Cardiovascular Drugs

Dr. April Dawn R. Lucero

Cardiovascular Drugs

I. Drugs Used in Hypertension

II. Drugs Used in the Treatment of Angina Pectoris

III. Drugs Used in Heart Failure

IV. Antiarrhythmic Drugs

V. Diuretic Agents
Drugs for Hypertension
 Hypertension
• Clinically, hypertension might be defined
as that level of blood pressure at which
the institution of therapy reduces blood
pressure–related morbidity and
mortality.

• Cardiovascular disease risk DOUBLES for

every 20-mmHg increase in systolic and
10-mmHg increase in diastolic pressure.
Hypertension

• Older individuals
systolic blood pressure & pulse pressure  more powerful predictors of
cardiovascular disease than diastolic blood pressure

• Current clinical criteria for defining hypertension are generally based

on the average of 2 or more seated blood pressure readings during
each of 2 or more outpatient visits.
 Hypertension
Doubles the risk of Cardiovascular Diseases, including:

Coronary heart disease (CHD)

Congestive heart failure (CHF)
Ischemic and hemorrhagic stroke
Renal failure
Peripheral arterial disease
Table 241-1 Blood Pressure Classification
Blood Pressure Classification Systolic, mmHg Diastolic, mmHg

Normal <120 and <80

Prehypertension 120–139 or 80–89
Stage 1 Hypertension 140–159 or 90–99
Stage 2 Hypertension ≥160 or ≥100
Isolated Systolic Hypertension ≥140 and <90

Blood Pressure (BP) is determined by cardiac output (CO) and total

peripheral resistance (TPR), as represented by the formula BP = CO x TPR.
Cardiac Output = Heart Rate x Stroke Volume
HYPERTENSION

• Less than 20% of cases of hypertension are due to (“secondary”)

factors that can be clearly defined and corrected.

• This type of hypertension is associated with pheochromocytoma,

coarctation of the aorta, renal vascular disease, adrenal cortical
tumors, and a few other rare conditions.
HYPERTENSION

• Most cases of hypertension are idiopathic, also called “primary” or

“essential” hypertension.
- No identifiable cause
Hypertensive Crisis

• an umbrella term for HYPERTENSIVE URGENCY and HYPERTENSIVE

EMERGENCY.

• These two conditions occur when blood pressure becomes very high,
possibly causing organ damage.
Hypertensive Urgency

• occurs when blood pressure spikes -- blood pressure readings are

180/110 or higher -- but there is no damage to the body's organs.

• Blood pressure can be brought down safely within a few hours with
blood pressure medication.
Hypertensive Emergency

• means blood pressure is so high that organ damage can occur.

• Blood pressure must be reduced immediately to prevent imminent

organ damage. This is done in an intensive care unit of a hospital.
Hypertensive Emergency

Organ damage associated with edema)

hypertensive emergency may • Heart attack (myocardial
include: infarction)
• Bleeding into the brain (stroke) • Aneurysm (aortic dissection)
• Chest pain (unstable angina)

• Fluid in the lungs (pulmonary

High-Yield Terms
BARORECEPTOR REFLEX
• Primary autonomic mechanism for blood pressure homeostasis

• Involves sensory input from carotid sinus and aorta to the vasomotor
center and output via the parasympathetic and sympathetic motor
nerves
 High-Yield Terms

END-ORGAN DAMAGE

Vascular damage in heart, kidney, retina, or brain

ESSENTIAL HYPERTENSION

Hypertension of unknown etiology; also called primary

hypertension
 High-Yield Terms

HYPERTENSIVE EMERGENCY
• “malignant hypertension”
• An accelerated form of severe hypertension associated with rising
blood pressure and rapidly progressing damage to vessels and end
organs.
• Often signaled by renal damage, encephalopathy, and retinal
hemorrhages or by angina, stroke, or myocardial infarction
 High-Yield Terms

ORTHOSTATIC HYPOTENSION
Hypotension on assuming upright posture; postural hypotension

REBOUND HYPERTENSION
Elevated blood pressure (usually above pretreatment levels) resulting
from loss of antihypertensive drug effect

REFLEX TACHYCARDIA
• Tachycardia resulting from lowering of blood pressure
• Mediated by the baroreceptor reflex
High-Yield Terms
STEPPED CARE
• Progressive addition of drugs to a regimen
• Starts with one (usually a diuretic) and adding in stepwise fashion a
sympatholytic, an ACE inhibitor, and (sometimes) a vasodilator

SYMPATHOLYTIC, SYMPATHOPLEGIC
Drug that reduces effects of the sympathetic nervous system
DIURETICS
Diuretics

• Lower blood pressure by reduction of blood volume (through water

and salt excretion) and probably also by a direct vascular effect that is
not fully understood

• Most important diuretics for treating hypertension:

1. Thiazides: eg, hydrochlorothiazide

2. Loop Diuretics: eg, furosemide

Thiazide Diuretics
• Initially, lower blood pressure by
increasing sodium and water excretion
 decrease in extracellular volume 
decrease in cardiac output and renal
blood flow

• With long-term treatment, plasma

volume approaches a normal value, but
peripheral resistance decreases.
 Thiazide Diuretics

• May be adequate in mild hypertension

• Low-dose thiazide diuretics are often used as first-line agents,

alone or in combination with other antihypertensive drugs

• Long term, they may also act as vasodilators

 Thiazide Diuretics

• Owing to an increased incidence of metabolic side effects

(HYPOKALEMIA, INSULIN RESISTANCE, INCREASED
CHOLESTEROL), higher doses are generally not recommended.

• Induce hypokalemia and hyperuricemia in 70 percent of

patients and hyperglycemia in 10 percent of patients
 Thiazide Diuretics

Serum potassium levels should be

monitored closely in patients who are
predisposed to cardiac arrhythmias
(particularly individuals with LVH, ischemic
heart disease, or chronic heart failure) and
who are concurrently being treated with
both thiazide diuretics and digoxin.
 Loop Diuretics

• used in moderate and severe hypertension and in hypertensive

emergencies

• Compared to all other classes of diuretics, these drugs have

the highest efficacy in mobilizing Na+ and Cl- from the body.
They produce copious amounts of urine.
 Loop Diuretics

• Generally reserved for patients with reduced

glomerular filtration rate (reflected in serum
creatinine >2.5 mg/dL), CHF, or sodium
retention and edema for some other reason.

• Cause decreased renal vascular resistance and

increased renal blood flow
SYMPATHOPLEGICS
Sympathoplegics
• interfere with sympathetic (SANS) control of cardiovascular function.
 Sympathoplegics

• The result is a reduction of one or

more of the following: venous
tone, heart rate, contractile force
of the heart, cardiac output, and
total peripheral resistance.
Baroreceptors
• stretch receptors in the walls of the
heart and blood vessels

• The carotid sinus and aortic arch

receptors monitor the arterial
circulation.
Baroreceptors

• Stimulated by distention of the structures in which they are located

 discharge at an increased rate when the pressure in these
structures rises.

• Their AFFERENT FIBERS pass via the glossopharyngeal and vagus

nerves to the medulla.
Baroreceptors

Increased baroreceptor discharge

• inhibits the tonic discharge of the vasoconstrictor nerves

• excites the vagal innervation of the heart, producing vasodilation,

venodilation, a DROP IN BLOOD PRESSURE, BRADYCARDIA, and a
decrease in cardiac output.
A. Baroreceptor-Sensitizing Agents

• A few natural products, such as VERATRUM ALKALOIDS, appear to

increase sensitivity of baroreceptor sensory nerves and reduce SANS
outflow while increasing vagal tone to the heart.

• These agents are TOXIC and no clinically available drugs act at this
site.
 Veratru
m

Veratrum nigrum, Poland

Veratrum album, Japan
 Veratrum

• a genus of flowering plants found in Europe, Asia, North America

• All parts of the plant are poisonous, with the root

and rhizomes being the most poisonous.

• Symptoms typically occur between thirty minutes and four hours

after ingestion and include nausea and vomiting, abdominal pain,
numbness, headache, bradycardia, hypotension, cardiac arrhythmia,
and seizures.
Veratrum

• The toxins are only produced during active growth.

• In the winter months, the plant degrades and metabolizes most of its
toxic alkaloids. Native Americans harvested the roots for medicinal
purposes during this dormant period.
 Uses

• Native Americans: juice pressed from the roots of this plant to

poison arrows before combat

• The dried powdered root: insecticide

 Uses

• During the 1930s Veratrum extracts were investigated in the

treatment of high blood pressure in humans.
- Patients often suffered side effects  narrow therapeutic index

- DUE TO THEIR TOXICITY AND THE AVAILABILITY OF OTHER LESS TOXIC

DRUGS, USE AS TREATMENT FOR HPN WAS DISCONTINUED.
 B. Central Nervous System-Active Agents

ALPHA2-SELECTIVE AGONISTS

• eg, CLONIDINE, METHYLDOPA

• activates α2 receptors in the CNS  ↓ sympathetic outflow 

↓ cardiac output &/or vascular resistance  ↓ blood pressure

• Readily enter the CNS when given orally.

• Major compensatory response: salt retention

 Clonidine

• Used primarily for the treatment of

hypertension that has not responded
adequately to treatment with two or
more drugs
• Does not decrease renal blood flow or
glomerular filtration
 useful in the treatment of hypertension
complicated by renal disease
 Clonidine

• Can be used for hypertensive

urgencies

• (Oral/PO) onset of action: 30-60

minutes & maximal effects seen
within 2-4 hours
 Clonidine

• Adverse effects are generally mild

• Most common adverse effect in acute setting:

drowsiness
- 45% of patients

• Sudden discontinuation causes rebound hypertension,

which may be severe
- The drug should therefore be withdrawn slowly if the
clinician wishes to change agents
 Methyldopa

• A prodrug converted to methylnorepinephrine centrally to diminish the

adrenergic outflow from the CNS  ↓ TOTAL PERIPHERAL RESISTANCE 
↓ BLOOD PRESSURE
• Cardiac output is not decreased
• Blood flow to vital organs is not diminished
• Used in hypertensive pregnant patients.
 Methyldopa

• Blood flow to the kidney is not diminished

- especially valuable in treating hypertensive patients
with renal insufficiency

• Given orally or IV

• Most common SE: sedation/drowsiness

• Occasional SE: hematologic immunotoxicity

(positive Coomb’s test)  hemolytic anemia
C. Ganglion-Blocking Drugs

• Nicotinic blockers that act in the ganglia

are extremely powerful blood pressure-
lowering drugs

• Now OBSOLETE because of their severe

adverse effects (eg. excessive
hypotension)

• HEXAMETHONIUM, TRIMETHAPHAN
C. Ganglion-Blocking Drugs

Interfere with neurotransmission within autonomic ganglia

• ↓ sympathetic outflow to the heart  ↓ heart rate &

contractility  ↓ cardiac output

• ↓ sympathetic output to the vasculature  ↓ sympathetic

vascular tone  vasodilation and ↓ systemic vascular resistance
 ↓ arterial pressure
 D. Postganglionic Sympathetic Nerve
Terminal Blockers

• OBSOLETE for hypertension

• Deplete the adrenergic nerve terminal of its norepinephrine stores

 eg. RESERPINE

• deplete and block release of the stores

 eg. GUANETHIDINE, GUANADREL

• In HIGH DOSAGES, these drugs are very efficacious but produce SEVERE ADVERSE EFFECTS.
 Reserpine: depression that may be severe enough to lead to suicide, peptic ulcer, hypotension
 D. Postganglionic Sympathetic Nerve
Terminal Blockers

Monoamine Oxidase (MAO) Inhibitors

• OBSOLETE

• once used in hypertension because they cause the formation of

a false transmitter (octopamine) in sympathetic postganglionic
neuron terminals and lower blood pressure.
MAO Inhibitors
• Large doses, on the other hand (eg, the
tyramine in a meal of fermented foods),
may cause release of very large
amounts of stored norepinephrine
(along with the octopamine) and result
in a hypertensive crisis.
MAO inhibitors

• Tyramine normally metabolized by MAO  very low bioavailability

• With MAO inhibitors  not metabolized  much higher

bioavailability

• Still occasionally used for treatment of severe depressive disorder.

E. Adrenoceptor Blockers

1. Alpha1-selective agents

2. Non-selective alpha blockers

3. Selective beta blockers

4. Non-selective beta blockers

Alpha Blockers Reduce vascular resistance & venous return
Alpha Blockers

NONSELECTIVE α BLOCKERS

• PHENTOLAMINE, PHENOXYBENZAMINE

• Of no value in chronic hypertension because of EXCESSIVE

TACHYCARDIA
 Alpha Blockers

ALPHA1-SELECTIVE AGENTS

• PRAZOSIN, DOXAZOSIN, TERAZOSIN

• Cause only minimal changes in cardiac output, renal blood flow, and
glomerular filtration rate  long-term tachycardia does not occur

• They do, however, cause orthostatic hypotension, especially with the

first few doses.
 Alpha Blockers

ALPHA1-SELECTIVE AGENTS

• Seldom used: side-effect profile, development of tolerance, and the

advent of safer antihypertensives

• TAMSULOSIN
- has greater selectivity for prostate muscle  relax smooth muscle in the
prostate
- useful in benign prostatic hyperplasia
Beta Blockers

• Used very heavily in the treatment of hypertension

• Initially ↓ cardiac output

• After a few days their action may include a ↓ vascular resistance as a

contributing effect
- may result from reduced angiotensin levels

- β blockers reduce renin release from the kidney

 Nonselective Beta Blockers

• PROPRANOLOL
prototype beta blocker

• CARVEDILOL

• Contraindicated in asthma
blocks β2-mediated bronchodilation
Selective Beta Blockers

• METOPROLOL

• ATENOLOL

• may be administered cautiously to

hypertensive patients who also have
asthma
 Labetalol

• A combined α1- and nonselective β-adrenergic blocker

• Given as an intravenous bolus or infusion in hypertensive
emergencies
• Does not cause reflex tachycardia
• Carries the contraindications of a nonselective β-blocker.
• The major limitation: longer half-life
- precludes rapid titration
Common Effects of β blockers
• Bradycardia

• CNS side effects: fatigue, lethargy,

insomnia, and hallucinations

• Hypotension

• Decreased libido

• Impotence
 Other Adverse Effects of β Blockers

Alterations in serum lipid patterns

• ↓ HDL (high-density lipoprotein) cholesterol
• ↑ plasma triglycerides

Drug withdrawal
• Abrupt withdrawal  angina, myocardial infarction, or even sudden
death in patients with ischemic heart disease
• Taper dose over 2 to 3 weeks in patients with hypertension and
ischemic heart disease.
A 73-year-old man with a history of falling at home is found to have
moderately severe hypertension. Which of the following drug groups is most
likely to cause postural hypotension and thus an increased risk of falls?

A. Atenolol.

B. Hydrochlorothiazide.

C. Nifedipine.

D. Prazosin.

E. Verapamil.
 Answer: D

• Prazosin produces first-dose hypotension

blocks α-receptors  venous pooling

• This effect is minimized by initially giving the drug

in small, divided doses.

• The other agents do not have this adverse effect.

Which one of the following antihypertensive drugs can precipitate a
hypertensive crisis following abrupt cessation of therapy?

A. Clonidine.

B. Diltiazem.

C. Enalapril.

D. Losartan.

E. Hydrochlorothiazide.
 Answer: A (Clonidine)

• Increased sympathetic nervous system activity occurs if clonidine

therapy is abruptly stopped after prolonged administration.

• Uncontrolled elevation in blood pressure can occur.

• Patients should be slowly weaned from clonidine while other

antihypertensive medications are initiated.

• The other drugs on the list do not produce this phenomenon.

VASODILATORS
VASODILATORS

• Dilate blood vessels by acting DIRECTLY on smooth muscle cells through

nonautonomic mechanisms

 relaxation  ↓ resistance  ↓ blood pressure

• Produce reflex stimulation of the heart

 ↑ myocardial contractility, ↑ heart rate, and ↑ oxygen consumption

Vasodilators

• These actions may prompt angina pectoris, myocardial infarction, or

cardiac failure in predisposed individuals.

• Increase plasma renin concentration  sodium and water retention.

• These undesirable side effects can be blocked by concomitant use of a

diuretic and a β-blocker.
 Hydralazine & Minoxidil

• These older vasodilators have more effect on arterioles than on

veins.
HYDRALAZINE
• Acts through the release of nitric oxide from endothelial cells
• Used to treat moderately severe hypertension
• Rarely used at high dosage because of its toxicity
• Hydralazine-induced lupus erythematosus with high dosage
reversible upon stopping the drug
lupus is uncommon at dosages below 200 mg/d.
 MINOXIDIL
• Reserved for severe hypertension
•a prodrug; its metabolite,
minoxidil sulfate, is a potassium
channel opener that
hyperpolarizes and relaxes
vascular smooth muscle.
• Because it can cause hirsutism,
minoxidil is also available as a
topical agent for the treatment of
baldness.
Calcium-Channel Blockers

• Moderately effective vasodilators

• Suitable for chronic use in hypertension of any severity

• Produce fewer compensatory responses  much more commonly

used than hydralazine or minoxidil.
3 Chemical Classes of Calcium-Channel Blockers

Chemical Class Member/s

Diphenylalkylamines Verapamil
Benzothiazepines Diltiazem
Dihydropyridines
First generation Nifedipine
Second generation Amlodipine
Felodipine
Isradipine
Nicardipine
Nisoldipine
 3 Chemical Classes of Calcium-Channel Blockers

Chemical Class Member/s Remarks

Diphenylalkylamines Verapamil  Least selective calcium-channel blocker
 Has significant effects on BOTH cardiac and
vascular smooth muscle cells
 Used to treat angina, supraventricular
tachyarrhythmias, and migraine headache
 3 Chemical Classes of Calcium-Channel Blockers

Chemical Class Member/s Remarks

Benzothiazepines Diltiazem  Like verapamil, it affects BOTH cardiac and
vascular smooth muscle cells
 However, it has a less pronounced negative
inotropic effect on the heart compared to
verapamil.
 Has a favorable side-effect profile
Chemical Class Member/s Remarks

Dihydropyridines All dihydropyridines have a much greater affinity for vascular calcium channels
than for calcium channels in the heart. They are therefore particularly attractive
in treating hypertension.

First generation Nifedipine

Second generation Amlodipine  Some of the newer agents, such as amlodipine

Felodipine and nicardipine, have the advantage that they
Isradipine show little interaction with other
Nicardipine cardiovascular drugs, such as digoxin or
Nisoldipine warfarin, which are often used concomitantly
with calcium-channel blockers.
 Mechanism of Action

• Intracellular concentration of calcium helps maintains the tone

of smooth muscle and contraction of the myocardium.

• Calcium enters muscle cells through special voltage-sensitive

calcium channels  triggers release of calcium from the
sarcoplasmic reticulum and mitochondria  ↑ cytosolic level of
calcium
Mechanism of Action

• Drug binds to L-type calcium channels in the heart and in

smooth muscle of the coronary and peripheral vasculature 
block the inward movement of calcium  vascular smooth
muscle relax  dilation mainly of arterioles
 Therapeutic Uses

• Have an intrinsic natriuretic effect

• Therefore, do not usually require the addition of a diuretic.

• Useful in the treatment of hypertensive patients who also have

asthma, diabetes, angina, and/or peripheral vascular disease
 Nicardipine

• Also used in hypertensive emergencies

• Can be given as an intravenous infusion

• Major limitation of nicardipine in treating hypertensive emergency: long

half-time (approximately 8 hours), which precludes rapid titration.

• May have unique benefits in cerebrovascular disease: crosses the blood-

brain barrier and acts to vasorelax cerebrovascular smooth muscle
Adverse Effects

VERAPAMIL

• Constipation: 10% of patients

negative inotropic (force of cardiac muscle contraction) and

dromotropic (velocity of conduction) effects
 should be avoided in patients with congestive heart failure or with
atrioventricular block
 Nitroprusside, Diazoxide, and Fenoldopam

• These parenteral vasodilators are used in hypertensive emergencies.

NITROPRUSSIDE
• Administered intravenously
• short-acting agent (duration of action is a few minutes) that must be
infused continuously.
• Poisonous if given orally  hydrolysis to cyanide
• Light sensitive, and when in solution, it should be protected from
light
 Nitroprusside

NITROPRUSSIDE

• Release of nitric oxide (from the drug molecule itself)  stimulates guanylyl cyclase 
↑ cyclic guanine monophosphate (cGMP) concentration in smooth muscle  prompt
vasodilation with reflex tachycardia

• The drug has little effect outside the vascular system, acting equally on arterial and
venous smooth muscle.

• Note: Because nitroprusside also acts on the veins, it can reduce cardiac preload
ANGIOTENSIN ANTAGONISTS
 Two Primary Groups of
Angiotensin Antagonists

1. Angiotensin-Converting Enzyme (ACE)

Inhibitors

2. Angiotensin II Receptor Blockers

(ARBs)
 ACE inhibitors

• ACE inhibitors ↓ angiotensin II and ↑ bradykinin levels

• Vasodilation
diminished levels of angiotensin II
potent vasodilating effect of increased bradykinin

• ↓ angiotensin II levels, ACE inhibitors  ↓ secretion of aldosterone

 ↓ sodium and water retention

 ACE inhibitors

• Useful in heart failure and diabetes as well as in hypertension

• Slow the progression of diabetic nephropathy
• ACE inhibitors are also effective in the management of patients with
chronic heart failure.
• ACE inhibitors are a standard in the care of a patient following a
myocardial infarction. Therapy is started 24 hours after the end of
the infarction.
Adverse Effects
• Cough (up to 30% of patients)
 thought to be due to increased levels of bradykinin in the
pulmonary tree

• Renal damage in occasional patients with preexisting renal

vascular disease and in the fetus (although they protect
the diabetic kidney).

• Absolutely contraindicated in pregnancy

 fetotoxic
 Angiotensin II Receptor Blockers (ARBs)

• Competitively inhibit angiotensin II at its AT1 receptor site

• Appear to be as effective in lowering blood pressure as the ACE

inhibitors

• Also produce arteriolar and venous dilation and block

aldosterone secretion  ↓ blood pressure and ↓ salt and water
retention
 Angiotensin II Receptor Blockers (ARBs)

• Advantage: lower incidence of cough

•  do not increase bradykinin levels

• Decrease the nephrotoxicity of diabetes

hypertensive diabetics

• Fetal renal toxicity  contraindicated in pregnancy

 Renin Inhibitors: Aliskiren

• The newest drug in the antihypertensive group

• Directly inhibits renin’s action on its substrate, angiotensinogen.

• It thus reduces the formation of angiotensin I and, in consequence,

angiotensin II

• It lowers blood pressure about as effectively as ARBs, ACE inhibitors,

and thiazides.
Renin Inhibitors: Aliskiren

• It does not appear to cause cough

• It does not show reproductive toxicity in animals but is considered to

be contraindicated in pregnancy because of the toxicity of ACE
inhibitors and ARBs.
 Angiotensin Antagonists & Renin Inhibitors
Cause Hyperkalemia

• Reduce aldosterone levels (angiotensin II is a major

stimulant of aldosterone release)  potassium retention

• If the patient has renal impairment, is consuming a high-

potassium diet, or is taking other drugs that tend to
conserve potassium, potassium concentrations may reach
toxic levels.
CLINICAL USES OF
ANTIHYPERTENSIVE
DRUGS
Stepped Care (Polypharmacy)

• Drugs may cause major compensatory responses and significant

toxicities

• Overall toxicity can be reduced and compensatory responses

minimized by the use of multiple drugs at lower dosages in patients
with moderate or severe hypertension.
 Stepped Care (Polypharmacy)

• Typically, drugs are added to a patient’s regimen in stepwise fashion.

• The usual steps include

(1) Lifestyle measures such as salt restriction and weight reduction

(2) Diuretics (a thiazide)

(3) Sympathoplegics (a β blocker)

(4) ACE inhibitors

(5) Vasodilators (usually calcium channel blocker is chosen first)

 Monotherapy

• Large clinical studies: many patients do well on a single drug (eg, an ACE
inhibitor, calcium channel blocker, or combined α and β blocker).

• Treatment of mild and moderate hypertension

• Has become more popular than stepped care because of its simplicity,
better patient compliance, and—with modern drugs—a relatively low
incidence of toxicity.
Hypertensive Emergency

• An accelerated form of severe hypertension associated with rising

blood pressure and rapidly progressing damage to vessels and end
organs.

• Management of hypertensive emergency must be carried out on an

urgent basis in the hospital.
Hypertensive Emergency

• Powerful vasodilators (nitroprusside, fenoldopam, or diazoxide) are

combined with diuretics (furosemide) and β blockers to lower blood
pressure to the 140–160/90–110 mm Hg range promptly (within a
few hours).

• Further reduction is then pursued more slowly.

A 32-year-old woman with hypertension wishes to become pregnant. Her
physician informs her that she will have to switch to another
antihypertensive drug. Which of the following drugs is absolutely
contraindicated in pregnancy?
(A) Atenolol
(B) Captopril
(C) Methyldopa
(D) Prazosin
(E) Propranolol
Answer: B (Captopril)

• Methyldopa is often recommended in pregnant patients because it

has a good safety record.

• Alpha (choice D) and β blockers (choices A and E) are not

contraindicated.

• In contrast, ACE inhibitors (choice B) and ARBs have been shown to be

teratogenic. The answer is B.
A significant number of patients started on ACE inhibitor therapy for
hypertension are intolerant and must be switched to a different class of drug.
What is the most common manifestation of this intolerance?
(A) Diarrhea
(B) Glaucoma
(C) Incessant cough
(D) Lupus-like syndrome
(E) Vomiting
 Answer: C (incessant cough)

• Chronic, intolerable cough is an important adverse effect of captopril and other

ACE inhibitors.

• It may be relieved by prior administration of aspirin.

• These drugs are very commonly used in hypertensive diabetic patients because
of their proven benefits in reducing diabetic renal damage.

• The ACE inhibitors do not cause glaucoma or gastrointestinal disturbances.