Cardiovascular medications

Vasodilators
Vasodilators are useful agents in the treatment of heart failure and hypertension.
Several groups of drugs can lead to vasodilatation; including those inhibiting the
renin-angiotensin-aldosterone system (RAAS), direct-acting vasodilators,
calcium channel blockers, organic nitrates, and α-adrenergic blockers (discussed
under “antiadrenergic agents” in this chapter).

Inhibitors of the Renin-Angiotensin-Aldosterone System

Angiotensin II is one of the most potent vasoconstrictor peptides in the body.
Therefore, inhibitors of the renin-angiotensin-aldosterone system (RAAS) are
frequently used in the treatment of hypertension and heart failure. It plays an
important role in preventing the remodeling of the left ventricle following
myocardial infarction. Figure 17.1 summarizes some actions of angiotensin II.
Angiotensin-converting enzyme (ACE) inhibitors suppress angiotensin II
formation (Fig. 17.2), whereas angiotensin receptor antagonists directly block the
receptors of angiotensin II and minimize its effect.
Angiotensin-Converting Enzyme Inhibitors
Captopril is the short-acting active prototype of this group. Enalapril is an oral
prodrug that is converted by hydrolysis to an active compound, enalaprilat, with
effects similar to those of captopril. Enalaprilat itself is available only for
intravenous use, primarily for hypertensive emergencies. Lisinopril is a lysine
derivative of enalaprilat. Benazepril, fosinopril, moexipril, perindopril, quinapril,
ramipril, and trandolapril are other long-acting members of this class. All are
prodrugs, like enalapril, and are converted to active agents by hydrolysis,
primarily in the liver.
 Antianginal drugs

The three main types of angina are:

• stable angina (angina of effort), where atherosclerosis restricts blood flow in
the coronary vessels; attacks are usually caused by exertion and relieved by
rest
• unstable angina (acute coronary insufficiency), which is considered to be an
intermediate stage between stable angina and myocardial infarction
• Prinzmetal angina (variant angina), caused by coronary vasospasm, in which
attacks occur at rest.
Management depends on the type of angina and may include drug treatment, coronary
artery bypass surgery, or percutaneous transluminal coronary angioplasty.
.
 NITRATES
Organic nitrates have a vasodilating effect; they are sometimes used alone,
especially in elderly patients with infrequent symptoms. Tolerance leading to reduced
antianginal effect is often seen in patients taking prolonged-action nitrate
formulations. Evidence suggests that patients should have a ‘nitrate-free’ interval to
prevent the development of tolerance. Adverse effects such as flushing, headache, and
postural hypotension may limit nitrate therapy but tolerance to these effects also soon
develops. The short-acting sublingual formulation of glyceryl trinitrate is used both
for prevention of angina before exercise or other stress and for rapid treatment of
chest pain. A sublingual tablet of isosorbide dinitrate is more stable in storage than
glyceryl trinitrate and is useful in patients who require nitrates infrequently; it has a
slower onset of action, but effects persist for several hours.
 BETA-BLOCKERS

Beta-adrenoceptor antagonists (beta-blockers), such as atenolol , block

betaadrenergic receptors in the heart, and thereby decrease heart rate and
myocardial
contractility and oxygen consumption, particularly during exercise. Beta-blockers
are
first-line therapy for patients with effort-induced chronic stable angina; they
improve
exercise tolerance, relieve symptoms, reduce the severity and frequency of angina
attacks, and increase the anginal threshold.
Beta-blockers should be withdrawn gradually to avoid precipitating an anginal
attack;
they should not be used in patients with underlying coronary vasospasm
(Prinzmetal
 CALCIUM-CHANNEL BLOCKERS

A calcium-channel blocker, such as verapamil, is used as an alternative to a

betablocker to treat stable angina. Calcium-channel blockers interfere with the
inward movement of calcium ions through the slow channels in heart and vascular
smooth muscle cell membranes, leading to relaxation of vascular smooth muscle.
Myocardial contractility may be reduced, the formation and propagation of
electrical impulses within the heart may be depressed and coronary or systemic
vascular tone may be diminished.

Calcium-channel blockers are used to improve exercise tolerance

patients with chronic stable angina due to coronary atherosclerosis or with
abnormally small coronary arteries and limited vasodilator reserve.

Calcium-channel blockers can also be used in patients with unstable angina with a
vasospastic origin, such as Prinzmetal angina
Unstable angina
Unstable angina requires prompt aggressive treatment to prevent progression to
myocardial infarction.
Initial treatment is with acetylsalicylic acid to inhibit platelet aggregation,
followed by heparin. Nitrates and beta-blockers are given to relieve ischaemia; if
beta-blockers are contraindicated, verapamil is an alternative, provided left
ventricular function is adequate.
Prinzmetal angina
Treatment is similar to that for unstable angina, except that a calcium-channel
blocker is used instead of a beta-blocker.

Verapamil hydrochloride
Tablets, verapamil hydrochloride 40 mg, 80 mg
Uses:
angina, including stable, unstable, and Prinzmetal; arrhythmias
Dosage:
Angina, by mouth, ADULT 80–120 mg 3 times daily (120 mg 3 times daily usually
required in Prinzmetal angina)
 Antiarrhythmic drugs

Sinus bradycardia (less than 50 beats/minute) associated with acute

myocardial
infarction may be treated with atropine. Temporary pacing may be required
in
unresponsive patients. Drugs are of limited value for increasing the sinus
rate long term in the presence of intrinsic sinus node disease and
permanent pacing is usually
required.
Cardiac arrest
In cardiac arrest, epinephrine (adrenaline) is given by intravenous injection
in a dose
of 1 mg (10 ml of 1 in 10 000 solution) as part of the procedure for
cardiopulmonary
resuscitation.
 Atenolol
Atenolol is a representative beta-adrenoceptor antagonist. Various drugs can
serve as
alternatives
Tablets , atenolol 50 mg, 100 mg

Uses:
arrhythmias; angina , hypertension; migraine prophylaxis

Dosage:
Arrhythmias, by mouth, ADULT 50 mg once daily, increased if necessary to 50 mg
twice daily or 100 mg once daily
 Digoxin

Tablets , digoxin 62.5 micrograms, 250 micrograms

Oral solution , digoxin 50 micrograms/ml
Injection (Solution for injection), digoxin 250 micrograms/ml, 2-ml ampoule
Uses:
supraventricular arrhythmias, particularly atrial fibrillation; heart failure

Dosage:
Atrial fibrillation, by mouth , ADULT 1–1.5 mg in divided doses over 24 hours for
rapid digitalization or 250 micrograms 1–2 times daily if digitalization less urgent;
maintenance 62.5–500 micrograms daily (higher dose may be divided), according to
renal function and heart rate response; usual range 125–250 micrograms daily (lower
dose more appropriate in elderly)
Emergency control of atrial fibrillation, by intravenous infusion over at least 2 hours,

(
 Epinephrine (adrenaline)

Injection (Solution for injection), epinephrine hydrochloride 100

micrograms/ml (1 in
10 000), 10-ml ampoule
Uses:
cardiac arrest; anaphylaxis (section 3.1)
Precautions:
heart disease, hypertension, arrhythmias, cerebrovascular disease;
hyperthyroidism,
diabetes mellitus; angle-closure glaucoma; second stage of labour; interactions:
 Lidocaine hydrochloride

Injection (Solution for injection), lidocaine hydrochloride 20 mg/ml, 5-ml

ampoule
Uses:
ventricular arrhythmias (especially after myocardial infarction); local
anaesthesia

Dosage:
Ventricular arrhythmias, by intravenous injection, ADULT , loading dose of 50–
100
mg (or 1–1.5 mg/kg) at a rate of 25–50 mg/minute, followed immediately by
intravenous infusion of 1–4 mg/minute, with ECG monitoring of all patients
 Procainamide hydrochloride

Procainamide hydrochloride is a representative antiarrhythmic drug.,

procainamide hydrochloride 250 mg, 500 mg Injection (Solution for injection),
procainamide hydrochloride 100 mg/ml, 10-mlampoule

Uses:
severe ventricular arrhythmias, especially those resistant to lidocaine or those
appearing after myocardial infarction; atrial tachycardia, atrial fibrillation;
maintenance of sinus rhythm after cardioversion of atrial fibrillation
 Quinidine sulfate

Initial test dose of 200 mg to detect hypersensitivity to quinidine

Arrhythmias, by mouth, ADULT 200–400 mg 3–4 times daily;
frequent ECG monitoring required

Verapamil hydrochloride
Tablets, verapamil hydrochloride 40 mg, 80 mg
Injection (Solution for injection), verapamil hydrochloride 2.5 mg/ml, 2-
ampoul

Uses:
supraventricular arrhythmias; angina
 Antihypertensive drugs

Management of hypertension
Treatment of hypertension should be integrated into an overall programme to
manage factors that increase the risk of cardiovascular events (such as stroke and
myocardial infarction). Treatment is often life-long. Hypertension was formerly
classified as mild, moderate or severe, but a grading system is now preferred. Grade 1
hypertension is defined as 140–159 mmHg systolic blood pressure and 90–99 mmHg
diastolic blood pressure, Grade 2 hypertension 160–179 mmHg systolic and 100–109
mmHg diastolic and Grade 3 hypertension more than 180 mmHg systolic and more
than 110 mmHg diastolic. The goal of treatment is to obtain the maximum tolerated
reduction in blood pressure.
Lifestyle changes should be introduced for all patients; they include weight reduction,
reduction in alcohol intake, reduction of dietary sodium, stopping tobacco smoking,
and reduction in saturated fat intake. The patient should eat a healthy nutritious diet
including adequate fruit and vegetables and should exercise regularly. These measures
alone may be sufficient in mild hypertension, but patients with moderate to severe
hypertension will also require specific antihypertensive therapy.
Drug treatment of hypertension

1. angiotensin-convertingenzyme (ACE) inhibitors.

2. Angiotensin2 blocker
3. Calcium-channel blockers are considered first-line in
specific populations only e.g. Africans or the elderly.
4.(beta-blockers
5. Thiazide diuretics,

Thiazide diuretics, such as hydrochlorothiazide . have been

used as first-line antihypertensive therapy, and are particularly indicated in the
elderly. They have few adverse effects in low doses, but in large doses they may
cause a variety of unwanted metabolic effects (principally potassium depletion),
reduced glucose tolerance, ventricular ectopic beats and impotence; they should
be avoided in gout.
These effects can be reduced by keeping the dose as low as possible; high
doses do not produce an increased reduction in blood pressure. Thiazides are
inexpensive and, when used in combination, can enhance the effectiveness of
many other classes of antihypertensive drug
Beta-adrenoceptor antagonists (beta-blockers) such as atenolol are effective in all
grades of hypertension, and are particularly useful in angina and following myocardial
infarction; they should be avoided in asthma, chronic obstructive pulmonary disease,
and heart block.
Angiotensin-converting enzyme inhibitors (ACE inhibitors) such as enalapril are
effective and well tolerated by most patients. They can be used in heart failure, left
ventricular dysfunction and diabetic nephropathy, but should be avoided in
renovascular disease and in pregnancy. The most common adverse affect is a dry
persistent cough.
Dihydropyridine calcium-channel blockers such as nifedipine are useful for isolated
systolic hypertension, in populations unresponsive to other antihypertensives (e.g.
Africans) and in the elderly when thiazides cannot be used. Short-acting formulations
of nifedipine should be avoided as they may evoke reflex tachycardia and cause large
variations in blood pressure.
Drugs acting on the central nervous system are also effective antihypertensive drugs.
In particular, methyldopa is effective in the treatment of hypertension in pregnancy.
A single antihypertensive drug is often not adequate and other antihypertensive drugs
are usually added in a stepwise manner until blood pressure is controlled.
Hypertensive emergencies
In situations where immediate reduction of blood pressure is essential and treatment
by mouth is not possible, intravenous infusion of sodium nitroprusside is effective.
Over-rapid reduction in blood pressure is hazardous and can lead to reduced organ
perfusion and cerebral infarction.

Hypertension in pregnancy
This is defined as a sustained diastolic blood pressure of 90 mmHg or more. Drug
therapy for chronic hypertension during pregnancy remains controversial. If diastolic
blood pressure is greater than 95 mmHg, methyldopa is the safest drug. Betablockers
should be used with caution in early pregnancy, since they may retard fetal
growth; they are effective and safe in the third trimester. ACE inhibitors are
contraindicated in pregnancy since they may damage fetal and neonatal blood
pressure control and renal function. Women who are taking these drugs and become
pregnant should have their antihypertensive therapy changed immediately.
Pre-eclampsia and eclampsia . If pre-eclampsia or severe hypertension occurs
beyond the 36th week of pregnancy, delivery is the treatment of choice. For acute
severe hypertension in pre-eclampsia or eclampsia, intravenous hydralazine can be
used. Magnesium sulfate (section 22.1) is the treatment of choice to prevent
eclamptic convulsions in eclampsia and severe pre-eclampsia.
Enalapril

Enalapril is a representative angiotensin-converting enzyme inhibitor.

Tablets, enalapril 2.5 mg

Uses:
hypertension; heart failure (
Contraindications:
hypersensitivity to ACE inhibitors (including angioedema); renovascular disease;
pregnancy
Dosage:
Hypertension by mouth , initially 5 mg once daily; if used in addition to
diuretic, in
elderly patients, or in renal impairment, initially 2.5 mg daily; usual
maintenance dose
10–20 mg once daily; in severe hypertension may be increased to maximum 40
mg
once daily
Hydrochlorothiazide
Hydrochlorothiazide is a representative thiazide diuretic.
Tablets, hydrochlorothiazide 25 mg
Uses:
alone in mild hypertension, and in combination with other drugs in
moderate to severe
hypertension; heart failure oedema
Dosage:
Hypertension, by mouth , ADULT 12.5–25 mg daily; ELDERLY initially 12.5
mg
daily
Methyldopa
Tablets , methyldopa 250 mg
Uses:
hypertension in pregnancy
Dosage:
Hypertension in pregnancy, by mouth, ADULT initially 250 mg 2–3 times daily;
if
necessary, gradually increased at intervals of 2 or more days, maximum 3 g daily

;
Nifedipine
Nifedipine is a representative dihydropyridine calcium-channel blocker.
nifedipine 10 mg Sustained-release (prolonged-release) tablets are available
for once daily administration.
Uses:
hypertension
Dosage:
Hypertension, by mouth (as sustained-release tablets), ADULT usual range
20–100
mg daily in 1–2 divided doses, according to manufacturer’s directions
Sodium nitroprusside

Sodium nitroprusside is a complementary drug for the treatment of hypertensive

crisis
Infusion (Powder for solution for infusion), sodium nitroprusside, 50-mg
ampoule
Uses:
hypertensive crisis (when treatment by mouth not possible)
ACE inhibitor
Angiotensin receptors blockers
B Blocker
 Lipid lowering agent
 1. Hypolipidemic drugs are important!
 • They’re used to prevent the number one killer of
 North American men and women (coronary heart disease).
 • They’re among the most often prescribed drugs in the United States
 (over 120 million prescriptions for this class of drugs in 2004; ATORVASTATIN
(Lipitor)
 was ranked #2 in prescriptions and #1 in sales).

 1. LDL level2. The most effective agents for reducing s are (“statins”),
because they block cholesterol synthesis at its rate limiting step.

 2. EZETIMIBE is the newest hypolipidemic drug (approved in 2003). It is the

first of a new class of agents that block cholesterol absorption, and it is
typically given
 with a statin (EZETIMIBE + SIMVASTATIN = Vytorin).
 3. NICOTINIC ACID has the “perfect” therapeutic profile (it significantly

 increases HDL while decreasing LDL, TGs and total cholesterol) but its adverse

 side effects can limit its usefulness because of decreased patient compliance.

 4. GEMFIBROZIL and other fibrates are extremely useful in the treatment of

 patients with elevated triacyglycerol (TG) levels (i.e., Types III, IV and V),

 because they produce a 20-50% decrease in TGs

 Simvastatin 20mg Tablets
 Therapeutic indications
 Hypercholesterolaemia
 Treatment of primary hypercholesterolaemia or mixed dyslipidaemia,
as an adjunct to diet, when response to diet and other non-
pharmacological treatments (e.g. exercise, weight reduction) is
inadequate
 Cardiovascular prevention
 Reduction of cardiovascular mortality and morbidity in patients with
manifest atherosclerotic cardiovascular disease or diabetes mellitus,
with either normal or increased cholesterol levels, as an adjunct to
correction of other risk factors and other cardioprotective therapy
 Atorvastatin
 Therapeutic indications
 Hypercholesterolaemia:

Prevention of cardiovascular disease

Prevention of cardiovascular events in adult patients estimated to have a
high risk for a first cardiovascular event (see section 5.1), as an adjunct to
correction of other risk factors.
 Trental® (pentoxifylline)
Clinical Use
Trental® (pentoxifylline) is indicated for the
symptomatic treatment of:

patients with chronic occlusive peripheral vascular

disorders of the extremities

The recommended starting dosage of Trental

(pentoxifylline) is 400 mg twice daily after meals
 Corvasal
Description
Molsidomine is an orally active, long-acting vasodilator, which belongs to the
class of medications known as syndnones. Interestingly
decreases intracellular calcium ions in smooth muscle cells. This leads to
relaxation of smooth muscle in the blood vessels, and inhibits platelet
aggregation.
. Indication
The indications for use of molsidomine include ischemic heart disease, angina,
chronic heart failure, and pulmonary hypertension 9,10.
Dosage ;
Oral
Angina pectoris; Heart failure; Post myocardial infarction
Adult: 1-4 mg 2-4 times daily.
Vastarel
 this medicine is intended for use in adult
patient, in combination with other medicines to
treat angina pectoris (chest pain caused by
coronary disease). It protects the heart cells
from the effects of a reduced oxygen supply
during an episode of anginahe recommended
dose of Trimetazidine 35 mg is one tablet to be
taken two times a day during meals in the
morning and evening. If you have kidney
problems or if you are older than 75 years old,
your doctor may adjust the recommended dose
 Indapamide
 Mechanism of action

 Indapamide is a non-thiazide sulphonamide with an indole ring, belonging to

the diuretic family. At the dose of 2.5 mg per day indapamide exerts a
prolonged antihypertensive activity in hypertensive human subjects. Posology

 Dosage ;

 The dosage is one tablet, containing 2.5 mg indapamide hemihydrate, daily, to

be taken in the morning.
 Dicynene 250 MG Tablet
 Dicynene 250 MG Tablet is a haemostatic drug. Haemostatic
also known as Antihemorrhagic is a drug that helps in
stopping excessive bleeding from capillaries or vessels.
Other kinds of bleeding include Neonatal intraventricular
haemorrhage, Melena, Hematuria, Epistaxis, Secondary
bleeding caused by thrombocytopenia, and so on.
 Dicynene 250 MG Tablet functions in the restoration of your
capillary endothelial resistance. It improves platelet
adhesion by improving it and inhibits the process of
biosynthesis. Common side effects of Dicynene 250 MG
Tablet include headache, feelings of nausea, hypotension
and outbreaks on the skin in the form of rashes.