● The cardiovascular system
delivers oxygen and nutrients to all
cells in the body and to eliminate
waste products for excretion.
● It consists of the heart as a pump
and an interconnected series of
vessels that continually move blood
throughout the body.
● Heart - hollow muscle responsible
for pumping oxygenated blood to
every cell in the body and for picking
up waste products from the tissues.
○ divided into right and left
sides by a thick septum and
into four chambers.
■ Two upper atria
■ Two lower ventricles
○ Right side: receives all
deoxygenated blood from the
body through the veins &
directs it to the heart
○ Left side: receives
oxygenated blood from lungs
and pumps it out to every cell
in the body through the
arteries.
● Cardiac Cycle - consists of diastole
(period of rest) when blood returns
to the heart by veins and systole
(period of contraction) when the
blood is pumped out of the heart.
● Heart muscle - possess
automaticity (ability to generate an
action potential in the absence of
stimulation and conductivity (ability
to rapidly transmit an action
potential).
○ Stimulated to contract by
impulses generated in the
heart, not by stimuli in the
brain. The autonomic
nervous system can affect
the heart to increase
(sympathetic) or decrease
(parasympathetic) activity.
● Normal sinus rhythm, cells in
sinoatrial (SA) nodes generate an
impulse that is transmitted through
atrioventricular (VA) nodes before
being sent down the bundle of HIS
into the ventricles. When cardiac
muscles are stimulated, they
contract.
● Alterations in the generation of
conduction of impulses in the heart
cause arrhythmias (dysrhythmias),
which can upset the normal balance
in the cardiovascular system and
lead to a decrease in cardiac output,
affecting all of the cells in the body.
● Actin & Myosin - protein molecules
that slide together to make the heart
muscle contract.
○ Called a “sarcomere” in a
functioning unit
○ Requires energy and calcium
for filaments to react and
slide with each other.
● Heart muscle needs constant supply
of blood
○ Furnished by the coronary
arteries.
○ Alterations in heart rate,
preload, afterload, or stretch
in the muscle will require an
increase in oxygen demand.
● Blood pressure is maintained by
stimulus from the sympathetic
system, reflex control of blood
volume, pressure by the
renin-angiotensin system, &
aldosterone-ADH system.
● Alteration such as hypotension or
hypertension can affect the balance
of the cardiovascular system and
lead to problems in blood delivery.
SEARES
ANTIHYPERTENSIVE AGENTS
● Because an underlying cause of
hypertension is usually unknown,
altering the body’s regulatory
mechanisms is the best treatment
currently available. Drugs used to
treat hypertension work to alter the
normal reflexes that control blood
pressure. Treatment for essential
hypertension does not cure the
disease but is aimed at maintaining
the blood pressure within normal
limits to prevent the damage that
hypertension can cause. Not all
patients respond in the same way to
antihypertensive drugs because
different factors may contribute to
each person’s hypertension.
Patients may have complicating
conditions, such as diabetes or
acute myocardial infarction that
make it unwise to use certain drugs.
● Several different types of drugs that
affect different areas of blood
pressure control may need to be
used in combination to maintain a
patient’s blood pressure within
normal limits. Trials of drugs and
combinations of drugs are often
needed to develop an individual
regimen that is effective without
producing adverse effects that are
unacceptable to the patient
● Antihypertensive agents include
ACE inhibitors, angiotensin
II–receptor blockers (ARBs), calcium
channel blockers, vasodilators, and
other antihypertensive agents,
including diuretic agents, renin
inhibitors, and sympathetic nervous
system drugs.
● If hypertension is controlled, the
patient’s risk of cardiovascular death
and disease is reduced. The risk of
developing cardiovascular
complications is directly related to
the patient’s degree of hypertension
REMEMBER!
● The cardiovascular system
depends on pressure changes to
circulate blood to the tissues and
back to the heart.
● Heart rate, stroke volume, and
peripheral vascular resistance are
factors that determine blood
pressure.
● Constriction and relaxation of the
arterioles result in peripheral
resistance.
● The baroreceptors stimulate the
medulla, which stimulates the
sympathetic nervous system to
constrict the blood vessels and
increase fluid retention if pressure
is low in the aorta and the carotid
arteries. If pressure is too high,
vasodilation and loss of fluid
result.
● A decrease in blood flow to the
kidneys triggers the
renin–angiotensin–aldosterone
system, by which the blood
vessels constrict and water is
retained. This activity increases
blood pressure and restores blood
flow to the kidney.
● Hypertension is a sustained state
of higher-than-normal blood
pressure that can lead to blood
vessel damage, atherosclerosis,
and damage to small vessels in
end organs.
● The cause of essential
hypertension is unknown;
treatment varies among
individuals.
 ANTIHYPERTENSIVE AGENTS
(Drugs in Focus)
Angiotensin-Converting-Enzyme (ACE)
Inhibitors
Therapeutic ACE inhibitors act in the lungs to
Actions and prevent ACE from converting
Indications angiotensin I to angiotensin II, a
powerful vasoconstrictor and
stimulator of aldosterone release.
This action leads to a decrease
in blood pressure and in
aldosterone secretion, with a
resultant slight increase in serum
potassium and a loss of serum
sodium and fluid.
These drugs are indicated for the
treatment of hypertension, alone
or in combination with other
drugs. They are also used in
conjunction with digoxin and
diuretics for the treatment of
heart failure and left ventricular
dysfunction. Their therapeutic
effect in these cases is thought to
be related to a decrease in
cardiac workload associated with
the decrease in peripheral
resistance and blood volume.
They are also approved for the
treatment of diabetic
nephropathy. It is thought that the
decrease in the stimulation of the
angiotensin receptors in the renal
artery will slow the damage to
the renal artery that occurs in
diabetes.
Pharmacokin All of the ACE inhibitors are
etics administered orally. Enalapril
also has the advantage of
parenteral use (enalaprilat
[Vasotec IV]) if oral use is not
feasible or rapid onset is
desirable. These drugs are well
absorbed, widely distributed,
metabolized in the liver, and
excreted in the urine and feces.
They have been detected in
breast milk, are known to cross
the placenta, and have been
associated with serious fetal
abnormalities, and so they
should not be used during
pregnancy.
Contraindicati ACE inhibitors are
ons and contraindicated in the presence
Cautions of allergy to any of the ACE
inhibitors to prevent
hypersensitivity reactions and
impaired renal function, which
could be exacerbated by the
effects of this drug in decreasing
renal blood flow. Caution should
be used in patients with heart
failure because the change in
hemodynamics could be
detrimental in some cases and in
those with salt/volume depletion,
which could be exacerbated by
the drug effects. Women of
childbearing age who choose to
use one of these drugs should be
encouraged to use barrier
contraceptives to avoid
pregnancy while taking the drug.
Use is contraindicated during
pregnancy because of the
potential for serious adverse
effects on the fetus and during
lactation because of a potential
decrease in milk production and
effects on the neonate.
Adverse The adverse effects most
Effects commonly associated with ACE
inhibitors are related to the
effects of vasodilation and
alterations in blood flow. Such
effects include reflex tachycardia,
chest pain, angina, heart failure,
and cardiac arrhythmias;
gastrointestinal (GI) irritation,
ulcers, constipation, and liver
injury; renal insufficiency, renal
failure, and proteinuria; and rash,
alopecia, dermatitis, and
photosensitivity (Figure 43.5).
Quinapril, ramipril, and
trandolapril are fairly well
tolerated and not associated with
as many adverse effects as
some of the other agents are.
Benazepril, enalapril, and
fosinopril are generally well
tolerated but cause an
unrelenting cough, possibly
related to effects in the lungs,
where the ACE is inhibited, that
may lead patients to discontinue
the drug. Captopril, moexipril,
and perindopril are associated
with more-serious adverse
effects. Captopril has been
associated with sometimes-fatal
pancytopenia, cough, and
unpleasant GI distress. Moexipril
is associated with many
unpleasant GI and skin effects,
 cough, and cardiac arrhythmias; because of the potential
fatal myocardial infarction and adverse effects on the
pancytopenia have sometimes fetus or neonate;
been associated with this drug as salt/volume depletion
well. Perindopril and lisinopril are and heart failure, which
associated with sometimes-fatal could be exacerbated
pancytopenia, as well as by these drugs.
serious-to-fatal airway
obstruction (found to occur more Drug Name Usual Dosage Usual
frequently in African American Indications
patients).
benazepril 20–40 mg/d Approved only
Clinically The risk of hypersensitivity (Lotensin) PO, reduce for the
Important reactions increases if these dose with older treatment of
Drug–Drug drugs are taken with allopurinol. patients and hypertension in
Interactions There is a risk of decreased patients with adults
antihypertensive effects if taken renal
with nonsteroidal impairment
anti-inflammatory drugs; patients
should be monitored. aptopril 25 mg PO Treatment of
(Capoten) b.i.d. to t.i.d. hypertension;
Clinically Absorption of oral ACE inhibitors for adjunct
Important decreases if they are taken with hypertension, therapy for HF;
Drug–Food food. They should be taken on 50–100 mg PO treatment of
Interactions an empty stomach 1 hour before t.i.d. for heart left ventricular
or 2 hours after meals. failure (HF), 50 dysfunction
mg PO t.i.d. for after
Nursing ● Assess baseline status ventricular myocardial
Consideration before beginning dysfunction, 25 infarction (MI),
s for Patients therapy to determine mg PO t.i.d. for diabetic
Receiving any potential adverse diabetic nephropathy;
ACE effects. This includes nephropathy; for use in
Inhibitors body temperature and reduce dose in adults
weight; skin color, patients with
lesions, and renal
temperature; pulse, impairment
blood pressure, and in geriatric
baseline patients
electrocardiogram, and
perfusion; respirations enalapril 10–40 mg/d Treatment of
and adventitious breath (Vasotec) PO; reduce hypertension,
sounds; bowel sounds dose in HF, left
and abdominal geriatric ventricular
examination; and renal patients and dysfunction in
function tests, complete patients with adults
blood count with renal
differential, and serum impairment;
electrolytes. 2.5 mg PO
● Assess for the following b.i.d. for HF or
conditions, which could left ventricular
be cautions or dysfunction
contraindications to
using of the drug: any enalaprilat 1.25 mg q6h IV Short-term
known allergies to these (Vasotec IV) over 5 min treatment of
drugs to prevent acute
hypersensitivity hypertension
reactions; impaired when oral
kidney function, which therapy is not
could be exacerbated feasible
by these drugs;
pregnancy or lactation
fosinopril 20–40 mg/d Treatment of patients and
(Monopril) PO hypertension, patients with
adjunct renal
therapy for HF, impairment
for use in
adults trandolapril 1–2 mg PO Treatment of
(Mavik) q.i.d. for hypertension,
lisinopril 20–40 mg/d Treatment of hypertension; HF, and after
(Prinivil, PO for hypertension, 4 mg/d PO, MI; for use in
Zestril) hypertension, HF; treatment titrate slowly to adults
5–20 mg/d PO of stable that level for
for HF, 5–10 patients within HF; reduce
mg/d PO after 24 h after dose in
MI; decrease acute MI to patients with
dose in increase renal or
geriatric survival; for hepatic
patients and use in adults impairment
patients with
renal Angiotensin II–Receptor Blockers
impairment
Therapeutic The ARBs selectively bind with
moexipril 7.5–30 mg/d Treatment of Actions and the angiotensin II receptors in
(Univasc) PO, based on hypertension in Indications vascular smooth muscle and in
response; adults the adrenal cortex to block
reduce dose in vasoconstriction and the release
patients with of aldosterone. These actions
renal block the blood pressure–raising
impairment effects of the renin–angiotensin
and in geriatric system and lower blood
patients pressure. They are indicated to
be used alone or in combination
perindopril 4 mg/d PO; Treatment of therapy for the treatment of
(Aceon) reduce dose in hypertension, hypertension and for the
geriatric may be used treatment of heart failure in
patients and alone or as patients who are intolerant to
patients with combination ACE inhibitors. Recently, they
renal drug to control were also found to slow the
impairment blood progression of renal disease in
pressure, for patients with hypertension and
use in adults type 2 diabetes. This action is
thought to be related to the
quinapril 20–80 mg/d Treatment of effects of blocking angiotensin
(Accupril) PO, based on hypertension, receptors in the vascular
response for adjunctive endothelium.
hypertension; treatment of
10–20 mg PO HF, for use in Pharmacokin These agents are all given orally.
b.i.d. for HF; adults etics They are well absorbed and
reduce dose in undergo metabolism in the liver
patients with by the cytochrome P450 system.
renal They are excreted in feces and in
impairment urine. The ARBs cross the
and in geriatric placenta. It is not known whether
patients they enter breast milk during
lactation.
ramipril 2.5–20 mg/d Treatment of
(Altace) PO for hypertension, Contraindicati The ARBs are contraindicated in
hypertension, adjunctive ons and the presence of allergy to any of
5 mg PO b.i.d. treatment of Cautions these drugs to prevent
for HF; reduce HF, for use in hypersensitivity reactions.
dose in adults Caution should be used in the
geriatric
 presence of hepatic or renal drug is combined with
dysfunction, which could alter the ketoconazole, fluconazole, or
metabolism and excretion of diltiazem. Monitor the patient
these drugs, and with closely and adjust the dose as
hypovolemia, because of the needed.
blocking of potentially life-saving
compensatory mechanisms. Nursing ● Assess for the following
These drugs are also Consideration conditions, which could
contraindicated during s for Patients be cautions or
pregnancy: candesartan, Receiving contraindications to use
eprosartan, irbesartan, Angiotensin of the drug: any known
olmesartan, and telmisartan II–Receptor allergies to these drugs
should not be used during the Blockers to prevent
second or third trimester of hypersensitivity
pregnancy because of reactions; impaired
association with serious fetal kidney or liver function,
abnormalities and even death which could be
when given in the second or third exacerbated by these
trimester; azilsartan, losartan, drugs; pregnancy and
and valsartan should not be used lactation because of the
at any time during pregnancy. potential adverse effects
Although it is not known whether on the fetus and
the ARBs enter breast milk neonate; and
during lactation, these drugs hypovolemia, which
should not be used during could potentiate the
lactation because of the potential blood
for serious adverse effects in the pressure–lowering
neonate. Women of childbearing effects
age should be advised to use ● Assess baseline status
barrier contraceptives to avoid before beginning
pregnancy; if a pregnancy does therapy to determine
occur, the ARB should be any potential adverse
discontinued immediately. effects; this includes
body temperature and
Adverse The adverse effects most weight; skin color,
Effects commonly associated with ARBs lesions, and
include the following: headache, temperature; pulse,
dizziness, syncope, and blood pressure,
weakness, which could be baseline
associated with drops in blood electrocardiogram, and
pressure; hypotension; GI perfusion; respirations
complaints, including diarrhea, and adventitious breath
abdominal pain, nausea, dry sounds; bowel sounds
mouth, and tooth pain; symptoms and abdominal
of upper respiratory tract examination; and renal
infections and cough; and rash, and liver function tests.
dry skin, and alopecia. In
preclinical trials, these drugs Drug Name Usual Dosage Usual
have been associated with the Indications
development of various cancers.
azilsartan 80 mg/d PO Used alone or
Clinically The risk of decreased serum (Edarbi) as part of
Important levels and loss of effectiveness combination
Drug–Drug increases if the ARB is taken in therapy for
Interactions combination with phenobarbital, treatment of
indomethacin, or rifamycin. If this hypertension in
combination is used, the patient adults
should be monitored closely and
dose adjustments made. There candesartan 16–32 mg/d Used alone or
may be a decrease in anticipated (Atacand) PO as part of
antihypertensive effects if the combination
 therapy for treatment of
treatment of hypertension in
hypertension in adults
adults
valsartan 80–320 mg/d Used alone or
eprosartan 400–800 mg/d Used alone or (Diovan) PO based on as part of
(Teveten) PO as part of response combination
combination therapy for
therapy for treatment of
treatment of hypertension in
hypertension in adults,
adults treatment of
heart failure in
irbesartan 150–300 mg/d Used alone or patients who
(Avapro) PO as part of are intolerant
combination to ACE
therapy for inhibitors
treatment of
hypertension in Calcium Channel Blockers
adults, slowing Calcium channel blockers decrease blood
progression of
diabetic pressure, cardiac workload, and
nephropathy in myocardial oxygen consumption.
patients with
hypertension Therapeutic Calcium channel blockers inhibit
and type 2 Actions and the movement of calcium ions
diabetes Indications across the membranes of
myocardial and arterial muscle
losartan 25–100 mg/d Used alone or cells, altering the action potential
(Cozaar) PO as part of and blocking muscle cell
combination contraction. This effect
therapy for depresses myocardial
treatment of contractility, slows cardiac
hypertension in impulse formation in the
adults, slowing conductive tissues, and relaxes
progression of and dilates arteries, causing a
diabetic fall in blood pressure and a
nephropathy decrease in venous return.
with elevated
serum Pharmacokin Calcium channel blockers are
creatinine and etics given orally and are generally
proteinuria in well absorbed, metabolized in
patients with the liver, and excreted in the
hypertension urine. These drugs cross the
and type 2 placenta and enter breast milk.
diabetes Nicardipine and clevidipine are
available in an intravenous form
olmesartan 20–40 mg/d Used alone or for short-term use when oral
(Benicar) PO as part of administration is not feasible.
combination
therapy to treat Contraindicati These drugs are contraindicated
hypertension in ons and in the presence of allergy to any
adults (newest Cautions of these drugs to prevent
angiotensin hypersensitivity reactions; with
II–receptor heart block or sick sinus
blocker) syndrome, which could be
exacerbated by the
telmisartan 40–80 mg/d Used alone or conduction-slowing effects of
(Micardis) PO as part of these drugs; and with renal or
combination hepatic dysfunction, which could
therapy for alter the metabolism and
 excretion of these drugs. Receiving
Although there are no Calcium
well-defined ned studies about Channel
effects during pregnancy, fetal Blockers
toxicity has been reported in
animal studies; therefore, these Drug Name Usual Dosage Usual
drugs should not be used during Indications
pregnancy unless the benefit to
the mother clearly outweighs any amlodipine 5–10 mg/d Used alone or
potential risk to the fetus (Norvasc) PO, reduce in combination
because of the potential for dose in with other
adverse effects on the fetus or patients with agents for
neonate. Because of the hepatic treatment of
potential for serious adverse impairment hypertension
effects on the baby, another and in geriatric and angina in
method of feeding the infant patients adults
should be used if these drugs are
required during lactation. clevidipine Initially 1–2 Reduction of
(Cleviprex mg/h by IV blood pressure
Adverse The adverse effects associated infusion, titrate when oral
Effects with these drugs relate to their quickly by therapy is not
effects on cardiac output and on doubling the possible or
smooth muscle. Central nervous dose every 90 desirable
system effects include dizziness, s, usual
light-headedness, headache, and maintenance
fatigue. GI problems include dose 4–6 mg/h
nausea and hepatic injury related
to direct toxic effects on hepatic diltiazem 60–120 mg PO Extended-relea
cells. Cardiovascular effects (Cardizem, b.i.d. se preparation
include hypotension, Dilacor CR) used to treat
bradycardia, peripheral edema, hypertension in
and heart block. Skin flushing adults, other
and rash may also occur. preparations
are used for
Clinically Drug–drug interactions vary with angina
Important each of the calcium channel
Drug–Drug blockers used to treat felodipine 10–15 mg/d Used alone or
Interactions hypertension. A potentially (Plendil) PO, do not in combination
serious effect to note is an exceed 10 with other
increase in serum levels and mg/d in agents for
toxicity of cyclosporine if taken geriatric treatment of
with diltiazem. patients or in hypertension in
patients with adults
Clinically The calcium channel blockers hepatic
Important are a class of drugs that interact impairment
Drug–Food with grapefruit juice. When
Interactions grapefruit juice is present in the isradipine 2.5–10 mg PO Used alone or
body, the concentrations of (DynaCirc) b.i.d., 5–10 in combination
calcium channel blockers mg/d with thiazide
increase, sometimes to toxic PO—controlled diuretics for
levels. Advise patients to avoid release treatment of
the use of grapefruit juice if they hypertension in
are taking a calcium channel adults
blocker. If a patient on a calcium
channel blocker reports toxic nicardipine 20–40 mg PO Used alone or
effects, ask whether he or she is (Cardene) t.i.d.; 0.5–2.2 in combination
drinking grapefruit juice. mg/h IV based with other
on response, agents for
Nursing the main use of calcium channel switch to oral treatment of
Consideration blockers is for the treatment of form as soon hypertension
s for Patients angina.
 as feasible; and angina, IV Therapeutic The vasodilators act directly on
reduce dose in form for Actions and vascular smooth muscle to cause
geriatric short-term use Indications muscle relaxation, leading to
patients and in when oral vasodilation and drop in blood
patients with route is not pressure. They do not block the
hepatic or feasible, for reflex tachycardia that occurs
renal use in adults when blood pressure drops.
impairment; They are indicated for the
30–60 mg PO treatment of severe hypertension
b.i.d.—sustain that has not responded to other
ed release therapy.

nifedipine 30–60 mg/d Extended-relea Pharmacokin Nitroprusside is used

(Procardia XL) PO se etics intravenously; hydralazine is
preparations available for oral, intravenous,
only for the and intramuscular use; and
treatment of minoxidil is available as an oral
hypertension in agent only. These drugs are
adults, other rapidly absorbed and widely
preparations distributed. They are metabolized
are used for in the liver and primarily excreted
angina in urine. They cross the placenta
and enter breast milk.
nisoldipine 20–40 mg/d Extended-relea
(Sular) PO; reduce se tablets used Contraindicati The vasodilators are
dose in as ons and contraindicated in the presence
geriatric monotherapy Cautions of known allergy to the drug to
patients and in or as part of prevent hypersensitivity reactions
patients with combination and with any condition that could
hepatic therapy for be exacerbated by a sudden fall
impairment treatment of in blood pressure, such as
hypertension in cerebral insufficiency. Caution
adults, other should be used in patients with
preparations peripheral vascular disease,
are used for CAD, heart failure, or
angina tachycardia, all of which could be
exacerbated by the fall in blood
verapamil 120–240 mg/d Extended-relea pressure. These drugs are also
(Calan SR) PO, reduce se formulations contraindicated with pregnancy
dose in the for the unless the benefit to the mother
morning; treatment of clearly outweighs the potential
extended-relea essential risk because of the potential for
se capsules: hypertension, adverse effects on the fetus or
100–300 mg/d other neonate. If they are needed by a
PO at bedtime preparations nursing mother, another method
are used for of feeding the baby should be
angina and selected, because of the
treating potential for adverse effects on
various the baby.
arrhythmias in
adults Adverse Eff The adverse effects most
ects frequently seen with these drugs
Vasodilators are related to the changes in
blood pressure. These include
If other drug therapies do not achieve the dizziness, anxiety, and
desired reduction in blood pressure, it is headache; reflex tachycardia,
sometimes necessary to use a direct heart failure, chest pain, and
vasodilator. Most of vasodilators are edema; skin rash and lesions
reserved for use in severe hypertension (abnormal hair growth with
minoxidil); and GI upset, nausea,
or hypertensive emergencies. and vomiting. Cyanide toxicity
 (dyspnea, headache, vomiting, necessary
dizziness, ataxia, loss of Pediatric:
consciousness, imperceptible 1.7–3.5 mg/kg
pulse, absent refl exes, dilated per 24 h IV or
pupils, pink color, distant heart IM in four to six
sounds, and shallow breathing) divided doses
may occur with nitroprusside,
which is metabolized to cyanide minoxidil Adult: 10–40 Treatment of
and also suppresses iodine (Loniten) mg/d PO in severe
uptake and can cause divided doses hypertension
hypothyroidism. Pediatric (<12 unresponsive
y): 0.25–1 to other
Clinically Each of these drugs works mg/kg/d PO as therapy
Important differently in the body, so each a single dose
Drug–Drug drug should be checked for
Interactions potential drug–drug interactions nitroprusside Adult and Treatment of
before use. (Nitropress) pediatric hypertensive
patients: 3 crisis, also
Nursing ● Assess for the following mcg/kg/min, do used to
Consideration conditions, which could not exceed 10 maintain
s for Patients be cautions or mcg/kg/min controlled
Receiving contraindications to hypotension
Vasodilators using of the drug: any during surgery
known allergies to these
drugs, impaired kidney OTHER ANTIHYPERTENSIVE AGENTS
or liver function,
pregnancy or lactation Diuretic Agents Diuretics are drugs that increase
because of the potential the excretion of sodium and
adverse effects on the water from the kidney. Diuretics
fetus or neonate, and are very important for the
cardiovascular treatment of hypertension. These
dysfunction, which drugs are often the first agents
could be exacerbated tried in mild hypertension; they
by a fall in blood affect blood sodium levels and
pressure. blood volume.
● Assess baseline status
before beginning
therapy to determine
any potential adverse
Questions (PIT STOPS)
effects; this includes 1. It acts in the lungs to prevent ACE from
body temperature and converting angiotensin I to angiotensin II.
weight; skin color, ANSWER: Angiotensin Converting Enzyme
lesions, and (ACE) Inhibitor
temperature; pulse,
blood pressure, 2. They selectively bind with the angiotensin II
baseline receptors in vascular smooth muscle and in
electrocardiogram, and the adrenal cortex to block vasoconstriction
perfusion; respirations and the release of aldosterone.
and adventitious breath ANSWER: Angiotensin II–Receptor Blockers
sounds; bowel sounds (ARBs)
and abdominal
examination; renal and 3. They inhibit the movement of calcium ions
liver function tests; and across the membranes of myocardial and
blood glucose. arterial muscle cells.
ANSWER: Calcium channel blockers
Drug Name Usual Dosage Usual
Indications 4. Patients taking calcium channel blockers
should avoid ingesting this food to avoid
hydralazine Adult: 20–40 Treatment of unwanted food-drug interactions.
(Apresoline) mg IM or IV severe ANSWER: Grapefruit juice
repeated as hypertension
5. Acts directly on vascular smooth muscle to
cause muscle relaxation. They are indicated
for the treatment of severe hypertension that
has not responded to other therapy.
ANSWER: Vasodilators
CASAS, CRISTHA (PHARMA)
CHAPTER 44: CARDIOTONIC AGENTS
● Cardiotonic agents are drugs used to
increase the contractility of the heart
muscle for patients experiencing heart
failure (HF).
● Heart failure (HF) is a condition in which
the heart fails to pump blood around the
body effectively. Because the cardiac
cycle normally involves a tight balance
between the pumping of the right and
left sides of the heart, any failure of the
muscle to pump blood out of either side
of the heart can result in a backup of
blood.
● If this happens, the blood vessels
become congested; eventually, the
body’s cells are deprived of oxygen and
nutrients, and waste products build up in
the tissues.
● The primary treatment for HF involves
helping the heart muscle to contract
more efficiently to restore system
balance.
REMEMBER!
● In HF, the heart pumps blood so
ineffectively that blood builds up,
causing congestion in the
cardiovascular system.
● HF can result from damage to the
heart muscle combined with an
increased workload related to CAD,
hypertension, cardiomyopathy,
valvular disease, or congenital heart
abnormalities.
● As the heart pump fails, the muscle
cells can no longer work to move
calcium into the cell, and cardiac
contractions become weak and
ineffective.
● Signs and symptoms of HF result
from the backup of blood in the
vascular system and the loss of fluid
in the tissues.
○ Right-sided HF is
characterized by edema, liver
congestion, elevated JVP,
and nocturia,
○ whereas left-sided failure is
marked by tachypnea,
dyspnea, orthopnea,
hemoptysis, anxiety, and poor
oxygenation of the blood.
● Treatment agents include
○ vasodilators (to lighten the
heart’s workload),
○ diuretics (to reduce blood
volume and workload),
○ beta-blockers (to decrease
the heart’s workload by
activating sympathetic
reaction),
○ human B-type natriuretic
peptides (to decrease the
heart’s workload by
vasodilation and suppression
of the response to the
sympathetic reaction), and
○ cardiotonic (inotropic) agents
(to stimulate more effective
muscle contractions).
CARDIOTONIC AGENTS
● Cardiotonic (inotropic) drugs affect the
intracellular calcium levels in the heart
muscle, leading to increased
contractility.
● This increase in contraction strength
leads to increased cardiac output,
which causes increased renal blood
flow and increased urine production.
Increased renal blood flow decreases renin
release, interfering with the effects of the
renin–angiotensin–aldosterone system, and
increases urine output, leading to decreased
blood volume.
● The result is a decrease in the heart’s
workload and relief of HF Two types
of cardiotonic drugs are used: the
classic cardiac glycosides, which
have been used for hundreds of
years, and the newer
phosphodiesterase inhibitors.
 Children should be monitored closely for any
sign of impending digitalis toxicity and should
have serum digoxin levels monitored.

The phosphodiesterase inhibitors are not

CARDIOTONIC AGENTS recommended for use in children.
(Drugs in Focus)
ADULTS
Drug Usual Dosage Usual
Name Indications
Adults receiving any of these drugs need to
be instructed as to what adverse reactions to
Cardiac Glycosides report immediately. They should learn to take
their own pulse and should be encouraged to
digoxin Adult: loading dose Treatment of
keep track of rate and regularity on a
(Lanoxin) 0.75–1.25 mg PO or acute heart
0.125–0.25 mg IV, failure (HF), calendar. They may be asked to weigh
then maintenance atrial themselves in the same clothing and at the
dose of 0.125–0.25 arrhythmias same time of the day to monitor for fluid
mg/d PO; decrease retention. Any changes in diet, gastrointestinal
dose with renal (GI) activity, or medications should be
impairment reported to the health care provider because
Pediatric (dose of the potential for altering serum levels and
based on age): causing toxic reactions or ineffective dosing.
10–60 mcg/ kg PO
or 8–50 mcg/kg IV
loading dose; Patients should also be advised against
maintenance is switching between brands of digoxin because
25%–30% of loading there have been reports of different
dose bioavailabilities, leading to toxic reactions.

Phosphodiesterase Inhibitors The safety for the use of these drugs during
pregnancy has not been established. They
milrinone 50 mcg/kg IV bolus Short-term should not be used in pregnancy unless the
(Primacor) over 10 min, then management benefit to the mother clearly outweighs the
0.375– of HF in potential risk to the fetus. The drugs do enter
0.75 mcg/kg/min IV adults breast milk, but they have not been
infusion; do not receiving
associated with any adverse effects in the
exceed digoxin and
1.13 mg/kg/d; diuretics
neonate. Caution should be exercised,
reduce dose in renal however, if one of these drugs is needed
impairment during lactation.

OLDER ADULTS

Older adults frequently are prescribed one of

DRUG THERAPY ACROSS THE LIFESPAN these drugs. They, like children at the other
(Cardiotonic Agents) end of the life spectrum, are more susceptible
to the toxic effects of the drugs and are more
CHILDREN
likely to have underlying conditions that could
interfere with their metabolism and excretion.
Digoxin is used widely in children with heart
defects and related cardiac problems. The
Renal impairment can lead to accumulation of
margin of safety for the dosage drug is very
digoxin in the body. If renal dysfunction is
small with children. The dosage needs to be
present, the dosage needs to be reduced and
very carefully calculated and should be
the patient monitored very closely for signs of
double-checked by another nurse before
digoxin toxicity.
administration.
The total drug regimen of the older patient
should be coordinated, with careful attention
to interacting drugs or alternative therapies.
For backup in situations of stress or illness, a
significant other should be instructed in how to
take the patient’s pulse and the adverse
effects to watch for while the patient is taking
this drug.
CARDIAC GLYCOSIDES
The cardiac glycosides were originally derived
from the foxglove or digitalis plant. These
plants were once ground up to make digitalis
leaf. Today, digoxin (Lanoxin) is the drug most
often used to treat HF.
Therapeutic Actions and Indications
Digoxin increases intracellular calcium and
allows more calcium to enter myocardial cells
during depolarization, causing the following
effects:
● Increased force of myocardial
contraction (a positive inotropic effect)
● Increased cardiac output and renal
perfusion (which has a diuretic effect,
increasing urine output and
decreasing blood volume while
decreasing renin release and
activation of the
renin–angiotensin–aldosterone
system)
● Slowed heart rate, owing to slowing of
the rate of cellular repolarization (a
negative chronotropic effect)
● Decreased conduction velocity
through the atrioventricular (AV) node
The overall effect is a decrease in the
myocardial workload and relief of HF. Digoxin
is indicated for the treatment of HF, atrial
flutter, atrial fibrillation, and paroxysmal atrial
tachycardia. Digoxin has a very narrow
margin of safety (meaning that the therapeutic
dose is very close to the toxic dose), so
extreme care must be taken when using this
drug.
Pharmacokinetics
Digoxin is available for oral and parenteral
administration. The drug has a rapid onset of
action and rapid absorption (30–120 minutes
when taken orally, 5– 30 minutes when given
intravenously). It is widely distributed
throughout the body. Digoxin is primarily
excreted unchanged in the urine. Because of
this, caution should be exercised in the
presence of renal impairment because the
drug may not be excreted and could
accumulate, causing toxicity.
Contraindications and Cautions
Cardiac glycosides are contraindicated in the
presence of allergy to any component of the
digitalis preparation to prevent hypersensitivity
reactions.
Digoxin is contraindicated in the following
conditions:
● ventricular tachycardia or fibrillation,
which are potentially fatal arrhythmias
and should be treated with other
drugs;
● heart block or sick sinus syndrome,
which could be made worse by
slowing of conduction through the AV
node;
● idiopathic hypertrophic subaortic
stenosis (IHSS) because the increase
in force of contraction could obstruct
the outflow tract to the aorta and
cause severe problems;
● acute MI because the increase in
force of contraction could cause more
muscle damage and infarct;
● renal insufficiency because the drug is
excreted through the kidneys and
toxic levels could develop;
● and electrolyte abnormalities (e.g.,
increased calcium, decreased
potassium, decreased magnesium),
which could alter the action potential
and change the effects of the drug.
Digoxin should be used cautiously in patients
who are pregnant or lactating because of the
potential for adverse effects on the fetus or
neonate. It is not known whether digoxin
causes fetal toxicity; it should be given during
pregnancy only if the benefit to the mother
clearly outweighs the risk to the fetus.
Digoxin does enter breast milk, but it has not
been shown to cause problems for the
neonate. Caution should be exercised,
however, during lactation. Pediatric and
geriatric patients also are at higher risk for
adverse effects and should be monitored
closely.
Adverse Effects
The adverse effects most frequently seen with
the cardiac glycosides include headache,
weakness, drowsiness, and vision changes (a
yellow halo around objects is often reported).
GI upset and anorexia also commonly occur.
Arrhythmias may develop because the
glycosides affect the action potential and
conduction system of the heart.
Digoxin toxicity is a serious syndrome that can
occur when digoxin levels are too high. The
patient may present with anorexia, nausea,
vomiting, malaise, depression, irregular heart
rhythms including heart block, atrial
arrhythmias, and ventricular tachycardia.
This can be a life-threatening situation. A
digoxin antidote, digoxin immune Fab, has
been developed to rapidly treat digoxin
toxicity.
ADDITIONAL INFORMATION!
Digoxin Antidote: Digoxin Immune Fab
Digoxin immune Fab (DigiFab) is an
antigen-binding fragment (Fab) derived from
specific anti digoxin antibodies. These
antibodies bind molecules of digoxin, making
them unavailable at their site of action. The
digoxin antibody–antigen complexes
accumulate in the blood and are excreted
through the kidney. Digoxin immune Fab is
used for the treatment of life-threatening
digoxin intoxication (serum levels >10 ng/mL
with serum potassium >5 mEq/L in a setting of
digoxin intoxication) and potential
life-threatening digoxin overdose.
The amount of digoxin immune Fab that is
infused intravenously is determined by the
amount of digoxin ingested or by the serum
digoxin level if the ingested amount is
unknown. The patient’s cardiac status should
be monitored continually while the drug is
given and for several hours after the infusion
is finished. Because there is a risk of
hypersensitivity reaction to the infused
protein, life-support equipment should be on
standby.
Serum digoxin levels will be very high and
unreliable for about 3 days after the digoxin
immune Fab infusion because of the high
levels of digoxin in the blood. The patient
should not be redigitalized for several days to
1 week after digoxin immune Fab has been
used because of the potential of remaining
fragments in the blood.
Clinically Important Drug-Drug Interactions
There is a risk of increased therapeutic effects
and toxic effects of digoxin if it is taken with
verapamil, amiodarone, quinidine, quinine,
erythromycin, tetracycline, or cyclosporine. If
digoxin is combined with any of these drugs, it
may be necessary to decrease the digoxin
dose to prevent toxicity. If one of these drugs
has been part of a medical regimen with
digoxin and is discontinued, the digoxin dose
may need to be increased. The risk of cardiac
arrhythmias could increase if these drugs are
taken with potassium-losing diuretics. If this
combination is used, the patient’s potassium
levels should be checked regularly and
appropriate replacement done. Digoxin may
be less effective if it is combined with thyroid
hormones, metoclopramide, or penicillamine,
and increased digoxin dose may be needed.
Absorption of oral digoxin may be decreased
if it is taken with cholestyramine, charcoal,
colestipol, antacids, bleomycin,
cyclophosphamide, or methotrexate. If it is
used in combination with any of these agents,
the drugs should not be taken at the same
time but should be administered 2 to 4 hours
apart.
NURSING CONSIDERATIONS FOR
PATIENTS RECEIVING CARDIAC
GLYCOSIDES
Assessment: History and Examination
● Assess for contraindications or
cautions: known allergies to any
digitalis product to avoid
hypersensitivity reactions; impaired
kidney function, which could alter the
excretion of the drug; ventricular
tachycardia or fibrillation, which
require treatment with other lifesaving
drugs; heart block, sick sinus
syndrome, or idiopathic hypertrophic
subaortic stenosis, which could be
exacerbated by the drug; acute
myocardial infarction, which could
lead to increased muscle damage and
infarction; electrolyte abnormalities
(increased calcium, decreased
potassium, or decreased
magnesium), which could alter the
action potential and drug effects; and
current status of pregnancy or
lactation to evaluate benefits versus
potential risk to the fetus when using
the drug.
● Perform a physical assessment to
establish baseline status before
beginning therapy, determine the
effectiveness of therapy, and evaluate
for any potential adverse effects.
● Obtain the patient’s weight, noting any
recent increases or decreases, to
determine the patient’s fluid status.
● Assess cardiac status closely,
including pulse and blood pressure, to
identify changes requiring a change in
dosage of the drug or the presence of
adverse effects, and auscultate heart
sounds, noting any evidence of
abnormal sounds, to identify
conduction problems.
● Inspect the skin and mucous
membranes for color, and check nail
beds and capillary refill for evidence
of perfusion.
● Monitor affect, orientation, and
reflexes to evaluate central nervous
system (CNS) effects of the drug.
● Assess the patient’s respiratory rate
and auscultate lungs for evidence of
adventitious breath sounds to monitor
for evidence of left-sided heart failure
(HF).
● Examine the abdomen for distention;
auscultate bowel sounds to evaluate
gastrointestinal motility.
● Assess voiding patterns and urinary
output to provide a gross indication of
renal function.
● Obtain a baseline electrocardiogram
(ECG) to identify rate and rhythm and
evaluate for possible changes.
● Monitor the results of laboratory tests,
including serum electrolyte levels and
renal function tests, to determine the
need for possible dose adjustment.
Nursing Diagnosis
Nursing diagnoses related to drug therapy
might include the following:
● Risk for Imbalanced Fluid Volume
related to increased renal perfusion
secondary to effects of the drug
● Decreased Cardiac Output related to
ineffective cardiac muscle function
● Ineffective Tissue Perfusion (Total
Body) related to change in cardiac
output
● Impaired Gas Exchange related to
changes in cardiac output
● Deficient Knowledge related to
prescribed drug therapy
Implementation with Rationale
● Consult with the prescriber about the
need for a loading dose when
beginning therapy to achieve desired
results as soon as possible.
● Monitor apical pulse for 1 full minute
before administering the drug to
monitor for adverse effects. Hold the
dose if the pulse is less than 60
beats/min in an adult or less than 90
beats/min in an infant; retake the
pulse in 1 hour. If the pulse remains
low, document it, withhold the drug,
and notify the prescriber because the
pulse rate could indicate digoxin
toxicity.
● Monitor the pulse for any change in
quality or rhythm to detect
arrhythmias or early signs of toxicity.
● Check the dose and preparation
carefully because digoxin has a very
small margin of safety, and
inadvertent drug errors can cause
serious problems.
● Check pediatric dose with extreme
 care because children are more apt to
develop digoxin toxicity. Have the
dose double-checked by another
nurse before administration.
● Follow dilution instructions carefully
for intravenous use; use promptly to
avoid drug degradation.
● Administer intravenous doses very
slowly over at least 5 minutes to avoid
cardiac arrhythmias and adverse
effects.
● Avoid intramuscular administration,
which could be quite painful.
● Arrange for the patient to be weighed
at the same time each day, in the
same clothes, to monitor for fluid
retention and HF. Assess dependent
areas for edema; note the amount
and degree of pitting to evaluate the
severity of fluid retention.
● Avoid administering the oral drug with
food or antacids to avoid delays in
absorption.
● Maintain emergency equipment on
standby: potassium salts, lidocaine
(for treatment of arrhythmias),
phenytoin (for treatment of seizures),
atropine (to increase heart rate), and
a cardiac monitor, in case severe
toxicity should occur.
● Obtain digoxin level as ordered;
monitor the patient for therapeutic
digoxin level (0.5–2 ng/mL) to
evaluate therapeutic dosing and to
monitor for the development of
toxicity.
● Provide comfort measures to help the
patient tolerate drug effects. These
include small, frequent meals to help
alleviate GI upset or nausea; access
to bathroom facilities if GI upset is
severe and to accommodate
increased urination related to
increased cardiac output; safety
precautions to reduce the risk of injury
secondary to weakness and
drowsiness; adequate lighting to
accommodate vision changes if they
occur; positioning for comfort; and
frequent rest periods to balance
supply and demand of oxygen.
● Offer support and encouragement to
help the patient deal with the
diagnosis and the drug regimen.
● Provide thorough patient teaching,
including the name of the drug,
dosage prescribed, technique for
monitoring pulse and acceptable
pulse parameters, dietary measures if
appropriate, measures to avoid
adverse effects, warning signs of
possible toxicity and need to notify
health care provider, and the need for
periodic monitoring and evaluation,
including ECGs and laboratory
testing, to enhance patient knowledge
about drug therapy and to promote
compliance.
Evaluation
● Monitor patient response to the drug
(improvement in signs and symptoms
of HF, resolution of atrial arrhythmias,
serum digoxin level of 0.5–2 ng/mL).
● Monitor for adverse effects (vision
changes, arrhythmias, HF, headache,
dizziness, drowsiness, GI upset,
nausea).
● Monitor the effectiveness of comfort
measures and compliance with the
regimen.
● Evaluate the effectiveness of the
teaching plan (patient can name drug,
dosage, proper administration,
adverse effects to watch for, specific
measures to avoid them, and the
importance of continued follow-up).
PHOSPHODIESTERASE INHIBITORS
The phosphodiesterase inhibitors belong to a
second class of drugs that act as cardiotonic
(inotropic) agents. These include milrinone
(Primacor).
Therapeutic Actions and Indications
The phosphodiesterase inhibitors block the
enzyme phosphodiesterase. This blocking
effect leads to an increase in myocardial cell
cyclic adenosine monophosphate (cAMP),
which increases calcium levels in the cell.
Increased cellular calcium causes a stronger
contraction and prolongs the effects of
sympathetic stimulation, which can lead to
vasodilation, increased oxygen consumption,
and arrhythmias.

These drugs are indicated for the short-term
treatment of HF that has not responded to
digoxin or diuretics alone or that has had a
poor response to digoxin, diuretics, and
vasodilators. Because these drugs have been
associated with the development of potentially
fatal ventricular arrhythmias, their use is
limited to severe situations.
occur with milrinone. Hypersensitivity
reactions associated with these drugs include
vasculitis, pericarditis, pleuritis, and ascites.
Burning at the intravenous injection site is
also a frequent adverse effect.
Variety of adverse effects and toxicities
associated with cardiotonic agents.

Pharmacokinetics

Inamrinone and milrinone are available only

for intravenous use. These drugs are widely
distributed after injection. They are
metabolized in the liver and excreted primarily
in the urine.

Contraindications and Cautions

Phosphodiesterase inhibitors are

contraindicated in the presence of allergy to
either of these drugs or to bisulfites to avoid
hypersensitivity reactions. They also are
contraindicated in the following conditions:
severe aortic or pulmonic valvular disease,
which could be exacerbated by increased
contraction; acute MI, which could be
exacerbated by increased oxygen
consumption and increased force of
contraction; fluid volume deficit, which could
be made worse by increased renal perfusion;
and ventricular arrhythmias, which could be
exacerbated by these drugs.

Caution should be exercised in the elderly,

who are more likely to develop adverse
effects. There are no adequate studies about
the effects of these drugs during pregnancy,
and their use should be reserved for situations
in which the benefit to the mother clearly
outweighs the potential risk to the fetus. It is
not known whether these drugs enter breast
milk, so caution should be exercised if a
patient is breast-feeding.
Clinically Important Drug-Drug Interactions
Precipitates form when these drugs are given
in solution with furosemide. Avoid this
combination in solution. Use alternate lines if
both of these drugs are being given
intravenously.

Adverse Effects

The adverse effects most frequently seen with NURSING CONSIDERATIONS FOR
these drugs are ventricular arrhythmias (which PATIENTS RECEIVING
can progress to fatal ventricular fibrillation),
hypotension, and chest pain. GI effects
PHOSPHODIESTERASE INHIBITORS
include nausea, vomiting, anorexia, and
Assessment: History and Examination
abdominal pain. Thrombocytopenia occurs
frequently with inamrinone, and it also can
 ● Assess for contraindications or
cautions: any known allergies to these
drugs or to bisulfites to avoid
hypersensitivity reactions; acute aortic
or pulmonic valvular disease, acute
myocardial infarction or fluid volume
deficit, and ventricular arrhythmias,
which could be exacerbated by these
drugs; and current status of
pregnancy and lactation to prevent
potential adverse effects to the fetus
or baby.
● Perform a physical assessment to
establish baseline status before
beginning therapy, determine the
effectiveness of therapy, and evaluate
for any potential adverse effects.
● Assess cardiac status closely,
including pulse and blood pressure, to
identify changes or the presence of
adverse effects; auscultate heart
sounds, noting any evidence of
abnormal sounds.
● Obtain the patient’s weight, noting any
recent increases or decreases, to
determine the patient’s fluid status.
● Inspect skin and mucous membranes
for color, and check nail beds and
capillary refill for evidence of
perfusion.
● Examine the abdomen for distention;
auscultate bowel sounds to evaluate
gastrointestinal (GI) motility.
● Assess voiding patterns and urinary
output to provide a gross indication of
renal function.
● Obtain a baseline electrocardiography
to identify rate and rhythm and
evaluate for possible changes.
● Monitor the results of laboratory tests,
including serum electrolyte levels,
complete blood count, and renal and
hepatic function tests, to determine
the need for possible dose
adjustment.
Nursing Diagnosis
Nursing diagnoses related to drug therapy
might include the following:
● Decreased Cardiac Output related to
development of arrhythmias or
hypotension
● Risk for Injury related to central
nervous system (CNS) or
cardiovascular effects
● Ineffective Tissue Perfusion (Total
Body) related to hypotension,
thrombocytopenia, or arrhythmias
● Deficient Knowledge related to drug
therapy
Implementation with Rationale
● Protect the drug from light to prevent
drug degradation.
● Ensure that the patient has a patent
intravenous access site available to
allow for intravenous administration of
the drug.
● Monitor pulse and blood pressure
frequently during administration to
monitor for adverse effects so that the
dose can be altered if needed to
avoid toxicity.
● Monitor input and output and record
daily weight to evaluate the resolution
of heart failure (HF).
● Monitor platelet counts before and
regularly during therapy to ensure that
the dose is appropriate, inspect the
skin for bruising or petechiae to detect
early signs of thrombocytopenia, and
consult with the prescriber about the
need to decrease the dose at the first
sign of thrombocytopenia.
● Monitor intravenous injection sites
and provide comfort measures if
infusion is causing irritation.
● Provide life-support equipment on
standby in case of severe reaction to
the drug or development of ventricular
arrhythmias.
● Provide comfort measures to help the
patient tolerate drug effects. These
include small, frequent meals to
alleviate GI upset and anorexia;
access to bathroom facilities to
provide needed facilities if GI upset is
severe and when increased urination
occurs secondary to increased
cardiac output; safety precautions to
protect the patient if visual changes,
dizziness, or weakness occurs; and
orientation to surroundings to support
the patient if CNS changes occur.
● Offer support and encouragement to
help the patient deal with the
diagnosis and the drug regimen.
● Provide thorough patient teaching,
 including the name of the drug,
dosage prescribed, measures to avoid
adverse effects, warning signs of
problems, and the need for periodic
monitoring and evaluation, to enhance
patient knowledge about drug therapy
and to promote compliance.
Evaluation
● Monitor patient response to the drug
(alleviation of signs and symptoms of
HF).
● Monitor for adverse effects
(hypotension, cardiac arrhythmias, GI
upset, thrombocytopenia).
● Monitor the effectiveness of comfort
measures and compliance with the
regimen.
● Evaluate the effectiveness of the
teaching plan (patient can name drug,
dosage, adverse effects to watch for,
specific measures to avoid them, and
the importance of continued
follow-up).
REMEMBER!
● The cardiac glycoside digoxin
increases the movement of calcium
into the heart muscle. This results in
increased force of contraction, which
increases blood flow to the kidneys
(causing a diuretic effect), slows the
heart rate, and slows conduction
through the AV node. All of these
effects decrease the heart’s workload.
● Phosphodiesterase inhibitors block
the breakdown of cAMP in the cardiac
muscle. This allows more calcium to
enter the cell (leading to more intense
contraction) and increases the effects
of sympathetic stimulation (which can
lead to vasodilation but also can
increase pulse, blood pressure, and
workload on the heart).
● Phosphodiesterase inhibitors are
associated with severe effects. They
are reserved for use in extreme
situations. They are only available for
IV use.
Questions (PIT STOP)
SUMMARY!
● HF, a condition in which the heart
muscle fails to effectively pump blood
through the cardiovascular system,
can be the result of a damaged heart
muscle and increased demand to
work harder.
● The sarcomere—the functioning unit
of the heart muscle—is made up of
protein fibers: thin actin fibers and
thick myosin fibers, which react with
each other when calcium is present to
inactivate troponin. The fibers slide
together, resulting in contraction.
Failing cardiac muscle cells lose the
ability to effectively use energy to
move calcium into the cell, and
contractions become weak and
ineffective.
● Cardiotonic (inotropic) agents are one
class of drugs used in the treatment of
heart failure. These agents directly
stimulate the muscle to contract more
effectively.
● Cardiac glycosides increase the
movement of calcium into the heart
muscle. This results in increased
force of contraction, which increases
blood flow to the kidneys (causing a
diuretic effect), slows the heart rate,
and slows conduction through the AV
node. All of these effects decrease
the heart’s workload. Digoxin is the
cardiac glycoside most commonly
used to treat HF.
● Phosphodiesterase inhibitors block
the breakdown of cAMP in the cardiac
muscle. This allows more calcium to
enter the cell (leading to more intense
contraction) and increases the effects
of sympathetic stimulation (which can
lead to vasodilation but also can
increase pulse, blood pressure, and
workload on the heart). Because
these drugs are associated with
severe effects, they are reserved for
use in extreme situations.

1. Are drugs used to increase the
contractility of the heart muscle for
patients experiencing heart failure.
ANSWER: Cardiotonic agents
2. These were originally derived from the
foxglove or digitalis plant. These plants
were once ground up to make digitalis
leaf.
ANSWER: Cardiac glycosides
3. Give one contraindication of Digoxin
ANSWER:
○ ventricular tachycardia or
fibrillation, which are potentially
fatal arrhythmias and should be
treated with other drugs;
○ heart block or sick sinus
syndrome, which could be made
worse by slowing of conduction
through the AV node;
○ idiopathic hypertrophic subaortic
stenosis (IHSS) because the
increase in force of contraction
could obstruct the outflow tract
to the aorta and cause severe
problems;
○ acute MI because the increase
in force of contraction could
cause more muscle damage
and infarct;
○ renal insufficiency because the
drug is excreted through the
kidneys and toxic levels could
develop;
○ and electrolyte abnormalities
(e.g., increased calcium,
decreased potassium,
decreased magnesium), which
could alter the action potential
and change the effects of the
drug.
4. These block the enzyme
phosphodiesterase.
ANSWER: Phosphodiesterase Inhibitor
5. T/F: Protect phosphodiesterase
inhibitors from light to avoid drug
degradation.
ANSWER: TRUE
Antiarrhythmic Agents
● Arrhythmias involve changes to the
automaticity or conductivity of the heart
cells. These changes can result from
several factors, including electrolyte
imbalances that alter the action
potential, decreased oxygen delivery to
cells that changes their action potential,
structural damage that changes the
conduction pathway, or acidosis or
waste product accumulation that alters
the action potential. In some cases,
changes to the heart’s automaticity or
conductivity may result from drugs that
alter the action potential or cardiac
conduction.
REMEMBER!
■ Arrhythmias (also called dysrhythmias) are
disruptions in the normal rate or rhythm of the
heart.
■ The cardiac conduction system determines
the heart’s
rate and rhythm. The property by which the
cardiac
cells generate an action potential internally to
stimulate the cardiac muscle without other
stimulation is
known as automaticity.
■ Electrolyte disturbances, decreases in the
oxygen
delivered to the cells, structural damage in the
conduction pathway, drug effects, acidosis, or
the accumulation of waste products can
trigger arrhythmias.
■ Changes in the heart rate, uncoordinated
heart muscle
contractions, or blocks that alter the
movement of
impulses through the system can disrupt heart
rhythm.
■ Arrhythmias change the mechanics of blood
circulation (hemodynamics), which can
interrupt delivery of blood to the brain, other
tissues, and the heart.
ANTIARRHYTHMIC AGENTS
● Antiarrhythmics affect the action
potential of the cardiac cells by
altering their automaticity,
conductivity, or both. Because of this
effect, antiarrhythmic drugs can also
produce new arrhythmias—that is,
they are proarrhythmic.
Antiarrhythmics are used in
emergency situations when the
hemodynamics arising from the
patient’s arrhythmia are severe and
could potentially be fatal. Box 45.2
contains information regarding use of
antiarrhythmic agents across the
lifespan.
● Antiarrhythmics were widely used on
a long-term basis to suppress any
abnormal arrhythmia, until the
publication of the Cardiac Arrhythmia
Suppression Trial (CAST) in the early
1990s. This multicenter, randomized,
long-term study conducted by the
National Heart, Lung, and Blood
Institute looked at the mortality rate of
patients with asymptomatic,
non–life-threatening arrhythmias
being treated with antiarrhythmics.
The results showed that long-term
use of some antiarrhythmics was
associated with an increased risk of
death. In fact, the risk of death for
some patients was two to three times
greater than that for untreated
patients. These results prompted
more clinical trials to look at the
effectiveness of long-term use of
antiarrhythmics.
● It was found that antiarrhythmics may
block some reflex arrhythmias that
help to keep the cardiovascular
system in balance, or they may
precipitate new, deadly arrhythmias.
Therefore, it is important to document
the arrhythmia being treated and the
rationale for treatment and to monitor
a patient regularly when using these
drugs.
ANTIARRHYTHMIC AGENTS
CLASS I ANTIARRHYTHMICS
Therapeutic The class I antiarrhythmics
Actions and stabilize the cell membrane by
Indications binding to sodium channels,
depressing phase 0 of the action
potential and changing the
duration of the action potential
(Figure 45.6). Class Ia drugs
depress phase 0 of the action
potential and prolong the
duration of the action potential.
Class Ib drugs depress phase 0
somewhat and actually shorten
the duration of the action
potential. Class Ic drugs
markedly depress phase 0, with
a resultant extreme slowing of
conduction, but have little effect
on the duration of the action
potential. These drugs are local
anesthetics or
membrane-stabilizing agents.
They bind more quickly to
sodium channels that are open
or inactive—ones that have been
stimulated and are not yet
repolarized. This characteristic
makes these drugs preferable in
conditions such as tachycardia,
in which the sodium gates are
open frequently. These drugs are
indicated for the treatment of
potentially life-threatening
ventricular arrhythmias and
should not be used to treat other
arrhythmias because of the risk
of a proarrhythmic effect.
Pharmacokin These drugs are widely
etics distributed after injection or after
rapid absorption through the
gastrointestinal (GI) tract. They
undergo extensive hepatic
metabolism and are excreted in
urine. These drugs cross the
placenta and are found in breast
milk (see Contraindications and
Cautions). Disopyramide is
available in oral form.
Procainamide is available in
intramuscular (IM) and
intravenous (IV) forms. Quinidine
is also available for oral, IM, or IV
administration and is
administered to adults only.
Lidocaine is administered by the
IM or IV route and can also be
given as a bolus injection in
emergencies when monitoring is
not available to document the
 exact arrhythmia. Mexiletine is
an oral drug administered to
adults only. Flecainide and
propafenone are available in oral
form.
Contraindicati Class I antiarrhythmics are
ons and contraindicated in the presence
Cautions of allergy to any of these drugs to
prevent hypersensitivity
reactions; with bradycardia or
heart block unless an artifi cial
pacemaker is in place, because
changes in conduction could lead
to complete heart block; with
heart failure (HF), hypotension,
or shock, which could be
exacerbated by effects on the
action potential; and with
electrolyte disturbances, which
could alter the effectiveness of
these drugs. Caution should be
used in patients with renal or
hepatic dysfunction, which could
interfere with the
biotransformation and excretion
of these drugs. These drugs
cross the placenta, and although
no specifi c adverse effects have
been associated with their use, it
is suggested that they be used in
pregnancy only if the benefi ts to
the mother clearly outweigh the
potential risks to the fetus. Class
I antiarrhythmics enter breast
milk, and because of the
potential for adverse effects on
the neonate, they should not be
used during lactation. Another
method of feeding the baby
should be chosen.
Adverse The adverse effects of the class I
Effects antiarrhythmics are associated
with their membrane-stabilizing
effects and effects on action
potentials. Central nervous
system (CNS) effects can include
dizziness, drowsiness, fatigue,
twitching, mouth numbness,
slurred speech, vision changes,
and tremors that can progress to
convulsions. GI symptoms
include changes in taste,
nausea, and vomiting.
Cardiovascular effects include
the proarrhythmic effects that
lead to the development of
arrhythmias (including heart
blocks), hypotension,
vasodilation, and the potential for
cardiac arrest. Respiratory
depression progressing to
respiratory arrest can also occur.
(Figure 45.7) Other adverse
effects include rash,
hypersensitivity reactions, loss of
hair, and potential bone marrow
depression. Moricizine, a class Ia
drug, is found to increase cardiac
deaths because of its
proarrhythmic effects. Flecainide
is a class Ic drug that was found
to increase the risk of death in
the CAST study.
Clinically Several drug–drug interactions
Important have been reported with these
Drug–Drug agents, so the possibility of an
Interactions interaction should always be
considered before any drug is
added to a regimen containing
an antiarrhythmic. The risk for
arrhythmia increases if these
agents are combined with other
drugs that are known to cause
arrhythmias, such as digoxin and
the beta-blockers.
Clinically Quinidine requires a slightly
Important acidic urine (normal state) for
Drug–Food excretion. Patients receiving
Interactions quinidine should avoid foods that
alkalinize the urine (e.g., citrus
juices, vegetables, antacids, milk
products), which could lead to
increased quinidine levels and
toxicity. Grapefruit juice has been
shown to interfere with the
metabolism of quinidine, leading
to increased serum levels and
toxic effects; this combination
should be avoided.
REMEMBER!
■ Antiarrhythmics are drugs that alter the
action potential of the heart cells and interrupt
arrhythmias. The CAST study found that the
long-term treatment of arrhythmias may
actually cause cardiac death, so these drugs
are now indicated only for the short-term
treatment of potentially life-threatening
ventricular arrhythmias.
■ Class I antiarrhythmics block sodium
channels, depress phase 0 of the action
potential, and generally prolong the action
potential, leading to a slowing of conduction
and automaticity.
■ Class I antiarrhythmics are membrane
stabilizers; the adverse effects seen are
related to the stabilization of cell membranes,
including those in the CNS and the GI tract.
ANTIARRHYTHMIC AGENTS
CLASS II ANTIARRHYTHMICS
Therapeutic The class II antiarrhythmics
Actions and competitively block betareceptor
Indications sites in the heart and kidneys.
The result is a decrease in heart
rate, cardiac excitability, and
cardiac output, a slowing of
conduction through the AV node,
and a decrease in the release of
renin. These effects stabilize
excitable cardiac tissue and
decrease blood pressure, which
decreases the heart’s workload
and may further stabilize hypoxic
cardiac tissue. These drugs are
indicated for the treatment of
supraventricular tachycardias
and PVCs.
Pharmacokin Acebutolol is an oral drug.
etics Esmolol is administered
intravenously. Propranolol may
be administered orally or
intravenously. These drugs are
absorbed from the GI tract or
have an immediate effect when
given intravenously and undergo
hepatic metabolism. They are
excreted in the urine. Food has
been found to increase the
bioavailability of propranolol,
although this effect has not been
found with other beta-adrenergic
blocking agents.
Contraindicati The use of these drugs is
ons and contraindicated in the presence
Cautions of sinus bradycardia (rate less
than 45 beats/min) and AV block,
which could be exacerbated by
the effects of these drugs; with
cardiogenic shock, HF, asthma,
or respiratory depression, which
could worsen due to blockage of
betareceptors; and with
pregnancy and lactation because
of the potential for adverse
effects on the fetus or neonate.
Caution should be used in
patients with diabetes and
thyroid dysfunction, which could
be altered by the blockade of the
beta-receptors, and in patients
with renal and hepatic
dysfunction, which could alter the
metabolism and excretion of
these drugs.
Adverse The adverse effects associated
Effects with class II antiarrhythmics are
related to the effects of blocking
beta-receptors in the sympathetic
nervous system. CNS effects
include dizziness, insomnia,
dreams, and fatigue.
Cardiovascular symptoms can
include hypotension,
bradycardia, AV block,
arrhythmias, and alterations in
peripheral perfusion. Respiratory
effects can include
bronchospasm and dyspnea. GI
problems frequently include
nausea, vomiting, anorexia,
constipation, and diarrhea. Other
effects to anticipate include a
loss of libido, decreased exercise
tolerance, and alterations in
blood glucose levels.
Clinically The risk of adverse effects
Important increases if these drugs are
Drug–Drug taken with verapamil; if this
Interactions combination is used, dose
adjustment will be needed. There
is a possibility of increased
hypoglycemia if these drugs are
combined with insulin; patients
should be monitored closely.
Other specifi c drug interactions
may occur with each drug; check
a drug reference before
combining these drugs with any
others.

REMEMBER!
■ Class II antiarrhythmics are beta-adrenergic
receptor blockers that prevent sympathetic
stimulation.
■ Adverse effects related to class II
antiarrhythmics are associated with blocking
of the sympathetic response
ANTIARRHYTHMIC AGENTS
CLASS III ANTIARRHYTHMICS
Therapeutic The class III antiarrhythmics
Actions and block potassium channels and
Indications slow the outward movement of
potassium during phase 3 of the
action potential, prolonging it
(Figure 45.7). All of these drugs
are proarrhythmic and have the
potential of inducing arrhythmias.
Although amiodarone has been
associated with such serious and
even fatal toxic reactions, in
2005 the American Heart
Association issued new
guidelines for Advanced Cardiac
Life Support that named
amiodarone the drug of choice
for treating ventricular fi brillation
or pulseless ventricular
tachycardia in cardiac arrest
situations.
Pharmacokin Amiodarone is available in an
etics oral or IV form. Dofetilide and
sotalol are administered only in
oral form. Ibutilide is given IV.
These drugs are well absorbed
after oral administration and are
immediately available after IV
administration and widely
distributed. Absorption of sotalol
is decreased by the presence of
food. They are metabolized in
the liver and excreted in urine.
Contraindicati When these drugs are used to
ons and treat life-threatening arrhythmias
Cautions for which no other drug has been
effective, there are no
contraindications. Ibutilide and
dofetilide should not be used in
the presence of AV block, which
could be exacerbated by the
drug. Because sotalol is known
to be proarrhythmic, patients
should be monitored very closely
at the initiation of therapy and
periodically during therapy.
Caution should be used with all
of these drugs in the presence of
shock, hypotension, or
respiratory depression; with a
prolonged QTc interval, which
could worsen due to the
depressive effects on action
potentials; and with renal or
hepatic disease, which could
alter the biotransformation and
excretion of these drugs.
Adverse The adverse effects associated
Effects with these drugs are related to
the changes they cause in action
potentials. Nausea, vomiting, and
GI distress; weakness and
dizziness; and hypotension, HF,
and arrhythmia are common.
Amiodarone has been
associated with a potentially fatal
liver toxicity, ocular
abnormalities, and the
development of very serious
cardiac arrhythmias..
Clinically These drugs can cause serious
Important toxic effects if they are combined
Drug–Drug with digoxin or quinidine. There
Interactions is an increased risk of
proarrhythmias if they are
combined with antihistamines,
phenothiazines, or tricyclic
antidepressants. There is an
increased risk of serious adverse
effects if dofetilide is combined
with ketoconazole, cimetidine, or
verapamil, and so these
combinations should be avoided.
Sotalol may have a loss of
effectiveness if it is combined
with nonsteroidal anti-infl
ammatory drugs, aspirin, or
antacids. Other specific
drug–drug interactions have
been reported with individual
drugs; a drug reference should
always be consulted when
adding a new drug to a regimen
containing any of these agents.

REMEMBER!
■ Class III antiarrhythmics block potassium
channels and prolong phase 3 of the action
potential.
■ Amiodarone is the drug recommended for
use during life support measures. It is
associated with serious to potentially fatal
hepatotoxicity.
ANTIARRHYTHMIC AGENTS
CLASS IV ANTIARRHYTHMICS
Therapeutic The class IV antiarrhythmics
Actions and block the movement of calcium
Indications ions across the cell membrane,
depressing the generation of
action potentials and delaying
phases 1 and 2 of repolarization,
which slows automaticity and
conduction (see Figure 45.7).
Both diltiazem and verapamil are
used as antihypertensives (see
Chapter 43) and to treat angina
(see Chapter 46).
Pharmacokin Diltiazem is administered
etics intravenously. When used as an
antiarrhythmic, verapamil is used
intravenously. These drugs are
well absorbed after IV
administration. They are highly
protein bound, metabolized in the
liver, and excreted in the urine.
They cross the placenta and
enter breast milk.
Contraindicati These drugs are contraindicated
ons and with known allergy to any
Cautions calcium channel blocker to avoid
hypersensitivity reactions, with
sick sinus syndrome or heart
block (unless an artifi cial
pacemaker is in place) because
the block could be exacerbated
by these drugs, with pregnancy
or lactation because of the
potential for adverse effects on
the fetus or neonate, and with HF
or hypotension because of the
hypotensive effects of these
drugs. Caution should be used in
cases of idiopathic hypertrophic
subaortic stenosis, which could
be exacerbated, or impaired
renal or liver function, which
could affect the metabolism or
excretion of these drugs.
Adverse The adverse effects associated
Effects with these drugs are related to
their vasodilation of blood
vessels throughout the body.
CNS effects include dizziness,
weakness, fatigue, depression,
and headache. GI upset, nausea,
and vomiting can occur.
Hypotension, HF, shock,
arrhythmias, and edema have
also been reported.
Clinically Verapamil has been associated
Important with many drug–drug
Drug–Drug interactions, including increased
Interactions risk of cardiac depression with
beta-blockers; additive AV
slowing with digoxin; increased
serum levels and toxicity of
digoxin, carbamazepine,
prazosin, and quinidine;
increased respiratory depression
with atracurium, pancuronium,
and vecuronium; and decreased
effects if combined with calcium
products or rifampin. There is a
risk of severe cardiac effects if
these drugs are given IV within
48 hours of IV beta-adrenergic
drugs. The combination should
be avoided. Diltiazem can
increase the serum levels and
toxicity of cyclosporine if the
drugs are taken concurrently.
REMEMBER!
■ Class IV antiarrhythmics are calcium
channel blockers that shorten the action
potential, disrupting ineffective rhythms and
rates
■ Whichever type of antiarrhythmic is used,
the patient receiving an antiarrhythmic drug
needs to be constantly monitored while being
stabilized and throughout the course of
therapy to detect the development of
arrhythmias or other adverse effects
associated with alteration of the action
potentials of other muscles or nerves.
Nursing Considerations for Patients
Receiving Antiarrhythmic Agents
Assessment: History and Examination
● Assess for contraindications or
cautions: any known allergies to these
drugs to avoid hypersensitivity
reactions; impaired liver or kidney
function, which could alter the
metabolism and excretion of the drug;
any condition that could be
exacerbated by the depressive effects
of the drugs (e.g., heart block, heart
failure Nursing Considerations for
Patients Receiving Antiarrhythmic
Agents [HF], hypotension, shock,
respiratory dysfunction, electrolyte
disturbances) to avoid exacerbation of
these conditions; and current status of
pregnancy and lactation to prevent
potential adverse effects on the fetus
or baby.
■ Perform a physical assessment to
establish a baseline before beginning
therapy and during therapy to
determine the effectiveness of therapy
and evaluate for any potential adverse
effects.
■ Assess the patient’s neurological
status, including level of alertness,
speech and vision, and refl exes, to
identify possible central nervous
system (CNS) effects.
■ Assess cardiac status closely,
including pulse, blood pressure, heart
rate, and rhythm, to identify changes
requiring a change in the dosage of
the drug or the presence of adverse
effects; auscultate heart sounds,
noting any evidence of abnormal
sounds, for early detection of HF; and
anticipate cardiac monitoring to
evaluate heart rate and rhythm and
aid in identifying arrhythmia.
■ Monitor respiratory rate and depth
and auscultate lungs, for evidence of
adventitious sounds to identify
respiratory depression and detect
changes associated with HF.
■ Inspect abdomen for evidence of
distention; auscultate bowel sounds to
evaluate gastrointestinal (GI) motility.
■ Evaluate skin for color, lesions, and
temperature to detect adverse
reactions and to assess cardiac
output.
■ Obtain a baseline electrocardiogram
to evaluate heart rate and rhythm;
monitor the results of laboratory tests,
including complete blood count, to
identify possible bone marrow
suppression, and renal and liver
function tests, to determine the need
for possible changes in dose and
identify toxic effects.
SUMMARY!
■ Disruptions in the normal rate or rhythm of
the heart are called arrhythmias (also known
as dysrhythmias).
■ Electrolyte disturbances, decreases in the
oxygen delivered to the cells leading to
hypoxia or anoxia, structural damage that
changes the conduction pathway, acidosis or
the accumulation of waste products, or drug
effects can lead to disruptions in the
automaticity of the cells or in the conduction of
the impulse that result in arrhythmias. The
result can be changes in heart rate
(tachycardias or bradycardias), stimulation
from ectopic foci in the atria or ventricles that
cause an uncoordinated muscle contraction,
or blocks in the conduction system (e.g., AV
heart block, bundle-branch blocks) that alter
the normal movement of the impulse through
the system.
■ Arrhythmias cause problems because they
alter the hemodynamics of the cardiovascular
system. They can cause a decrease in
cardiac output related to the uncoordinated
pumping action of the irregular rhythm,
leading to lack of fi lling time for the ventricles.
Any of these effects can interfere with the
delivery of blood to the brain, to other tissues,
 or to the heart muscle.
■ Antiarrhythmics are drugs that alter the
action potential of the heart cells and interrupt
arrhythmias. The CAST study found that the
long-term treatment of arrhythmias may
actually cause cardiac death, so these drugs
are now indicated only for the short-term
treatment of potentially life-threatening
ventricular arrhythmias.
■ Class I antiarrhythmics block sodium
channels, depress phase 0 of the action
potential, and generally prolong the action
potential, leading to a slowing of conduction
and automaticity.
■ Class II antiarrhythmics are beta-adrenergic
receptor blockers that prevent sympathetic
stimulation.
■ Class III antiarrhythmics block potassium
channels and prolong phase 3 of the action
potential.
■ Class IV antiarrhythmics are calcium
channel blockers that shorten the action
potential, disrupting ineffective rhythms and
rates.
■ A patient receiving an antiarrhythmic drug
needs to be constantly monitored while being
stabilized and throughout the course of
therapy to detect the development of
arrhythmias or other adverse effects
associated with alteration of the action
potentials of other muscles or nerves..
Chapter 46: Antianginal Agents
What is antianginal agents?
➔ Antianginal agents are drugs used
to provide immediate relief from
angina symptoms and prevent
angina attacks. Angina is chest
pain or discomfort that happens
because of reduced blood flow to the
heart. Angina results from an
imbalance in the oxygen
supply/demand ratio.
➔ Used to help restore appropriate
supply-and-demand ratio in oxygen
delivery to the myocardium. An
imbalance in this ratio, manifested
by pain, is most commonly due to
coronary artery disease (CAD).
➔ These drugs can work to improve
blood delivery to the heart muscle in
one of two ways
◆ (1) by dilating blood vessels
(i.e., increasing the supply of
oxygen) or
◆ (2) by decreasing the work of
the heart (i.e., decreasing the
demand for oxygen).
➔ All antianginal agents are effective
and may be used in combination to
achieve good pain control. The type
of drug that is best for a patient is
determined by tolerance of adverse
effects and response to the drug.
The drugs discussed in this chapter are
used to prevent myocardial cell death when
the coronary vessels are already seriously
damaged and are having trouble
maintaining the blood flow to the heart
muscle. To further discuss, here are the
keypoints to remember about some certain
diseases.
KEY POINTS TO REMEMBER!
● CAD involves changes in the
coronary vessels that promote
atheromas (tumors), which narrow
the coronary arteries and decrease
their elasticity and responsiveness to
normal stimuli.
● Angina pectoris occurs when the
narrowed vessels cannot
accommodate the myocardial
demand for oxygen.
● Stable angina occurs when the heart
muscle is perfused adequately
except during exertion or increased
demand. Unstable or preinfarction
angina occurs when the vessels are
so narrow that the myocardial cells
 are deprived of suffi cient oxygen
even at rest. Prinzmetal angina is a
spasm of a coronary vessel that
decreases the fl ow of blood through
the narrowed lumen.
● When a coronary vessel is
completely occluded, the cells that
depend on that vessel for oxygen
become ischemic, then necrotic, and
die. The result is known as an MI.
PLS SUMMARIZE!DRUG THERAPY
ACROSS THE LIFESPAN
ANTIANGINAL AGENTS
CHILDREN
The antianginals are not indicated for
any condition commonly found in
children. But in some situations, if
ever, the child should be very carefully
monitored for adverse reactions,
including potentially dangerous
changes in blood pressure.
ADULTS
Adults who receive these drugs should be
instructed in their proper administration. It
is important that the patient know how to
use the drug, how to store it and how
much to take before seeking emergency
medical care so that they can take
measures to avoid those circumstances.
Patients should know that regular medical
follow-up is important and should be
instructed in nonpharmacological
measures—weight loss, smoking
cessation, activity changes, diet
changes—that could decrease their risk of
coronary artery disease and improve the
effectiveness of the antianginal therapy.
The safety for the use of these drugs
during pregnancy has not been
established. There is a signifi cant
potential for adverse effects on the fetus
related to blood fl ow changes and direct
drug effects when the drugs cross the
placenta. The drugs do enter breast milk,
and it is advised that another method of
feeding the baby be used if one of these
drugs is prescribed during lactation.
OLDER ADULTS
Older adults frequently are prescribed one
of these drugs. Older adults are more
likely to develop adverse effects
associated with the use of these
drugs—arrhythmias, hypotension, and
heart disease. Safety measures may be
needed if these effects occur and interfere
with the patient’s mobility and balance.
Older adults are also more likely to have
renal and/or hepatic impairment related to
underlying medical conditions, which
could interfere with the metabolism and
excretion of these drugs. The dose for
older adults should be started at a lower
level than that recommended for younger
adults. The patient should be monitored
very closely and dose adjusted based on
patient response. If other drugs are added
to or removed from the drug regimen,
appropriate dose adjustments may need
to be made. If the patient is using a
different form of nitroglycerin, special care
should be taken to make sure that the
proper administration, storage, and timing
of use are understood.
ANTIANGENAL AGENTS
NITRATES
Nitrates are drugs that act directly on
smooth muscle to cause relaxation and to
depress muscle tone. Because the action
is direct, these drugs do not influence any
nerve or other activity, and the response
is usually quite fast. Nitrates include amyl
nitrate (generic), isosorbide dinitrate
(Isordil), isosorbide mononitrate (Imdur,
Monoket), and nitroglycerin (Nitro-Bid,
Nitrostat, and others).
Therapeutic Actions and Indications
➔ The nitrates relax and dilate veins,
arteries, and capillaries, allowing
increased blood flow through the
vessels and lowering systemic
blood pressure because of a drop
in resistance. Because CAD
causes a stiffening and lack of
responsiveness in the coronary
arteries, the nitrates probably have
very little effect on increasing
blood fl ow through these arteries.
However, they do increase blood fl
ow through healthy coronary
arteries. Therefore, the blood
supply through any healthy
vessels in the heart increases,
possibly helping the heart to
compensate somewhat.
➔ The main effect of nitrates,
however, seems to be related to
the drop in blood pressure that
occurs. The vasodilation causes
blood to pool in veins and
capillaries, decreasing preload,
while the relaxation of the vessels
decreases afterload. The
combination of these effects
greatly reduces the cardiac
workload and the demand for
oxygen, thus bringing the
supplyand-demand ratio back into
balance. Nitrates are indicated for
the prevention and treatment of
attacks of angina pectoris.
Pharmacokinetics
➔ Nitroglycerin is available as a
sublingual tablet, a translingual
spray, an intravenous solution (for
bolus injection or infusion), a
transdermal patch, a topical
ointment or paste, or a already has a decreased ability to
transmucosal agent. It can be
carried with the patient, who then
can use it when the need arises.
Slow-release forms also are
available for use in preventing
anginal attacks.
➔ Amyl nitrate is supplied as a
capsule that is broken and waved
under the patient’s nose for
inhalation. The administration is
somewhat awkward for the patient
to use by himself or herself. It
usually requires another person to
administer it properly. Isosorbide
dinitrate and isosorbide
mononitrate are available in oral
form.
➔ Nitrates are very rapidly absorbed,
metabolized in the liver, and
excreted in urine. They cross the
placenta and enter breast milk.
Nitroglycerin is available in many
forms, and absorption, onset of
action, and duration vary with the
form used. Amyl nitrate, upon
inhalation, has an onset of action
of about 30 seconds. Isosorbide
dinitrate and isosorbide
mononitrate, when given orally,
have an onset of action in 14 to 45
minutes, or up to 4 hours if the
sustained-release (SR) form is
used. The drug may have a
duration of action of 4 to 6 hours,
or 6 to 8 hours if the SR form is
used.
Contraindications and Cautions
● Nitrates are contraindicated in the
presence of any allergy to nitrates
to prevent hypersensitivity
reactions. These drugs also are
contraindicated in the following
conditions:
1. severe anemia because the
decrease in cardiac output could
be detrimental in a patient who
deliver oxygen because of a low
 red blood cell count
2. head trauma or cerebral
hemorrhage because the
relaxation of cerebral vessels
could cause intracranial bleeding
3. pregnancy or lactation because of
potential adverse effects on the
neonate and ineffective blood fl ow
to the fetus
● Caution should be used in patients
with hepatic or renal disease,
which could alter the metabolism
and excretion of these drugs.
● Caution also is required for
patients with hypotension,
hypovolemia, and conditions that
limit cardiac output (e.g.,
tamponade, low ventricular fi lling
pressure, low pulmonary capillary
wedge pressure) because these
conditions could be exacerbated,
resulting in serious adverse
effects.

Adverse Effects

The adverse effects associated with these Clinically Important Drug-Drug

drugs are:
● related to vasodilation and the
decrease in blood flow that occurs.
● Central nervous system (CNS)
effects include headache,
dizziness, and weakness.
● Cardiovascular problems include
hypotension, which can be severe
and must be monitored; refl ex
tachycardia that occurs when
blood pressure falls; syncope; and
angina, which could be
exacerbated by the hypotension
and changes in cardiac output.
● Skin related effects include fl
ushing, pallor, and increased
perspiration. With the transdermal
preparation, there is a risk of
contact dermatitis and local
hypersensitivity reactions
Interactions
● There is a risk of hypertension and
decreased antianginal effects if
these drugs are given with ergot
derivatives.
● There is also a risk of decreased
therapeutic effects of heparin if
these drugs are given together
with heparin; if this combination is
used, the patient should be
monitored and appropriate dose
adjustments made.
● Patients should not combine
nitrates with sildenafi l, tadalafi l,
or vardenafi l, drugs used to treat
erectile dysfunction, because
serious hypotension and
cardiovascular events could occur.

NURSING CONSIDERATIONS FOR

PATIENTS RECEIVING NITRATES
Assessment: History and Examination
● Assess for contraindications or
cautions: any known allergies to
nitrates to avoid hypersensitivity
reactions; impaired liver or kidney
function, which could alter the
metabolism and excretion of the
drug; any condition that could be
exacerbated by the hypotension
and change in blood fl ow caused
by these drugs, such as early
myocardial infarction (MI), head
trauma, cerebral hemorrhage,
hypotension, hypovolemia,
anemia, or low–cardiac output
states; and current status of
pregnancy or lactation because of
the potential for adverse effects on
the fetus or nursing baby.
● Perform a physical assessment to
establish baseline status before
beginning therapy and during
therapy to determine effectiveness
and to evaluate for any potential
adverse effects.
● Inspect the skin for color,
intactness, and any signs of
redness, irritation, or breakdown,
especially if the patient is using
the transdermal or topical form of
the drug, to prevent possible skin
reaction and ensure adequate
surface for application and
absorption of transdermal or
topical drug. Also check the
patient’s oral or buccal mucosa
(including the area under the
tongue) if sublingual or buccal
forms are ordered to reduce the
risk of irritation and ensure
adequate surface for absorption.
● Assess the patient’s complaint of
pain, including onset, duration,
intensity, location, and measures
used to relieve it. Investigate
activity level prior to and after the
onset of pain to aid in identifying
possible contributing factors to the
pain and its progression.
● Assess the patient’s neurological
status, including level of alertness,
affect, and refl exes, to evaluate
for central nervous system (CNS)
effects.
● Monitor respirations and
auscultate lungs to evaluate
changes in cardiac output.
● Assess cardiopulmonary status
closely, including pulse rate, blood
pressure, heart rate, and rhythm,
to determine the effects of therapy
and identify any adverse effects.
● Obtain an electrocardiogram as
ordered to evaluate heart rate and
rhythm, which could indicate
changes in cardiac perfusion.
● Monitor laboratory test results,
including liver and renal function
tests, complete blood count, and
hemoglobin level, to determine the
need for possible dose
adjustment.
Nursing Diagnoses
Nursing diagnoses related to drug therapy
might include the following:
● Decreased Cardiac Output related
to vasodilation and hypotensive
effects
● Risk for Injury related to CNS or
cardiovascular effects
● Ineffective Tissue Perfusion (Total
Body) related to hypotension or
change in cardiac output
● Defi cient Knowledge regarding
drug therapy
Implementation With Rationale
● Give sublingual preparations
under the tongue or in the buccal
pouch, and encourage the patient
not to swallow, to ensure that
therapeutic effectiveness is
achieved (see Pharmacokinetics
for discussion of safe medication
administration).
● Ask the patient if the tablet “fi
zzles” or burns, which indicates
potency. Always check the
expiration date on the bottle and
protect the medication from heat
and light because these drugs are
volatile and lose their potency.
● Instruct the patient that a
sublingual dose may be repeated
in 5 minutes if relief is not felt, for
a total of three doses; if pain
persists, the patient should go to
an emergency room to ensure
proper medical support if an MI
should occur.
● Give sustained-release forms with
water, and caution the patient not
to chew or crush them because
these preparations need to reach
the gastrointestinal (GI) tract
intact.
● Rotate the sites of topical forms to
decrease the risk of skin abrasion
and breakdown; monitor for signs
of skin breakdown to arrange for
appropriate skin care as needed.
● Make sure that translingual spray
is used under the tongue and not
inhaled to ensure that the
therapeutic effects can be
achieved.
● Break an amyl nitrate capsule and
wave it under the nose of the
angina patient to provide rapid
relief using the inhalation form of
the drug; this may be repeated
with another capsule in 3 to 5
minutes if needed.
● Keep a record of the number of
sprays used if a translingual spray
form is used to prevent running
out of medication and episodes of
untreated angina.
● Have emergency life support
equipment readily available in
case of severe reaction to the drug
or myocardial infarction.
● Taper the dose gradually (over 4
to 6 weeks) after long-term
therapy because abrupt
withdrawal could cause a severe
reaction, including MI.
● Provide comfort measures to help
the patient tolerate drug effects.
These include small, frequent
meals to alleviate GI upset;
access to bathroom facilities if GI
upset is severe or the patient
experiences incontinence;
environmental controls such as
temperature, controlled lighting,
and noise reduction to decrease
stresses that could aggravate
cardiac workload; safety
precautions such as lying or sitting
down after taking the drug and
assistance with ambulation, to
reduce the risk of injury;
reorientation; and appropriate skin
care as needed.
● Offer support and encouragement
to help the patient deal with the
diagnosis and the drug regimen.
● Provide thorough patient teaching,
including the name of the drug;
dosage prescribed; proper
technique for administration (oral,
sublingual, transbuccal,
transdermal, inhalation spray, or
topical); need for removal of
transdermal or topical drug before
application of the next dose; the
importance of having an adequate
supply of drug (e.g., teaching the
patient to count the number of
sprays used for a translingual
spray so as not to run short);
measures to prevent anginal
attacks, and actions to take when
an attack occurs; use of
medication during an attack (such
as the number of tablets and time
span that the patient can take
sublingual tablets); measures to
avoid adverse effects, warning
signs of problems, and signs and
symptoms to report immediately;
and the need for periodic
monitoring and evaluation to
enhance patient knowledge about
 drug therapy and to promote
compliance.
Evaluation
● Monitor patient response to the
drug (alleviation of signs and
symptoms of angina, prevention of
angina).
● Monitor for adverse effects
(hypotension, cardiac arrhythmias,
GI upset, skin reactions,
headache).
● Evaluate the effectiveness of the
teaching plan (patient can name
drug, dosage, proper
administration, adverse effects to
watch for, specifi c measures to
avoid them, and the importance of
continued follow-up).
● Monitor the effectiveness of
comfort measures and compliance
with the regimen.
KEY POINTS
● Nitrates cause blood vessels to
relax and dilate. This results in a
drop in peripheral resistance and
blood pressure and a decrease in
venous return to the heart. These
actions will decrease myocardial
workload and can restore the
appropriate balance in the supply–
demand ratio in the heart.
● Nitrates are available in many
forms that vary in time of onset
and duration of action. Fast-acting
nitrates are used to treat acute
anginal attacks. Slower-acting
nitrates are used to prevent
anginal attacks from occurring.
BETA-ADRENERGIC BLOCKER
Beta-adrenergic blockers are used to
block the stimulatory effects of the
sympathetic nervous system. The
beta-blockers recommended for use in
angina include metoprolol (Toprol),
propranolol (Inderal), and nadolol
(Corgard).
Therapeutic Actions and Indications
➔ The beta-blockers competitively
block beta-adrenergic receptors in
the heart and juxtaglomerular
apparatus, decreasing the infl
uence of the sympathetic nervous
system on these tissues. The
result is a decrease in the
excitability of the heart, a
decrease in cardiac output, a
decrease in cardiac oxygen
consumption, and a lowering of
blood pressure. They are indicated
for the long-term management of
angina pectoris caused by
atherosclerosis. These drugs are
sometimes used in combination
with nitrates to increase exercise
tolerance.
➔ Beta-blockers are not indicated for
the treatment of Prinzmetal angina
because they could cause
vasospasm due to blocking of
beta-receptor sites. Propranolol
and metoprolol can also be used
to prevent reinfarction in stable
patients 1 to 4 weeks after an MI.
This effect is thought to be caused
by the suppression of myocardial
oxygen demand for a prolonged
period.
Pharmacokinetics
➔ These drugs are absorbed from
the GI tract after oral
administration and undergo
hepatic metabolism. They reach
peak levels in 60 to 90 minutes
and have varying duration of
effects, ranging from 6 to 19
hours. Food has been found to
increase the bioavailability of
 propranolol, but this effect has not
been found with other
beta-adrenergic blocking agents.
Contraindications and Cautions
● The beta-blockers are
contraindicated in patients with
bradycardia, heart block, and
cardiogenic shock because
blocking of the sympathetic
response could exacerbate these
diseases.
● They also are contraindicated with
pregnancy and lactation because
of the potential for adverse effects
on the fetus or neonate.
● Caution should be used in patients
with diabetes, peripheral vascular
disease, asthma, chronic
obstructive pulmonary disease, or
thyrotoxicosis because the
blockade of the sympathetic
response blocks normal refl exes
that are necessary for maintaining
homeostasis in patients with these
diseases.
● Many patients with these
complicating disorders receive
beta-blockers, and these patients
need to be monitored carefully to
avoid serious adverse effects.
Adverse Effects
● Beta-blockers have many adverse
effects associated with the
blockade of the sympathetic
nervous system. However, the
dose used to prevent angina is
lower than doses used to treat
hypertension. Therefore, there is a
decreased incidence of adverse
effects associated with this specifi
c use of beta-blockers.
Adverse effects do occur:
● CNS effects include dizziness,
fatigue, emotional depression, and
sleep disturbances
● GI problems include gastric pain,
nausea, vomiting, colitis, and
diarrhea.
● Cardiovascular effects can include
HF, reduced cardiac output, and
arrhythmias.
● Respiratory effects can include
bronchospasm, dyspnea, and
cough.
● Decreased exercise tolerance and
malaise are also common
complaints.
Clinically Important Drug-Drug
Interactions
● A paradoxical hypertension occurs
when clonidine is given with
beta-blockers, and an increased
rebound hypertension with
clonidine withdrawal may also
occur; it is best to avoid this
combination.
● A decreased antihypertensive
effect occurs when betablockers
are given with nonsteroidal anti-
infl ammatory drugs; if this
combination is used, the patient
should be monitored closely and a
dose adjustment made.
● An initial hypertensive episode
followed by bradycardia occurs if
these drugs are given with
epinephrine and a possibility of
peripheral ischemia exists if
betablockers are taken in
combination with ergot alkaloids.
● There also is a potential for a
change in blood glucose levels if
these drugs are given with insulin
or antidiabetic agents, and the
patient will not have the usual
signs and symptoms of
hypoglycemia or hyperglycemia to
alert him or her to potential
problems. If this combination is
used, the patient should monitor
blood glucose frequently
throughout the day and should be
alert to new warnings about
glucose imbalance.
 DIFFERENCE BETWEEN SELECTIVE
AND NONSELECTIVE
BETA-ADRENERGIC
They don't further gave details on the
nursing considerations since it was
discussed on chapter 31 under Drugs
Acting on the Autonomic Nervous
System
Note: Only put the keypoints (naka
highlight color blue) of selective and
nonselective on the PPT. Ayaw na
ibutang ang tanan.
NURSING CONSIDERATIONS FOR
PATIENTS RECEIVING NONSELECTIVE
BETA-ADRENERGIC
Assessment: History and Examination
● Assess for contraindications or
cautions: known allergy to any
drug or to any components of the
drug to avoid hypersensitivity
reactions; bradycardia or heart
blocks, shock, or heart failure,
which could be exacerbated by the
cardiac-suppressing effects of
these drugs; bronchospasm,
chronic obstructive pulmonary
disease, or acute asthma, which
could worsen with blocking of the
sympathetic bronchodilation;
diabetes or hypoglycemia, which
could lead to altered blood
glucose levels; thyrotoxicosis
because of adrenergic blocking
effects on the thyroid gland; renal
or hepatic dysfunction, which
could interfere with the excretion
or metabolism of these drugs; and
status of pregnancy and lactation
because of the potential effects on
the fetus or neonate
● Perform a physical assessment to
establish baseline data for
determining the effectiveness of
the drug and the occurrence of
any adverse effects.
● Assess level of orientation and
sensory function to evaluate for
possible central nervous system
(CNS) effects.
● Monitor cardiopulmonary status,
including pulse, blood pressure,
and respiratory rate; auscultate
lungs for adventitious breath
sounds; obtain an
electrocardiogram as ordered to
evaluate for changes in heart rate
or rhythm; check color, sensation,
and capillary refi ll of extremities to
evaluate for possible peripheral
vascular insuffi ciency.
● Assess abdomen, including
auscultating bowel sounds, to
monitor for gastrointestinal (GI)
effects.
● Monitor the results of laboratory
tests, such as electrolyte levels, to
monitor for risks for arrhythmias,
adrenal and hepatic function
studies, to determine the need for
possible dose adjustment.
 Nursing Diagnoses
Nursing diagnoses related to drug therapy
might include the following:
● Acute Pain related to CNS, GI,
and systemic effects
● Decreased Cardiac Output related
to CV effects
● Ineffective Tissue Perfusion
related to CV effects
● Risk for Injury related to central
nervous system effects
● Risk for Activity Intolerance related
to suppression of the sympathetic
system
● Deficient Knowledge regarding
drug therapy
Implementation With Rationale
● Do not stop these drugs abruptly
after chronic therapy, but taper
gradually over 2 weeks because
longterm use of these drugs can
sensitize the myocardium to
catecholamines, and severe
reactions could occur.
● Do not stop these drugs abruptly
after chronic therapy, but taper
gradually over 2 weeks because
longterm use of these drugs can
sensitize the myocardium to
catecholamines, and severe
reactions could occur.
● Monitor blood pressure, pulse,
rhythm, and cardiac output
regularly to evaluate drug
effectiveness and to monitor for
changes that may indicate a need
to adjust dose or discontinue the
drug if CV effects are severe.
● Arrange for supportive care and
comfort measures (rest,
environmental control, other
measures) to relieve CNS effects;
institute safety measures if CNS
effects occur to prevent patient
injury; provide small, frequent
meals and mouth care to help
relieve the discomfort of GI
effects; establish daily activity
program, spacing activities to help
the patient deal with activity
intolerance
● Offer support and encouragement
to help the patient deal with the
drug regimen.
● Provide thorough patient teaching,
including drug name, dose, and
schedule of administration; use of
drug with food or meals, if
appropriate; possible adverse
effects and measures to prevent
them; warning signs to report;
safety measures, such as
changing position slowly, avoiding
driving or using hazardous
machinery, and pacing activities;
and the need for follow-up
evaluation and possible changes
in dose to achieve therapeutic
effectiveness, to enhance patient
knowledge about drug therapy and
to promote compliance.
Evaluation
● Monitor patient response to the
drug (lowering of blood pressure,
decrease in anginal episodes,
improvement in condition being
treated).
● Monitor for adverse effects (GI
upset, CNS changes, respiratory
problems, CV effects, loss of
libido, and impoten
● Evaluate the effectiveness of the
teaching plan (patient can name
drug, dosage, adverse effects to
watch for, and specifi c measures
to avoid them).
● Monitor the effectiveness of
comfort measures and compliance
with the regimen
KEY POINTS
● Beta-blockers are drugs used to
block the betareceptors within the
SNS. These drugs are used for a
wide range of conditions, including
hypertension, stage fright,
migraines, angina, and essential
 tremors.
● Nonselective blockade of all
beta-receptors results in a loss of
the reflex bronchodilation that
occurs with sympathetic
stimulation. This limits the use of
these drugs in patients who smoke
or have allergic or seasonal
rhinitis, asthma, or COPD.
NURSING CONSIDERATIONS FOR
PATIENTS RECEIVING
BETA1-SELECTIVE ADRENERGIC
Assessment: History and Examination
● Assess for contraindications or
cautions: known allergies to any
drug or any components of the
drug to avoid hypersensitivity
reactions; bradycardia or heart
blocks, shock, or heart failure,
which could be exacerbated by the
cardiac-suppressing effects of
these drugs; diabetes, thyroid
disease, or chronic obstructive
pulmonary disease to reduce risk
of adverse effects on these
conditions due to sympathetic
blockade; and current status of
pregnancy or lactation because of
the potential effects on the fetus or
neonate.
● Perform a physical assessment to
establish baseline status before
beginning therapy to determine
the effectiveness of therapy and
evaluate for any potential adverse
effects.
● Assess neurological status,
including level of orientation and
sensation, to evaluate for central
nervous system (CNS) effects.
● Monitor cardiac status, including
pulse, blood pressure, and heart
rate, to identify changes, and
obtain an electrocardiogram as
ordered to evaluate for changes in
heart rate or rhythm.
● Assess pulmonary status,
including respirations, and
auscultate lungs for adventitious
sounds, to monitor respiratory
status.
● Examine the abdomen and
auscultate bowel sounds to
evaluate gastrointestinal (GI)
effects.
● Monitor urine output to monitor the
effectiveness of cardiac output
and any changes in renal
perfusion.
● Monitor the results of laboratory
tests, including electrolyte levels,
to monitor for risk of arrhythmias,
and renal and hepatic function
studies, to determine the need for
possible dose adjustment.
Nursing Diagnoses
Nursing diagnoses related to drug therapy
might include the following:
● Acute Pain related to CNS, GI,
and systemic effects
● Decreased Cardiac Output related
to cardiovascular (CV) effects
● Ineffective Tissue Perfusion
related to CV effects
● Risk for Injury related to CNS
effects
● Activity Intolerance related to
sympathetic blocking
● Deficient Knowledge regarding
drug therapy
Implementation With Rationale
● Do not stop these drugs abruptly
after chronic therapy, but taper
gradually over 2 weeks to prevent
the possibility of severe reactions.
Long-term use of these drugs can
sensitize the myocardium to
catecholamines, and severe
reactions could occur
● Consult with the physician about
discontinuing these drugs before
surgery because withdrawal of the
drug before surgery when the
patient has been maintained on
the drug is controversial
● Give oral forms of the metoprolol
 with food to facilitate absorption. ● Evaluate the effectiveness of the
● Continuously monitor any patient teaching plan (patient can name
receiving an intravenous form of drug, dosage, adverse effects to
these drugs to detect severe watch for, and specifi c measures
reactions to sympathetic blockade to avoid them).
and to ensure rapid response if ● Monitor the effectiveness of
these reactions occur comfort measures and compliance
● Arrange for supportive care and with the regimen.
comfort measures, including rest,
environmental control, and other KEY POINTS
measures, to relieve CNS effects;
safety measures if CNS effects ● .Beta1-selective adrenergic
occur, to protect the patient from blocking agents do not block the
injury; small, frequent meals and beta1-receptors that are
mouth care to relieve the responsible for bronchodilation
discomfort of GI effects; and an and therefore are preferred in
activity program and daily energy patients with respiratory problems.
management ideas to help to deal ● Beta1-selective adrenergic
with activity intolerance. blocking agents are used to treat
● Offer support and encouragement hypertension and angina in
to help the patient deal with the extended-release forms and to
drug regimen. treat HF.
● Provide thorough patient teaching, ● All of the adrenergic blocking
including drug name, dosage and drugs must be tapered when they
schedule for administration; use of are discontinued after longterm
drug with food or meals if use. The blocking of the receptor
appropriate; technique for sites makes them hypersensitive
ophthalmic administration if to catecholamines, and extreme
indicated; potential adverse hypertension, angina, MI, or stroke
effects, measures to avoid could occur.
drug-related problems, and
warning signs of problems; safety
measures such as changing
position slowly and avoiding
driving or operating hazardous
machinery; and energy CALCIUM CHANNEL BLOCKERS
conservation measures as
appropriate to provide drug Therapeutic Actions and Indications
education and improve
compliance to the drug regimen ● Calcium channel blockers inhibit
the movement of calcium ions
Evaluation across the membranes of
● Monitor patient response to the myocardial and arterial muscle
drug (lowered blood pressure, cells, altering the action potential
fewer anginal episodes, lowered and blocking muscle cell
intraocular pressure). contraction.
● Monitor for adverse effects (GI ● A loss of smooth muscle tone,
upset, CNS changes, CV effects, vasodilation, and decreased
loss of libido and impotence, peripheral resistance occur.
potential respiratory effects). Subsequently, preload and
 afterload are decreased, which in
turn decreases cardiac workload
and oxygen consumption.
● Calcium channel blockers are
indicated for the treatment of
Prinzmetal angina, chronic
angina, effortassociated angina,
and hypertension. In Prinzmetal
angina, these agents relieve
coronary artery vasospasm,
increasing blood fl ow to the
muscle cells. Verapamil is also
used to treat cardiac
tachyarrhythmias because it slows
conduction more than the other
calcium channel blockers do.
Pharmacokinetics
● These drugs are generally well
absorbed after oral administration,
metabolized in the liver, and
excreted in urine.
● They have an onset of action of
20 minutes and a duration of
action of 2 to 4 hours.
● These drugs cross the placenta
and enter breast milk.
Contraindications and Cautions
Calcium channel blockers are
contraindicated in the presence of allergy
to any of these drugs:
● to avoid hypersensitivity reactions
and with pregnancy or lactation
because of the potential for
adverse effects on the fetus or
neonate.
● Caution should be used with heart
block or sick sinus syndrome,
which could be exacerbated by
the conduction-slowing effects of
these drugs
● with renal or hepatic dysfunction,
which could alter the metabolism
and excretion of these drugs
● and with HF, which could be
exacerbated by the decrease in
cardiac output that could occur.
Adverse Effects
The adverse effects associated with
these drugs are
● related to their effects on cardiac
output and on smooth muscle
● CNS effects include dizziness,
light-headedness, headache, and
fatigue
● GI effects can include nausea and
hepatic injury related to direct
toxic effects on hepatic cells.
● . Cardiovascular effects include
hypotension, bradycardia,
peripheral edema, and heart
block.
● Skin effects include flushing and
rash.
Clinically Important Drug-Drug
Interation
Drug–drug interactions vary with each of
the calcium channel blockers. Potentially
serious effects to keep in mind include
● increased serum levels and
toxicity of cyclosporine if they are
taken with diltiazem
● increased risk of heart block and
digoxin toxicity if they are
combined with verapamil
(because verapamil increases
digoxin serum levels)
Both verapamil and digoxin depress
myocardial conduction. If any
combinations of these drugs must be
used, the patient should be monitored
very closely and appropriate dose
adjustments made. Verapamil has also
been associated with serious respiratory
depression when given with general
anesthetics or as an adjunct to
anesthesia.
NURSING CONSIDERATIONS FOR
PATIENTS RECEIVING CALCIUM
CHANNEL BLOCKERS
Assessment: History and Examination
● Assess for contraindications or
cautions: known allergies to any
of these drugs to avoid
hypersensitivity reactions;
impaired liver or kidney function,
which could alter the metabolism
and excretion of the drug; heart
block, which could be
exacerbated by the conduction
depression of these drugs; and
current status of pregnancy or
lactation because of the risk of
adverse effects to the fetus or
nursing baby.
● Perform a physical assessment to
establish baseline status before
beginning therapy and during
therapy to determine the
effectiveness and evaluate for any
potential adverse effects.
● Inspect skin for color and integrity
to identify possible adverse skin
reactions
● Assess the patient’s complaint of
pain, including onset, duration,
intensity, and location and
measures used to relieve the
pain. Investigate activity level prior
to and after the onset of pain to
aid in identifying possible
contributing factors to the pain
and its progression.
● Assess cardiopulmonary status
closely, including pulse rate, blood
pressure, heart rate, and rhythm,
to determine the effects of therapy
and identify any adverse effects.
● Obtain an electrocardiogram as
ordered to evaluate heart rate and
rhythm.
● Monitor respirations and
auscultate lungs to evaluate
changes in cardiac output.
● Monitor laboratory test results,
including liver and renal function
tests, to determine the need for
possible dose adjustment.
Nursing Diagnosis
Nursing diagnoses related to drug
therapy might include the following:
● Decreased Cardiac Output related
to hypotension and vasodilation
● Risk for Injury related to central
nervous system or cardiovascular
effects
● Ineffective Tissue Perfusion (Total
Body) related to hypotension or
change in cardiac output
● Deficient Knowledge regarding
drug therapy
Implementation With Rationale
● Monitor the patient’s blood
pressure, cardiac rhythm, and
cardiac output closely while the
drug is being titrated or dose is
being changed to ensure early
detection of potentially serious
adverse effects.
● Monitor blood pressure very
carefully if the patient is also
taking nitrates because there is an
increased risk of hypotensive
episodes.
● If a patient is on long-term
therapy, periodically monitor blood
pressure and cardiac rhythm while
the patient is using these drugs
because of the potential for
adverse cardiovascular effects.
● Provide comfort measures to help
the patient tolerate drug effects.
These include small, frequent
meals to alleviate gastrointestinal
(GI) upset; environmental
controls, such as limiting light,
maintaining temperature, and
avoiding excessive noise and
interruptions, which could
aggravate stress and increase
myocardial demand; and taking
safety precautions, such as
providing periodic rests and
assisting with ambulation if
dizziness occurs, to prevent injury.
● Offer support and encouragement
to help the patient deal with the
 diagnosis and the drug regimen. heart rate, hypotension, dizziness,
● Provide thorough patient teaching, and headache.
including the name of the drug
and dosage prescribed; measures
to avoid adverse effects and
prevent anginal attacks; actions to
take when an attack occurs; PIPERAZINE ACETAMIDE AGENT
warning signs of problems, and
signs and symptoms to report ● In late 2006, the Food and Drug
immediately; and the need for Administration approved the first
periodic monitoring and evaluation new drug in more than 10 years
to enhance patient knowledge for the treatment of chronic
about drug therapy and to angina. Since its approval,
promote compliance. postmarketing studies have shown
that the drug is very effective in
Evaluation treating angina and has the added
benefits of decreasing blood
● Monitor patient response to the
glucose levels when used in
drug (alleviation of signs and
diabetic patients and decreasing
symptoms of angina, prevention
the incidence of ventricular
of angina).
fibrillation, atrial fibrillation, and
● Monitor for adverse effects
bradycardia in chronic angina
(hypotension, cardiac
patients. Ranolazine (Ranexa) is
arrhythmias, GI upset, skin
available in an extended-release
reactions, headache)
tablet form for oral use.
● Monitor the effectiveness of
● The mechanism of action of the
comfort measures and
drug is not understood. It does
compliance with the regimen.
prolong the QT interval, it does not
● Evaluate the effectiveness of the
decrease heart rate or blood
teaching plan (patient can name
pressure, but it does decrease
drug, dosage, proper
myocardial workload, bringing the
administration, adverse effects to
supply and demand for oxygen
watch for, specifi c measures to
back into balance.
avoid them, and the importance of
continued follow-up). RANOLAZINE
KEY POINTS Contraindications and Cautions
● Calcium channel blockers block
Ranolazine is contraindicated for use with
muscle contraction in smooth
any known sensitivity to the drug:
muscle and decrease the heart’s
● with preexisting prolonged QT
workload, relax vasospasm in
interval or in combination with
Prinzmetal angina, and possibly
drugs that would prolong QT
block the proliferation of the
intervals
damaged endothelium in coronary
● and with hepatic impairment and
vessels.
lactation. Caution should be used
● Patients on calcium channel
with pregnancy or renal
blockers need to be monitored for
impairment.
signs of decreased cardiac output
Caution should be used with pregnancy or
and response, including slow
renal impairment.
 Clinically Important Drug-Drug
Interation
Drug–drug interactions can occur with
● ketoconazole, diltiazem,
verapamil, macrolide antibiotics,
and HIV protease inhibitors; these
combinations should be avoided
because ranolazine levels may
become extremely high.
● Digoxin levels may become high if
the two drugs are combined; if this
combination is needed, the digoxin
dose will need to be decreased.
● Tricyclic antidepressants and
antipsychotic drug levels may
increase if these agents are
combined with ranolazine; if they
are combined, the dose of these
drugs may need to be decreased.
● Grapefruit juice should be avoided
while taking this drug.
Adverse Effects
● Dizziness, headache, nausea, and
constipation are the most
commonly experienced adverse
effects.
● Patients must be cautioned not to
cut, crush, or chew the tablets,
which need to be swallowed
whole. Safety precautions may be
needed if dizziness is an issue.
Antianginal Agents
Nitrates ➢ amyl nitrate
➢ isosorbide
dinitrate
➢ isosorbide
mononitrate
➢ nitroglycerin
Beta-blockers ➢ metoprolol
➢ Nadolol
➢ propranolol
Calcium ➢ amlodipine
Channel ➢ diltiazem
Blockers ➢ nicardipine
➢ nifedipine
➢ verapamil
Piperazineac ➢ ranolazine
etamide
SUMMARY
● CAD, the leading cause of death
in the United States and most
Western nations, develops when
changes in the intima of coronary
vessels lead to the development of
atheromas or fatty tumors,
accumulation of platelets and
debris, and a thickening of arterial
muscles, resulting in a loss of
elasticity and responsiveness to
normal stimuli.
● Narrowing of the coronary arteries
secondary to the atheroma buildup
is called atherosclerosis.
● Narrowed coronary arteries
eventually become unable to
deliver all the blood that is needed
by the myocardial cells, causing a
problem of supply and demand.
● Angina pectoris, or “suffocation of
the chest,” occurs when the
myocardial demand for oxygen
cannot be met by the narrowed
vessels. Pain, anxiety, and fatigue
develop when the
supply-and-demand ratio is upset.
Types of angina include stable,
unstable, and Prinzmetal angina.
● MI occurs when a coronary vessel
is completely occluded and the
cells that depend on that vessel
for oxygen become ischemic, then
necrotic, and die.
● Angina can be treated by drugs
that either increase the supply of
oxygen or decrease the heart’s
workload, which decreases the
 3. Used to block the stimulatory effects
demand for oxygen.
of the sympathetic nervous system.
● Nitrates and beta-blockers are
ANSWER: Beta-adrenergic blockers
used to cause vasodilation and to
decrease venous return and
4. Give one adverse effects associated
arterial resistance—effects that
with calcium channel blockers
decrease cardiac workload and
ANSWERS:
oxygen consumption.
○ Can affect cardiac output and
● Nitroglycerin is the drug of choice
smooth muscle
for treating an acute anginal
○ CNS effects: dizziness,
attack. It is available in various
light-headedness, headache,
forms.
and fatigue
● Nitroglycerin is the drug of choice
○ GI effects: nausea and
for treating an acute anginal
hepatic injury related to direct
attack. It is available in various
toxic effects on hepatic cells.
forms.
○ .Cardiovascular effects:
● Calcium channel blockers block
hypotension, bradycardia,
muscle contraction in smooth
peripheral edema, and heart
muscle and decrease the heart’s
block.
workload, relax vasospasm in
○ Skin effects: flushing and
Prinzmetal angina, and possibly
rash.
block the proliferation of the
damaged endothelium in coronary
5. Give a piperazine acetamide agent.
vessels.
ANSWER: Ranolazine
● The newest drug approved for the
treatment of angina is the
piperazineacetamide agent
ranolazine. The mechanism of
action of this drug is not
understood. It prolongs QT
intervals, does not slow heart rate
or blood pressure, but decreases
myocardial oxygen demand.

QUESTIONS (Pit stop)::

1. Drugs used to provide immediate

relief from angina symptoms and
prevent angina attacks.
ANSWER: Antianginal agents

2. Drugs that act directly on smooth

muscle to cause relaxation and to
depress muscle tone. It relaxes and
dilates veins, arteries, and
capillaries, allowing increased blood
flow through the vessels and
lowering systemic blood pressure.
ANSWER: Nitrates