DRUGS AFFECTING THE

CARDIOVASCULAR SYSTEM
• Hypertension is defined a systolic blood pressure (SBP) greater
than 140 mmHg or diastolic blood pressure (DBP) greater than
90 mmHg.

• Isolated systolic hypertension (SBP)> 140mmHg and DBP<

90mmHG.

• Hypertension can be classified as stage 1, 2, 3, or 4 based on

the degree of Bp elevation.
 Classification of BP

Category Systolic Diastolic

Normal < 120 < 80
High Normal 120 – 139 80 - 89
Hypertension -
Stage 1 140 – 159 90 - 99
Stage 2  160  100

Regulation of BP: in short and long term mechanisms

 Short-Term Regulation

• BP is regulated by ANS reflex and humoural system(RAS)

• Mediated by the ANS Reflex pathway

– Change in MAP sensed by baroreceptors

– Processed by VMC (vasomotor center) in the medulla

• Which regulates sympathetic and parasympathetic NS output

–  BP (sensed by Baroreceptors)  VMC neuronal

activity  in sympathetic tone and  in Parasympathetic
(vagal) tone

–  BP  in baroreceptor neuronal activity

 in vagal tone and  in sympathetic tone.

 Short-Term Regulation

• Increases in sympathetic tone result in increased

▪ peripheral vascular resistance (PVR)

▪  venous tone

▪  heart rate and

▪  contractility of the myocardium.

• Increases in vagal tone lead to lowering of heart rate.

 Long-Term Regulation

• Mediated by hummoral factors that control blood volume by

regulating Na+ and water retention.
• The reflex pathways are described below:
– Changes in RBF(renal blood flow) and Pressure, which are
directly related to MAP, result in changes in Renin secretion.

– Drop in RBF or pressure results in an increase in renin

release from the kidney.
– High sympathetic outflow also causes an increase in renin
secretion
 Long-Term Regulation

• An increase in renin release leads to an increase in

circulating Angiotensin II.

• The primary actions of angiotensin II are:

– To stimulate the synthesis and secretion of aldosterone.

– To raise blood pressure by direct vasoconstrictor effects

(angiotensin II is one of the most potent vasoconstrictors
known).

• Aldosterone acts on the kidney to retain Na+ (and therefore

water), leading to an increase in blood volume.
• BP = CO x PVR

• CO = HR x SV

• Hypertension could be

– Primary or essential

– Secondary
 Management of hypertension

• To treat hypertension, one can lower heart rate,

stroke volume, or TPR.

• Pharmacologic and non-pharmacologic interventions may

help an individual reduce his or her blood pressure.
 Non-pharmacologic therapy

• Life style modification

– If overweight, lose weight
– Limit alcohol intake
– Reduce sodium to more than 2.4 g sodium per day
– Exercise
– Stop smoking
– Reduce intake of dietary fat and cholesterol.
– Dietary Approaches to Stop Hypertension (DASH)
 Pharmacological therapy

• Drug therapy is indicated if Bp is still excessive 3-6 months after implementation of

life style changes.
• Antihypertensive drugs

– Any one of the following classes of drugs could be used as first step agents:

• Diuretics

• Beta blockers

• Calcium antagonists

• Angiotensin converting enzyme inhibitors

• Angiotensin II receptor blockers

– Alternative Agents

• Alpha blockers

• Centrally acting antihypertensives E.g. Methyl dopa

• Arterial vasodilators e.g. hydralazine, minoxidil

 1. Diuretics

• Are drug which induce a state of increased urine flow

• Are ion transport inhibitors that decrease reabsorption of Na+

and Cl- at different sites in the nephron; which creates an
osmotic pressure within the nephron to prevent passive
diffusion of water.

• Increase volume of the urine and change its PH as the ionic

composition of the urine & blood changes

• They affect the volume of blood, acid –base balance, and

electrolyte level in the blood
Fig- the Segments of nephron and its sites drug action
a. high ceiling diuretics (Loop diuretics)

• Eg -Bumetanide, Furosemide, Torsemide & ethacrynic acid

• Major action on the ascending limb of loop of Henle

• They are the most efficacious.

Mechanism of action

➢ Inhibit Na+/K+/2Cl- transport system; so inhibit reabsorption of

these electrolyte

➢ Increase Ca++ content of the urine and induces the secretion of

prostagladin; leads to decrease renal vascular resistance &
increase blood flow (Useful for patients with poor renal
function)

➢ Decrease the secretion of uric acid but increases its

reabsorption
Therapeutic use:-
✓ Because of their rapid onset of action useful in emergency –
acute pulmonary edema of congestive heart failure

✓ Hypercalcemia and hyperkalemia treatment

✓ Treatment of hypertension which has been unresponsive to

other diuretics

✓ Treatment of halide toxicity.

✓ Edema related to cardiac, hepatic or renal problem.

Adverse effects:-

▪ Ototoxicity – when used in conjunction with amino glycosides.

▪ Hyperuricmia – compete with uric acid tubular secretion –

exacerbate gout attack

▪ Acute hypovolemia – hypotension, shock & cardiac arrhythmia

▪ Hypokalemia – At collecting duct, high Na+ reach leads to

increase exchange of Na+ for K+
b. Thiziade & related drugs
✓ Eg-Chlorothiazide,Hydrochlorothiazide (prototype),
chlorthalidone
✓The most widely used – inexpensive and well tolerated
✓Greater diuretic activity than acetazolamide
Mechanism of Actions:-
✓Decreased the reabsorption of Na+ & Cl- by inhibiting the
Na+ /Cl- Co- transport system on the distal tubule
✓Cause loss of k+ in the collecting duct
✓KCl supplement or k+ sparing diuretics, (spironolactone) is used
in conjunction
✓Cause decrease urinary calcium excretion (opposite to loop
diuretics)-reduce incidence of kidney stones.
✓Cause hyperglycemia due to a decrease in insulin secretion and
of glucose intolerance.
Therapeutic Uses:-
✓Hypertension
✓Congestive heart failure
✓Hypercalciuria useful patients
✓cardiac edema
Adverse effects:-
•Potassium depletion:-
•Hyperuricemia – exacerbate gouty attack
•Hypercalcemia
•Hypersensitivity
•Caution in the case of diabetic and gouty patients.
c. Potassium sparing diuretics

Spirolactone (Aldactone)

• Mechanism of action: - prevent K+ secretion by

antagonizing aldosterone action at aldosterone receptor
in collecting duct

• Therapeutic use:-

• Given with thiazide or loop diuretics to prevent

hypokalemia

• Secondary hyperaldasteronism
Adverse effect:

• Hyperkalemia

• Gynaecomastia,androgen like effect and minor GIT

disturbance

• Drug interaction:-avoid potassium containing drugs and of

ACE inhibitors.
 2. Sympatholyics (adrenergic antagonists)

• Suppress the influence of the sympathetic nervous system.

• Five categories of sympatholytic drugs

I. Beta adrenergic blockers

E.g. Propranolol, Metoprolol, atenolol, labetalol etc

– have at least three useful actions in hypertension

• Blockade of cardiac beta 1 receptors → decreases heart rate

and contractility

• Suppress reflex tachycardia caused by vasodilators

• Blockade of beta 1 receptors on juxtaglomerualr cells of the

kidney releases of rennin→ reducing angiotensin II mediated
vasoconstriction and aldosterone volume expansion
There are two groups of β -blockers

• Non selective β1 and β2 adrenergic -blockers: Propranolol,

Timolol

• Selective β1 adrenergic blockers: Atenolol, metoprolol-

– preferred in case of asthma.

– Do not disturb blood glucose level

Therapeutic uses

• Hypertension- lowers B.P. by decreasing cardiac output.

• Angina pectoris -decreases oxygen requirement of heart

muscle.

• Cardiac arrhythmias (tachyarrhythmias).

• Prophylaxis for migraine headache.

 Adverse effects of beta blockers:

• Bradycardia, decreased AV conduction, and reduction of

contractility.

• Blockade of beta 2 receptors on the lung promote

bronco constriction

• Mask signs of hypoglycemia; must be used with caution

in patients with diabetes

• Action on the CNS cause insomnia , depression , bizarre

dreams and sexual dysfunction
 II. Centrally acting agents( α-2 agonists)

Drugs

– Clonidine (Catapress, Catapress-TTS), Methyldopa (Aldomet)

– Guanabenz, Guanfacine

• Acts within the brainstem to suppress sympathetic out flow to

the heart and blood vessels.
Mechanism of methyl dopa

▪ Methyl dopa is an α - agonist which is converted to methyl

norepinephrine/false neurotransmitter/ centrally to diminish
the adrenergic output from the CNS

✓ decrease of peripheral resistance or cardiac output

Uses: Mild to moderate hypertension in pregnancy.

Side effects:

• CNS - Sedation,headache, dizziness

• GIT - dry mouth, nausea, vomiting

• Others - Postural hypotension, impotence, allergic reactions

 III. Alpha 1 adrenergic blockers

e.g. prazocin, terazocin

– prevent stimulation of α1 receptors on arteries and veins →

vasodilation→ reduces PR

– Orthostatic hypotension is the major adverse effect.

– Agent of choice if BPH is underlying condition along with

hypertension

• Use: treatment of hypertension and heart failure.

• Adverse effect: - postural hypotension, nasal stuffiness,

failure of ejaculation in males.
 3. Calcium channel blockers

• Are important groups of drugs used for long term treatment of

HTN

• Inhibit Voltage-sensitive Ca2+ channels (L-type or slow

channels) in smooth muscle and cardiac myocytes

• In vascular smooth muscle, this leads to relaxation, especially

in arterial beds.

• These drugs also may produce negative inotropic and

chronotropic effects in the heart
 …
• All the Ca2+ channel blockers approved for clinical use decrease
coronary vascular resistance and increase coronary blood flow.

Two subclasses

– Dihydropyridines

– Non-dihydropyridines

Vessel selective CCBs)

➢Amlodipine, Felodipine, Isradipine

➢Nicardipine, Nifedipine

➢Nisoldipine

(Cardioselective CCBs)

➢Verapamil

➢Deltiazem
 have direct negative effect on
…
the heart while the dihydropyridines don’t

• So concurrent use of β-blockers with verapamil or diltiazem

can magnify the negative chronotropic effect of these drugs &
cause heart block

cause reflex tachycardia

• But verapamil & diltiazem don’t cause reflex tachycardia due

to their negative chronotropic effect

Clinical uses:

• Hypertention, Angina pectoris

• Dysrhythmia (Verapamil - to slow ventricular rate)

 …
Side effects

– Varies among the drugs in this class

– Nifedipine (immediate release capsules): cause headache,

flushing, dizziness & peripheral edema

– Verapamil: constipation, exacerbation of GERD, urinary

retention

– Both verapamil & diltiazem can lead to bradycardia but not

the dihydropyridines

Drug-drug interactions

– Verapamil blocks P-glycoprotein drug transporter w/h is

necessary for excretion of digoxin
• Drugs:

– Captopril, Enalapril, Lisinopril, Quinapril

 …

• ACE is in many tissues, but primarily in endothelial cells

(epithelial cells of blood vessels).

• Increase bradykinin adds to vasodilation, but also to dry

cough

• Mainly vasodilators. Do not affect CO

• Lower Bp by preventing conversion of angiotensin I into

angiotensin II
 ACEIs…
• Untoward effects:
✓ rash, dry cough, angioedema, hyperkalemia , hypotension.
Contraindications
– Angioedemia
– Pregnancy: Pregnancy Category D
• Drug interaction:
✓ potassium supplements
✓ Potassium sparing diuretics
✓ NSAIDS- retentin of fluid and decrease synthesis of PGI2
 5. Angiotensin Receptor Blockers (ARBs)

• Angiotensin II receptor antagonists

• Are alternative to ACE inhibitors

• MOA:- inhibit

– the vasoconstrictor effect of angiotensin II by blocking their

receptors.

– Aldosterone release

• Donot affect bradykinin synthesis

• avoid dry cough and angioedema

 …

➢ Used in treatment of hypertension and heart failure

Side Effects

– are not safe for pregnant women, dizziness

– Lowest incidence of side effects

– Hyperkalemia

– Hypotension

– Decrease in GFR
 Direct acting vasodilators
Include:
a)Arterial vasodilators eg. hydralazine, minoxidil,diazoxide
b)Arterial and venous dilators eg. Nitroprusside
Vasodilators:
• Produce relaxation of the vascular smooth muscle-decrease
peripheral resistance- decrease BP.
• But, they cause reflex tachycardia and rennin secretion which
increases water and salt retention.
• Therefore, the vasodilators are given with β-blockers and/or
diuretics
• Used for treatment of emergency hypertension.
a) Hydralazine

• Cause a selective decrease in vascular resistance in the

coronary, cerebral, and renal circulations, with a smaller effect
in skin and muscle.

• Hydralazine: first line drug for Hypertensive

Emergencies

• Hydralazine is the second line drug for hypertensive

pregnant women.

– 5 -10mg intravenous every 20 minutes whenever the

diastolic BP> 110 mmHg.
 …

Minoxidil excessive hair growth on

• By opening K+ channels in face, back, arms & legs

smooth muscle and thereby – Topical minoxidil is

permitting K+ efflux, it causes marketed for
hyperpolarization and treatment of male
relaxation of smooth muscle pattern baldness

• Side effects

• Fluid & water retention

• Hypertrichosis: refers to
Sodium Nitroprusside

• It dilates both arterial and venous vessels,

– resulting in reduced peripheral vascular resistance and

venous return.

• It rapidly reduces venous return and may result in excessive

hypotension.

• Used in the treatment of hypertension and heart failure by

reducing both preload and the afterload.

• Adverse effect:- overdose hypotension, cyanide related

metabolic acidosis which can be treated by sodium thiosulfate.
45
– Refers to CVS disorder characterized by sever
pain of the heart
– Often starts as crushing pain of chest which
usually radiates to Left arm, shoulder, jaw and
neck
– Angina occurs as result of an imbalance b/n
myocardial O2 demand and supply

46
 Angina is caused by an imbalance
between O2 supply and demand
O2 supply O2 demand
No anginal symptoms
A

B Angina

47
• There are three types of angina
➢Stable angina(angina of effort)
– Also called angina of effort, typical angina
– Is the most common type
– Usually triggered by physical activity
– Also emotional excitement, large meal, cold exposure
can precipitate this type of angina
– Caused by atherosclerosis blockade of blood vessels
➢Variant angina
– Also called Prinzmetal’s or vasospastic angina
– Occurs due to spasm of coronary arteries
– Associated with pain at rest
– May occur with stable angina 48
➢ Unstable angina
– Also c/d crescendo or preinfarction angina
– It is a medical emergency
– Associated with pain at rest
– Occurs as result of high degree of atherosclerosis in the
coronary arteries
– It is the worst of all types of angina
– It has high risk for Myocardial infarction and Death
– Caused by severe stenosis with probable plaque rupture
leading to platelet aggregation, thrombosis and/or
vasoconstriction
Therapeutic Objectives of angina treatment
– Increase blood flow to ischemic heart muscle and/or
decrease myocardial oxygen demand
49
The causes of angina includes:
• atheriosclerotic heart disease, and almost
invariably associated with a significant
obstruction of coronary artery.
• Vasospasm of the coronary artery due to the
effect of sympathetic neurotransmitters
• An increase in workload on the heart due to an
increase in heart rate , contractility and of
ventricular blood volume
• Emboli, etc
▪ Goals of angina treatment
✓ Terminate acute angina pain
✓ Reduce the frequency (recurrence) of angina
attacks
• Reducing myocardial oxygen demand
• Increasing oxygen supply to the myocardium
✓ Prevention of myocardial infarction & death
• This can be achieved by:
– Slowing heart-rate
– Reducing the preload by dilating veins
– Causing heart to contract with less force
– Lowering blood pressure – less resistance in heart
to pushing blood from chambers (reduce after-load)
– Preventing (reducing) lipid & platelet accumulation
in the blood vessels 52
• Classes of Drugs available for angina
treatment
Nitrates
Calcium channel blockers
Beta blockers
Antiplatelet agents

53
– Includes: nitroglycerin, isosorbide mononitrate, isosorbide
dinitrate, pentaerythritol tetranitrate
– Except nitroglycerin which volatile liquid, these drugs are
solid at room temperature
– MOA: nitrates are thought to work by interacting with nitrate
receptors found on vascular smooth muscles
• Nitrate receptors contain sulfohydryl (SH) groups which
reduces nitrates to nitric oxide (NO)
• NO stimulates guanylyl cyclase which synthesizes cGMP
• cGMP causes smooth muscle relaxation which leads to
vasodilation
– Nitrates produce more pronounced dilation on the veins than
the arteries
• Nitrates relieve the symptoms of angina by
restoring the balance b/n myocardial O2 demand &
supply
• O2 demand is lowered as result of:
– Reduction in cardiac preload (as result of venous pooling
of blood)
– Reduction in cardiac afterload (as result of arteriolar
dilation)
• O2 supply is increased as result of:
– Increased blood flow to ischemic areas as result of direct
vasodilatory effects of nitrates on coronary arteries
– Nitrates were also found to prevent platelet aggregation
• Preparations: based on their duration of
action nitrates can be divided into three
groups:
– Short acting (several minutes)
• Amyl nitrate: inhalant, very rapid absorption
• Sublingual: Nitroglycerin, isosorbide dinitrate
• Avoid hepatic first pass metabolism, very short
duration of action
– Intermediate-acting (several hours)
• Oral Erythrityl tetranitrate and pentaerythritol
tetranitrate
• Oral Isosorbide dinitrate, Buccal nitroglycerin slow-
release
• Oral isosorbide mononitrate
– Long-acting
• Transdermal, nitroglycerin slow–release (8-10 hours)
56
• Tolerance & dependence
– Repeated & frequent exposure to organic
nitrates is accompanied by dev’t of tissue
tolerance to the drugs vasodilatory effects
– The mechanism for tolerance to nitrates is not
well understood but could be due to:
• Depletion of SH group
• Decrease in sensitivity of guanylyl cyclase to NO
• Activation of RAAS
– To reduce/prevent nitrate tolerance, clinicians
should employ the smallest effective dose &
administer the drugs infrequently
– A daily nitrate free period is also recommended
• Side effects
– Headache
– Postural hypotension
– Flushing
– Reflex tachycardia are common side effects
• Since an increase in SNS activity is a common
feature of anginal attacks, the use of β-
antagonists is rational
• β-antagonists approved for secondary angina in
USA includes:
– Propranolol & nadolol(non selective β1 &2
antagonists)
– Metoprolol & atenolol (β1 selective antagonists)
• MOA:
– Antagonize the actions of catecholamines on the
heart & reduce HR, FC
• Mechanism not well known but expected to be due
to:
– Reduced HR & FC produces reduced cardiac output
– Reduce plasma renin activity
– An action on the central nervous system
• So, β-antagonists reduce myocardial O2 demand by
reducing 3 of the major determinants of myocardial O2
demand
– HR, FC,
– Generally, β-antagonists produce their antianginal effects
by:
– Decreasing O2 demand (by decreasing HR, FC)
• β-antagonists are particularly indicated in the management of
patients whose anginal attack are frequent & unpredictable

– They can be combined with nitroglycerin

• Side effects

– Abrupt interruption of β-antagonists can lead to

• Reappearance of angina

• Acute myocardial infarction

• Death
– The dose should gradually be tapered off
• They are contraindicated to
– bronchospastic conditions

– Bradycardia

– diabetic cases

– left ventricular failure.

• Are orally active group of drugs approved for
treatment of vasospastic & effort angina
• Are particularly effective in the prophylaxis of
coronary vasospasm or variant angina
• MOA: bock L-type calcium channels in
vascular smooth muscles & heart producing:
– Decreased HR & FC (decrease demand)
– Decrease PVR (decrease demand)
– Dilate coronary arteries (increase supply)
• Different classes of CCBs are available
– Phenyalkylamines: verapamil, with T1/2 3-6 hours

– Benzothiazepines: Diltiazem; T1/2 3-6 hours

– Both verapamil & diltiazem are cardioselective CCBs

– Dihydropyridines:
• Nimodipine-: T1/2 1-2 hours

• Nifedipine- T1/2 2-6 hours

• Nifedipine sustained-release, Isradipine - T1/2 8-12 hours

• Amlodipine – very long acting – T1/230-50 hours

65
Side effects
• Serious side effects
• Cardiac depression (non-DHPs)
– Cardiac arrest
– Bradycardia
– Atrio-ventricular block
– Heart failure
• Minor side effects
– Headache, flushing, dizziness, nausea,
constipation, coughing, wheezing
– Peripheral edema due to greater arteriolar than
venous dilation
66
• Congestive heart failure is a condition in which

the heart is unable to pump sufficient blood to

meet the needs of the body due to

– impaired ability of cardiac muscle to contract or

increased work load imposed on the heart

Causes of heart failure
• Ischaemic heart disease
• Hypertention
• Heart muscle disorders-decrease in contractility.
• Valvular heart disease
• Drugs that has negative inotropic effects.
• Pressure and volume overload (an increase in
afterload and preload).
• Etc.
Therapeutic strategies in heart failure
includes:
➢ Reduction in physical activity
➢ Low dietary intake of sodium
➢ Avoid agents that exacerbate heart failure.
➢ Treatment with drugs(positive inotropic and
diuretics).
➢ The current approach to therapy for CHF involves
preload reduction, after load reduction, and
enhancement of inotropic state.
– Reduced tissue perfusion as result of reduced CO
initiates the d/f compensatory mechanisms
• Increased SNS activity
• Activation of the RAAS

– Activation of the SNS causes:

• Increased arterial & venous constriction which increases the
afterload & preload respectively
• Increased HR & FC which increases the CO

– Activation of the RAAS causes:

• Vasoconstriction
• Increased salt & water retention
✓ Unfortunately, each of these compensatory responses will also
promote disease progression

– Elevations of both the preload & afterload leads to

increased diastolic & systolic wall stress

• Impairs myocardial energetics & will induce hypertrophic

remodeling of ventricles
 Drugs used in the management of HF
POSSITIVE INOTROPIC AGENTS
i) Cardiac glycosides: eg Digoxin
• Cardiac glycosides come from fox gloves (Digitalis spp.) and
related plants.
• Digoxin is by far the most important of these compounds.
Mechanism of action
• Glycosides inhibit Na+/K+ ATPase transport system.
• Inhibition of Na+/K+ ATPase inhibits out flux of Na+ and
increase intracellular Na+ concentration.
• Increased Na+ concentration slows extrusion
of Ca++ via the Na+/Ca++ exchange
transporter.
➢The overall effect is increased intracellular calcium
level.→ increase the force of myocardial
contraction→increase in the cardiac output.
• Relationship of k+ to inotropic action
– K compete with C.glycosides for binding to Na/K
ATPase
– when k+ levels are low , binding of C.glycosides
to Na+/K ATPase will increase excessive
inhibition  toxicity
– when K+ levels are high, inhibition is decreased
reduction in therapeutic response
– Hence, it is imperative that K+ levels be kept
within physiologic range(3.5-5meq/l)
Therapeutic uses
• Congestive heart failure emergencies as it has fast onset
of action
• Cardiac arrhythmias(supraventricular tachycardia)
– Atrial fibrillation
– Atrial flutter
– Paroxysmal tachychardia (has vagotonic action)
Adverse effects
• Digitalis glycosides have a low therapeutic index.
• Digitalis toxicity includes, anorexia, nausea, vomiting,
visual disturbance and ventricular fibrillation at high dose
Drug interaction:
• Diuretics that deplete potassium in the blood increase
digitalis toxicity.

• Enzyme inducer (rifampicin) decrease the level of digoxin

in the blood

• Antacid and kaolin decrease the bioavailability of digoxin

• Potassium increase in the blood decrease the effect of

digoxin

• An increase in the blood calcium increases the action of

digoxin
ii)Beta- adrenergic agonists

Mechanism of action

• Increase the force of myocardial contractility and

then increase cardiac output.

• Improve cardiac performance by positive inotropic

effects.

• Dobutamine IV infusion is used in treatment of acute

heart failure.

• NOTE: Other positive inotropic agents include

bipyridines (eg-inamrinone, milrinone)
 DRUGS WITHOUT POSITIVE INOTROPIC EFFECTS
Are the first line drugs for chronic heart failure management.

i) Vasodilators:

• The vasodilators are effective in acute heart failure because

they provide a reduction in preload or after load.

• Dilation of venules decrease cardiac preload.

• Dilation of arteries decreases cardiac afterload.

• Hydralazine has a direct vasodilator effect on arteries→

decrease vascular resistance (afterload) → improves in
cardiac output.
• Sodium nitroprusside dilates both the arteries and
veins→decrease both the afterload and the preload. In general,
nitroprusside initiation in patients with severe heart failure
results in increased cardiac output and a parallel increase in
renal blood flow, improving both glomerular filtration and
diuretic effectiveness.

• Nitrates are the common Venus dilators (decrease the

preload) used in the treatment of congestive heart failure.

• Most vasodilators, cause hypotension .

• Calcium channel blockers should be avoided.

ii) Angiotensin converting enzyme inhibitors:

mechanism

• ACEIs, by blocking the formation of angiotensinII, reduce the

vascular resistance →improve tissue perfusion and reduce
cardiac after load.

• They also cause natriuresis and diuresis by inhibiting

secretion of aldosterone.

• Angiotensin II receptor blockers (like losartan) can

substitute ACEI in those patients who cannot tolerate the latter.
iii) Diuretics
• Diuretics are important in increasing salt and water
excretion, especially if there is edema.
• They decrease preload and blood pressure→results
in a decrease in workload and oxygen demand.
• Loop diuretics are used for patients who require
extensive diuresis (like with edema) and in those with
renal insufficiency, but avoid over dose to prevent
hypovolemia.
• Thiazides are mild diuretics (effective in normal
kidney functions)