sequestration into the SR
Inactivation of MLCK
Calcium-calmodulin complex formation
3. Organ-system effects
a.) SMOOTH MUSCLE - their contraction-relaxation is dependent upon Ca2+ influx.
Calcium antagonists cause relaxation. Arterioles > veins  reduction in
peripheral vascular resistance. Arterial blood pressure reduces
b.) CARDIAC MUSCLE - is highly dependent upon Ca2+ influx for normal function.
• Impulse generation in SA node and impulse conduction through the AV node is
based on slow inward current. Ca-blockers  bradycardia and negative
domotropic effect
• Contractility of the myocardium is also depending on Ca2+ influx. Ca-blockers
result in negative inotropic effect  reduction in myocardial O2 demand (ATP
preservation increases)  reduction in ischaemic damage (infarct size)
c.) SKELETAL MUSCLE - is not depressed by calcium antagonists (contraction not
requires Ca influx, utilizes intracellular pools of calcium)
COMPARISON OF CARDIOVASCULAR EFFECTS OF CALCIUM
ANTAGONISTS
1. Reduction in coronary vascular resistance
NIFEDIPINE >> DILTIAZEM > VERAPAMIL
2. Reduction in peripheral vascular resistance
NIFEDIPINE >> VERAPAMIL > DILTIAZEM
3. Negative inotropic effect
VERAPAMIL > DILTIAZEM >>>>> NIFEDIPINE
4. Depression of sinus node pacemaker
DILTIAZEM > VERAPAMIL (NIFEDIPINE, reflex tachycardia)
5. Slowing of AV conduction
VERAPAMIL > DILTIAZEM (NIFEDIPINE has no effect)
4. Side and toxic effects of calcium antagonists
Direct extension of their therapeutic action
Bradycardia, AV-block (especially verapamil), cardiac arrest, heart failure.
Palpitation, reflex tachycardia, headache (especially after nifedipine) Flushing,
edema, dizziness, nausea, constipation.
5. Mechanism of clinical effects
Negative inotropic effect  O2 requirements   ANTIANGINAL EFFECT
Vascular relaxation
CORONARY ARTERIES • improved collateral flow  infarct size 
• relief and prevention of coronary spasm
Both result in ANTIANGINAL EFFECT
PERIPHERAL ARTERIES • reduced vascular resistance (afterload and
preload)
ANTIANGINAL AND ANTIHYPERTENSIVE EFFECT
Negative chronotropic (bradycardiac) effect
Slowing HR  O2 consumption  improved myocardial perfusion during diastole)
ANTIANGINAL AND ANTIARRHYTHMIC EFFECT
Negative dromotropic effect
Slowing conduction through the AV node  ANTIARRHYTHMIC EFFECT
6. Clinical use of calcium antagonists
(1) ANGINA PECTORIS (chronic stable angina, variant angina, unstable angina)
VERAPAMIL, DILTIAZEM, NIFEDIPINE etc.
Combinations with other antianginal drugs
VERAPAMIL +  BLOCKER (AV block and strong negative inotropy)
NIFEDIPINE +  BLOCKER (in HF patients, BUT in low pressure states
NIFEDIPINE is contraindicated
(2) HYPERTENSION - NIFEDIPINE, VERAPAMIL, DILTIAZEM
(3) ATRIAL TACHYARRHYTHMIAS - WPW SYNDROME
VERAPAMIL,
DILTIAZEM
7. Drugs
VERAPAMIL (ISOPTIN, CALAN) - antianginal, antiarrhythmic (Tabl.: 40,
80, 120 mg), ISOPTIN retard (better kinetic)
NIFEDIPINE (ADALAT, PROCARDIA, CORINFAR) - vasospastic
(Prinzmetal) and stable chronic angina, hypertension (Tabl. 10 mg)
NITRENDIPINE and FELODIPINE hypertension
NIMODIPINE profilactically after subaracnoid hemorrhage to prevent vasospasm
DILTIAZEM (CARDIZEM, DILZEM) vasospastic and chronic stable angina (Tabl.:
30, 60, 90, 120 mg)
FENDILINE (SENSIT) - calmodulin antagonist - antianginal, antihypertensive
C: BETA RECEPTOR BLOCKING DRUGS
• They are not vasodilators. Their beneficial effects are related to the reduction in
HR, blood pressure and contractility. These are all reduce myocardial oxygen
requirements.
• They result in redistribution of blood flow from the non-ischaemic to the
ischaemic myocardial areas.
• They decrease the episodes of anginal pain but not normalize ischaemic STdepression.
1. Pharmacological actions
a.) Effect on myocardial oxygen demand
(1) Reduction in O2 demand (due to ß-rceptor antagonism)
• decreased contractility
• decreased heart rate
(2) Increase in O2 demand (secondary to reduced contractility)
• increased LVEDP (preload)
• increased wall tension (due to increased heart size)
These are undesirable effects.
b.) Combination of ß-blockers with nitrates
Aimed to offset each-other's deleterious effects on myocardial oxygen requirements
Heart rate
Blood pressure
LVEDP
TPR
Myocardial contractility
LV ejection fraction
Ejection time
Diastolic perfusion time
NITRATES
reflex



reflex 
variable


ß-BLOCKERS








COMBINATION


0/
0
0

0

Individual titration: against both rest and exercise (HR monitoring with BP and cardiac
function measurements).
• HR at rest: 50-60 beats/min and during exercise: 100-120 beats/min
• ß-blockers, however can precipitate heart failure (?) and bronchoconstriction may
aggravate angina.
2. Drugs
POPRANOLOL (INDERAL, ß1, ß2)
METOPROLOL (LOPRESSOR, ß1)
NADOLOL (ß1, ß2)
ATENOLOL (TENORMIN, ß1)
PINDOLOL (ß1, ß2, partial agonist)
ACEBUTOLOL (ß1 partial agonist)
ALPRENOLOL (ß1, ß2, partial agonist)
TIMOLOL (ß1, ß2).
GENERAL MANAGEMENT OF PATIENTS WITH ANGINA PECTORIS
1. Pharmacological
2. Surgical interventions
AIM: Producing symptomatic relief and prolonging life
PROGNOSTIC DETERMINANTS: • degree of LV dysfunction
• event of coronary atherosclerosis
• severity of myocardial ischaemia
High risk of AMI  coronary arteriography  severe multiple vessel disease



bypass surgery
Absence of high risk of AMI

pharmacological treatment
Immediate relief: NITRATES (sublingual, spray)
Long term treatment:
a.) Chronic stable angina: NITRATES + ß BLOCKERS (Ca ANTAGONISTS)
b.) Unstable angina: immediate therapy - agressive NITRATE, ß-BLOCKER
and Ca ANTAGONIST
continuous manifestation  revascularisation
angioplasty
c.) Variant angina: Ca ANTAGONISTS and NITRATES
Patients with obstructive CAD ß-blockers may also be used
In the presence of severe fixed obstructive coronary artery lesions, angioplasty and
revascularisation.
Drugs used in the treatment of angina pectoris
-Blockers
propranolol
Reduced
afterload
Systemic
circulation
CalciumCa2+
antagonists
Ca2+
Ca2+ calmodulin complex
nifedipine
diltiazem
verapamil
Ca2+ -channels
Heart rate
Contractility
Calmodulin
Dilate
Oxygen
demand
Dilate
Arterial
resistance vessels
Tissue thiols
gliceril-trinitrát
izosorbide-dinitrate
izosorbide-5mononitrate
Dilate
Ischaemic
area
MLCKa
MLCK
RELAXATION
+
MLC- P
MLC
Actin
Nitrates
REDUCED
PRELOAD
Stored
Ca2+
Miosin
light chain
(MLC)
Dilate
Dilate
+
Venous
capacitance vessels
cGMP
GTP
Contraction
Guanilatecyclase
+
RSNO
RSH
Reduced venous
return
NO-3
RSH
NO
NO-2
Drugs used in the treatment of angina pectoris
-Blockers
propranolol
Reduced
afterload
Systemic
circulation
CalciumCa2+
antagonists
Ca2+
Ca2+ calmodulin complex
nifedipine
diltiazem
verapamil
Ca2+ -channels
Heart rate
Contractility
Calmodulin
Dilate
Oxygen
demand
Dilate
Arterial
resistance vessels
Tissue thiols
gliceril-trinitrát
izosorbide-dinitrate
izosorbide-5mononitrate
Dilate
Ischaemic
area
MLCKa
MLCK
RELAXATION
+
MLC- P
MLC
Actin
Nitrates
REDUCED
PRELOAD
Stored
Ca2+
Miosin
light chain
(MLC)
Dilate
Dilate
+
Venous
capacitance vessels
cGMP
GTP
Contraction
Guanilatecyclase
+
RSNO
RSH
Reduced venous
return
NO-3
RSH
NO
NO-2
ORGANIC NITRITES AND NITRATES
Route of administration
(1) To achieve an acute effect (to relief anginal pain)
For this purpose: Sublingual or buccal tablets or spray - (rapid absorption)
NITROGLYCERIN (Tabl. 0.5 mg) onset: 10-20 sec, duration 20 min
ISOSORBIDE DINITRATE (ISORDIL) (Tabl. 2.5, 5 and 10 mg)
Side effects: warmth, flushing, throbbing headache, dizziness, syncop
postural hypotension
(2) For long term treatment (to prevent anginal attacks)
For this purpose: oral tablets, transdermal patches, oinments
- high degree of "first pass" hepatic biotransformation
NITROGLYCERIN (NITRONG, SUSTAC) (Tabl: 0.5 mg),
onset: 15 min, duration: several hours
PENTAERYTHRYL TETRANITRATE, ERYTRYL
TETRANITRATE, ISOSORBID MONONITRATE (ISMN), ISOSORBID DINITRAT
(ISDN)
NITRO-BID (NTG) for iv. infusion
Topical administration - longer duration (6-24 h)
NITRO-BID (2 % ointment)
Transdermal patches:
DEPONIT (NTG 5 mg/24h),
NITRODUR (N