Chapter-Three

Cardiovascular Drugs

1
• Components of CVS?

• The base for BP measurement ?

• Non pharmacological treatment for

hypertension
• Pharmacological therapy

2
FUNCTIONS OF THE CARDIOVASCULAR SYSTEM

The cardiovascular system consists of the

heart, blood vessels, and blood.
Blood is a fluid tissue that transports oxygen
and nutrients to the other body tissues.

3
 Function…

 Blood returns some waste products from

these tissues to the kidneys and carries carbon
dioxide back to the lungs.
 Blood cells also play important roles in the
immune System

4
CVS composed of
 Heart: Pumping Center
 Blood vessels
 Arteries

 Capillaries
 Veins

Blood: circulating connective tissue

5
Division of the circulatory system
• In the CVS, blood passes through two (double)
circulations:
 Systemic circulation

 Pulmonary circulation

6
7
Pathway of Blood Through the Heart and Lungs
 Right atrium tricuspid valve right ventricle
 Right ventricle pulmonary semilunar valve
pulmonary arteries lungs
 Lungs pulmonary veins left atrium
 Left atrium bicuspid valve left ventricle
 Left ventricle aortic semilunar valve aorta
 Aorta systemic circulation.

8
Properties of cardiac muscles
Cardiac muscles have 4 physiological properties,
which are essential for pumping
These are
 Autorythmicity is the ability of the heart to
generate cardiac impulse and to beat regularly
independent of any external stimulus.
 Excitability; They generate rhythmic cardiac
impulse
 Conductivity; They conduct cardiac impulse
 Contractility
9
 The constant contraction and relaxation of this
muscle creates the pumping movement that
maintains the flow of blood throughout the body.
Blood Vessels: Transport blood to and from all areas

of the body.

Arteries: are large blood vessels and transport blood

away from the heart to all parts of the body.

10
Capillaries: Permit the exchange of nutrients and

waste products between the blood and the cells.

Veins: Return blood from all body parts to the

heart.

Blood: Brings oxygen and nutrients to the cells

and carries away waste.

11
 The most commonly encountered cardiovascular

disorders include:

1. hypertension,

2. congestive heart failure,

3. angina pectoris and

4. cardiac arrhythmias.
 Most drugs available currently are able to reduce
the morbidity and mortality due to these disorders.
12
 Cont…
I. Antihypertensive drugs
a. General consideration:-
• Is an elevation of arterial blood pressure above
an arbitrarily defined normal value.
• Is arterial blood pressure higher than
140/90mmHg based on three measurements at
different times.
• According to the level of diastolic blood
pressure:
13
 Hypertension:
• Usually symptom-free(silent killer)

• Consequences: Heart failure, kidney damage,

stroke, blindness
 Blood pressure is the measurement of the
amount of systolic and diastolic pressure exerted
against the walls of the arteries.
14
 Systolic pressure
– occurs when the ventricles contract,
– is the highest pressure against the walls of an
artery.
 Diastolic pressure,
– occurs when the ventricles are relaxed,
– is the lowest pressure against the walls of an
artery.
15
 Cont…
Category Systolic BP (mm Hg) Diastolic BP (mm Hg)
Normal 90-119 60-79
Pre-hypertension 120-139 80-89
Hypertension
Stage 1 140-15990-99
Stage 2 160-159100-109
Stage 3 180-209110-119
Stage 4 ≥ 210≥ 120

16
 Hypertension may be classified in to 3 categories,
according to the level of diastolic blood pressure:
• Mild hypertension with a diastolic blood pressure
between 95-105 mmHg

• Moderate hypertension with a diastolic blood

pressure between 105 – 115mmHg
• Severe hypertension with a diastolic blood
pressure above 115mmHg.
17
Sustained arterial hypertension damages blood
vessels in kidney, heart and brain and
 leads to an increased incidence of renal
failure, cardiac failure, and stroke.
 Effective pharmacologic lowering of blood
pressure prevents the damage to blood vessels
and reduces the morbidity and mortality rate.
18
 Two factors which determine blood pressure are
cardiac out put (stroke volume x heart rate) and
total peripheral resistance of the vasculature.
 Blood pressure is regulated by an interaction
between nervous, endocrine and renal systems.

19
• Blood pressure is a function of the flow of
blood produced by contraction of the heart &
the resistance to blood flow through the
vessels.
• P= FxR
• F= flow
• R= resistance

20
• Blood Flow - is essentially equal to cardiac out put
w/c is equal to stroke volume multiplied by heart
rate.
• CO = SV X HR
i.e. *If ↓ SV  ↓ CO
* If  HR  Co
Resistance Friction among the cells & other blood
components & between the blood & the vessel
walls caused resistance to blood flow.
21
 Elevated blood pressure is usually caused by a
combination of several abnormalities such as
psychological stress,
genetic inheritance,

environmental and

dietary factors and others.

22
 Etiology:
1. Primary hypertension (> 90%): of unknown
cause
2. Secondary hypertension may be due to:
- Renal disease
- Endocrine disease
- Drug induced
- Atherosclerosis (reduction in arterial blood
flow)

23
 Cont…
• Blood pressure is regulated by an interaction
between nervous, endocrine and renal
systems
• Elevated blood pressure is usually caused by :
- Psychological stress
- Genetic inheritance
- Environmental and dietary factors

24
• The central issue of antihypertensive therapy is to
lower arterial blood pressure, irrespective of the
cause.
• Factors to be considered during therapy:- age, sex,
race, body build, life style, cause of the disease, other
co-existing disease, rapid of inset and severity of
hypertension, presence of other risk factors (smoking,
alcohol consumption, obesity and personality type)

25
Antihypertensive therapies
1. Non pharmacological therapy of hypertension
include:
• Low sodium chloride diet
• Weight reduction
• Exercise
• Cessation of smoking
• Decrease in excessive consumption of alcohol
• Psychological methods (relaxation, meditation …etc)
• Dietary decrease in saturated fats.

26
 The sensitivity of patients differs to these non-
pharmacological approaches, but, on the average, only
modest reductions (5 to 10 mmHg) in blood pressure
can be achieved.
This may be sufficient for the treatment of some mild
hypertensive cases.
 The major advantage of non-pharmacological
approaches is the relative safety and freedom
from side effects, compared with drug therapy. 27
 Drugs include
• Diuretics

• Sympatholytics (Sympathoplegic agents)

• Direct vasodilators

• Renin-Angiotensine system targeting drugs

• Calcium channel blockers

28
 Cont…

I. Diuretics:
• Deplete body sodium stores

• Reduce blood volume

• Reduce peripheral resistance

29
 Classification of diuretics:-

Most of the diuretics used therapeutically act by interfering

with sodium reabsorption by the tubules. The major
groups are:
I. Thiazides and related diuretics: e.g. Hydrochlorothiazide
chlorthalidone, bendrofluazide, etc.
II. Loop diuretics: e.g. furosemide, ethacrynic acid, etc.
III. Potassium sparing diuretics e.g. triamterene, amiloride,
spironolactone, etc.
IV. Carbonic anhydrase inhibitors e.g. acetazolamide
V. Osmotic diuretics e.g. mannitol, glycerol

30
 I. Diuretics

• Reduce blood pressure when used alone and they

can enhance the effect of hypertensive drugs
1. Thiazides diuretics eg. hydrochlortizide
• Reduce Bp by two mechanisms
i) Reduction of blood volume
- responsible for critical antihypertensive effect
ii) Reduction of arterial resistance
- Responsible for long term antihypertensive
effect
31
ADR:- Hypokalimia, to solve such problem
consume K rich food , supplement and potassium
sparing diuretics
- Dehydration,
• hyperglycemia and

• hyperuricemia
32
 2. High-ceiling (Loop) diuretics
Examples :- furosimide ,Ethacrynic acid ,Bumetanide

- Produce much greater diuresis than thiazides

- For most individuals with chronic hypertension,

the amount of fluid loss that loop diuretics can
produce is greater than seeded or desirable

- Consequently, loop diuretic are not used routinely,

rather, they reserved for
33
 Cont…
1) Patients who need greater diuretics (the effect
can’t be achieved by thiazide)

2) Patients with low glomerular filtration rate

(because thiazide won‟t work when is low)

ADR:- Hypokalimia, hyperglycemia, dehydration and

hyperuriecemia

34
 3. Potassium sparing diuretics

• Examples: - spiranolactone, Triameterene, Amilorid

- Less diuretic effect

- Role is to balance K loss caused by thiazide

or loop diuretics

- Shouldn’t be used with :- K supplements,

acetyl choline inhibitors because hyperkalimic effect

35
 4. Carbonic anhydrase inhibitors
these drugs like acetazolamide inhibit the enzyme
carbonic anhydrase in renal tubular cells and lead to
increased excretion of bicarbonate, sodium
and potassium ions in urine. In eye it results in
decrease information of aqueous humor.
• Therefore these are used in treatment of acute angle
glaucoma.
• Main adverse effects of these agents are drowsiness,
hypokalemia, metabolic acidosis and epigastric
distress.
36
 5. Osmotic diuretics
these drugs like mannitol and glycerine (glycerol) are
freely filtered at the glomerulus and are relatively inert
pharmacologically and undergo limited reabsorption by
renal tubule.
These are administered to increase significantly the
osmolality of plasma and tubular fluid. Some times
they produce nausea, vomiting, electrolyte imbalances.
They are used in cerebral edema and management of
poisoning.

37
 II. Sympatholytic agents
• Antihypertensive drugs acting in the brain stem
suppress the sympathetic out flow to the heart
and blood vessel as a result HR decrease and
Myocardial contractility also decrease.
• Influence symphatatic nervous system on heart,
blood vessel and other Structures
38
 Based on the site or mechanism of action
sympathoplegic drugs are divided into:
a) Centrally acting antihypertensive agents
b) Adrenoceptor antagonists
c) Adrenergic neuron – blocking agents
d) Drugs which deplete catecholamine stores
e) Ganglion blockers

39
A. Centrally acting antihypertensive agents

• Example includes methyldopa, clonidine

Effect
• vasodilation
• Decrease cardiac output

40
 Cont…
• Stimulate α2 – receptors located in the
vasomotor centre of the medulla so that
reduce sympathetic output.
• Total peripheral resistance or cardiac output
decreases
effect- vasodilation
-low volume of blood

41
 Cont…
Methyldopa is prodrug of α methylnorepinephrine
Methyldopa is useful in the treatment of
hypertension in pregnancy, mild to moderately
severe hypertension.
• In particular, methyldopa is effective in the
treatment of hypertension in pregnancy, and may
also be used in asthma and heart failure
Contraindications: depression, active liver disease,
phaeochromocytoma, haemolytic anemia
42
Side effects of methyldopa
- sedation - nausea
- vertigo - vomiting
- dry mouth - diarrhea
Dose: Adult, 250mg 2-3 times daily gradually
increased at
intervals of two or more days to maximum daily
dose 3gm
43
 Cont…
- postural hypotension
- impotence
- haemolytic anemia
- weight gain and hypersensitive reactions
(fever, liver damage, thrombocytopenia)

44
 B. Adrenoceptor antagonists
e.g propranolol (beta blocker), prazosin (alpha
blocker), labetalol(alpha and beta blocker), atenolol
• β – blockers cardiac acceleration following
sympathetic stimulation
The beta blocker have at least four useful actions in
hypertension
a) Inhibition B1 heart
• decrease HR and contractility ,decrease cardiac out
put

45
b) Suppress reflex tachycardia caused by vasodilators
c)Inhibition B1 receptor in kidney
• decrease release of rennin decrease
angiotension II results in vasodilatation and decrease
adlestrone
d)Reduce peripheral vascular resistance
Treatment with prazosin should be initiated with low
dose (1mg 3 times daily) to prevent postural
hypotension

46
Propranolol

Contraindications: -asthma or bronchospasm, or

those with a history of obstructive airways disease,
cardiogenic shock, sinus bardycardia, 2nd or 3rd degree
heart block, uncontrolled heart failure, should not
receive beta blockers without
concomitant alpha-adrenoceptor blocking therapy.
47
Preparation:
• Injection, 1 mg/ml in 1 ml ampoule
• Tablet, 10 mg, 40 mg

48
 Cont…
C) Adrenergic neuron – blocking agents, e.g.
guanethidine
• Blocks adrenergic nerve transmission,
preventing the release of transmitter.
• It lowers blood pressure by reducing both
cardiac out put and total peripheral resistance.
•  Recommended for treatment of severe forms
of hypertension.

49
 Cont…
D) Drugs which deplete catecholamine stores, e.g.
reserpine
• Interferes with the storage of endogenous
catecholamines in storage vesicles.
• leads to reduction of cardiac out put and
peripheral vascular resistance.
• is a second-line drug for treatment of
hypertension.

50
 Cont…

E) Ganglion blockers, e.g. trimethaphan

• Is ganglion blocking drug which is reserved for
use in hypertensive emergencies only.

51
 III. Direct vasodilators
- Arterial vasodilators

e.g. hydralazine

- Arteriovenous vasodilators

e.g. sodium nitroprusside

52
 Cont…
Hydralazine:
• Dilates arterioles but not veins.

Indication:
• Management of moderate-to-severe
hypertension.
• Heart failure; hypertension secondary to pre-
eclampsia/eclampsia 53
 Hydralazine…
Drug interactions:
• May enhance the hypotensive effect of other
Antihypertensives.
• Nonsteroidal Anti-Inflammatory agents: May
diminish the antihypertensive effect of
Hydralazine

54
 Hydralazine…
Contraindications:
• Hypersensitivity to hydralazine or any
component of the formulation
• mitral valve rheumatic heart disease.
• Hepatic impairment, renal impairment (dosage
adjustment).
• Avoid during first and second trimester, no
report on serious harm following use in third
trimester
55
 Sodium nitroprusside

• A powerful vasodilator

• Dilates both arterial and venous vessels

• Reduce peripheral vascular resistance and

venous return.
• Rapidly lowers blood pressure

56
 Sodium nitroprusside…
• Given by intravenous infusion.

• used in treating hypertensive emergencies as

well as severe cardiac failure.
• Metabolic acidosis, arrhythmias, excessive
hypotension and death are most serious toxicities.

57
 IV. Renin-Angiotensine system targeting drugs

A. Angiotensin converting enzyme inhibitors

e.g. captopril, enalapril

• Captopril inhibits angiotensin converting enzyme that
hydrolyzes angiotensin I (Inactive) to angiotensin II
(Active)
• A potent vasoconstrictor

• Decrease peripheral vascular resistance.

58
 Cont…
Drug interactions:
• potassium-sparing diuretics or potassium
supplements (ACE inhibitors are ‘potassium-
sparing’ agents);
• aspirin, indomethacin and probably other
NSAIDs, antacids, digoxin and lithium,
probenecid,
59
 Drug interactions…
• Food decreases absorption-take 30-60 minutes
before meals
• ACE inhibitors are fetotoxic and should not be
used by women who are pregnant
• ACEIs should be discontinued as soon as possible
once pregnancy is detected.
60
Avoid ACE inhibitors in
• Renal artery stenosis
• Fluid-depleted patients
• Pregnancy
• The most common adverse effect is a dry
persistent cough.

61
B) Angiotensin II receptor antagonists.
Eg. Losartan, Candesartan ,Eprosartan Valsartan
 Do not interfer with renin processing => no
cough

62
 Calcium channel blockers
Drugs used to treat disorders of the cardiovascular
system like
• High blood pressure (hypertension),
• Angina pectoris (chest pains caused by reduced
oxygen flow to the heart muscle), and
• Irregular heartbeat.
These drugs are also effective in treating migraine
headaches

63
e.g. nifedipine, verapamil, nicardipine, Deltiazem,
amlodipine etc.
• Verapamil more selective on cardiac muscle
• Diltiazem acts equally on both cardiac and smooth
muscles
• Nifedipine more selective on blood vessels
64
 Cont..
• Inhibit calcium influx in to arterial smooth
muscle cells
• Decrease peripheral resistance
• Verapamil has the greatest cardiac depressant
effect and may decrease heart rate and cardiac
out put as well
65
 Most important toxic effects of Calcium
channel blockers

• Cardiac arrest
• Bradycardia
• Atrioventricular block
• Congestive heart failure

66
 Lines of treatment of primary hypertension

– Non-pharmacologic
– Pharmacological
• Selection of drug(s) depends on various factors such
as
– the severity of hypertension,
– patient factors (age, race, coexisting diseases, etc).
67
 Cont…

• For mild moderate hypertension monotherapy

can be sufficient using

- Thiazide
- Beta blockers

- Calcium channel blockers

- Angiotensin converting enzyme inhibitors

- Central sympathoplegic agents
68
Beta-blockers
• reduce heart rate and the amount of blood
the heart pumps
• are preferred in young patients,

• Used in high renin hypertension and patients

with tachycardia or angina and hypertension.
69
 Cont…
• Black patients respond well to diuretics and calcium
channel blockers than to beta-blockers and ACE
inhibitors
• Thiazide diuretics may be used in conjunction with:
– a beta-blocker, calcium channel blocker or an
angiotensin converting enzyme inhibitor if
monotherapy is unsuccessful.
70
 Cont…
• If hypertension is still not under control, a
third drug e.g. vasodilator such as hydralazine
may be combined
• When three drugs are required, combining a
diuretic, a sympathoplegic agents or an ACE
inhibitor, and a direct vasodilator or calcium
channel block is effective
71
hypertensive emergencies
• is usually started with furosemide given by
parenteral route at dose of 20-40mg.
• In addition, parenteral use of sodium nitroprusside,
hydralazine, trimethaphan, labetalol can be
indicated.
72
 II. Drug used in heart failure
Over view of heart failure

Heart failure:- is a serious, progressive disorder

characterized by
- Ventricular dysfunction,
- reduced cardiac output,

- insufficient tissue perfusion and signs of fluid

retention (eg. Peripheral edema, shortness tissues.
73
Over view of heart failure …
- Heart failure was commonly referred to as CHF
– because heart failure frequently causes fluid
accumulation in the lung and peripheral tissues.
- Is a syndrome in which the heart is unable to pump
sufficient blood to meet the metabolic needs of tissues

74
The major underlying causes of heart failure are
• Chronic hypertension,

• Valvular heart disease,

• coronary artery disease ,

• Myocardial infarction and

• Dysarthmia, occurs when blood flow to region of

myocardium is stopped. 75
 Rx goals and strategies

1- Relief of pulmonary and peripheral congestive

symptoms
2- Improvement of functional capacity & quality of

life
3- Prolongation of life expectancy

76
Non-Drug therapy of HF
• Salt intake should be limited to 2g/day

• Excessive fluid should be avoids

• Alcohol ingestion should be discouraged

77
 Cont…

Etiology
• It can occur in the people of any age, even in young
children
• More common among older people
• The disorder become more common because people are
living longer
• Risk factors: smoking, high blood pressure, a high –fat
diet, diabetes, faulty heart valves
78
 Cont…

Types of heart failure

– Systolic dysfunction
– Diastolic dysfunction
– Some people with heart failure have both types of
dysfunction

79
1.Systolic dysfunction
• The heart contracts less forcefully and cannot
pump out as much of the blood that is
returned to it as it normally does
• As a result, more blood remains in the
ventricles
• Blood then accumulates in lungs, veins or both

80
 Cont…
2. Diastolic dysfunction
• The heart is stiff and does not relax normally
after contracting, which impairs its ability to fill
with blood
• The heart contracts normally, so it is able to
pump a normal proportion of blood out of the
ventricles
81
 Cont…

Drugs used to treat heart failure can be broadly

divided into:
A. Drugs with positive inotropic effect.
B. Drugs without positive inotropic effect

82
 Drugs with positive inotropic effect

Increase the force of contraction of the heart muscle.

Includes:
– Cardiac glycosides,
– Phosphodiasterase inhibitors,
– Sympathomimetics, and

– Methylxanthines
83
 Cont…
1. Cardiac glycosides
• Comprise a group of steroid compounds that
can increase cardiac out put and alter the
electrical functions

e.g. digoxin (oral and IV and digitoxin)

84
 Cardiac glycosides…
• Inhibit the membrane-bound Na+/K+ ATPase
often called the “Sodium Pump” leading to an
increase in the intracellular calcium that acts
on contractile proteins.
• digitoxin is more lipid soluble and has long
half-life than digoxin.
85
 Cont…
Therapeutic uses of cardiac glycosides include:
– Congestive heart failure

– Atrial fibrillation(the heart begins beating in

a fast but irregular pattern)
– Atrial flutter, and

– Paroxysmal atrial tachycardia

86
 Toxicity of cardiac glycosides…
Include:

• Gastrointestinal effects such as anorexia, nausea,

vomiting, diarrhoea (could be managed by reducing dose)

• Cardiac effects such as heart block, arrhythmias

• CNS effects such as headache, malaise, hallucinations,

delirium, visual disturbances (yellow vision) (could be
managed by reducing dose)

87
 Cont…
2. Bipyridine derivatives (phosphodiasterase
inhibitors)
e.g. inamrinone, milrinone
• Possess both positive inotropic effect (increase the
force of myocardial contraction by increasing ca2+
influx) and vasodilator effects (by increasing Camp
to blood vessel)
• Used in cases of heart failure resistant to treatment
with cardiac glycosides and vasodilators.
88
 Cont…
3. Beta - adrenergic stimulants
e.g. dobutamine (increase renal blood flow),
dopamine(tachycardiya)
• Rapidly acting inotropic agent
• Increase in myocardial contractility by beta
stimulants increase the cardiac out put.
• It is reserved for management of acute failure or
failure refractory to other oral agents.
• For critically ill patient, preferable than digoxine
89
• Increase mycocarial contractility
improving cardiac performance Increase
heart rate creating a risk of tachycardia

90
 Cont…

4. Methylxanthines,

e.g. theophylline in the form of aminophylline

• Has a positive inotropic effect, bronchodilating
effect, modest effect on renal blood flow.
• Used for management of acute left ventricular
failure or pulmonary edema.
91
 Cont…

B. Drugs without positive inotropic effect. These

include:
• Diuretics, e.g. hydrochlorothiazide, furosemide

• Vasodilators, e.g. hydralazine, sodium

nitroprusside
• ACE inhibitors e.g. captopril, enalapril
92
 Cont…
1. Diuretics
• Are first – line drugs

• Thiazides – mild failure, however ineffective at

low glomerular filtration rate.
• Loop diuretics – moderate or severe failure.
• In acute failure, play important role by reducing
ventricular preload 93
 Cont…
2. Vasodilators.
• provide a reduction in preload (through venous
dilation), or reduction in after-load (through
arteriolar dilation), or both.
• reserved for patients who are intolerant of or
who have contraindications to ACE inhibitors.

e.g. Hydralazine, sodium nitroprusside

94
 Cont…

3. Angiotensin converting enzyme (ACE) inhibitors

• Reduce after load by reducing peripheral
resistance and
• Also reduce preload by reducing salt and water
retention by way of reduction in aldosterone
secretion
95
 The following are essential for long-term management of chronic heart failure:

• Modify cardiovascular risk factor profile,

e.g. cigarette smoking, obesity, salt intake

• Underlying causes should be treated,

e.g. anemia, hypertension, valvular disease If this

proves inadequate, diuretic should be given.

96
 III) Pharmacotherapy of Angina pectoris

• Is a clinical syndrome characterized by episodes

of chest pain, result of an imbalance between
the oxygen supply and the oxygen demand of
the myocardium (myocardial ischemia)

97
 Cont…

Most often caused by

– atherosclerotic plaque in the coronary arteries
(caused by a buildup of fatty deposits called plaques
that block blood flow through the coronary arteries )
– coronary vasospasm

– uncontrolled high blood pressure

98
• The result is

– impaired blood flow to the myocardium,

especially with exercise or other factors that
increases the cardiac workload and need for
oxygen

99
 Cont…
types of angina
1. Classic angina : (also stable, typical, exertion
angina)
• Occurs when atherosclerotic plaque obstructs coronary
arteries
• chest pain is usually precipitated by situations that
increase the workload of the heart such as physical
exertion, exposure to cold and emotional upset.
100
 Cont…
2. Variant angina : (atypical, prinzimental’s or vasospastic
angina)
• Caused by spasms of the coronary artery
• The spasm occur most often in coronary arteries that are
already partly blocked by atherosclerotic plaque
• Usually occurs during rest or with minimal exercise and
often occurs at night
• Arterial spasms are most often treated with calcium
channel blockers 101
 Cont…
3. Unstable angina(rest, preinfarction and
crescendo angina)
• is due to episodes of increased epicardial
coronary artery tone or small platelet clots
occurring in the vicinity of an atherosclerotic
plaque (non occlusive thrombi at the site of
ulcerated plaque).
102
• Unstable angina occurs unexpectedly, often while the
person is resting.
• It generally lasts longer—as much as 30 minutes—and is
more painful than stable angina.
• An attack of unstable angina is considered a medical
emergency.
• It can indicate that a blood clot is partially blocking a
coronary artery, a condition that may lead to a heart
attack.
103
 Drugs used in angina pectoris
• Organic nitrates (increase oxygen supply)

e.g. nitro-glycerine, isosorbide dinitrate, etc.

• Beta adrenergic blocking agents( decrease oxygen demand)

e.g. propranolol, atenolol, etc.

• Calcium channel blocking agents

e.g. verapamil, nifedipine, etc.

• Miscellaneous drugs

e.g. aspirin, heparin, dipyridamole. 104

 1. Organic nitrates
• Potent vasodilators
• Effects are mediated through the direct
relaxant action on smooth muscles.
• Mimic the vasodilator action of nitric oxide
• organic nitrates are reduced to organic
nitrites, which is then converted to nitric oxide
105
 Cont…
• The action of nitrates begins after 2-3 minutes when
chewed or held under tongue and action lasts for 2
hours.
Therapeutic uses:
• prophylaxis and treatment of angina pectoris
• post myocardial infarction
• coronary insufficiency
• acute LVF (left ventricle failure)
106
 Cont…

2. Adrenergic blocking agents

• Beta blockers e.g. atenolol, propranolol
metoprolol, labetolol.
• Net effect is a beneficial reduction in cardiac
workload and myocardial oxygen consumption

107
 Cont…
3. Calcium channel blockers:

• Interfere with the calcium entry onto the

mayocardial and vascular smooth muscles

e.g. nifedipine, felodipine, verapamil and

diltiazem

Other therapeutic uses: hypertension, acute

coronary insufficiency, tachycardia
108
 Cont…
4. Miscellaneous drugs

e.g. Acetylsalicylic acid

• Low doses given intermittently decreases the synthesis

of thromboxne A2

• At the doses of 75 mg per day it can produce

antiplatelet activity and reduce the risk of myocardial

infarction in anginal patients.

109
 IV) Anti - arrhythmics

Arrhythmia is an abnormality of rate or rhythm

of heart beats

Types of arrhythmia:
• Bradycardia: HR< 60beats/min

• Tachycardia: HR>100beats/min

110
 Factors that may alter arrhythmia includes

• Hypoxia (inadequate oxygen in body tissue)

• electrolyte imbalance,

• cardiac surgery,

• reduced coronary blood flow,

• myocardial infarction

111
Arrhythmia leads to:
• Too rapid, too slow or asynchronous
contraction, reduction of cardiac output,
syncope (loss of sound), dizziness or palpitations
• Severe arrhythmia may lead to death

112
 Cont…
Cardiac arrhythmias arise as the result of either of

a) Disorders of impulse formation and/ or

b) Disorders of impulse conduction.
Pharmacotherapy of cardiac arrhythmias
• Antiarrhythmic drugs are used to prevent or
correct cardiac arrhythmias (tachyarrhythmias)
113
 Cont…
Antiarrhythmic drugs could be:
Class (I): Sodium channel blockers
 Local anaesthetic effect
 -Ve inotropic action
Class I A. quinidine, procainamide and disopyramide
• Prolongs duration of action potential and refractory period
• Have K+ channel blocking effect
• Antimuscarinic and hypotensive effects
Class I B. Lidocaine, phenytoin, mexiletine and tocainide
• shorten the duration of action potential
Class I C. Flecainide, encainide and propafenone
• no effect on the duration of action potential or refractory period

114
 Cont…
Class (II): Beta adrenergic blockers which
include propranolol, atenolol, etc.
Class (III): Potassium channel blockers e.g.
amiodarone, bretylium.
Class (IV): Calcium channel blockers e.g.
verapamil, etc.
Class (V): Digitalis e.g.digoxin

115
 Cont…
Class – I drugs
Quinidine:
• blocks sodium channel so that there is an increase in threshold
for excitability
• well absorbed orally

Adverse effects: SA block, cinchonism(The symptoms are headache,

ringing in the ears, temporary deafness, and dizziness ), severe
headache, diplopia (double vision) and photophobia.

116
 Cont…
Lidocaine: a local anaesthetic blocks both open
and inactivated sodium channel and decreases
automaticity.
• It is given parenterally
Flecainide: A procainamide analogue and well
absorbed orally.
• is used in ventricular ectopic beats in patients
with normal left ventricular function

117
 Cont…
Class –II drugs: Beta-adrenergic receptor blockers
Propranolol:
• Myocardiac sympathetic beta receptor stimulation
increases automaticity, enhances A.V. conduction
velocity and shortens the refractory period.
• Can reverse these effects.
• Beta blockers may potentiate the negative
inotropic action of other antiarrhythmics.

118
 Cont…
Therapeutic uses:
• Tachyarrhythmias
• pheochromocytoma
• thyrotoxicosis crisis
• Atrial fibrillation and flutter refractory to
digitalis.

119
 Cont…
Class – III: Potassium channel blockers
AMIODARONE (broad spectrum antiarrhythmic)
Cardiac action:
• Block K-channel leading to prolongation of the AP and QT
interval in ECG
• block inactivated Na channels
• weak β- adrenergic blocker
• weak Ca channel blocker
extra cardiac actions:
• peripheral vasodilatation
120
 Cont…
pharmacokinetics:
• IV administration , action quick
• Oral administration, action delayed (days to weaks)
• It takes many months to eliminate the drug
use:
• supraventricular and ventricular tachycardia
Adverse effects: anorexia, nausea, abdominal pain,
tremor, hallucinations, peripheral neuropathy, A.V.
block
121
 Cont…
Class IV drugs: Calcium channel blockers
Verapamil:
• Blocking the movement of calcium ions
through the channels
• drug of choice in case of paroxysmal
supraventricular tachycardia for rapid
conversion to sinus rhythm.

122
 Cont…
Class - V drugs:
• Causes shortening of the atrial refractory
period with small doses (vagal action)
prolongation with the larger doses (direct
action).
• prolongs the effective refractory period of A.V
node directly and through the vagus.

123
Drugs used in hypotensive states and shock

• Are used to elevate a low blood pressure

I. Agents intended to increase the volume of blood

in active circulation
Include:
intravenous fluids such as whole blood, plasma,
plasma components, plasma substitutes
124
 Cont…
II. Vasoconstrictor drugs these include:
• Peripherally acting vasoconstrictors

- Sympathomimetic drugs e.g. adrenaline,

noradrenaline, methoxamine, phenylephrine,
mephentermine and ephedrine.

- Direct vasoconstrictors e.g. vasopressin and

angiotensin 125
 Cont…
Treatment of shock
• Shock is a clinical syndrome characterized by
decreased blood supply to tissues.
• Common signs and symptoms include heart
failure, disorientation, mental confusion, seizures,
cold extremities, and comma.
• Most, but not all people in shock are hypotensive.
• The treatment varies with type of shock. The
choice of drug depends primarily on the patho-
physiology involved
126
 Cont…
• For cardiogenic shock and decreased cardiac
out put
- dopamine
• With severe CHF characterized by decreased
CO and high PVR, vasodilator drugs
(nitropruside, nitroglycerine) may be given
along with the cardiotonic drug.
• Diuretics may also be indicated to treat
pulmonary congestion if it occurs.
127
 Cont…
• vasoconstrictor drug (e.g. levarterenol) is first
line drug For anaphylactic shock or neurogenic
shock characterized by severe vasodilation
• For hypovolemic shock, intravenous fluids that
replace the type of fluid lost should be given
• For septic shock, appropriate antibiotic
therapy in addition to other treatment
measures.

128
 Drugs for the treatment of hyperlipedemia
and atherosclerosis
• Hyperlipidemia is a major cause of
atherosclerosis
• Atherosclerosis is associated with conditions,
such as:
Coronary heart disease
Ischemic cerebrovascular disease
Peripheral vascular disease

129
 Cont…
Arteriosclerosis
• Thickening and loss of elasticity of arterial walls
• Hardening of the arteries
Narrowing
Weakening
• Is chronic inflammatory disorder of large blood
vessels characterized by formation of fibrofatty
plaques called atheroma.
• Hardening of arteries – atrteriosclerosis
130
 Cont…
Antilipemic agents (Lipid lowering drugs)
1. HMG-CoA reductase inhibitors (statins)
Fluvastatin, lovastatin, pravastatin, simvastatin, atrovastatin,
rosuvastatin
2. Specific cholestrol absorption inhibitors
Ezetimbe
3. Bile acid binding (resins):
Cholestryramine, colestipol, colesevelam
4. Fibrates:
Clofibrate, gemifbrozil, benzafibrate, fenofibrate etc..
4. Nicotonic acid (niacin)

131
 Cont…
1. HMG-CoA reductase inhibitors (statins)
• MOA: competitively inhibit HMG-CoA reductase (3-
hydroxy-3-methyl glutaryl co enzyme A (HMG-CoA)
reductase, the rate determining enzyme for
cholesterol synthesis )
• Inhibits cholesterol synthesis increase LDL
receptors decrease LDL concentration

132
• Inhibit synthesis of VLDL, decrease TG,
decrease LDL
• Increase HDL
• They are potent reducers of plasma LDL
cholesterol and triglyceride.

133
 Cont…
Effect of statins
• Have antioxidant properties
• Have antiinflammatory effects
• Have anti thrombotic effects
• Decrease blood viscosity, increase blood flow
• Decrease LDL
• Decrease TG
• Increase HDL
• Inhibit bone loss
134
 Cont…
Pharmacokinetics
• Absorption of fluva and Prava 95% others 30- 75%
• Absorption of Lova is enhanced by food
• Absorption of simva, rosuva, atrova not affected by food
• Most of the absorbed dose is excreted in bile
C/I
• In severe liver, kideny disease, pregnancy, lactation, children
S/E
• The commonest side effects of therapy with statins are
gastrointestinal disturbances, Myalgia (muscle pain), muscle
enzyme release,
135
 Cont…
2. Specific cholesterol absorption inhibitors : Ezetimibe
MOA
• Acts at the brush border of the intestinal mucosa to specifically
inhibit cholesterol absorption
Effect
• Cholesterol absorption is inhibited by 55% but not TG, bile acids or
fat soluble vitamins
• LDL lowering
Pharmacokinetics
• Rapidly but incompletely absorbed in the gut
• Metabolized in Gut and liver by conjugation
• 80% excreted in bile to feces
CI
• Pregnancy, lactation, severe renal or hepatic insufficiency, children
136
 Cont…
3. Bile acid sequestrates (resins)
MOA:
• Resins are insoluble, non absorbable polymers that
bind bile acids and prevent their re-absorption
• Decrease of dietary cholesterol absorption indirectly
• Increase LDL clearance
Cholestyramine, colestipol
• Used for high LDL
• In conjunction with statins
• Limited use due to side effects
137
 Cont…
4. Fibrates
E.g. Gemfibrozil, fenofibrate
• Inhibits the synthesis of cholesterol and bile
acids, and enhance the secretion of cholesterol
in bile.
• Reduce TG by stimulation of Fatty acid oxidation
• Increase HDL
• Increase risk of muscle toxicity if used with
statins
138
 Cont…
5. Niacin (nicotinic acid)
MOA:
• Inhibit lipolysis of TG
• Reduces transport of free fatty acids to the
liver and decreases hepatic TG synthesis
• Can be used in hypercholesterolemia
• Has got poor tolerability

139
 Cont…
Exercises 
1. Discuss briefly the different groups of antihypertensive
drugs.
 2. Which of the antihypertensive drugs can also be used
in angina pectoris?
3. What are the common adverse effects of vasodilators?
4. Discuss how digitalis and loop diuretics interact.
5. Describe the pharmacological approaches used in the
management of shock.

140