Cardiovascular Drugs

Prof.Dr.M.Aydın Barlas
 Functional Components
of the Heart
• Myocardium: cardiac muscle fibers are arranged into
four chambers, 2 atria and 2 ventricles
• Conduction system: specialized tissue that conducts
nerve impulses throughout the heart, SA and AV
node, bundle of His, bundle branches, and Purkinje
fibers
• Nerve supply: nerve branches from both the
sympathetic and parasympathetic divisions of the
autonomic nervous system, regulate heart rate and
force of contraction
Structure of the Heart
Normal electrocardiogram at rest
 Main Diseases of the
Cardiovascular System
• Hypertension(HT)
• Congestive heart failure(CHF)
• Coronary artery disease(CAD)
or Ischemic heart disease(IHD)
• Myocardial infarction(MI)
• Angina Pectoris
• Cardiac arrhythmias………
 Congestive Heart Failure
• Contractile function is reduced below normal by disease
or life style(ejection fraction found decreased in
echocardiogram)
• Cardiac output unable to maintain normal blood pressure

• Blood accumulates in heart (cardiac dilatation), lungs

(pulmonary congestion), abdomen (ascites), and lower
extremities (peripheral edema)

• Patient is weak and has difficulty breathing(orthopnea)

 Coronary Artery Disease
• Due to arterio & atherosclerosis of the
coronary arteries(LAD,LCA,RCA,CA,.….)
• Fatty plaques(atheroma) cause blockage and
decreased blood flow to the myocardium
• Main symptom is angina pectoris or chest
pain, caused by lack of blood and oxygen
• Myocardial infarction (MI) occurs when
an artery is totally blocked
 Myocardial Infarction(MI)
• Caused by complete blockage of one of the
coronary arteries
• Heart cells deprived of blood/oxygen become
ischemic, die, and form an infarct
• MI may result in sudden death, or the infarct
undergoes a healing process and is replaced with
connective tissue
• After an MI the heart may be weakened & develop
congestive failure or cardiac arrhythmias
 Cardiac Arrhythmias(dysrhythmias)
• Arrhythmias are disturbances in the normal
electrical activity(rhythm) of conduction system
• The electrical disturbance interferes with the
ability of the heart to pump blood, and may cause
angina pectoris or congestive heart failure
• Severe arrhythmias can cause ventricular
fibrillation & sudden death(atrial fibrillation is less severe)
Use of ECG for Diagnosis (ST
depression)
 Hypertension
• Hypertension is the leading cause of
cardiovascular disease and mortality
• Disease symptoms and organ damage
caused by hypertension are not evident until
10–15 years after the disease has started
• Proper medication and patient compliance
will control most cases of hypertension
 Causes of Hypertension
• Most people have essential hypertension where the
exact cause is not known(particularly in elderly)
• Increased sympathetic activity and sodium overload
increase blood pressure (BP)
• Renal disease & increased renin-angiotensin-aldosterone
activity(RAS) raise BP & cause sodium and fluid
retention(reno- vascular hypertension is severe but rarely seen)
• Smoking, stress, body overweight(plus hyperlipideamia),
increased sodium consumption contribute to hypertension
 Drug Classes Used to Treat
Hypertension
• Diuretics
• Sympatholytic drugs(alpha & beta blockers)
• Vasodilator drugs(drugs acting directly on vascular smooth m)
• Calcium antagonist drugs(Ca channel blockers)
• Angiotensin-converting enzyme(ACE) inhibitor
& angiotensin receptor blocking drugs(ARB)
 Diuretic Therapy
• Diuretics increase sodium excretion and relax arterial
blood vessels(causes to vasodilation; particularly thiazides)
• Thiazides are preferred in patients with adequate renal
function(hydrochlorothiazide(usually in combination with
antihypertensives & indapamide(Fludex) alone are popular)
• Organic acid diuretics (loop diuretics-furosemide(Lasix))have
high efficacy & used in patients with reduced renal function
• Diuretics can be used alone or in combination with other
antihypertensive drugs
• Excessive loss of fluid, sodium, and potassium are
common adverse effects
 Diuretics
• Most diuretics act by increasing sodium excretion by
the kidney.Basic mechanism is the inhibition of
tubular reabsorption (only 1 % reduction of tubular
reabsorption will double daily urine excretion)
• Where sodium goes, so does water, so that when the
sodium remains in the kidney filtrate (urine), more
water will be removed, and thus urine volume or fluid
excretion goes up.

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 Diuretics
• As sodium is excreted, so is potassium, so these
drugs can considerably upset potassium levels
in the blood, leading to cardiac abnormalities.
• Potassium supplements would be necessary
• Potassium-sparing diuretics(amiloride,triamterene,
spironolactone) do not increase K excretion

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 Sympathetic Blocking Drugs
• Alpha blockers lower BP by vasodilation(not very
popular drugs today except their use in BPH)
• Beta blockers lower BP by decreasing heart rate
and cardiac output(also they may inhibit renin secretion)
• Centrally acting sympatholytic drugs decrease the
activity of the cardiovascular centers in the
medulla oblongata(alpha methyl dopa(Alfamet-not pop)
Clonidine(centrally acting alpha-2 agonist)once used as antihyp
 Vasodilator Drugs
• Vasodilators decrease the muscular tone and
contractile function of blood vessels(directly act on
vascular smooth muscle)
• Hydralazine and minoxidil are potent
vasodilators that must be used with diuretics
and sympathetic blocking drugs(not popular)
• Minoxidil causes hirsutism and is sold topically
for treatment of baldness(Minoxil,Rogain,Regain…)
 Calcium Antagonists
(Ca channel blockers)
• Block the influx of calcium into the heart
and arterial blood vessels
• Verapamil(İsoptin), diltiazem(Diltizem) act on
both the heart and blood vessels to lower BP
• Nifedipine(Adalat) & amlodipine(Norvasc)
lower BP only by vasodilation
• Calcium antagonists are also used to treat
angina pectoris and cardiac arrhythmias (they
have also extracardiac uses)
 Angiotensin-Converting Enzyme
Inhibitors (ACEIs)
• ACEIs inhibit the formation of angiotensin II which is a
potent vasoconstrictor(angiotensın I is not)
• ACEIs also decrease the release of aldosterone which
retains sodium and water
• The ACEIs can be used with thiazide and organic
acid diuretics, but not potassium-sparing
diuretics(risk of hyperkalemia(hyperpotassemia)
• These drugs produce a low incidence of adverse effects
and do not interfere with mental activity or renal
function(persistant dry cough is most common side-effects)
 Angiotensin Converting Enzyme
Inhibitors (ACEIs)
• Acts on renin-angiotensin-aldosterone system(RAS)

• If the conversion of angiotensin I to angiotensin II

by enzymes(ACE) is blocked, there will be
reduction in blood pressure by vasodilation

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 Angiotensin Converting Enzyme Inhibitors
_ Captopril (Kapril)
– Lisinopril(Sinopryl)
– Enalapril (Enapril)pro-drug converted to enalaprilat (all the
followings are pro-drug except captopril & lisinopril)
– Fosinopril (Monopril)
– Ramipiril (Delix)
– Silazepril(İnhibace)
– Perindopril(Coversyl)
– Quinapril(Acuitel)
– Benazepril (Cibadrex)
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 Angiotensin Receptor Blockers(ARB)
• These drugs block angiotensinII receptors (AT1)
on blood vessels and adrenal cortex
• Like the ACEIs, these drugs produce vasodilation
and decrease the activity of aldosterone
• The angiotensin receptor blockers generally produce
lower incidence of adverse effects than the ACEIs ?!
 Angiotensin II Receptor Blockers(ARB)
• They block angiotensin II effect at the
angiotensin type 1 receptors.(angiotensin II has two
types of receptors; 1 & 2) Thus there is vasodilation
and blood pressure lowering.

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 Angiotensin II receptor antagonists or ARB

_ Losartan (Cozaar)
– Valsartan (Diovan) If there is a co prefix or

– Eprosartan(Teveten) ‘plus’ at the end of

– Irbesartan(Irda) the brand name a
– Kandesartan(Atacand) diuretic(mostly hyd-
– Olmesartan(Hipersar) rochlorothiazide) is
– Telmisartan(Micardis) added to ARB

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 Treatment of
Hypertensive Crisis
• Severe hypertension is a medical emergency
that can lead to stroke and sudden death
• Immediate parenteral administration of
antihypertensive drugs can avoid severe
complications and irreversible damage
• Diazoxide and nitroprusside are potent
vasodilators used in hypertensive crisis
 Angina Pectoris
• Chest pain due to coronary artery disease
(CAD) and myocardial ischemia(IHD)
• Exertional angina (pain) usually occurs during
physical exercise or stress
• Vasospastic angina(Prinzmetal) may occur at
any time and is due to coronary artery spasm
• Untreated CAD and angina pectoris may lead
to myocardial infarction and death
Drugs Used to Treat CAD
• Nitrites(NO2) and nitrates(NO3)
• Beta adrenergic blocking drugs
• Calcium antagonists, also referred
to as calcium channel blockers
 Nitrites and Nitrates
• Drugs stimulate the formation of nitric oxide(NO) a
potent vasodilator of blood vessels
• Vasodilation of veins and arteries decreases cardiac
work and cardiac oxygen consumption to relieve the
pain of myocardial ischemia
• Nitrites and nitrates cause a drop in blood
pressure(hypotension) and reflex tachycardia
• These drugs can be used to treat acute attacks of
angina or to prevent anginal attacks
• Nitroglycerin(Trinitrine sublingual) was popular
 Drugs Used to Relieve Acute
Attacks of Angina
• Amyl nitrite(not available) is administered by
inhalation from a glass ampule, it has a sudden
onset and duration of action of 5–10 minutes
• Nitroglycerin is administered as sublingual tab.
& spray(Nitrolingual pump spray) which require few
minutes for onset and may last 30–45 min
• Nitroglycerin may also be administered
intravenously in more severe cases(Nitronal amp.)
 Drugs Used Prophylactically to
Prevent Angina Pectoris
• Nitroglycerin can be administered as an ointment,
as extended release tablets or capsules, or by
transdermal patch(Nitroderm TTS)
• Isosorbide and pentaerythritol nitrates are usually
administered orally 3–4 times/day depending on
the frequency of anginal attacks
Isosorbite mononitrate(Monoket tb.)
Isosorbite dinitrate(Cardioket &,İsordil subligual or oral tb.)
Adverse Effects of Nitrites and
Nitrates
• Vasomotor flushing, dizziness & headache
are common due to vasodilation
• When administered for acute angina, the
sudden onset of vasodilation may cause
hypotension, fainting, and tachycardia
• Patients should be seated when inhaling or
taking these drugs sublingually
 Beta Adrenergic Blockers
• Sympathetic beta receptor stimulation of the heart
increases heart rate(+chronotrop), force of
contraction(+inotrop), and oxygen consumption

• Blockade of beta receptors(beta1) decreases cardiac

work and cardiac oxygen demand

• Beta blockers are used prophylactically to prevent

angina and can be combined with other antianginal drugs
 Beta Adrenergic Blocking Agents
• These drugs block the beta-receptors in the
sympathetic nervous system
• Can be useful in situations where sympathetic
activity is excessive or inappropriate. E.g.
hypertension, angina, dysrythmias
• Beta blockers have other uses than cardiovas-
cular problems(particularly non-selective blockers)

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 Calcium Antagonists
• These drugs block influx of calcium ions into the heart & blood
vessels to vasodilate and lower blood pressure, cardiac work, and
oxygen demand
• Verapamil(Isoptin) and diltiazem(Diltizem) act on both the heart and
blood vessels
• Nifedipine(Nidilat) &other calcium antagonists amlodipine
(Norvasc),benidipine(Coniel),lacidipine(Lacipil) act mainly on
arterial blood vessels to dilate.They belong to dihydropyridines
group & usually used as antihypertensive
• Calcium antagonists are used prophylactically to prevent angina
• Adverse effects include excessive vasodilation, hypotension,
cutaneous flushing, and headache
 Calcium Channel Blocking Agents(cont.)
• Contractions of cardiac and smooth muscle
cells are dependent on the movement of
calcium ions into the cells through specific
channels.
• If calcium reduced, there will be changes in
cardiac electrical activity and vasodilation
• Used in dysrythmias, angina, hypertension

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 Congestive Heart Failure (CHF)
• CHF due to weakening of the contractile function
of the heart
Blood and fluid accumulate in the heart, lungs,
abdomen, and lower extremities(edema)
• Decreased cardiac output and blood pressure are
unable to meet body requirements
• Cardiovascular reflexes cause vasoconstriction,
tachycardia, and sodium and fluid retention which
try to maintain blood pressure, but usually fail
 Cardiac Glycosides
• Drugs originally obtained from plant source, Digitalis
purpurea and Digitalis lanata
• Digoxin and digitoxin(not available in Tur.) are the only
cardiac glycosides currently available
• Main pharmacologic effect of cardiac glycosides is
to increase the contractile force of myocardial
contraction
• Cardiac glycosides also decrease heart rate and
atrioventricular conduction(probably vagal effect)
 Mechanism of Action
• Cardiac glycosides inhibit Na/K ATPase the “sodium
pump” which causes more Na to remain inside
myocardial cells
• Increased intracellular Na stimulates Na/Ca exchange
that brings more Ca inside the heart cells to increase
the force of contraction
• Cardiac glycosides also stimulate the vagus nerve
(parasympathetic)which decreases heart rate
 Pharmacokinetics and Dosing
• Digoxin is water soluble and eliminated mostly
unmetabolized by the urinary tract
• Digitoxin(not avail.) is more lipid soluble, requires
metabolism, and has a longer half-life
• In acute CHF, initial “digitalization” doses are
administered to rapidly attain effective therapeutic
concentration(loading dose).
• Lower daily maintenance doses are then given to
maintain desired therapeutic concentrations
 Electrolyte and Cardiac Glycoside
Interactions
• Low serum potassium (K) levels “hypokalemia”
increase drug toxicity & can cause cardiac arrhythmias
• High serum potassium levels “hyperkalemia” decrease
the actions of the cardiac glycosides
• Increased serum calcium levels “hypercalcemia” can
increase the actions & toxicity of the cardiac glycosides
• Hypocalcemia may cause ‘CATS go numb’ Convulsions,
arrhytmias, tetany & numbness/parasthesias in hands, feet, mouth
and lips)
 Adverse Effects
• Common complaints include headache, dizziness,
nausea, and vomiting
• Visual disturbances “halo effect” around lights
often signals overdosage
• Bradycardia, ectopic beats, and a variety of other
cardiac arrhythmias can occur and can be life-
threatening
• They have low therapeutic index(narrow margin of
safety or therapeutic window) Require monitoring
Phosphodiesterase(PDE) inhibitors
 Diuretic Therapy of CHF
• Diuretic drugs are used to eliminate excess sodium
& fluid retention(to decrease preload & afterload)
• Elimination of excess fluid allows the heart to
function more efficiently
• Diuretics can be administered with cardiac glycosides
and other drugs used to treat CHF (watch out for
electrolytes level!)
 Vasodilator Therapy of CHF
• Vasodilator drugs relax and dilate blood vessels
• Vasodilation decreases peripheral resistance,
allows more efficient blood flow(decreases after-
load) and usually increases cardiac output
• Angiotensin-converting enzyme(ACE) inhibitors
and angiotensin receptor blocking drugs(ARB) are
particularly useful in CHF
 Cardiac Arrhythmias
• Arrhythmias are disturbances in the normal
electrical activity of the heart
• Arrhythmias can be detected on a recording of the
electrocardiogram (ECG-EKG)
• Supraventricular arrhythmias occur above the
ventricles in the atria, SA node, and AV node
• Ventricular arrhythmias occur in the ventricles and
Purkinje fibers and are usually more serious and
life-threatening
 Electrophysiological Properties
of the Heart
• Excitability – associated with membrane
depolarization and the influx of Na ions
• Refractory period – associated with repolarization
and the efflux of K ions
• Automaticity – ability of the SA and AV nodes to
initiate membrane depolarizations
• Under conditions of hypoxia and excessive
sympathetic stimulation, the ventricles can also
demonstrate automaticity to cause ectopic beats or
PVC’s(Premature Ventricular Contractions)
 ANTI ARRHYTHMIC DRUGS
Cardiac arrythmias commonly occur in presence of pre-existing heart d.
1) CLASS I: Membrane stabilizing drugs; SODİUM CHANNEL
BLOCKERS
CLASS I a- Quinidine, Procainamide, Disopyramide
CLASS I b- Lidocaine, Phenytoin
CLASS I c- Propafenone
2) CLASS II: BETA BLOCKERS- Acebutolol, Atenolol,
Esmolol,Metoprolol, Propranolol…….
3) CLASS III: POTASSIUM CHANNEL BLOCKERS- Amiodarone
Sotalol !!(beta blocker)
4) CLASS IV: CALCIUM CHANNEL BLOCKERS- Verapamil,
Diltiazem
 Quinidine and Procainamide
• Classified as class 1a antiarrhythmic drugs
• Possess local anesthetic activity and block the influx of Na
ions during depolarization
• Main effects are to decrease excitability, slow conduction,
and prolong the refractory period
• ECG: prolong the PR, QRS, and QT intervals
• Used for supraventricular and ventricular arrhythmias

Hydroxychloroquine may prolong QT interval and may

cause biventricular cardiomyopathy
 Lidocaine
• Class 1b local anesthetic-type antiarrhythmic
used only for ventricular arrhythmias
• Must be administered IV by infusion
• The drug of choice in acute and emergency
ventricular arrhythmias
• Main effect is to decrease automaticity
• Mexiletine and tocainide are similar to
lidocaine and can be administered orally
 Propranolol & Selective Beta Blockers
• Classified as a class 2 antiarrhythmic drug
• Blocks cardiac beta receptors (B1) to slow heart
rate, AV conduction, and prolong the refractory
period
• ECG: mainly increases the PR interval
• Used for both supraventricular and ventricular
arrhythmias
 Amiodarone
• Classified as a class 3 antiarrhythmic drug
• Usually reserved for more serious
arrhythmias when other drugs have failed
• Main effect is to prolong the refractory period
and increase the QT interval
• Amiodarone(Cordalin,Cordarone) contains iodine
and can interfere with thyroid function
 Verapamil and Diltiazem
• Classified as class 4 antiarrhythmic drugs
• Act by blocking calcium ions(Ca channels blockers)
• Main effects are to decrease heart rate and AV
conduction, increase the PR interval
• Mainly used to treat supraventricular arrhythmia
• May cause cardiac depression at higher doses

• Dihydropyridine group Ca channel blockers

(amlodipine,lacidipin) are used for HT, nifedipine for both
HT and CAD
 Adenosine
• Administered i.v. in emergency situations
• Main action is to decrease AV conduction
and slow the heart rate
• Used to treat acute supraventricular
tachycardia
• Duration of action is 15–30 seconds
 Medications in the Context of
Cardiac Arrest
• Inotropes (Sympathomimetics)
• Antidysrythmics(antiarrhythmics)
• Vasodilators
• Beta Blockers
• Diuretics
• Analgesics(aspirine,morphine……)
• Thrombolytics(fibrinolytics)

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