CVS, 2021

Pharmacology of Cardiovascular system
Drugs acting on
cardiovascular system
By
Fathi M Sherif
Cardiac vascular disease (heart + blood vessels)
What are the common cardiovascular diseases
Abnormal heart arrhythmia
Heart failure, coronary heart diseases
Hypertension, angina, ,,,,,,,,,,
90% of CVS are preventable,

by lifestyle changes (diet, exercise, smoking quit,…)
CVS are the leading cause of death in the world

System: heart, blood vessels (arteries, & veins) and blood
Blood rich with oxygen and

nutrients moves through vessels
called arteries to narrower arterioles
to capillaries where the rich
blood is absorbed by bodies cells
and waste products are absorbed
(CO2, urea and ammonia) →
deoxygenated blood returned
to circulation via venules to veins
for elimination through the lungs and kidneys.
Heart:
4 Chambers –
R & L atria,
R & L ventricles
Blood from circulation to R atrium to R ventricle

to pulmonary artery to lungs for gas exchange
(CO2 & O2) to L atrium to L ventricle to aorta
to systemic circulation
Heart muscle = myocardium & surrounds the atria & ventricles

Conduction: generated & conducted by myocardium
Originates in sinoatrial (SA) node →

atrioventricular (AV) node →
Bundle of HIS →
purkinje fibers
ventricular muscle tissue →
contraction forcing blood →
lungs and circulating system
Heart Failure - HF
Management of Congestive Heart Failure - CHF
Most common syndrome & incidence is increasing

CHF is a condition in which the heart is unable to pump
sufficient blood to meet the needs of the body.
Causes: impaired ability of the cardiac muscle to contract & an increased

workload imposed on the heart which leads to ↑ BV and interstitial fluid
Common causes of
chronic HF is hypertension
acute failure is myocardial infraction
The therapeutic goal for CHF is to ↑ CO. Thus, CHF is treated with drugs
that increase the strength of the cardiac muscle (+ve inotropic action)
Compensatory response of heart muscle in CHF:
↑ sympathetic activity, fluid retention & myocardial hypertrophy
Decompensated HF:
adaptive mechanism fail to maintain cardiac output
Classification of heart failure

Class I (asymptomatic)
No symptoms with ordinary activity & no limitation of physical activity
Class II (mild)
Symptoms with ordinary activity & slight limitations of physical activity
Class III (moderate)
Symptoms with ordinary activity but confort at rest, market limitation..
Class IV (severe)
Symptoms even at rest & patients are unable to carry out any activity
Classification of drugs used in HF
1. Positive inotropic drugs

a. Cardiac glycosides Digoxin & Digitoxin
b. B-adrenergic agonists Dopamine & Dobutamine
c. Antiarrhythmic agents Amrinone & Milrinone
2. Diuretics thiazides, frusemide

3. ACEIs Captopril, enalapril, ramipril
4. Vasodilators Sod. nitroprusside, hydralazine
Digitalis is about 20 species commonly called foxgloves, and
The best known species is digitalis purpurea
The term digitalis is also used for preparations of

cardiac glycosides ------ digoxin & digitoxin
Digitoxin & digoxin differs in pharmacokinetics

(lipid solubility, oral bioavailability, Vd, PP bindings,
metabolism, t1/2 and excretion.
Digoxin is most widely used: oral is common & IV in Emergnecy.
Has narrow safety margin (1.5 ng/ml plasma conc. for therap. & 2 ng/ ml for toxic conc.).
Loading dose especially in severe CHF for rapid effect

Maintenance dose used for mild and moderate CHF
Digitalis inhibits the membrane Na/K ATPase responsible for Na pump in exchange with K → to
↑cystosolic Ca → ↑ Contractility and ↑ COP.
The net effect is a decreased intracellular K+ concentration and an increased Na+ and
Ca2+ concentration. The increased Ca2+ augments myofibril interaction in cardiac muscle and leads
to positive inotropic action responsible for digitalis's usefulness in clinical practice
Also : ↓vascular tone & cardiac load
↓ heart rate
↓ renin release & Na & water retention
CNS: vagal center stimulation, CTZ stimulation, visual

disturbance & convulsion, hallucination
Adverse effects: Cardiac arrhythmia

GIT upsets & CNS manifestations
Hormonal disturbances
Factors increasing digitalis toxicity: overdose, renal failure, elderly patients, hyperkalemia,
hypercalcemia (metabolic as K, Ca, Mg – drugs as Quinidine, thiazides – diseases as renal, kidney).
Toxicity: commonly confusion, irregular pulse, anorexia, vomiting, headache, vision
Treatment of toxicity
Stop digoxin & diuretics, give anti-arrhythmic drugs as lidocaine or phenytoin & atropine
for bradycardia & heart block.
propranolol for ventricular tachycardia
Digoxin antibodies (feb-fragments, in severe acute posioning)
Drug-drug interactions
Antacids, erythromycin & tetracyclines …. absorption
Quinidine, verapamil …….. excretion
Diuretics increase digoxin toxicity ….. dynamic
beta-blockers & clonidine, methyldopa…….. dynamic
Digoxin (lanoxin®)
Protein binding = low
t1/2 = 36 hrs
Drug accumulation can occur
Monitor SE & serum levels closely
Metabolized by liver & excreted by kidney
Kidney function can affect excretion of digoxin
Do not confuse digoxin and digitoxin
Digitoxin = highly protein bound with a long t1/2 – seldom prescribed

Digoxin
Action: increase myocardial contraction (+ inotropic) Metabolism: liver (16%)
slows HR (-chronotropic), therefore regulating Protein binding: 25%
the rate and rhythm of the heart. Elimination t1/2: 36-48 hs &
5 days for impaired kidneys
Therapeutic serum level = 0.5 – 2.0 ng/ml
Uses: moderate to severe systolic CHF, arrhythmias
SEs: digitalis toxicity, bradycardia (pulse < 60), anorexia,

diarrhea, N & V, blurred vision, breast enlargement,
lethargy - older adults more prone to toxicity,
DIs: Other heart medications

Other Drugs +ve inotropes
Beta agonists: dopamine, dobutamine, adrenaline & NA

They increase cAMP levels in the myocardium
They indicated in acute HF
Phosphodiesterase III inhibitors: anti-arrhythmic drugs

Amrinone & milrinone: They are selective inhibitors of PDE type
III but have side effects (rapid tolerance, vomiting, hepato-toxicity,
cardiac arrhythmia).
Diuretics: Thiazides, loop diuretic: They are used in symptomatic HF with

fluid retention (ankle & pulmonary), reduces fluid volume (1st line)
ACEIs: dilate venules & arterioles & improves renal blood flow & ↓ blood
fluid volume Captopril, enalapril & lisinopril
They ↓ production of angiotensin II & NA release.
They ↓ preload and afterload. They have indirect diuretic activity.
They are use in all types of CHF
Beta-adrenoceptor blockers Carvedilol, metoprolol, bisoprolol

They ↓ mortality in patients with CHF
Precautions used in mild CHF & combined with ACEIs & diuretics.
Vasodilators: ↓ venous blood return to heart & ↓ cardiac filling, vent.

Stretching & CO2 demand.
Preload reducers: nitrates
Afterload reducers: hydralazine
Combined pre- & afterload reducers: ACEIs & nitroprussides

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Pharmacology of Cardiovascular system

90% of CVS are preventable,

CVS are the leading cause of death in the world

Blood rich with oxygen and

Blood from circulation to R atrium to R ventricle

Heart muscle = myocardium & surrounds the atria & ventricles

Originates in sinoatrial (SA) node →

Most common syndrome & incidence is increasing

Causes: impaired ability of the cardiac muscle to contract & an increased

Classification of heart failure

1. Positive inotropic drugs

2. Diuretics thiazides, frusemide

The term digitalis is also used for preparations of

Digitoxin & digoxin differs in pharmacokinetics

Digoxin is most widely used: oral is common & IV in Emergnecy.

Loading dose especially in severe CHF for rapid effect

CNS: vagal center stimulation, CTZ stimulation, visual

Adverse effects: Cardiac arrhythmia

Do not confuse digoxin and digitoxin

Digitoxin = highly protein bound with a long t1/2 – seldom prescribed

Action: increase myocardial contraction (+ inotropic) Metabolism: liver (16%)

slows HR (-chronotropic), therefore regulating Protein binding: 25%

Uses: moderate to severe systolic CHF, arrhythmias

SEs: digitalis toxicity, bradycardia (pulse < 60), anorexia,

DIs: Other heart medications

Beta agonists: dopamine, dobutamine, adrenaline & NA

Phosphodiesterase III inhibitors: anti-arrhythmic drugs

Diuretics: Thiazides, loop diuretic: They are used in symptomatic HF with

Beta-adrenoceptor blockers Carvedilol, metoprolol, bisoprolol

Vasodilators: ↓ venous blood return to heart & ↓ cardiac filling, vent.

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