Cardiovascular Drugs

Abiy G(Msc)
Diuretics
• Diuretics are drugs that increase the volume of urine
excreted

• Most diuretic agents are inhibitors of renal ion

transporters that decrease the reabsorption of Na+ at
different sites in the nephron

• Na+ and other ions, such as Cl−, enter the urine in

greater than normal amounts along with water, which is
carried passively to maintain osmotic equilibrium
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Normal regulation of fluid and electrolytes by the
kidneys
• The kidney regulates the ionic composition and volume of
urine by active reabsorption or secretion of ions and/or passive
reabsorption of water at five functional zones along the
nephron:

1) the proximal convoluted tubule

2) the descending loop of Henle

3) the ascending loop of Henle

4) the distal convoluted tubule, and

5) the collecting tubule and ductAbiy G

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Major locations of ion and water exchange in the nephron, showing sites of action of the diuretic drugs

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 Proximal convoluted tubule

• Located in the cortex of the kidney, almost all the

glucose, bicarbonate, amino acids, and other
metabolites are reabsorbed

• Approximately two-thirds of the Na+ is also

reabsorbed

• Chloride enters the lumen of the tubule in exchange

for an anion, such as oxalate, as well as
paracellularly through the lumen

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Cont…

• Water follows passively from the lumen to the

blood to maintain osmolar equality

• Carbonic anhydrase in the luminal membrane and

cytoplasm of the proximal tubular cells modulates
the reabsorption of bicarbonate

• The proximal tubule is the site of the organic acid

and base secretory systems

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• The organic acid secretory system, located in the
middle-third of the proximal tubule, secretes a
variety of organic acids, such as uric acid, some
antibiotics, and diuretics, from the bloodstream into
the proximal tubular lumen

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Descending loop of Henle
• The remaining filtrate, which is isotonic, next enters
the descending limb of the loop of Henle and passes
into the medulla of the kidney

• The osmolarity increases along the descending

portion of the loop of Henle because of the
countercurrent mechanism that is responsible for
water reabsorption

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• Results in a tubular fluid with a threefold increase
in salt concentration

• Osmotic diuretics exert part of their action in this

region

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 Ascending loop of Henle

• The cells of the ascending tubular epithelium are

unique in being impermeable to water

• Active reabsorption of Na+, K+, and Cl− is

mediated by a Na+/K+/2Cl− cotransporter

• Both Mg2+ and Ca2+ enter the interstitial fluid via

the paracellular pathway

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• A diluting region of the nephron

• Because the ascending loop of Henle is a major site

for salt reabsorption, drugs affecting this site, such
as loop diuretics have the greatest diuretic effect

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 Distal convoluted tubule

• The cells of the distal convoluted tubule are also

impermeable to water

• About 10% of the filtered sodium chloride is

reabsorbed via a Na+/Cl− transporter that is
sensitive to thiazide diuretics

• Calcium reabsorption is mediated by passage

through a channel and then transported by a
Na+/Ca2+-exchanger into the interstitial fluid
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• Ca2+ excretion is regulated by parathyroid hormone
in this portion of the tubule

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 Collecting tubule and duct

• Responsible for Na+, K+, and water transport

• Sodium enters the principal cells through channels

(epithelial sodium channels) that are inhibited by
amiloride and triamterene

• Na+ reabsorption relies on a Na+/K+-ATPase pump

to be transported into the blood

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• Aldosterone receptors in the principal cells
influence Na+ reabsorption and K+ secretion

• Aldosterone increases the synthesis of Na+

channels and of the Na+/K+-ATPase pump

• Antidiuretic hormone (ADH; vasopressin)

receptors promote the reabsorption of water from
the collecting tubules and ducts
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 Thiazides and related agents

• The most widely used diuretics

• Affect the distal convoluted tubule, and all have

equal maximum diuretic effects, differing only in
potency

• Sometimes called “low ceiling diuretics,” because

increasing the dose above normal therapeutic doses
does not promote further diuretic response

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 Thiazides

• Chlorothiazide was the first orally active diuretic

that was capable of affecting the severe edema often
seen in hepatic cirrhosis and heart failure with
minimal side effects

• Its properties are representative of the thiazide

group, although

• hydrochlorothiazide and chlorthalidone are now

used more commonly

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• Hydrochlorothiazide is more potent, so the required
dose is considerably lower than that of
chlorothiazide, but the efficacy is comparable to
that of the parent drug

• In all other aspects, hydrochlorothiazide resembles

chlorothiazide

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 Mechanism of action

• To decrease the reabsorption of Na+, apparently by

inhibition of a Na+/Cl− cotransporter on the luminal
membrane of the tubules
• Have a lesser effect in the proximal tubule

• The efficacy of these agents may be diminished

with concomitant use of NSAIDs, such as
indomethacin, which inhibit production of renal
prostaglandins, thereby reducing renal blood flow

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Actions Therapeutic uses
• Increased excretion of Na+ • Hypertension
and Cl−
• Heart failure
• Loss of K+
• Hypercalciuria
• Loss of Mg2+
• Diabetes insipidus
• Decreased urinary calcium
excretion

• Reduced peripheral
vascular resistance
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 Pharmacokinetics

• The drugs are effective orally

• Most thiazides take 1 to 3 weeks to produce a

stable reduction in blood pressure, and they exhibit
a prolonged half-life

• All thiazides are secreted by the organic acid

secretory system of the kidney

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 Adverse effects

• Potassium depletion

• Hyponatremia

• Hyperuricemia

• Volume depletion

• Hypercalcemia

• Hyperglycemia

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 Loop or high-ceiling diuretics

• Bumetanide , furosemide , torsemide, and ethacrynic

acid have their

• major diuretic action on the ascending limb of the

loop of Henle

• Of all the diuretics, these drugs have the highest

efficacy in mobilizing Na+ and Cl− from the body

• They produce copious amounts of urine

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• Furosemide is the most commonly used of these
drugs

• Bumetanide and torsemide are much more potent

than furosemide, and the use of these agents is
increasing

• Ethacrynic acid is used infrequently due to its

adverse effect profile

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Mechanism of action

• Inhibit the cotransport of Na+/K+/2Cl− in the

luminal membrane in the ascending limb of the loop
of Henle

• Reabsorption of ions is decreased

• Agents have the greatest diuretic effect of all the

diuretic drugs

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 Actions

• Loop diuretics act promptly, even in patients with

poor renal function or lack of response to other
diuretics

• Unlike thiazides, loop diuretics increase the Ca2+

content of urine

• In patients with normal serum Ca2+ concentrations,

hypocalcemia does not result, because Ca2+ is
reabsorbed in the distal convoluted tubule
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• The loop diuretics may increase renal blood flow,
possibly by enhancing prostaglandin synthesis

• NSAIDs inhibit renal prostaglandin synthesis and

can reduce the diuretic action of loop diuretics

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 Therapeutic uses

• The drugs of choice for reducing acute pulmonary

edema and acute/chronic peripheral edema

• Have rapid onset of action

• The drugs are useful in emergency situations such

as acute pulmonary edema

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• Loop diuretics (along with hydration) are also
useful in treating hypercalcemia, because they
stimulate tubular Ca2+ excretion

• They also are useful in the treatment of

hyperkalemia

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 Pharmacokinetics

• Loop diuretics are administered orally or

parenterally

• Their duration of action is relatively brief (2 to 4

hours), allowing patients to predict the window of
diuresis
• They are secreted into urine

Adverse effects

• Ototoxicity, Hyperuricemia, Acute hypovolemia,

Potassium depletion andAbiyHypomagnesemia
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Potassium-sparing diuretics

• Act in the collecting tubule to inhibit Na+

reabsorption and K+ excretion

• Used in the treatment of hypertension (most often in

combination with a thiazide) and in heart failure
(aldosterone antagonists)

• It is extremely important that potassium levels are

closely monitored in patients treated with potassium-
sparing diuretics
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• These drugs should be avoided in patients with

renal dysfunction because of the increased risk of

hyperkalemia

• There are drugs with two distinct mechanisms of

action: aldosterone antagonists and sodium channel

blockers

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 Aldosterone antagonists: spironolactone and
eplerenone

Mechanism of action

• Spironolactone is a synthetic steroid that

antagonizes aldosterone at intracellular cytoplasmic
receptor sites rendering the spironolactone–receptor
complex inactive

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• Prevents Na+ reabsorption and, therefore, K+ and
H+ secretion

• Eplerenone has actions comparable to those of

spironolactone, although it may have less endocrine
effects than spironolactone

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Actions

• Spironolactone antagonizes the activity of aldosterone,

resulting in retention of K+ and excretion of Na+

Therapeutic uses

• Diuretic

• Secondary hyperaldosteronism

• Heart failure

• Resistant hypertension

• Ascites

• Polycystic ovary syndrome

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Pharmacokinetics

• Both spironolactone and eplerenone are absorbed after

oral administration and are significantly bound to plasma
proteins

• Spironolactone is extensively metabolized and

converted to several active metabolites

• The metabolites, along with the parent drug, are thought

to be responsible for the therapeutic effects

• Spironolactone is a potent inhibitor of P-glycoprotein,

and eplerenone is metabolized by cytochrome P450 3A4
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 Adverse effects

• Spironolactone can cause gastric upset

• Because it chemically resembles some of the sex

steroids, Spironolactone may induce gynecomastia
in male patients and menstrual irregularities in
female patients

• Hyperkalemia, nausea, lethargy, and mental

confusion can occur

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• At low doses, spironolactone can be used
chronically with few side effects

• Potassium-sparing diuretics should be used with

caution with other medications that can induce
hyperkalemia, such as angiotensin-converting
enzyme inhibitors and potassium supplements

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 Triamterene and amiloride

• Triamterene and amiloride block Na+ transport

channels, resulting in a decrease in Na+/K+
exchange

• Ability to block the Na+/K+-exchange site in the

collecting tubule does not depend on the presence of
aldosterone

• are not very efficacious diuretics

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• Both triamterene and amiloride are commonly used
in combination with other diuretics, usually for their
potassiumsparing properties

• The side effects of triamterene include increased

uric acid, renal stones, and K+ retention

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Carbonic anhydrase inhibitor
Acetazolamide

Mechanism of action

• Inhibits carbonic anhydrase located intracellularly

(cytoplasm) and on the apical membrane of the proximal
tubular epithelium

• Carbonic anhydrase catalyzes the reaction of CO2 and

H2O, leading to H2CO3, which spontaneously ionizes to
H+ and HCO3 − (bicarbonate)

• The decreased ability to exchange Na+ for H+ in the

presence of acetazolamide results in a mild diuresis
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 Therapeutic uses
• Glaucoma
• Mountain sickness

Pharmacokinetics

• Acetazolamide can be administered orally or

intravenously

• It is approximately 90% protein bound and

eliminated renally by both active tubular secretion
and passive reabsorption

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 Adverse effects

• Metabolic acidosis (mild), potassium depletion,

renal stone formation, drowsiness, and paresthesia
may occur

• The drug should be avoided in patients with hepatic

cirrhosis, because it could lead to a decreased
excretion of NH4+

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 Osmotic diuretics

• Mannitol and urea result in some degree of diuresis

• Filtered substances that undergo little or no

reabsorption will cause an increase in urinary output

• Osmotic diuretics are a mainstay of treatment for

patients with increased intracranial pressure or acute
renal failure due to shock, drug toxicities, and trauma

• Mannitol is not absorbed when given orally and

should be given intravenously
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• Adverse effects include extracellular water
expansion and dehydration, as well as hypo- or
hypernatremia

• The expansion of extracellular water results because

the presence of mannitol in the extracellular fluid
extracts water from the cells and causes
hyponatremia until diuresis occurs

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• The most commonly encountered cardiovascular
disorders include hypertension, congestive heart
failure, angina pectoris and cardiac arrhythmias

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 Antihypertensive drugs

• Hypertension is defined as an elevation of arterial

blood pressure above an arbitrarily defined normal
value

• The American Heart Association defines

hypertension as arterial blood pressure higher than
140/90mmHg (based on three measurements at
different times)

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• Hypertension may be classified in to three
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
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• Sustained arterial hypertension damages blood
vessels in kidney, heart and brain and leads to an
increased incidence of renal failure, cardiac failure,
and stroke

• 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
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• Elevated blood pressure is usually caused by a
combination of several abnormalities such as
psychological stress, genetic inheritance,
environmental and dietary factors and others

• Primary hypertension (accounts for 80-90 % of

cases no specific cause of hypertension can be found

• Secondary hypertension arises as a consequence of

some other conditions such as, atherosclerosis, renal
disease, endocrine diseases and others

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 Antihypertensive therapies

1. Non pharmacological therapy of hypertension

• Several non-pharmacological approaches to therapy

of hypertension are available these include:

 Low sodium chloride diet

Weight reduction

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Exercise

 Cessation of smoking

 Decrease in excessive consumption of alcohol

Psychological methods (relaxation, meditation …

etc)

 Dietary decrease in saturated fats

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Pharmacological therapy of hypertension

• Currently available drugs lower blood pressure by

decreasing either cardiac output (CO) or total
peripheral vascular resistance (PVR) or both
although changes in one can indirectly affect the
other

• Anti - hypertensive drugs are classified according to

the principal regulatory site or mechanism on which
they act

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A) Diuretics

 lower blood pressure by depleting the body sodium

and reducing blood volume

Diuretics are effective in lowering blood pressure

by 10 – 15 mmHg in most patients

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a) Thiazides and related drugs, e.g.
hydrochlorthiazide bendrofluazide, chlorthalidone, etc

• Thiazide diuretics reduce blood pressure by

reducing blood volume and cardiac out put as a
result of a pronounced increase in urinary water and
electrolyte particularly sodium excretion

• Thiazides are appropriate for most patients with mild

or moderate hypertension and normal renal and
cardiac function

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 b) Loop diuretics, e.g. furosemide, ethacrynic acid,
etc.

• Loop diuretics are more potent than thiazides as

diuretics

• The antihypertensive effect is mainly due to

reduction of blood volume

• Loop diuretics are indicated in cases of severe

hypertension which is associated with renal failure,
heart failure or liver cirrhosis
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c) Potassium sparing diuretics, e.g. spironolactone

• Used as adjuncts with thiazides or loop diuretics to

avoid excessive potassium depletion and to enhance
the natriuretic effect of others

• The diuretic action of these drugs is weak when

administered alone

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 B) Sympathoplegic agents (Depressants of
sympathetic activity)

• Based on the site or mechanism of action

sympathoplegic drugs are divided into:

a) Centrally acting antihypertensive agents e.g.

methyldopa, clonidine
Centrally acting sympathetic depressants act by
stimulating α2 - receptors located in the vasomotor
centre of the medulla
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sympathetic out flow from the medulla is
diminished and either total peripheral resistance or
cardiac out put decreases
 Methyldopa is useful in the treatment mild to
moderately severe hypertension

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• Side effects of methyldopa include sedation,
vertigo, dry mouth, nausea, vomiting, diarrhea,
postural hypotension, impotence, haemolytic
anemia, weight gain and hypersensitivity reactions
(fever, liver damage, thrombocytopenia)

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b) Adrenoceptor antagonists, e.g propranolol (beta
blocker), prazosin (alpha blocker), labetalol (alpha
and beta blocker).
β – Blockers antagonize beta, receptors located on
the myocardium and prevent the cardio acceleration,
which follows sympathetic stimulation

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The rate and force of myocardial contraction is
diminished, decreasing cardiac out put and thus,
lowering blood pressure
The principal action of alpha adrenergic blocking
drugs is to produce peripheral vasodilation

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c) Adrenergic neuron – blocking agents, e.g.
guanethidine
an adrenergic neuron-blocking drug recommended
for treatment of severe forms of hypertension
Guanethidine blocks adrenergic nerve transmission,
preventing the release of transmitter
It lowers blood pressure by reducing both cardiac
out put and total peripheral resistance

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 d) Drugs which deplete catecholamine stores, e.g.
reserpine

• Interferes with the storage of endogenous

catecholamines in storage vesicles

• It leads to reduction of cardiac out put and

peripheral vascular resistance

• Reserpine is a second-line drug for treatment of

hypertension

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C) Direct vasodilators

• These include:-

 Arterial vasodilators, e.g. hydralazine

 Arteriovenous vasodilators, e.g. sodium

nitroprusside

Hydralazine:

• It dilates arterioles but not veins

• It is used particularly in severe hypertension

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• The most common adverse effects are headache,
nausea, anorexia, palpitations, sweating and
flushing which are typical to vasodilators

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Sodium nitroprusside:

• It is a powerful vasodilator that is used in treating

hypertensive emergencies as well as severe cardiac
failure

• It dilates both arterial and venous vessels, resulting

in reduced peripheral vascular resistance and
venous return

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• Rapidly lowers blood pressure and it is given by
intravenous infusion

• The most serious toxicities include metabolic

acidosis, arrhythmias, excessive hypotension and
death

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D) Angiotensin converting enzyme inhibitors, e.g.
captopril, enalapril, etc

Captopril

• Inhibits angiotensin converting enzyme that

hydrolyzes angiotensin I (Inactive) to angiotensin II
(Active)

• a potent vasoconstrictor, which additionally

stimulates the secretion of aldosterone

•
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• It lowers blood pressure principally by decreasing
peripheral vascular resistance

• The adverse effects include maculopapular rash,

angioedema, cough, granulocytopenia and
diminished taste sensation

• Enalapril is a prodrug with effects similar to those

of captopril

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 E) Calcium channel blockers, e.g. nifedipine,
verapamil, nicardipine, etc.

Verapamil

• The mechanism of action in hypertension is

inhibition of calcium influx in to arterial smooth
muscle cells, resulting in a decrease in peripheral
resistance

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• Has the greatest cardiac depressant effect and may
decrease heart rate and cardiac out put as well

• The most important toxic effects for calcium

channel blockers are cardiac arrest, bradycardia,
atrioventricular block and congestive heart failure

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• Mild hypertension and some patients with moderate
hypertension monotherapy with either of the
following drugs can be sufficient
 Thiazide diuretics

Beta blockers

Calcium channel blockers

Angiotensin converting enzyme inhibitors

 Central sympathoplegic agents

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• Beta-blockers are preferred in young patients, high
renin hypertension and patients with tachycardia or
angina and hypertension

• Black patients respond well to diuretics and

calcium channel blockers than to beta-blockers and
ACE inhibitors

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• If mono-therapy is unsuccessful, combination of
two drugs with different sites of action may be used

• Thiazide diuretics may be used in conjunction with

a beta-blocker, calcium channel blocker or an
angiotensin converting enzyme inhibitor

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• 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

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• The treatment of hypertensive emergencies is
usually started with furosemide given by parenteral
route at dose of 20-40mg

• In addition, parenteral use of diazoxide, sodium

nitroprusside, hydralazine, trimethaphan, labetalol
can be indicated

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Drug used in heart failure

• Congestive heart failure occurs when there is an inability

of the heart to maintain a cardiac out put sufficient to
meet the requirements of the metabolising tissues

• Heart failure is usually caused by one of the following:

schaemic heart disease

Hypertension

Heart muscle disorders

Valvular heart disease

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• Drugs used to treat heart failure can be broadly divided into:

A. Drugs with positive inotropic effect.

B. Drugs without positive inotropic effect

A. Drugs with positive inotropic effect:-

• Drugs with positive inotropic effect increase the force of

contraction of the heart muscle. These include:
 Cardiac glycosides

 Bipyridine derivatives,

 Sympathomimetics, and

 Methylxanthines
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 Cardiac glycosides
• Cardiac glycosides comprise a group of steroid compounds
that can increase cardiac out put and alter the electrical
functions

• Commonly used cardiac glycosides are digoxin and

digitoxin

• The mechanism of inotropic action of cardiac glycosides is

inhibition of the membrane-bound Na+/K+ ATPase often
called the “Sodium Pump”

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• An increased intracellular movement of sodium and
accumulation of sodium in the cell

• The higher intracellular sodium, decreased

transmembrane exchange of sodium and calcium
will take place leading to an increase in the
intracellular calcium that acts on contractile proteins

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• Digitoxin is more lipid soluble and has long half-
life than digoxin

• Therapeutic uses of cardiac glycosides include:

Congestive heart failure

Atrial fibrillation,

Atrial flutter, and

Paroxysmal atrial tachycardia

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• Toxicity of cardiac glycosides include:

 Gastrointestinal effects such as anorexia, nausea,

vomiting, diarrhea
 Cardiac effects such as bradycardia, heart block,
arrhythmias
 CNS effects such as headache, malaise,
hallucinations, delirium, visual disturbances (yellow
vision)

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 Bipyridine derivatives, e.g. amrinone, milrinone

• These drugs possess both positive inotropic effect

and vasodilator effects

• The suggested mechanism of action is inhibition of

an enzyme known as phophodiesterase, which is
responsible for the inactivation of cyclic AMP

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• Inhibition of this enzymes result in an increase in
cAMP

• Bipyridine derivatives are used in cases of heart

failure resistant to treatment with cardiac glycosides
and vasodilators

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Beta - adrenergic stimulants e.g. dobutamine, dopamine

• The increase in myocardial contractility by beta

stimulants increase the cardiac out put

• However, positive chronotropic effect of these agents

minimizes the benefit particularly in patients with
ischaemic heart disease

• The positive inotropic effect of dobutamine is

proportionally greater than its effect on heart rate

• It is reserved for management of acute failure or failure

refractory to other oral agents
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 Methylxanthines, e.g. theophylline in the form of
aminophylline

• Aminophylline has a positive inotropic effect, bronchodilating

effect and a modest effect on renal blood flow

B. Drugs without positive inotropic effect. These include:

 Diuretics, e.g. hydrochlorothiazide, furosemide

Vasodilators, e.g. hydralazine, sodium nitroprusside

Angiotensin converting enzyme inhibitors e.g. captopril,

enalapril

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Diuretics

• First – line drugs for treatment of patients with heart failure

• In mild failure, a thiazide may be sufficient but are

ineffective at low glomerular filtration rates

• Moderate or severe failure requires a loop diuretic

• In acute failure, diuretics play important role by reducing

ventricular preload

• The reduction in venous pressure causes reduction of edema

and its symptoms and reduction of cardiac size which leads
to improved efficiency of pump function
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 Vasodilators

• Effective in acute heart failure because they

provide a reduction in preload (through venous
dilation), or reduction in after-load (through
arteriolar dilation), or both

• Hydralazine has a direct vasodilator effect confined

to arterial bed

• Reduction in systemic vascular resistance leads to a

considerable rise in cardiac out put

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• Sodium nitroprusside is a mixed venous and
arteriolar dilator used also for acute reduction of
blood pressure

• Vasodilator agents are generally reserved for

patients who are intolerant of or who have
contraindications to ACE inhibitors

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Angiotensin converting enzyme (ACE) inhibitors

• These drugs reduce after load by reducing

peripheral resistance and also reduce preload by
reducing salt and water retention by way of
reduction in aldosterone secretion

• They are nowadays considered a head of cardiac

glycosides in the treatment of chronic heart failure

• The following are essential for long-term

management of chronic heart failure:
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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
Give ACE inhibitor and digitalis (ACE inhibitors
may be used before digitalis)
 In patients with persisting symptoms give
vasodilators besides increasing the dose of diuretic
and ACE inhibitors
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 Pharmacotherapy of Angina pectoris

• Angina pectoris develops as a result of an imbalance

between the oxygen supply and the oxygen demand
of the myocardium

• It is a symptom of myocardial ischemia

• When the increase in coronary blood flow is unable

to match the increased oxygen demand, angina
develops

• It has become apparent that spasm of the coronary

arteries is important in the
01/01/2026
production of angina
Abiy G 93
 Drugs used in angina pectoris

• Organic nitrates e.g. nitro-glycerine, isosorbide

dinitrate, etc.

• Beta adrenergic blocking agents e.g. propranolol,

atenolol, etc.

• Calcium channel blocking agents e.g. verapamil,

nifedipine, etc.

• Miscellaneous drugs e.g. aspirin, heparin,

dipyridamole
01/01/2026 Abiy G 94
 Organic nitrates

• potent vasodilators and successfully used in

therapy of angina pectoris

• The effects of nitrates are mediated through the

direct relaxant action on smooth muscles

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• Nitrates are believed to act by mimicking the
vasodilator action of endothelium derived relaxing
factor (EDRF) identified as nitric oxide
Vasodilating organic nitrates are reduced to organic
nitrites, which is then converted to nitric oxide

• The action of nitrates begins after 2-3 minutes when

chewed or held under tongue and action lasts for 2
hours

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• The onset of action and duration of action differs for
different nitrates and varying pharmaceutical
preparations

• Adverse effects include flushing, weakness, dizziness,

tachycardia, palpitation, vertigo, sweating, syncope
localized burning with sublingual preparation and
contact dermatitis with ointment

• Therapeutic uses: prophylaxis and treatment of angina

pectoris, post myocardial infarction, coronary
insufficiency, acute LVF (left ventricle failure)
01/01/2026 Abiy G 97
 Adrenergic blocking agents

• Exercise and emotional excitement induce angina in

susceptible subject by the increase in heart rate,
blood pressure and myocardial contractility through
increased sympathetic activity

• Beta receptor blocking agents prevent angina by

blocking all these effects

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• In most patients the net effect is a beneficial
reduction in cardiac workload and myocardial
oxygen consumption e.g. atenolol, propranolol
metoprolol, labetolol

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• Adverse effects: Lethargy, fatigue, rash, cold hands
and feet, nausea, breathlessness, nightmares and
bronchospasm

• Selective beta blockers have relatively lesser

adverse effects

• Therapeutic uses other than angina include

hypertension, Cardiac arrhythmias, post myocardial
infarction and pheochromocytoma

01/01/2026 Abiy G 100

 Calcium channel blockers

• Calcium is necessary for the excitation contraction

coupling in both the cardiac and smooth muscles

• Calcium channel blockers appear to involve their

interference with the calcium entry into the
myocardial and vascular smooth muscle, thus
decreasing the availability of the intracellular
calcium e.g. nifedipine, felodipine, verapamil and
diltiazem

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• Other therapeutic uses: hypertension, acute coronary
insufficiency, tachycardia,

• Adverse effects: flushing nausea/vomiting, headache,

Ankle swelling, dizziness, constipation,etc

Miscellaneous drugs,e.g. Acetylsalicylic acid

• Acetylsalicylic acid (aspirin) at low doses given

intermittently decreases the synthesis of thromboxne
A2 without drastically reducing prostacylin synthesis

01/01/2026 Abiy G 102

• At the doses of 75 mg per day it can produce
antiplatelet activity and reduce the risk of
myocardial infarction in angina patients

01/01/2026 Abiy G 103

 Anti - arrhythmics

• Electrophysiology of cardiac muscle: the

pathophysiological mechanisms responsible for the
genesis of cardiac arrhythmias are not clearly
understood

• However, it is generally accepted that cardiac

arrhythmias arise as the result of either of

a) Disorders of impulse formation and/ or

b) Disorders of impulse conduction.

01/01/2026 Abiy G 104
 Pharmacotherapy of cardiac arrhythmias

• Antiarrhythmic drugs are used to prevent or correct

cardiac arrhythmias (tachyarrhythmias)

• Drugs used in the treatment of cardiac arrhythmias

are traditionally classified into:

01/01/2026 Abiy G 105

• Class (I): Sodium channel blockers which include
quinidine, lidocaine, phenytion, flecainide, etc.
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 [Link]
01/01/2026 Abiy G 106
Class – I drugs

Quinidine

• It blocks sodium channel so that there is an increase in

threshold for excitability

• It is well absorbed orally

Adverse effects

• It has low therapeutic ratio

• Main adverse effects are SA block, cinchonism, severe

headache, diplopia and photophobia

01/01/2026 Abiy G 107

Lidocaine

• Used commonly as a local anaesthetic blocks both

open and inactivated sodium channel and decreases
automaticity

• It is given parenterally

Adverse effects

• Excessive dose cause massive cardiac arrest,

dizziness, drowsiness, seizures, etc.

01/01/2026 Abiy G 108

Flecainide

• It is a procainamide analogue and well absorbed

orally

• It is used in ventricular ectopic beats in patients

with normal left ventricular function

01/01/2026 Abiy G 109

 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

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• Beta blockers may potentiate the negative inotropic
action of other antiarrhythmics

Therapeutic uses

• Useful in tachyarrhythmias, in pheochromocytoma

and in thyrotoxicosis crisis

• It is also useful in patients with atrial fibrillation

and flutter refractory to digitalis

01/01/2026 Abiy G 111

 Class – III: Potassium channel blockers

AMIODARONE

• This drug is used in the treatment of refractory

supraventricular tachyarrhythmias and ventricular
tachyarrhythmias

• It depresses sinus, atrial and A.V nodal function

• The main adverse effects of this drug are anorexia,

nausea, abdominal pain, tremor, hallucinations,
peripheral neuropathy, A.V. block
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 Class IV drugs: Calcium channel blockers

Verapamil

• This drug acts by blocking the movement of

calcium ions through the channels

• It is absolutely contraindicated in patients on beta

blockers, quinidine or disopyramide

• It is the drug of choice in case of paroxysmal

supraventricular tachycardia for rapid conversion to
sinus rhythm
01/01/2026 Abiy G 113
 Class - V drugs

Digoxin

• Causes shortening of the atrial refractory period with

small doses (vagal action) and a prolongation with
the larger doses (direct action)

• It prolongs the effective refractory period of A.V

node directly and through the vagus

• This action is of major importance in slowing the

rapid ventricular rate in patients with atrial
fibrillation
01/01/2026 Abiy G 114