DRUGS AFFECTING THE CARDIOVASCULAR AND RENAL SYSTEM
Inotropic drugs- drugs that increase the force of myocardial
contraction.
Chronotropic drugs- drugs that increase the rate at which the
heart beats.
Dromotropic drugs- drugs that accelerate conduction
2 Main Classes of Positive Inotropic Drugs
1. Cardiac glycosides2. Phosphodiesterase Inhibitors
CARDIAC GLYCOSIDES
Cardiac Glycosides- one of the eldest and most effective groups
of cardiac drugs.
They were originally obtained from either the Digitalis purpurea
or Digitalis Ianata plant, both commonly referred to as foxglove.
For this reason, cardiac glycosides are sometimes referred to as
digitalis glycosides. Critically ill patients can often be restored
to near-normal states within hours after initiating digoxin
therapy, a process known as digitalization.
MECHANISM OF ACTION AND DRUG EFFECTS
The primary beneficial effect of a cardiac glycoside is thought
to be an increase in myocardial contractility. This occurs
secondarily to the inhibition of the sodium-potassium ATPase pump.
When the action of this enzyme complex is inhibited, the cellular
sodium concentration and subsequently the calcium concentration
increase. The overall result is enhanced myocardial
contraction.
INDICATION
Cardiac glycosides are primarily used in the treatment of heart
failure and supraventricular dysrhytmias. In heart failure the
therapeutic effects of digoxin are secondary to its ability to
increase the force of contraction-its positive inotropic action.
Because more blood is ejected with each contraction of the heart,
less blood remains in the ventricle and thus less pressure builds
up. With this, the symptoms of pulmonary edema, pulmonary
hypertension, and right-sided ventricular failure subside, and
tissue perfusion improves.
Another benefit of this positive inotropic action is that it
promotes diuresis by ensuring that adequate blood is supplied to
the kidneys. As a result, fluids are more completely filtered and
waste products removed, which relieves shortness of breath and
pulmonary edema.
CONTRAINDICATIONS
Drug allergy 2nd or 3rd degree heart block Atrial fibrillation
Ventricular tachycardia or fibrillation Heart failure resulting
from diastolic dysfunction Subaortic stenosis
ADVERSE EFFECTSThe primary cardiac glycoside in use today is
digoxin, and close monitoring of the patients development of toxic
symptoms is essential. Digoxin has a narrow therapeutic index; that
is, the range of blood drug levels that is considered therapeutic
is small. Monitoring of digoxin levels after the drug reaches
steady state is necessary only if there is suspicion of toxicity,
noncompliance, or deteriorating renal function. Low potassium
levels can increase the potential for toxicity, know specifically
for this drug as digitoxicity. Therefore, frequent serum
electrolyte level checks are also important.
TOXICITY AND MANAGEMENT OF OVERDOSE
Body SystemCommon adverse effects
cardiovasculardysrhythmia, (bradycardia or tachycardia
central nervousheadache, fatigue, malaise, confusion,
convulsions
eyecolored vision (i.e., green, yellow, or purple) halo vision,
or flickering lights
gastrointestinalanorexia, nausea, vomiting, diarrhea
DIGOXIN TOXICITY: STEP-BY-STEP MANAGEMENT
1Discontinue administration of drug.2Begin continuous ECG
monitoring for cardiac dysrhythmias; administer antidysrhythmic
drugs as ordered.3Determine serum digoxin and electrolyte
levels.4Administer potassium supplements for hypokalemia in
indicated, as ordered.5Institute supportive therapy for
gastrointestinal symptoms.6Administer digoxin antidote (digoxin
immune Fab) if indicated, as ordered.
INTERACTIONS
INTERACTING DRUGSMECHANISMRESULT
antidysrthymics calcium(parenteral) reserpineincrease cardiac
irritabilityincreased digoxin toxicity
sympathomimetics amphotericin B chlorthalidoneloop
diureticlaxativessteroids(adrenal)thiazides (diuretics)produce
hypokalemiaincreased digoxin toxicity
antacids,
antidiarrhealscholestyraminecolestipolsucralfatedecrease oral
absorptionreduced therapeutic effect
quinidineverapamilamiodaronedecrease clearanceincrease digoxin
levels (2x); digoxin dose should be reduced 50%
anticholinergics
increase oral absorptionincreased therapeutic effect
barbiturates
induce enzymereduced therapeutic effect
calcium channel blockersblock calcium channels in
myocardiumenhanced bradycardic and negative inotropic effects of
digoxin
-blockers
block b1 receptors in heartenhanced bradycardic effect of
digoxin
The herbal supplement hawthorne can reduce theeffectiveness of
cardiac glycosides. Hawthorne is used for hypertension and
angina.
DRUG PROFILES
Normal therapeutic levels of digoxin should be between 0.5-2
ng/ml. Levels higher than 2 ng/ml are typically desirable for the
treatment of atrial fibrillation.Digoxin is available in oral and
injectable forms.
PHOSPODIESTERASE INHIBITORS
Phosphodiesterase inhibitors (PDIs)- group of inotropicDrugs
that work by inhibiting the action of an enzyme called
phosphodiesterase.
The inhibition of this enzyme results in two very beneficial
effects in an individual with heart failure: a positive inotropic
response and vasodilation. For this reason this class of drugs may
also be referred to as inodilators (inotropics and dilators).
There are presently only two U.S. drugs in this category:
inamrinone and milrinone.
Inodilators are more specific for phosphodiesterase type III,
which is especially common in the heart and vascular smooth
muscles.
MECHANISM OF ACTION AND DRUG EFFECTS
Inhibition of phosphodiesterase results in the availability of
more calcium for the heart to use in muscle contraction. It also
results in dilation of systemic or pulmonary blood vessels, which
in return decreases the workload of the heart. The effects on the
heart muscle lead to an increase in the force of contraction.
INDICATIONS
PDIs are primarily used for the short-term management of heart
failure. Traditionally, PDIs are given to patients who can be
closely monitored and who have not responded adequately to digoxin,
diuretics, and/or vasodilators.
CONTRAINDICATIONS
Drug allergy Presence of severe aortic or pulmonary valvular
disease Heart failure resulting from diastolic dysfunction
ADVERSE EFFECTS
The adverse effect that is most worrisome with inamrinone is
thrombocytopenia. The primary adverse effect seen with milrinone
therapy is dysrhythmia. Milrinone-induced dysrthymias are mainly
ventricular.
TOXICITY AND MANAGEMENT OF OVERDOSE
No specific antidote exists for an overdose of either inamrinone
or milrinone. Hypotension secondary to vasodilation is the primary
effect seen with excessive doses of both drugs.
The recommendation is to reduce the dose or temporarily
discontinue the PDI if excessive hypotension occurs. This should be
done until the patients condition is stabilized.
INTERACTIONS
Concurrent administration of diuretics may cause significant
hypovolemia and reduced cardiac filling pressure. Furosemide must
not be injected into intravenous lines of inamrinone or milrinone
because it will precipitate immediately.
NURSING CONSIDERATIONS
Before a cardiac glycoside or other positive inotropic drug is
administered, a thorough assessment of the patient is required.
Patients need to be aware of conditions that predispose to
digitalis toxicity, including hypokalemia, hypercalcemia,
hypothyroid states, renal dysfunction and advanced age.
Patients must be educated to measure pulse rate, and daily
weight with daily journaling. Nurses should always take an apical
pulse for 1 full minute when digoxin is administered, and patients
should be instructed on taking radial pulses when at home.
Patients should be encouraged to notify the health care provider
immediately at the first signs of anorexia, nausea, or vomiting, or
the occurrence of bradycardia with a pulse rate below 60 beats/min
if the patient is taking digoxin.
If more than 12 hours have passed, the patient should know to
not skip that dose, not double up on the next digoxin dose, and to
contact the health care provider immediately for further
instructions.
Patients should not abruptly stop their digoxin because this
could precipitate more cardiac problems and complications.
Patients should avoid using antacids or eating ice cream, milk
products, yogurt, or cheese for 2 hours before or after taking
medication to avoid interference with the drug.
Nurses must be aware that hypotension, dysrthythmias, and
thrombocytopenia are major adverse effects of inamrinone and
milrinone use.
ANTIDYSRHYTHMIC DRUGS
The SA node, AV node, and bundle of His- Purkinje cells are all
areas in which there is automaticity. The SA node is the pacemaker
because it can spontaneously depolarize easier and faster than the
other areas.
Antidysrthythmic drugs are used to correct dysrthythmias;
however, they may also cause dysrthythmias and for this reason are
said to be prodysrthythmic.
Vaughan Williams classification- this system is based on the
electrophysiologic effect of particular drugs on the action
potential.
VAUGHAN WILLIAMS CLASSIFICATION AND MECHANISM OF ACTION
CLASSIFICATIONMECHANISM OF ACTION
Class I (Moricizine)Ia: quinidine, procainamideIb: lidocaine,
phenytoinIc: flecainide, propafenonemembrane- stabilizing drugs
Class II (- blockers)propanolol
-adrenergic blockers that depress phase 4 depolarization
Class III: Amiodaronedrugs that prolong repolarization in phase
3
Class IV: Verapamilcalcium channel blockers that depress phase 4
depolarization
INDICATION
DRUG CLASSINDICATIONS
Class Isymptomatic ventricular and life-threatening
dysrthythmias
Class IaAtrial fibrillation, premature atrial contractions,
premature ventricular contractions, ventricular tachycardia, Wolff-
Parkinson- White Syndrome
Class Ib
Class IbVentricular dysrthythmias only; Atrial and ventricular
tachydysrthythmias caused by digitalis toxicity; long QT
syndrome
Class Icsevere ventricular tachycardia and supraventricular
tachycardia dysrthythmias, atrial fibrillation and flutter
Class IIBoth supraventricular and ventricular dysrthythmias
Class IIILife- threatening ventricular tachycardia or
fibrillation; atrial fibrillation or flutter resistant to other
drug therapy
Class IVParoxysmal supraventricular tachycardia; rate control
for atrial fibrillation and flutter
CONTRAINDICATIONS Drug allergy Structural heart damage
ADVERSE EFFECTS Hypersensitivity reactions Nausea Vomiting
Diarrhea Dizziness Headache Blurred vision
TOXICITY AND MANAGEMENT OF OVERDOSE
The main toxic effects of the antidysrthythmics involve the
heart, circulation, and central nervous system. Specific antidotes
are not available, and the management of an overdose involves
maintaining adequate circulation and respiration using general
support measures and providing any required symptomatic
treatment.
INTERACTIONS
Antidysrthythmic drugs can interact with many different
categories of drugs. The most serious drug interactions are the
ones that can result in dysrthythmias, hypotension, respiratory
distress, or any excessive therapeutic or toxic drug effects. Drug
interaction occur when the presence of one drug strengthens or
weakens the pharmacologic effects of another. This is most commonly
seen when the first drug affects the activity of the enzymes that
metabolize the second drug, either speeding or slowing its
elimination.
One particular interaction common to many antidysrthythmics is
the potentiation of anticoagulant activity with warfarin
(Coumadin). Because many patients receiving antidysrthythmic
therapy also need warfarin, prothrombin time and international
normalized ratio should be monitored appropriately and necessary
adjustments made to warfarin dosage.
NURSING CONSIDERATIONS
Nursing actions for the various anti dysrthythmics include
astute nursing assessment and close monitoring of heart rate, blood
pressure, heart rhythms, general well-being, skin color,
temperature, and heart and breath sounds.
The therapeutic response to antidysrthythmics include a decrease
in blood pressure in hypertensive patients, a decrease in edema,
and restoration of a regular pulse rate or pulse rate without major
irregularities or with improved regularity compared to the
irregularity that existed before therapy.
Patient education about the dosage schedule and the adverse
effects the patient should report to the physician is important for
safe and effective therapy.
Inform patients that a daily or weekly journal of symptoms,
adverse effects, daily weights, a rating of how they feel, activity
tolerance, blood pressure, and pulse rates will help with therapy.
Also encourage them to weigh the same time every day and while
wearing the same amount of clothing.
Instruct the patient to call the physician immediately if there
is a weight gain of 2 lb or more in 24 hours or 5 lb or more in 1
week.
The patient should be cautioned to change position slowly
because postural hypotension can be an adverse effect of these
drugs. Moving too quickly may lead to dizziness, syncope, and
subsequent injury or falls.
Instruct the patient that they should not abruptly discontinue
their medication and should continue taking it as prescribed.
With amiodarone, photosensitivity is an adverse effect, so the
patient should avoid sun exposure and should wear sun-protective
clothing and dark glasses when going outside. The patient should be
instructed on the need to report any blue-gray discoloration of the
skin (often after 1 year, and especially on the face, neck, and
arms) immediately to the healthcare provider.
ANTIANGINAL DRUGS
3 Main Classes of Drugs1. Nitrates and nitrites2. - blockers3.
Calcium channel blockers (CCB)
3 Main Therapeutic Objectives1. Minimize the frequency of
attacks and decrease the duration and intensity of the angina
pain;2. Improve the patients functional capacity with as few
adverse effects as possible;3. Prevent or delay the worst possible
outcome, MI. The overall goal of antianginal drug therapy is to
increase blood flow to ischemic myocardium, decrease myocardial
oxygen demand, or both.
NITRATES AND NITRITES
This class of antianginal drugs was first discovered by Sir
Thomas Lauder Brunton in England. They are available in a wide
variety of preparations, including sublingual, chewable, and oral
tablets; capsules; ointments; patches; a translingual spray; and
intravenous solutions. The following are the rapid and long-acting
nitrates available for clinical use: Amyl nitrate (rapid acting)
Nitroglycerin (both rapid and long acting) Isosorbide dinitrate
(both rapid and long acting) Isosorbide mononitrate ( primarily
long acting)
MECHANISM OF ACTION AND DRUG EFFECTS
Medicinal nitrates and nitrites, more commonly referred to
simply as nitrates, dilate all blood vessels. These vasodilatory
effects are the result of relaxation of the smooth muscle cells
that are part of the wall structure of veins and arteries. This
causes redistribution of blood and therefore oxygen to previously
ischemic myocardial tissue and reduction of angina symptoms.
INDICATIONS
The nitrates are used for stable, unstable, and vasoplastic
(Prinzmetals) angina. Long-acting dosage forms are used more for
prevention of anginal episodes. Rapid-acting dosage forms, most
often sublingual nitroglycerin tablets, or an intravenous drip in
the hospital setting, are used to treat acute angina attacks.
CONTRAINDICATIONS
Drug allergy Severe anemia Closed-angle glaucoma Hypotension
Severe head injury
This is because the vasodilatory effects of nitrates can worsen
these latter conditions. In anemia, a drug-induced hypotensive
episode can further compromise already reduced tissue
oxygenation.
ADVERSE EFFECTS
The most common undesirable effect is headache, which generally
diminishes in intensity and frequency soon after the start of
therapy. Other cardiovascular effects include tachycardia and
postural hypotension.
If nitrate-induced vasodilation occurs too rapidly, the
cardiovascular system overcompensates and increases the heart rate,
a condition referred to as reflex tachycardia.
INTERACTIONS
Nitrate antianginal drugs can produce additive hypotensive
effects when taken in combination with alcohol, -blockers, CCBs,
phenothiazines, and erectile- dysfunction drugs such as sildenafil
(Viagra).
- BLOCKERS
- blockers approved as antianginal drugs: Atenolol Metropolol
Nadolol Propanolol
MECHANISM OF ACTION AND DRUG EFFECTS
When receptors are blocked by - blockers, the rate by which the
pacemaker (sinoatrial node) fires decreases, and the time it takes
for the node to recover increases. The - blockers also slow
conduction through the atrioventricular node and reduce myocardial
contractility (negative inotropic effect). Both of these effects
serve to slow the heart rate (negative chronotropic effect). These
effects reduce myocardial oxygen demand, which aids in the
treatment of angina by reducing the workload of the heart.
The - blockers also suppress the activity of the hormone renin,
a potent vasoconstrictor released by the kidneys when they sense
that they are not adequately perfused.
INDICATIONS
The -blockers are most effective in the treatment of typical
exertional angina.
The -blockers are also approved for the treatment of: MI
Hypertension Cardiac dysrhythmias Essential tremor
CONTRAINDICATIONS
Systolic heart failure and serious conduction disturbances
Bronchial asthma Diabetes mellitus Reduced mental alertness
Peripheral vascular disease
ADVERSE EFFECTS
BODY SYSTEMADVERSE EFFECTS
Cardiovascularbradycardia, hypotension, 2nd or 3rd degree heart
block, heart failure
Central Nervousdizziness, fatigue, mental depression, lethargy,
drowsiness
Metabolicaltered glucose and lipid metabolism
Otherwheezing, dyspnea, impotence
INTERACTIONS
INTERACTING DRUGMECHANISMRESULT
Anticholinergics, cimetidineAntagonistc effect; decreased
metabolismdecreased level of -blocker; increased levels and
pharmacodynamic effects of propanolol and metoprolol
Diuretics and antihypertensivesadditive effectshypotension
phenothiazineadditive hypotensive effectshypotension and cardiac
arrest
Phosphodiesterase type 5 inhibitors (e.g. Viagra)additive
hypotensive effectspotentially life-threatening hypotension
Insulin and oral diabetic drugsadditive hypoglycemic
effectshypogylemia; possibly requiring dosage adjustment of
-blocker or antidiabetic drugs
CALCIUM CHANNEL BLOCKERS
The 3 chemical classes of calcium channel blockers:1.
Phenylalkylamines (Verapamil)2. Benzothiazepines (Diltiazem)3.
Dihydropyridines (Amlodipine, nicardipine, nifedipine)
MECHANISM OF ACTION AND DRUG EFFECTS
Calcium plays an important role in the excitation-contraction
coupling process that occurs in the heart and vascular smooth
muscle cells, as well as in skeletal muscle. Preventing calcium
from entering into this process therefore prevents muscle
contraction and promotes relaxation instead. Relaxation of the
smooth muscles that surround the coronary arteries causes them to
dilate. This increases blood flow to the ischemic heart which in
return increases the oxygen supply and helps shift the supply and
demand ratio back to normal.INDICATIONS
CCBs are considered first-line drugs for the treatment of such
conditions as: Angina, Hypertension, and Supraventricular
tachycardia.
The CCBs are also used for short-termmanagement of: Atrial
fibrillation and flutter Migraine headaches Raynauds disease
CONTRAINDICATIONS
Drug allergy Acute MI 2nd or 3rd degree atrioventricular block
(unless the patient has a pacemaker) Hypotension
ADVERSE EFFECTS
BODY SYSTEMADVERSE EFFECTS
Cardiovascularhypotension, palpitation, tachycardia or
bradycardia, heart failure
GastrointestinalConstipation, nausea
Otherdermatitis, dyspnea, rash, flushing, peripheral edema,
wheezing
INTERACTIONS
INTERACTING DRUGMECHANISMRESULT
-blockeradditive effectsbradycardia and atrioventricular
block
Digoxininterference with eliminationpossible increased digoxin
levels
blockersdecreased clearanceelevated levels of calcium channel
blockers
NURSING CONSIDERATIONS
The patient should be instructed that keeping a journal is a
very good way of documenting how the patient feels, including how
many anginal episodes occur, what happens, the character and
intensity of pain, frequency, and precipitating and relieving
factors. Encourage the patient to also make notes about how the
medication is tolerated.
If patients are taking capsules or extended-dosage forms,
encourage them to not chew, crush, or alter the dosage form.
Educate the patient about the best place to keep the medication
away from moisture, light, heat, and cotton filler and to keep the
medication in its original packaging (e.g., nitroglycerin in
amber-colored glass container). Inform the patient to expect
burning or stinging once the medication is placed under the tongue;
it is does not burn, then the drug may have lost its potency and a
new prescription must be obtained.
It is important to emphasize that the medication is only potent
for 3 to 6 months. Remind the patient to always have a fresh supply
of the drug on hand, to plan ahead if traveling and (no matter the
dosage form) to be seated or lie down when taking the medication to
avoid falls secondary to a drop in blood pressure.
Educate the patient that while taking antianginals, they should
avoid alcohol, hot environment temperatures, saunas, hot tubs, and
excessive exertion because these will lead to worsening of
vasodilation with hypotension, possible fainting, or other cardiac
events.
If the physician prescribes it, educate the patient to take the
nitroglycerin before stressful activities or events such as
emotional situations, consumption of large meals, or sudden
increase in activity (e.g., sexual intercourse). The patient should
be instructed to follow the physicians directions very closely.
ANTIHYPERTENSIVE DRUGS
There are essentially seven main categories of pharmacologic
drugs:1. Adrenergic drugs2. Angiotensin- converting enzyme
inhibitor3. Angiotensin II receptor blockers4. Calcium channel
blockers5. Diuretics6. Vasodilators
ADRENERGIC DRUGS Centrally and peripherally acting adrenergic
neuron blockers
MECHANISM OF ACTION AND DRUG EFFECTS
The central acting adrenergic drugs work by stimulating the
-adrenergic receptors in the brain. The -adrenergic receptors are
unique in that receptor stimulating actually reduces sympathetic
outflow, in this case from the central nervous system. The
resulting lack of norepinephrine production reduces blood
pressure.
In the periphery the -blockers doxazosin, prazosin, and
terazosin also modify the function of the SNS. However, they do so
by blocking the -adrenergic receptors, which, when stimulated by
circulating norepinephrine, produce increased blood pressure. Thus,
when these receptors are blocked, blood pressure is decreased. The
-blockers also increase urinary flow rates and decrease outflow
obstruction by preventing smooth muscle contractions in the bladder
neck and urethra.
INDICATIONS
The drugs mentioned are used primarily for the treatment of
hypertension, either alone or in combination with other
antihypertensive drugs.
CONTRAINDICATIONS
Drug allergy Acute heart failure Concurrent use of monoamine
oxidase inhibitors Severe mental depression Peptic ulcer Colitis
Severe liver or kidney diseaseADVERSE EFFECTS
The most common adverse effects of these drugs are: Bradycardia
with reflex tachycardia Postural and postexercise hypotension Dry
mouth Drowsiness Sedation Dizziness Edema Constipation Sexual
dysfunction
Other effects include: Headaches Sleep disturbances Nausea Rash
Peripheral pooling of blood Palpitations
There is also a high incidence of orthosthatic hypotension. This
can even lead to a situation known as first-dose syncope, in which
the hypotensive effect is severe enough to cause the patient to
lose consciousness with even the first dose of medication.
INTERACTIONS
Adrenergic drugs interact primarily with CNS depressant such as
alcohol, benzodiazepines, and opioids. The additive effects of
these combinations of drugs increase CNS depression.
ANGIOTENSIN- CONVERTING ENZYME INHIBITORS
The available ACE inhibitors are: Captopril (Capoten) Benazepril
(Lotensin) Enalapril (Vasotec) Fosinopril (Menopril) Lisinopril
(Prinivil, Zestril) Moexipril (Univasc) Perindopril (Aceon)
Quinapril (Accupril) Ramipril (Altace), and Trandolapril
(Mavik)
These drugs are very safe and efficacious and are often used as
first-line drugs in the treatment of both heart failure and
hypertension.
Captopril has the shortest half-life and therefore must be dosed
more frequently than any of the other ACE inhibitors. Enalapril is
the only ACE inhibitor that is available in a parenteral
preparation. All other drugs are available only in oral form.
MECHANISM OF ACTION AND DRUG EFFECTS
They inhibit angiotensin- converting enzyme, which is
responsible for converting AI to AII. AII is a potent
vasoconstrictor and induces aldosterone secretion by the adrenal
glands. The ACE inhibitors are beneficial in the treatment of heart
failure because they prevent sodium and water resorption by
inhibiting aldosterone secretion. This causes dieresis, which
decreases blood volume and return to the heart.
INDICATIONS
They are excellent antihypertensive and adjunctive drugs for the
treatment of heart failure.
CONTRAINDICATIONS
Drug allergy,especially a previous reaction of angioedema
(laryngeal swelling) to an ACE inhibitor Patients with a baseline
potassium of level of 5 mEq/L or higher may not be a suitable
candidate because these drugs can promote hyperkalemia.
ADVERSE EFFECTS
Major CNS effects of the ACE inhibitors include: Fatigue
Dizziness Mood changes Headaches
A characteristic dry, nonproductive cough is reversible with
discontinuation of the therapy. A first-dose hypotensive effect can
cause a significant decline in blood pressure. In patients with
severe heart failure whose renal function may depend on the
activity of the rennin-angiotensin-aldosterone system, treatment
with ACE inhibitors may cause acute renal failure. ACE inhibitors
tent to promote potassium resorption in the kidney, although they
also promote sodium excretion due to their reduction of aldosterone
secretion. One rare, but potentially fatal, adverse effect is
angioedema, a strong vascular reaction involving inflammation of
submucosal tissues, which can progress to anaphylaxis.
TOXICITY AND MANAGEMENT OF OVERDOSE
The most pronounced symptom of an overdose of an ACE inhibitor
is hypotension. Treatment is symptomatic and supportive and
includes the administration of intravenous fluids to expand the
blood volume.
INTERACTIONS
Nonsteroidal anti-inflammatory drugs- can reduce the
antihypertensive effect Concurrent use of ACE inhibitor and other
antihypertensives or diuretics- can have hypotensive effects
Lithium + ACE inhibitors= lithium toxicity!
ANGIOTENSIN II RECEPTOR BLOCKERS
ARBs are one of the newest classes of antihypertensives.
Losartan (Cozaar) Eprosartan (Teveten) Valsartan (Diovan)
Irbesartan (Avapro) Candesartan (Atacand) Olmesartan (Benicar)
Telmisartan (Micardis)
MECHANISM OF ACTION AND DRUG EFFECTS
ARBs block the binding of A II to type 1 A II receptors . ARBs
block vasoconstriction and the secretion of aldosterone.
Clinically, ACE inhibitors and ARBs appear to be equally
effective for the treatment of hypertension. Both are well
tolerated, but ARBs do not cause cough.
INDICATIONS
Antihypertensive Adjunctive treatment of heart failureThese
drugs are used primarily in patients who have been intolerant of
ACE inhibitor.
CONTRAINDICATIONS
Drug allergy Pregnancy and lactation
ARBs such as losartan should be used very cautiously in elderly
patients with renal dysfunction.
ADVERSE EFFECTS
Most common adverse effects of ARBs are: Upper respiratory
infections Headache
Occasionally: Dizziness Inability to sleep Diarrhea Dyspnea
Heartburn Nasal congestion Back pain Fatigue
Rarely: Anxiety Muscle pain Sinusitis Cough Insomnia
TOXICITY AND MANAGEMENT
Overdose may manifest as hypotension and tachycardia;
bradycardia occurs less often. Treatment is symptomatic and
supportive and includes the administration of intravenous fluids to
expand the blood volume.
INTERACTION
DRUGMECHANISMRESULT
cimetidinecompetes for metabolismincreased ARB effect
lithiuminhibits lithium eliminationincreased lithium
concentration
Phenobarbital, rifampinincreased metabolismdecreased ARB
effect
DIURETICS
The diuretics are a highly effective class of antihypertensive
drugs. Their primary therapeutic effect is decreasing the plasma
and extracellular fluid volumes, which results in decreased
preload. This leads to a decrease in cardiac output and total
peripheral resistance, all of which decrease the workload of the
heart. The thiazide diuretics are the most commonly used diuretics
for hypertension.
VASODILATORS
Vasodilators act directly on arteriolar and/or venous smooth
muscle to cause relaxation (e.g., IV diazoxide and sodium
nitroprusside).
MECHANISM OF ACTION AND DRUG EFFECTS
The particular mechanism of action of the direct-acting
vasodilators that makes them useful as antihypertensive drugs is
their ability to directly elicit peripheral vasodilation. In
general, the most notable effect of the vasodilators is their
hypotensive effect.
INDICATIONS
All of the vasodilators can be used to treat hypertension,
either alone or in combination with other antihypertensives.
CONTRAINDICATIONS
Drug allergy Hypotension Cerebral edema Head injury Acute MI
CAD
ADVERSE EFFECTS
Diazoxide: Dizziness Headache Orthostatic hypotension
Dysrthythmias Sodium and water retention Nausea Vomiting Acute
pancreatitis(rare) Hyperglycemia (in diabetic patients)
Hydralazine: Dizziness Headache Anxiety Tachycardia Edema Nasal
congestion Dyspnea Anorexia Nausea Vomiting Diarrhea Anemia
Agranulocytosis Hepatitis Peripheral neuritis Systemic lupus
erythematosus Rash
Minoxidil: T-wave electrocardiographic echanges Pericardial
effusion or tamponade Angina Breast tenderness Rash
Thrombocytopenia
Sodium nitroprusside: Bradycardia Decreased platelet aggregation
Rash Hypothyroidism Hypotension
TOXICITY AND MANAGEMENT OF OVERDOSE
The main symptom of diazoxide overdose or toxicity is
hypotension, which can usually be controlled by placing the
patients bed in Trendelenbrug position.
Minoxidil overdose or toxicity can precipitate excessive
hypotension. Treatment is supportive and symptomatic and includes
the administration of IV fluids.
The main symptom of sodium nitroprusside overdose or toxicity is
excessive hypotension. This drug is normally administered only to
patients receiving intensive care. Treatment for the hypotension is
supportive and symptomatic.
NURSING CONSIDERATIONS
Educate patients to take medications exactly as prescribed by
the physician.
The patient should be informed about the fact that successful
therapy requires compliance to medications as well as any dietary
restrictions (e.g., decreasing fatty foods or those high in
cholesterol and salty foods).
The patient should always monitor stress levels and use
biofeedback, imagery, and/or relaxation techniques or massage, as
the management of hypertension and serves to relieve stress and is
usually inclusive of supervised, prescribed exercise.
The patient should avoid smoking and excessive alcohol intake as
well as excessive exercise, hot climates, saunas, hot tubs, and hot
environments.
Blood pressure should be recorded, including postural blood
pressures. The patient should be sure he or she feels comfortable
in taking his or her own blood pressure and pulse rate.
The patient should inform all health providers (e.g., dentist,
surgeon) that he or she in taking antihypertensive drugs.
The patient should be sure to move purposefully and cautiously
and to change positions slowly because of the possible adverse
effect of postural hypotension and associated risk for dizziness.
Lightheadedness, and possible fainting and falls.
With successful therapy, the patients condition will improve;
however , the patient should be cautioned not to stop taking the
medication just because he or she is feeling better. Lifelong
therapy is required.
Encourage patient to use saliva substitutes, sugar-free hard
candy, or frequent fluids for management of dry mouth.
Share with the patient measures to help with constipation, such
as forcing fluids, increasing fiber and roughage, and contacting
the physician if there is no relief of this adverse effect.
Patients should know to never abruptly stop taking the
medication for any reason, including sexual problems, because of
the risk of severe hypertensive rebound.
DIURETIC DRUGS
The potency of these diuretics is a function of where they work
in the nephron to inhibit sodium and water resorption. The more
sodium and water they inhibit from resorption , the greater the
amount of dieresis and therefore the greater the potency.
CLASSIFICATION OF DIURETICS
CLASSDRUGS
Carbonic anhydrase inhibitorsAcetazolamide, dichlorphenamide,
methazolamide
Loop diureticsBumetanide, ethacrynic acid, furosemide,
torsemide
Osmotic diureticsMannitol
Potassium- sparing diureticsAmiloride, spirolactone,
triamterene
Thiazide and thiazide-like diureticsChlorothiazide,
hydrochlorotiazide
CARBONIC ANHYDRASE INHIBITORS
The site of action of the CAIs is the location of the carbonic
anhydrase enzyme system along the nephron, primarily in the
proximal tubule.
MECHANISM OF ACTION
The carbonic anhydrase system in the kidney is located just
distal to the glomerulus in the proximal tubules, where roughly two
thirds of all sodium and water is resorbed in the blood. For sodium
and thus water to be resorbed back into the blood, hydrogen must be
exchanged for it. Without hydrogen, this cannot occur, and the
sodium and water will be eliminated with the urine. Carbonic
anhydrase helps to make the hydrogen ions.
When its actions are inhibited by a CAI such as acetazolamide,
little sodium and water can be resorbed into the blood and they are
eliminated with the urine.
The metabolic acidosis induced by CAIs is beneficial in the
prevention of certain seizures.
INDICATIONS
They are commonly used in the treatment of: Glaucoma Edema
Epilepsy High-altitude sickness
CONTRAINDICATIONS
Drug allergy Hyponatremia Hypokalemia Severe renal or hepatic
dysfunction
ADVERSE EFFECTS
The more common undesirable effects with CAIs Acidosis
HypokalemiaThese drugs may also cause: Drowsiness Anorexia
Paresthesias Hematuria Urticaria Photosensitivity Melena
INTERACTIONS
Increase in digitalis toxicity when CAIs and digitalis are given
together, stemming from the hypokalemia that CAIs may induce.
Concomitant use of CAIs and corticosteroids may also cause
hypokalemia. Their use with oral hypoglycemic drugs and quinidine
may induce greater activity or toxicity of the latter drug.
LOOP DIURETICS
Loop diuretics (bumetanide, ethacrynic acid, furosemide, and
torsemide) are very potent diuretics.
MECHANISM OF ACTION
Their renal effects are their major mechanism of action. These
drugs act primarily along the thick ascending limb of the loop of
Henle, blocking chloride and, secondarily, sodium resorption. Loop
diuretics are particularly useful when rapid dieresis is needed,
because of their rapid onset of action. In addition, the diuretic
effect last at least 2 hours.
The resulting decreased fluid volume leads to a decreased return
of blood to the heart, or decreased filling pressures. This has the
following cardiovascular effect: Reduces blood pressure Reduces
pulmonary vascular resistance Reduces systemic vascular resistance
Reduces central venous pressure
INDICATIONS
Edema associated with heart failure and hepatic or renal disease
Control hypertension Increase the renal excretion of calcium in
patients with hypercalcemia
CONTRAINDICATIONS
Drug allergy Hepatic coma Severe electrolyte loss
COMMON ADVERSE EFFECTS
BODY SYSTEMADVERSE EFFECTS
Central nervousDizziness, headache, tinnitus, blurred vision
GastrointestinalNausea, vomiting, diarrhea
HematologicAgranulocytosis, thrombocytopenia, neutropenia
MetabolicHypokalemia
TOXICITY AND MANAGEMENT OF OVERDOSE
Electrolyte loss and dehydration, which can result in
circulatory failure, are the main toxic effects of loop diuretics
that require attention. Treatment involves electrolyte and fluid
replacement.
INTERACTIONS
INTERACTING DRUGMECHANISMRESULTS
Aminoglycosides,Capreomycin,Chloroquine,Vancomycin,Additive
effectIncreased neurotoxicity, especially ototoxicity
Corticosteroids,DigoxinHypokalemiaAdditive hypokalemia,Increased
digoxin toxicity
LithiumDecrease in renal excretionIncreased lithium toxicity
NSAIDsInhibition of renal prostaglandinsDecreased diuretic
activity
SulfonylureasDecrease in glucose toleranceHyperglycemia
OSMOTIC DIURETICS
The osmotic diuretics include mannitol, urea, organic acids, and
glucose. Mannitol, a nonabsorbable solute, is the most commonly
used of these drugs.
MECHANISM OF ACTION AND DRUG EFFECTS
Mannitol works along the entire nephron. Its major action,
however, is the proximal tubule and descending limb of the loop of
Henle. It produces osmotic pressure in the glomerular filtrate,
which in turn pulls fluid, primarily water, into the renal tubules
from surrounding tissues. This process also inhibits the tubular
resorption of water and solutes, which produces rapid diuresis.
Mannitol may induce vasodilation and in doing so increase both
glomerular filtration and renal plasma flow. This makes it an
excellent drug for preventing kidney damage during acute renal
failure. It is also often used to reduce intracranial pressure and
cerebral edema resulting from head trauma.
INDICATIONS
Mannitol is the osmotic drug of choice. It is commonly used in
the treatment of patients in the early, oliguric phase of acute
renal failure.
CONTRAINDICATIONS Drug allergy Severe renal disease Pulmonary
edema (loop diuretics are used instead) Active intracranial
bleeding
ADVERSE EFFECTS Convulsions Thrombophlebitis Pulmonary
congestion
INTERACTIONS
There are no drugs that interact significantly with
mannitol.
POTASSIUM- SPARING DIURETICS
The currently available potassium- sparing diuretics are
amiloride, spironolactone, and triamterene.
MECHANISM OF ACTION AND DRUG EFFECTS
Spironolactone competitively binds to aldosterone competitively
binds to aldosterone receptors and therefore blocks the resorption
of sodium and water that is induced by aldosterone secretion. These
receptors are found primarily in the distal tubule.
Amiloride and triamterene do not bind to aldosterone receptors.
However, they inhibit both aldosterone-induced and basal sodium
reabsorption, working in both the distal tubule and collecting
ducts. They are often prescribed for children with heart failure,
because pediatric cardiac problems are frequently accompanied by an
excess secretion of aldosterone.
INDICATIONS
Spironolactone and triamterene are used to treat:
Hyperaldosteronism Hypertension Reverse potassium loss caused by
potassium wasting (e.g., loop, thiazide) diuretics. The uses for
amiloride are similar to those spironolactone and triamterene, but
amiloride is less effective in the long term.
CONTRAINDICATIONS
Drug allergy Hyperkalemia (serum potassium level exceeding 5.5
mEq/L) Severe renal failure or anuriaTriamterene use may also be
contraindicated in cases of severe hepatic failure.
ADVERSE EFFECTS
BODY SYSTEMADVERSE EFFECTS
Central nervousDizziness, headache
Gastrointestinal Cramps, nausea, vomiting, diarrhea
Other Urinary frequency, weakness, hyperkalemia
INTERACTIONS
The administration of ACE inhibitors or potassium supplements in
combination with potassium-sparing diuretics can result in
hyperkalemia.
When lithium and potassium-sparing diuretics are given together,
lithium toxicity can result.
NSAIDs can inhibit renal prostaglandins, decreasing blood flow
to the kidneys and therefore decreasing the delivery of diuretic
drugs to this site of action. This in turn can lead to a diminished
diuretic response.
THIAZIDES AND THIAZIDE-LIKE DIURETICS
Hydrochlorothiazide is undoubtedly the most commonly prescribed
and the least expensive of the generic preparations.
The thiazide diuretics include: bendroflumethiazide,
chlorothiazide, methyclothiazide, and trichlormethiazide.
The thiazide-like diuretics are very similar in action to the
thiazides and include: chlorthalidone, indapamide, and
metolazone.
Of all of the drugs just mentioned, hydrochlorothiazide and
metolazone are by far the most commonly prescribed in practice.
MECHANISM OF ACTION AND DRUG EFFECTS
The primary site of action of thiazides and thiazide-like
diuretics is the distal convoluted tubule, where they inhibit the
resorption of sodium, potassium, and chloride. This results in
osmotic water loss.
Thiazides generally should not be used if creatinine clearance
is less than 30 to 50 mL/min. Normal creatinine clearance is 125
mL/min. The only exception is metolazone, which remains effective
to a creatinine clearance of 10 mL/min.
INDICATIONS
Edematous states Diabetes insipidus HypertensionThis group of
diuretics may also be useful as adjunct drugs in the treatment of:
Edema related to heart failure, Hepatic cirrhosis, Corticosteroid
or estrogen therapy
CONTRAINDICATIONS
Drug allergy Hepatic coma (metolazone) Anuria Severe renal
failure
ADVERSE EFFECTS
BODY SYSTEMADVERSE EFFECTS
Central nervousDizziness, headache, blurred vision, presthesia,
decreased libido
GastrointestinalAnorexia, nausea, vomiting, diarrhea,
pancreatitis, cholecystitis
Genitourinary Impotence
Hematologic Jaundice, leukopenia, purpura, agranulocytosis,
aplastic anemia, thrombocytopenia
Integumentary Urticaria, photosensitivity
Metabolic Hypokalemia, glycosuria, hyperglycemia,
hyperuricemia
TOXICITY AND MANAGEMENT OF OVERDOSE
An overdose of these drugs can lead to an electrolyte imbalance
resulting from hypokalemia. Symptoms include: Anorexia Nausea
Lethargy Muscle weakness Mental confusion HypotensionTreatment
involves electrolyte replacement.INTERACTIONSINTERACTING
DRUGMECHANISMRESULTS
Corticosteroids Additive effect Hypokalemia
Diazoxide Additive effect Hyperkalemia
Digoxin Hypokalemia Increased digoxin toxicity
Lithium Decreased clearanceIncreased lithium toxicity
NSAIDsInhibition of renal prostaglandinsDecreased diuretic
activity
Oral hypoglycemicsAntagonism Reduced therapeutic hypoglycemic
effect
NURSING CONSIDERATIONS
Patient should maintain proper nutrition intake and fluid volume
status with attention to eating potassium-rich foods, except when
contraindicated or when taking potassium- sparing diuretics.
Foods high in potassium include bananas, oranges, dates, plums,
fresh vegetables, potatoes (white and sweet), meat, fish, apricots,
whole grain cereals, and legumes.
Patients need to change positions slowly and to rise slowly
after sitting or lying to prevent dizziness and possible fainting
(syncope).
Prevent constipation with an increase in fiber, bulk, roughage,
and fluids if not contraindicated.
For patients with diabetes mellitus who are also taking thiazide
and/or loop diuretics, educate them about close monitoring of blood
glucose levels. These diuretics may cause elevation of blood
glucose.
FLUIDS AND ELECTROLYTES
CONDITIONS LEADING TO FLUID LOSS OR DEHYDRATION AND ASSOCIATED
CORRESPONDING SYMPTOMS
CONDITIONASSOCIATED SYMPTOMS
Bleeding Tachycardia and hypotension
Bowel obstruction Reduced perspiration and mucous secretions
DiarrheaReduced urine output (oliguria)
Fever Dry skin and mucous membrane
Vomiting Reduced lacrimal (tears) and salivary secretions
When fluid that has been lost must be replaced, there are three
categories of agents that can be used to accomplish this:1.
Crystalloids2. Colloids3. Blood products
CRYSTALLOIDS
Crystalloids are fluids given by intravenous injection that
supply water and sodium to maintain osmotic gradient between the
extravascular and intravascular compartments. NS Hypertonic saline
Lactated Ringers W Plasma-Lyte
MECHANISM OF ACTION AND DRUG EFFECTS
Because crystalloids work by osmosis, hypertonic saline (3%
sodium chloride) is more efficient than normal saline (NS) (0.9%
sodium chloride) for expanding the PV.
Crystalloid solutions contain fluids and electrolytes that are
normally found in the body. They do not contain proteins
(colloids), which are necessary to maintain the colloid osmotic
pressure and prevent water from leaving the plasma compartment.
Crystalloids are also distributed faster into the interstitial
and intracellular compartments, which makes them better for
treating dehydration than for expanding the PV alone, such as in
hypovolemic shock.
INDICATIONS
Crystalloid solutions are most commonly used as maintenance
fluids. They are used to compensate for insensible fluid losses, to
replace fluids when there are body-fluid deficits. Manage specific
fluid and electrolyte disturbances. Less expensive than colloids
and blood products.
Following are the common indications for either crystalloid or
colloid replacement therapy: Acute liver failure Acute nephrosis
Adult respiratory distress syndrome Burns Cardiopulmonary bypass
Hypoproteinemia Reduction of the risk for deep vein thrombosis
(DVT) Renal dialysis Shock
CONTRAINDICATIONS
Drug allergy Hypervolemia Severe electrolyte disturbance
ADVERSE EFFECTS
Because they contain no large particles, such as proteins, they
do not stay within the blood vessels and can leak out of the plasma
into the tissues and cells. This may result in edema anywhere in
the body, due to osmosis from the crystalloid itself. Peripheral
edema and pulmonary edema are two common examples.
INTERACTIONS
Interactions with crystalloid solutions are rare because they
are very similar if not identical to normal physiologic
substances.
COLLOIDS
Colloids are protein substances that increase the capillary
osmotic pressure and effectively move fluid from the interstitial
compartment to the plasma compartment by pulling the fluid into the
blood vessels.Commonly used colloids: Dextran 70 Dextran 40
Hetastarch 5% Albumin 25% Albumin
MECHANISM OF ACTION AND DRUG EFFECTS
The mechanism of action of colloids is related to their ability
to increase COP. Because colloids increase the blood volume, they
are sometimes called plasma expanders.
INDICATIONS
Colloids are superior to crystalloids in their ability to
maintain PV for a longer term.
CONTRAINDICATIONS
Drug allergy Hypervolemia Severe electrolyte disturbance
ADVERSE EFFECTS
Colloids are relatively safe agents, although there are some
disadvantages to their use. They have no oxygen-carrying ability
and contain no clotting factors, unlike blood products. Because of
this, they can alter the coagulation system through dilutional
effect, resulting in: Impaired coagulation and, possibly
Bleeding.
INTERACTIONS
Because colloids are so compatible with many drugs, they are
sometimes used as medium for delivering them.
BLOOD PRODUCTS
Blood products can be thought of as biologic drugs. All of them
can augment the PV. Red blood cell (RBC)- containing products can
also improve tissue oxygenation, as well as augment PV.
Blood products are also expensive and are less available than
crystalloids and colloids because they are natural products and
require human donor.
MECHANISM OF ACTION AND DRUG EFFECTS Red blood cell (RBC)
products have the ability to carry oxygen. They can maintain the
COP for several hours to days, and because they come from human
donors, they have all the benefits (and hazards) that human blood
products have. They are administered when a persons body is
deficient in these products.
BLOOD PRODUCTS: INDICATIONS
BLOOD PRODUCTINDICATION
Cryoprecipitate and plasma protein fractions (PPF)To manage
acute bleeding
Fresh frozen plasma (FFP)To increase clotting factor levels in
patients with a demonstrated deficiency
Packed red blood cell (PRBC)To increase oxygen-carrying capacity
in patients with substantial hemoglobin deficits, and in patients
who have lost up to 25% of their total blood volume
Whole bloodSame as for PRBCs, except that whole blood is more
beneficial in cases of extreme (>25%) loss of blood volume since
whole blood also contains plasma, the chief fluid volume of the
blood; it also contains plasma proteins, the chief osmotic
component, which help draw fluid back into blood vessels from
surrounding tissues
CONTRAINDICATIONS
There are no absolute contraindications to the use of blood
products. However, because of the risk for transfer of infectious
disease, although remote, their use should be based on careful
clinical evaluation of the patients condition.
ADVERSE EFFECTS
Because these products come from other humans, they can be
incompatible with the recipients immune system. These
incompatibilities are tested for before the administration of the
particular blood product by determining the respective blood types
of the donor and recipient and by doing cross-matching tests to
screen for incompatibility between selected blood proteins.
These products can also transmit pathogens from the donor to the
recipient. Examples of such pathogens are hepatitis and HIV.
INTERACTIONS
They interact with very few substances.
POTASSIUM
Potassium is the most abundant cationic (positively charged)
electrolyte inside the cells (intracellular space), where the
normal concentration is approximately 150 mEq/L. The potassium
content outside the cells in the plasma ranges from 3.5 to 5
mEq/L.
Potassium is obtained from a variety of foods, the most common
being fruit and juices, fish, vegetables, poultry, meats, and dairy
products.
SYMPTOMS OF HYPOKALEMIA
Early Anorexia Hypotension Lethargy Mental confusion Muscle
confusion Nausea
Late Cardiac dysrthythmias Neuropathy Paralytic ileus Secondary
alkalosis
MECHANISM OF ACTION AND DRUG EFFECTS Functions of potassium in
our body: Muscle contraction Transmission of nerve impulse
Regulation of heartbeats
INDICATIONS
Potassium replacement therapy is called for in the treatment or
prevention of potassium depletion in patients whenever dietary
measures prove inadequate.
CONTRAINDICATIONS
Drug allergy Hyperkalemia Severe renal disease Acute dehydration
Severe hemolytic disease
ADVERSE EFFECTS
Gastrointestinal (occur with oral administration) Diarrhea
Nausea Vomiting GI bleeding UlcerationOccur with parenteral
administration Pain at the injection site Phlebitis
TOXICITY AND MANAGEMENT OF OVERDOSE
The toxic effects of potassium are the result of hyperkalemia.
Symptoms include: Muscle weakness Paresthesia Paralysis Cardiac
rhythm irregularities
The treatment instituted depends on the degree of the
hyperkalemia and ranges from regimens for reversible
life-threatening problems to simple dietary restrictions.
In the event of severe hyperkalemia, intravenous administration
of sodium bicarbonate, calcium gluconate or chloride, or dextrose
solution with insulin is often required. These drugs correct severe
hyperkalemia by causing rapid intracellular shift of potassium
ions, thus reducing the serum potassium concentration.
INTERACTIONS
Concurrent use of potassium-sparing diuretics and ACE inhibitors
can produce a hyperkalemic state. Concurrent use of diuretics,
amphotericin B, and mineralosteroids can produce a hypokalemic
state.
SODIUM
Sodium is the principal cation outside the cell. The normal
concentration of sodium outside cells is 135-145 mEq/L, and it is
maintained through dietary intake of sodium in the form of sodium
chloride, which is obtained from salt; fish; meats; and other foods
flavored, seasoned, or preserved with salt.
HYPONATREMIA SYMPTOMS
Lethargy Hypotension Stomach cramps Vomiting Diarrhea Seizures
Excessive perspiration(occurring during hot weather or physical
work) Prolonged diarrhea or vomiting (especially in young children)
Renal disorders Adrenocortical impairment
HYPERNATREMIA SYMPTOMS
Edema Hypertension Red, flushed skin Sticky mucous membranes
Increased thirst Temperature elevation Decreased or absent
urination
MECHANISM OF ACTION AND DRUG EFFECTS
Sodium is principally involved in the control of water
distribution, fluid and electrolyte balance, and osmotic pressure
of body fluids. Sodium is also capable of causing diuresis.
INDICATIONS
Sodium is primarily administered in the treatment or prevention
of sodium depletion when dietary measures have provided
inadequate.
Pronounced sodium depletion is treated with NS or lactated
Ringers solution administered intravenously.
CONTRAINDICATIONS
Drug allergy Hypernatremia
ADVERSE EFFECTS
Oral administration: Gastric upset Nausea Vomiting
CrampsParenteral administration Venous phlebitis
TOXICITY AND MANAGEMENT OF OVERDOSE
Treatment consists of increased fluid intake and dietary
restrictions.
INTERACTIONS
Sodium is not known to interact significantly with any
drugs.
NURSING CONSIDERATIONS
Blood products may cause hemolysis of RBCs, and, therefore,
adverse reactions such as fever, chills, and back pain should be
watched for continually.
Hematuria may occur if the hemolysis reaction is present.
If noted, the nurse should notify the physician immediately, the
IV infusion discontinued, and the nature of the reaction and all
actions taken documented.
Blood products should be given only with NS 0.9% because W will
cause hemolysis of the blood product.
As needed, educate the patient about the difference in signs and
symptoms of hyponatremia and hypernatremia, hypokalemia and
hyperkalemia.
COAGULATION MODIFIER DRUGS
These drugs can be broken down into several main categories
based on their actions:
Anticoagulants- inhibit the action or formation of clotting
factors and, therefore, prevent clots from forming.
Antiplatelet- prevent platelet plugs from forming by inhibiting
platelet aggregation, which can be beneficial in preventing heart
attacks and strokes. These are sometimes referred to as
hemorrheologic drugs.
Antifibrinolytic drugs- also known as hemostatic drugs, have the
opposite effect of these other classes of drugs; they actually
promote blood coagulation and are helpful in the management of
conditions which excessive bleeding would be harmful.
Thrombolytic drugs- lyse (break down) clots, or thrombi, that
have already formed.
ANTICOAGULANTS
Drug classes of anticoagulants include older drugs such as
unfractioned heparin and warfarin.
MECHANISM OF ACTION
Heparin works by binding to a substance called antithrombin III
(AT-III) which turns off 3 main activating factors: activated II
(also called thrombin), activated X, and activated IX.
Warfarin (Coumadin) also works by inhibiting vitamin K synthesis
by bacteria in the gastrointestinal tract.
INDICATIONS MI Unstable angina Atrial fibrillation Indwelling
devices such as mechanical heart valves Conditions in which blood
flow may be slowed and blood may pool
CONTRAINDICATIONS
Drug allergy Acute bleeding Thrombocytopenia Leukemia or other
blood dyscrasias Pregnancy GI obstruction Serious inflammation
Infection
ADVERSE EFFECTS
Bleeding is the main complication of anticoagulant therapy, and
the risk increases with increasing dosages. Such bleeding may be
localized or systemic.
INTERACTIONS
The main interaction mechanisms responsible for increasing
anticoagulant activity include the following: Enzyme inhibition of
biotransformation Displacement of the drug from inactive protein-
binding sites Decrease in vitamin K absorption or synthesis by the
bacterial flora of the large intestines Alteration in the platelet
count or activity
TOXICITY AND MANAGEMENT OF OVERDOSE
Symptoms that may be attributed to toxicity or an overdose of
anticoagulants are: Hematuria Melena Petechiae Ecchymoses Gum or
mucous membrane bleeding
In the event of either heparin or warfarin toxicity, the drug
should be discontinued immediately. In severe cases or when large
doses have been given intentionally, IV injection of protamine
sulfate is indicated.
ANTIPLATELET DRUGS
Aspirin Clopidogrel Dipyridamole Pentoxifylline Cilostazol
Anagrelide Abciximab Tirofiban Eptifibatide
MECHANISM OF ACTION
Many of the antiplatelet drugs affect the cyclooxygenase
pathway, which is one of the common final enzymatic pathways in the
complex arachidonic acid pathway that operates within platelets and
on blood vessel walls.
INDICATIONS
Aspirin: Officially recommended for stroke prevention by the
American Stroke Society
Clopidogrel: Used for reducing the risk for fatal and nonfatal
thrombotic stroke Used for prophylaxis against transient ischemic
attacks as well as post-MI thromboprevention.Dipyridamole Used as
adjunct to warfarin in the prevention of postoperative
thromboembolic complications. Also used to decrease platelet
aggregation in various other thromboembolic disorders.
Pentoxifylline Indicated for peripheral vascular disease
Cilostazol Indicated specifically for intermittent claudication
(pain and cramping in the calf muscle associated with walking)
CONTRAINDICATIONS
Drug allergy Thrombocytopenia Active bleeding Leukemia Traumatic
injury GI ulcer Vitamin K deficiency Recent stroke
ADVERSE EFFECTS
BODY SYSTEMADVERSE EFFECTS
Aspirin
Central nervousStimulation, drowsiness, dizziness, confusion,
flushing
GastrointestinalNausea, vomiting, GI bleeding, diarrhea,
heartburn
HematologicThrombocytopenia, agranulocytosis,
leucopenia,neutropenia, hemolytic anemia,bleeding
Clopidogrel
CardiovascularChest pain, hypertension, edema
Central nervousFlulike symptoms, headache, dizziness,
fatigue
GastrointestinalAbdominal pain, dyspepsia, diarrhea, nausea
MiscellaneousEpistaxis and integumentary disorders, including
rash and pruritis
INTERACTIONS
The concurrent use of dipyridamole, with aspirin, clopidogrel,
and/or nonsteroidal anti-inflammatory drugs (NSAIDs) produces
additive antiplatelet activity and increased bleeding
potential.
The combined use of aspirin and steroids or NSAIDs can increase
the ulcerogenic effects of aspirin.
When aspirin is given with oral antidiabetic drugs, the patient
can experience a loss of diabetic control.
ANTIFRIBINOLYTIC DRUGS
The term antifibrinolytic refers to what these drugs can do,
which is to prevent the lysis of fibrin; in doing so, they actually
promote clot formation.
There are three synthetic antifibrinolytics:1. Aminocaproic
acid2. Tranexamic acid3. Desmopressin
One natural antifibrinolytic drug:1. Aprotinin
MECHANISM OF ACTION AND DRUG EFFECTS
Aminocaproic acid, tranexamic acid, and aprotinin prevent
breakdown of fibrin, which prevents the destruction of the formed
platelet clot.
Desmopressin causes a dose-dependent increase in the
concentration of plasma factor VIII (von WIlleband factor), along
with an increase in the plasma concentration of tissue plasminogen
activator.
INDICATIONS
Antifibrinolytics are useful in both prevention and treatment of
excessive bleeding resulting from systemic hyperfibrinolysis or
surgical complications. They also have proved successful in
arresting excessive oozing from surgical sites such as chest
tubes.
Desmopressin may also be used in patients who have hemophilia A
or type I von Willebrands disease.
CONTRAINDICATIONS Drug allergy Disseminated intravascular
coagulation
ADVERSE EFFECTS
BODY SYSTEMADVERSE EFFECTS
Cardiovascular Dysrhythmias, orthostatic hypotension,
bradycardia
Central nervousHeadache, dizziness, fatigue, hallucination,
psychosis, convulsions
GastrointestinalNausea, vomiting, abdominal cramps, diarrhea
INTERACTIONS Concurrent use of drugs such as estrogens or oral
contraceptives with aminocaproic acid, tranexamic acid, and
aprotinin may have an additive effect, resulting in increased
coagulation.
THROMBOLYTIC DRUGSThrombolytics are coagulation modifiers that
lyse thrombi in the blood vessels that supply the heart with blood,
the coronary arteries.
MECHANISM OF ACTION AND DRUG EFFECTS
Thrombolytics accomplish its action by activating the conversion
of plasminogen to plasmin, which breaks down, or lyses, the
thrombus. This reestablishes blood flow to the blood-starved heart
muscle. If the blood flow is reestablished early, the heart muscle
and left ventricular function can be saved. If blood flow is not
reestablished early, the affected area of the heart muscle becomes
ischemic, and eventually necrotic and nonfunctional.
INDICATIONS
Acute MI Arterial thrombosis DVT Occlusion of shunts or
catheters Pulmonary embolism Acute ischemic stroke
CONTRAINDICATIONS
Drug allergy Concurrent use with other drugs that alter
clotting
ADVERSE EFFECTS
The most common undesirable effect of thrombolytic therapy is
internal, intracranial and superficial bleeding.
Other problems include: Hypersensitivity Anaphylactoid reactions
Nausea Vomiting Hypotension
These drugs can also induce cardiac dysrthythmias.
TOXICITY AND MANAGEMENT
Acute toxicity primarily causes an extension of the adverse
effects of the thrombolytic agent. Treatment is symptomatic.
INTERACTIONS
The most common effect of drug interactions is an increased
bleeding tendency resulting from the concurrent use of
anticoagulant, antiplatelet, or other drugs that affect platelet
function.
NURSING CONSIDERATIONS
Subcutaneous heparin injections After thorough checking the
physicians order, assess the patient for the existence of any
allergies, contraindications, cautions, or drug interactions. Check
injection site for bleeding or bruising and document any pertinent
information. The nurse should not massage or rub the injection. Do
not aspirate before injecting to avoid/prevent the occurrence of
hematoma.
Intravenous heparin administration Always double-check the
specific physicians order for dosage, rate of infusion, and time
and route before beginning the therapy.
For continuous IV administration of heparin, an IV pump must be
used to ensure a precise rate of infusion.
Intermittent infusions of heparin are usually ordered to be
given every 4 to 6 hours because of heparins short half-life.
Intermittent infusions and all other types of IV infusions include
use of needle-less system.
For intermittent infusions, a heparin lock was used in the past.
Heparin locks are now referred to as intermittent infusion locks or
salinelocks (because the locks are flushed with isotonic saline and
nit heparin).
Oral anticoagulant administration It is important to recheck the
physicians orders and the patients medication and medical history
before administering the drug. Always check to make sure the
patient has no known hypersensitivity to the drug.
Dosages of warfarin are calculated based upon INR blood values.
INRs are also used to monitor the effectiveness of therapy,
remember, however, dosing is highly individualized.
ANTILIPEMIC DRUGS
The decision to prescribe hyperlipemic drugs as an adjunct to
diet therapy in patients with an elevated cholesterol level should
be based on the patients clinical profile.
When the decision to institute drug therapy has been made, the
choice of drug should then be determined by the specific lipid
profile of the patient.
There are currently 4 established classes of drugs used to treat
dyslipidemia:1. HMG-CoA reductase inhibitors (statins)2. Bile acid
sequestrants3. B- vitamin niacin (vitamin , also known as nicotinic
acid)4. Fibric acid derivatives (fibrates)
In addition to all of these drugs, the newest drug, ezetimibe
(Zetia), is cholesterol absorption inhibitor.
HMG-CoA REDUCTASE INHIBITORS
The rate-limiting enzyme in cholesterol synthesis is known as
HMG-CoA reductase. This class of medication competitively inhibits
this enzyme. They are the most potent of the drugs available for
reducing plasma concentrations of LDL cholesterol.
Lovastatin- the first drug in this class to be approved for use,
and this occurred in 1987.
Since that time, 6 other HMG-CoA reductase inhibitors have
become available on the U.S. market: Pravastatin Simvastatin
Atorvastatin Cerivastatin Fluvastatin Rosuvastatin
MECHANISM OF ACTION AND DRUG AFFECTS
Statins lower the blood cholesterol level by decreasing the rate
of cholesterol production. The liver requires HMG-CoA reductase to
produce cholesterol. It is the rate-limiting enzyme in the
reactions needed to make cholesterol. The statins inhibit this
enzyme, thereby decreasing cholesterol production.INDICATIONS
First-line drug therapy for hypercholesterolemia, the most
common and dangerous form of dyslipidemia.
These drugs also appear to be equally effective in their ability
to reduce LDL cholesterol concentrations.
CONTRAINDICATIONS
Drug allergy Pregnancy Liver disease Elevation of liver
enzymes
ADVERSE EFFECTS
BODY SYSTEMADVERSE EFFECTS
Central nervousHeadache, dizziness, blurred vision,
opthalmoplegia, fatigue, nightmares, insomnia
GastrointestinalConstipation, cramps, diarrhea, nausea,changes
in bowel function
Other Myalgias, skin rashes
TOXICITY AND MANAGEMENT OF OVERDOSE
Very limited data are available on the nature of toxicity and
overdose in patients taking HMG-CoA reductase inhibitors.
Treatment, if needed, is supportive and based on presenting
symptoms.
INTERACTIONS
HMG-CoA reductase inhibitors should be used cautiously in
patients taking oral anticoagulants.
BILE ACID SEQUESTRANTS
Bile acid sequestrants, also called bile acid-binding resins and
ion-exchange resins, include: Cholestyramine Colestipol
Colesevelam
MECHANISM OF ACTION AND DRUG EFFECTS
Bile acids are necessary for the absorption of cholesterol from
the small intestine, yet are also synthesized from cholesterol by
the liver. This is one natural way that the liver excretes
cholesterol from the body. The more the bile acids are excreted in
the feces, the more the liver converts cholesterol to bile acids.
This reduces the level of cholesterol in the liver, and thus, the
circulation as well.
CONTRAINDICATIONS
Drug allergy Biliary or bowel obstruction
ADVERSE EFFECTS
BODY SYSTEMADVERSE EFFECTS
Gastrointestinal Constipation, heartburn, nausea, belching,
bloating
OtherBleeding, headache, tinnitus, burnt odor of urine
TOXICITY AND MANAGEMENT OF OVERDOSE
Because the bile acid sequestrants are not absorbed, an overdose
could cause obstruction of the GI tract. Therefore, treatment of an
overdose involves retoring gut motility.
INTERACTIONS
All drugs should be taken at least 1 hour before or 4 to 6 hours
after the administration of ion-exchange resins. In addition, high
doses of a bile sequestrants will decrease the absorption of
fat-soluble vitamins (A, D, E and K).
NIACIN
Niacin, or nicotinic acid, is not only a very unique
lipid-lowering drug, it is also a vitamin. It is often given in
combination with other antilipemic drugs to enhance the
lipid-lowering effects.
MECHANISM OF ACTION AND DRUG EFFECTS
Although the exact mechanism of action of niacin is unknown, the
beneficial effects are believed to be related to its ability to
inhibit lipolysis in adipose tissue and increase the activity of
lipoprotein lipase.
CONTRAINDICATIONS
Drug allergy Liver disease Hypertension Peptic ulcer disease Any
active hemorrhagic disease
ADVERSE EFFECTS
BODY SYSTEMADVERSE EFFECTS
Gastrointestinal Abdominal discomfort, GI distress
Integumentary Cutaneous flushing, pruritus,
hyperpigmentation
Other Blurred vision, glucose intolerance, hyperuricemia, dry
eyes(rare), hepatotoxicity
INTERACTIONS
The major drug interactions associated with niacin are minimal.
One interaction of note: when niacin is taken concomitantly with an
HMG-CoA reductase inhibitor, the likelihood of myopathy development
is increased.
FIBRIC ACID DERIVATIVES
Current fibric acid derivatives include gemifibrozil and
fenofibrate. They are often collectively referred to as
fibrates.
MECHANISM OF ACTION AND DRUG EFFECTS
Fibric acid drugs are believed to work by activating lipoprotein
lipase, an enzyme responsible for the breakdown of cholesterol.
CONTRAINDICATIONS
Drug allergy Severe liver or kidney disease, cirrhosis
Gallbladder disease
ADVERSE EFFECTS
BODY SYSTEMADVERSE EFFECTS
Gastrointestinal Nausea, vomiting, diarrhea, gallstones, acute
appendicitis
Genitourinary Impotence, decreased urine output, hematuria,
increased risk for urinary hematuria, increased risk for UTI and
viral infections
Other Drowsiness, dizziness, rash, pruritus, alopecia, eczema,
vertigo, headache
TOXICITY AND MANAGEMENT OF OVERDOSE
The management of fibrate overdose, which is uncommon, is
supportive care based on presenting symptoms. GI contamination or
use of gastric lavage may be indicated for large overdoses.
INTERACTIONS
Gemfibrozil can also enhance the action of oral anticoagulants,
thus also necessitating careful dose adjustment of these latter
drugs.
The risk for myalgia, myositis, and rhabdomyolysis is increased
when either gemfibrozil or fenofibrate is given with a statin.
NURSING CONSIDERATIONS
Educate patients about the need for eating plentiful amounts of
raw vegetables, fruit and bran and at least 2000mL of fluids a day
to prevent the constipation that is commonly experienced with
antilipemics.
Inform patients to engage in moderate daily exercise as ordered
by their physician and to exchange positions slowly.
If patients are taking a bile acid sequestrant, make sure they
contact their health care provider immediately if they notice their
stool appear black and tarry.
With statin drugs Take the medication with at least 6 oz of
water with meals to help minimize gastric upset.
It may take several weeks before therapeutic results are seen,
and frequent laboratory testing will occur at about every 3 to 6
months.
If taking one of the statin drugs, an ophthalmic examination is
needed prior to and during therapy due to the problems reported
with visual acuity.
Other side effects may include decreased in libido, severe
muscle pain, chest pain, or other unexplained pain, patients should
contact their physician immediately.
All patients should receive nutritional consultation and menu
planning assistance related to a low-fat diet.Page | 27