The Cardiovascular System and Drug Therapy

Anatomy and Physiology of the Cardiovascular System

Cardiovascular system – heart and blood vessels, circulates blood through the body,
bringing oxygen and nutrients to tissues, carrying away carbon dioxide and toxic by-
products.

Arteries – carry blood away from the heart.

Veins – carry blood to the heart.

Capillaries – tiny blood vessels; inside are critical fluids, gases, and nutrients that are
exchanged between the blood and body tissues.

Blood is pumped by the heart, through the lungs, where blood is replenished with oxygen and
releases carbon dioxide, which is exhaled
Cardiac Muscle Contraction and Relaxation
Cardiac muscle fibers make up the hearts four chambers: right and left atria, and right and
left ventricles. The atria receive blood brought into the heart, the ventricles push blood out.

Systole – period during which the heart is contacting and actively pumping.

Diastole – period when the heart muscle relaxes, allowing blood to passively flow into the
heart and fill the heart’s chambers.

Electrical signals in the heart control muscle contraction and relaxation by depolarizing and
repolarizing the surface of the cardiac muscle cells.

Waves of positive and negative charges are created by positively charged ions, potassium,
sodium, and calcium crossing the cell membrane through tiny channels.

Sinoatrial (SA) node is a bundle of conduction fibers in the right atrium; called the heart’s
natural pacemaker.

The electrical signal is carried through the atria down to the atrioventricular (AV) node.

The signal then travels through the bundle of His; then branches into the Purkinje fibers,
stretching into the ventricles to contract the lower, and largest part, of the heart.

Heart rate (HR) is reported in beats per minute (BPM) and is measured by a person’s pulse.

Electrical signal can be measured with an electrocardiogram (ECG or EKG) machine. The
machine translates the signal to waves seen on a paper or screen.
Blood Pressure
Blood pressure is the force of blood that fills the circulatory system. Blood pressure is a
function of:

o Capacitance – the amount of blood held in the system

o Peripheral vascular resistance (PVR) – degree to which blood vessels are

constricted or relaxed

o Cardiac output (CO) – force and volume of blood coming from the heart

o Renin-angiotensin system – feedback mechanism regulated by the kidneys that

balances fluid volume and vessel constriction

Constricted blood vessels causes the heart to work harder to maintain cardiac output,
keeping blood pressure stable. Constriction or dilation of blood vessels, lowers blood
pressure.

Blood Pressure Measurement:

Sphygmomanometer is the instrument used to measure blood pressure. The cuff is wrapped
around the patient’s arm and inflated to apply pressure; briefly cutting off blood flow to the
brachial artery in the upper arm; air is slowly released, lowering pressure to where blood, with
turbulence, flows again.

When blood flows again, the first number reported, is your systolic blood pressure (SBP); the
second number reported, is your diastolic blood pressure (DBP) – this is obtained at the
point which the cuff is loose enough to allow blood to flow without turbulence.
Hypertension
Hypertension (HTN), or high blood pressure can cause damage to vital organs such as the
heart, kidneys, eyes, and brain.

Elevated systolic or diastolic blood pressure, or both, is considered hypertension. Blood

pressure higher than 180/110 mm Hg, requires immediate medical attention. Factors that
contribute to high blood pressure include smoking, diabetes, kidney disease, age, family
history, gender, and lifestyle.

Drug Regimens and Treatments:

The article “2014 Evidence-Based Guideline for the Management of High Blood Pressure in
Adults” suggests treating high blood pressure when it exceeds 150/90 for people age 60 and
older and 140/90 for younger than 60.

Patients with diabetes and kidney disease should begin treatment when blood pressure
exceeds 140/90, no matter the age.

A staged system is used for diagnosis and treatment of high blood pressure:

o Stage 1 hypertension = systolic ≥ 140 mm Hg or diastolic ≥ 90 mm Hg

o Stage 2 hypertension = systolic ≥ 160 mm Hg or diastolic ≥ 100 mm Hg

o Hypertensive emergency = systolic ≥ 180 mm Hg or diastolic ≥ 110 mm Hg

ACE Inhibitors
Angiotensin-converting enzyme (ACE) inhibitors regulate blood pressure through the renin-
angiotensin system; protect kidneys from long-term damage.

Renin – an enzyme produced by the kidneys, is converted to angiotensin I in the bloodstream.

Angiotensin I is converted to angiotensin II by angiotensin-converting enzyme (ACE).

Angiotensin II is a vasoconstrictor; blocking production allows blood vessels to relax, lowering

vascular resistance and overall blood pressure.

Side effects include headache, dizziness, fatigue, mild diarrhea, and a dry, hacking cough. The cough
is caused by a build up of bradykinin in the respiratory tract.

Angioedema is a rare side effect; it is an allergic reaction wherein swelling of the tongue and face
are sufficiently severe to threaten breathing.

ACE inhibitors should not be used on patients who have experienced angioedema; pregnant patients
should not use ACE inhibitors because they can cause severe birth defects; patients with kidney
conditions (bilateral renal artery stenosis) should not use ACE inhibitors because the kidneys could
shut down.

Hypotension, low blood pressure, can occur when taking ACE inhibitors; elevated potassium levels
(hyperkalemia) is a rare side effect; patients with other kidney problems may take ACE inhibitors, but
doses are adjusted down.
 Medications to control blood pressure:
(1) Angiotensin receptor blockers (ARBs) are used for hypertension and heart failure and often used
as an alternative to ACE inhibitors.

ARBs work by binding to the same receptors to which angiotensin II binds; instead of stimulating
vasoconstriction, ARBs block receptors, preventing constriction and causing blood vessels to relax,
lowering blood pressure.

Side effects include headache, dizziness, fatigue, and mild diarrhea; patients may have more
respiratory tract infections, but why is unknown.

Patients with diabetes mellitus should not take ARBs. Patients taking diuretics with ARBs may
experience hypotension.

(2) Calcium-channel blockers are used to treat hypertension, heart failure, and arrhythmias. There
are not the first therapeutic choice for high blood pressure. Calcium-channel blockers decrease
blood pressure by preventing calcium from entering the smooth-muscle cells of arterial walls;
relaxing smooth-muscle cells allows them to open up blood vessels and lower blood pressure.

Side effects include headache, dizziness, fatigue, constipation, nausea, heartburn, and flushing.

Contraindications exist for clevidipine (IV medication), diltiazem, felodipine, nisoldipine, nicardipine,
nifedipine, and IV verapamil.

Fluid retention and heart palpitations could be caused by some calcium-channel blockers.

Once a day, extended-release calcium-channel blockers, should not be crushed or chewed.

Some extended-release forms work by releasing the drug from a capsule or tablet called a ghost
pill – which moves through the gastrointestinal system and appears in the patients’ stool.
(3) Thiazide diuretics work by eliminating sodium and fluid from the body, decreasing blood volume,
lowering blood pressure. It is either a first or second choice for blood pressure control.

Side effects include hypotension, dizziness, headache, skin rash, hair loss (alopecia), upset stomach,
diarrhea, and constipation.

Patients with hypersensitivity to sulfonamide-derived drugs and anuria should avoid taking thiazide
diuretics.

Thiazide diuretics can deplete potassium levels in the body; supplements may be necessary.

Patients should use caution when drinking alcohol while taking thiazide diuretics.

These medications can interact with diabetes medications, raising blood glucose levels; they also
interact with corticosteroids and lithium.

(4) Alpha and beta blockers are adrenergic inhibitors that control blood pressure by blocking certain
adrenaline receptor types found in the body.

Alpha blockers are useful for men with high blood pressure and benign prostatic hyperplasia (BPH).

Beta blockers are beneficial on the heart, especially after a heart attack.

Side effects include headache, dizziness, nausea, and fatigue. Patients should avoid driving until
they know how the medication is going to make them feel. Alpha blockers have no
contraindications.

Beta blockers are contraindicated in bradycardia, cardiogenic shock, and heart block.

Patients taking alpha blockers should be warned of hypotension and heart palpitations. Drinking
alcohol can intensify hypotensive effects. Patients with impaired respiratory function must take care
when using beta blockers because of its effect on constricting the airways in the lungs. Beta
blockers should not be stopped abruptly. OTC decongestants are vasoconstrictors and can raise
blood pressure.
Cardiac Arrhythmias

o Sinus rhythm – normal heart rhythm.

o Arrhythmia – deviation from sinus rhythm.

o Tachycardia – increased heart rate.

o Bradycardia – decreased heart rate.

o Flutter – when select portions are slightly out of sync with the rest of the heart.

o Fibrillation – large portions of the heart beat are out of sequence.

• Ventricular fibrillation – no blood flows through the heart

• Drug Regimens and Treatments:

Medications for arrhythmias are designed to restore normal sinus rhythm.

Antiarrhythmic drugs are chosen and dosed individually and are categorized into classes
based on their mechanisms of action.
Different drug classes:

Class I: Membrane-Stabilizing Agents

Membrane-stabilizing agents (Class I) include medications that block sodium channels in cardiac
muscles.

Slowing the influx of sodium allows the cell membrane to become more stable and less able to
depolarize.

The electrical charge must be stronger to stimulate the cardiac muscle cells to contract and make
the heart beat.

Side effects are drug specific. Contraindications are numerous and drug specific.

Antiarrhythmic drugs should be used with caution.

Class II: Beta Blockers

Some beta blockers inhibit beta-1 receptors; which inhibit sympathetic nervous system activity on
the heart; slowing conduction through the AV node; slowing rate and force of heartbeats just enough
to reduce arrhythmias.

Side effects are drug specific.

Beta blockers are contraindicated in bradycardia, cardiogenic shock, and heart block.

Sotalol should be used with caution.

Class III: Potassium-Channel Blockers
Potassium-channel blockers block potassium channels in cardiac muscle cells.

These drugs work by slowing the influx of potassium, which makes the cell membrane more stable
and less able to depolarize. Electrical charge must be stronger to make the heart beat; regulating
heart rhythm because it decreases the incidence of abnormal beats.

Side effects are drug specific. Amiodarone has contraindications, along with dofetilide.

Cautions and considerations are drug specific.

Class IV: Calcium-Channel Blockers

Diltiazem and verapamil are frequently used for atrial fibrillation. These drugs block calcium from
entering cardiac muscle cells; dilating cardiac arteries, providing better oxygen supply.

Side effects are drug specific.

Diltiazem should not be used in patients with sick sinus syndrome, secondary or third-degree AV
block, severe low blood pressure, acute heart attack, and pulmonary congestion.

Verapamil in IV form should not be used in patients taking beta blockers and those with ventricular
tachycardia. Antiarrhythmic drugs should be used with caution.
Digoxin (Class all by itself)
Digoxin is in a class all by itself; used for the treatment of atrial fibrillation. Digoxin works by
inhibiting sodium-potassium ATPase, an enzyme that regulates the influx of sodium and potassium
in cardiac muscle cells. Altering SA node conductivity, conduction velocity through the heart, and
rest time between beats; increases force and velocity of muscle contraction, making the heart pump
more efficiently.

Side effects include a narrow therapeutic window – the amount of drug to cause the desired effect
is not much greater than the amount of drug that causes toxicity.

Other side effects include gynecomastia (breast enlargement), anorexia, mental disturbances
(anxiety, depression, delirium, hallucination), and heart block (extremely slow heartbeat).

Patients hypersensitive to digitalis, digoxin, or diagnosed with ventricular fibrillation should not take
digoxin.

Patients should not change between brand and generic digoxin because small differences in tablet
strength can affect blood concentrations.
Vasodilators
Vasodilators – relax smooth muscle and dilate blood vessels. Dilation allows greater oxygen and
nutrient supply to reach cardiac muscle tissue, relieving chest pain and ischemia (low blood supply).

Nitrates are the most common vasodilator. They are short-acting products used for angina attacks;
long-acting forms are used to prevent frequent angina attacks. Nitroglycerin is a short-acting form,
designed to produce rapid absorption after one dose.

Side effects include headache, dizziness, blurred vision, flushing, increased heart rate, hypotension,
and agitation.

Nitrates are contraindicated for patients taking phosphor-diesterase-5 inhibitors (ED medications);
as well as patients with increased intracranial pressure and severe anemia. Short-acting forms
should not be swallowed, they are meant to go under the tongue (sublingual) and buccal (cheek).

Nitroglycerin must be kept in its original, amber-colored container and protected from light, heat, and
moisture.

Nitroglycerin tablets lose their effectiveness when exposed to warm and moist conditions; tablets
are only good for 6 months after the bottle is opened. Transdermal patches should be removed
before bedtime and left off overnight; a new patch should be applied in the morning.

Other Drugs for Angina (ACE inhibitors, Beta Blockers, and

Calcium-Channel Blockers):
Ace inhibitors, beta blockers, and calcium-channel blockers are all used to treat angina and heart
attack.

These drugs have shown beneficial effects on heart tissue that has already experienced ischemia.

They increase oxygen supply, increase pumping efficiency, and can reduce stress on the heart that
has suffered an infarction. Side effects are drug specific. Contraindications are class specific for
ACE inhibitors, beta blockers, and calcium-channel blockers.
Heart Failure
Heart failure is characterized by weakness, fatigue, severe fluid retention, and difficulty breathing
due to pulmonary edema.

High blood pressure and coronary blockage, over time, can cause the heart to no longer work
properly, resulting in enlargement and weakening. With the heart unable to pump sufficiently vital
organs will shut down due to lack of blood supply.

Factors that can contribute to this condition include hypertension and coronary artery disease, which
are primary causes; other factors include alcoholism, liver disease, kidney disease, valvular heart
disease, anemia, and drug therapy.

Drug Regimens and Treatments:

Drug therapy includes diuretics, ACE inhibitors, and beta blockers; some patients may use
vasodilators and digoxin.

Loop Diuretics
Loop diuretics work primarily in the ascending loop of Henle and distal renal tubule, sites of water
and sodium recovery.

These drugs work by inhibiting reabsorption of sodium, chloride and water, leading to fast and
profound diuresis (urine production). Loop diuretics include bumetanide, ethacrynate, furosemide
and torsemide.

Side effects include dizziness, headache, skin rash, upset stomach, diarrhea, and constipation. Not
to be used in patients with anuria.

Electrolyte balance, kidney function, and hydration must be monitored in patients taking loop
diuretics.

Patients often take potassium supplements with loop diuretics.

Hyperlipidemia
Hyperlipidemia – elevated cholesterol, phospholipids, and/or triglycerides in the blood, resulting in
cardiovascular disease and coronary artery blockage. Cholesterol is used to build cell membranes
and form hormones.

Diet can affect a person’s blood cholesterol; some make too much cholesterol in their liver.

Cholesterol is packaged into multiple types of molecules: lipoproteins and triglycerides.

Low-density lipoproteins (LDLs) is the bad kind of cholesterol.

High-density lipoproteins (HDLs) are the good kind of cholesterol.

Triglycerides – a lipid molecule, contribute to atherosclerosis (blocking and hardening of artery

walls). Hyperlipidemia exists when LDLs and triglycerides are elevated in the blood.

Drug therapy is started when reducing fat and cholesterol in the diet is unsuccessful.

Abnormal values:

o Total cholesterol > 200 mg/dL

o LDL varies, but usually > 160 mg/dL

o HDL < 45 mg/dL

o Triglycerides > 150 mg/dL

Lowering cholesterol levels has been found to significantly reduce the risk of a heart
attack. Hyperlipidemia drugs are either used to prevent a first heart attack or subsequent heart
attacks. A finger-stick test can test for lipids.
Lowering cholesterol levels:
(1) HMG-CoA reductase inhibitors (statins) primarily lowers LDL, with benefits on other lipids.

First-line choice therapy for hyperlipidemia. Statins reduce the amount of cholesterol made in the
body by blocking the enzyme HMG-CoA reductase, which is needed for cholesterol production.

Side effects include upset stomach, diarrhea, muscle aches and weakness; occasionally statins
cause liver toxicity.

Statins should not be used in patients with active liver disease or unexplained persistent elevations
of serum transaminase; not for women who are pregnant, plan to get pregnant or breastfeeding.

Grapefruit juice alters the activity of statins.

(2) Fibrates are an alternative to statins; lower LDL cholesterol but are best at lowering triglycerides
and increasing HDL cholesterol.

Side effects include upset stomach, diarrhea, indigestion, and abdominal cramps.

Patients with active liver disease, severe kidney function, and gallbladder disease should not take
fenofibrate and gemfibrozil.

Patients with gallbladder problems should not take fibrates; and should not be taken in combination
with statins.

(3) Ezetimibe (Zetia) inhibits cholesterol absorption from the GI tract.

Side effects include abdominal cramps and diarrhea.

Should not be used in patients with active liver disease; women who are pregnant or breastfeeding
should not take ezetimibe/simvastatin (Vytorin).

There are few problems with this medication because it is not systemically absorbed.
(4) Niacin, Vitamin B3 is a dietary supplement available over the counter as well as prescription.

Niacin reduces triglycerides and LDL while raising HDL.

Side effects include vasodilation of the face and neck, causing flushing and itching.

Flushing can be reduced by taking an aspirin 30 minutes prior to taking niacin.

Niacin should not be taken in patients with active liver disease or persistent elevations in hepatic
transaminases, active peptic ulcers, and arterial hemorrhage.

Blood glucose levels can raise if taken in large doses.

(5) Herbal and other remedies:

-Omega-3 fatty acids (DHA and EPA) are found in a variety of fish oil products.

Fish oil supplements or increased dietary intake of fish has shown to lower triglycerides
significantly.

Consuming 1g of fish oil a day or eating fish (3 oz) twice a week has been found to prevent
cardiovascular disease.

-Plant sterol esters significantly lower LDL and can be helpful adjuncts to diet and drug therapy.

-Beta-sitosterol is similar in chemical structure to cholesterol; found in food products like margarine
and juice.

-Red yeast rice a fermented rice used to lower cholesterol and improve cardiovascular health.

-Alpha tocopherol (Vitamin E) supplements are used for cardiovascular disease, cancer, and
diabetic neuropathy.

Garlic contains organosulfur compounds that have antihyperlipidemic, antihypertensive, and

antifungal properties.

• Allicin – the odorous, active ingredient produced upon crushing garlic gloves.
Anatomy and Physiology of the blood
Blood serves several functions, supplying the cells of the body with oxygen and nutrients, carrying
hormones and enzymes that control bodily functions and regulating body temperature. Blood is cells
suspended in plasma.

Plasma contains water, protein (albumin and immunoglobulins), and a variety of dissolved
substances. Drug molecules are carried by the blood either as dissolved substances or substances
bound to proteins like albumin.

Erythrocytes
Erythrocytes or red blood cells (RBCs), contain iron and hemoglobin to which oxygen and carbon
dioxide bind during transport. Erythrocytes are formed in bond marrow when molecules of iron
attach to hemoglobin.

Erythropoiesis is the process of erythrocytes being released into the bloodstream after being made;
this is stimulated by erythropoietin, a substance made by the kidneys.

Leukocytes
Leukocytes or white blood cells (WBCs) are a key component of the immune system.

Leukocytes are formed in bone marrow, found in both blood and tissue, where they fight infection.

Platelets
Platelets or thrombocytes are cells formed in the bone marrow and are stored in the spleen.
Coagulation Cascade
Coagulation cascade is the process by which blood clots form, this involves thrombin, fibrinogen,
and fibrin.

There are two pathways of the cascade, extrinsic and intrinsic. An abnormality in a step of either
pathway can affect coagulation and clotting. The pathways converge with the use of clotting factor
X, thrombin, and fibrin.

Blood Types
Blood type is determined by specific antigen proteins on the surface of red blood cells. Blood types
are categorized as A, B, AB, and O.

Rh Factor
Rh factor is another marker molecule on red blood cells which is included when typing blood for
transfusion. Rh factor is a protein that may be present on red blood cells.

Those with the protein marker are Rh-positive, those without the marker are Rh-negative.

If a mother is Rh-negative with an Rh-positive baby, the mother’s blood will form antibodies against
the baby’s red blood cells. This antibodies can build up and jeopardize the survival of the baby, and
effect subsequent pregnancies.
Common Blood Disorders - Anemia
Blood disorders can be acute or chronic, caused by a variety of reasons including nutritional deficits,
chronic illness, and genetic abnormalities.

Anemia, is a chronic illness characterized by a lower-than-normal number of healthy red blood cells
that contain functional hemoglobin in the blood. Anemia can be caused by inadequate production of
red blood cells, rapid destruction of red blood cells, or blood loss. Inadequate production of red
blood cells is the most common cause of anemia. Iron-deficiency anemia can happen quickly, but
takes months to replenish iron stores in the body. Folate-deficiency anemia is common in alcoholic
patients, due to lack of proper nutrition.

Pernicious anemia is a deficiency of vitamin B12, which can take weeks or months to develop, but
only days or weeks to replenish. Anemia of chronic disease is often caused by chronic kidney
disease, reducing the production of erythropoietin, which stimulates bone marrow to make red blood
cells. Erythropoietin must be given to increase red blood cell production, providing iron will not
produce more red blood cells.

Hemolytic anemia is a rapid destruction of red blood cells and can be triggered by infection,
malignancy, or drug therapy. Rapid-onset anemia is tied to rapid blood loss; signs of rapid-onset
anemia include accelerated heart rate, lightheadedness, and breathlessness; this condition may
require a transfusion. Chronic anemia is linked to chronic blood loss, caused by for example,
stomach ulcers. This anemia produces fatigue, weakness, headache, vertigo, lightheadedness,
sensitivity to cold, pallor (an unhealthy pale appearance), and loss of skin tone. Treatment is to stop
the bleeding at the source. Sickle-cell anemia is a genetic disorder resulting in malformed red blood
cells. The hemoglobin inside the cells is abnormal, which results in a misshapen half-moon
crescents or sickles.
Iron and Other Supplements
Iron, folic acid (folate), and vitamin B12 are supplements used to treat anemia caused by nutrient
deficiency. Iron can be used for iron-deficiency anemia or in combination with hematopoietic agents
to treat anemia associated with chronic kidney disease. Iron supplementation can take up to 6
months to replenish iron stores and produce normal red blood cells with adequate hemoglobin
content.

Folic acid is used for prenatal supplementation, in low doses, to support fetal brain and spinal
development; in higher doses it can be used to treat anemia caused by alcoholism.

Vitamin B12 is used to treat pernicious anemia and to prevent neuropathy and certain types of
dementia; replenishment of this vitamin only takes days to weeks.

Side Effects and Contraindications:

For iron supplements: constipation, upset stomach, urine discoloration, and dark stools.

Ferrous gluconate and sulfate are contraindicated in hemochromatosis and hemolytic anemia.

Iron dextran is contraindicated in any anemia not associated with iron deficiency.

For vitamin B12: itching, diarrhea, headache, and anxiety.

Vitamin B12 should not be used in patients with a hypersensitivity to cobalt.

IV ferrous gluconate, iron sucrose, and oral folic acid have no contraindications.

Cautions and Considerations:

Oral iron supplements should not be chewed.

Iron overdose in children can be fatal. Iron supplements should not be taken with antacids or other
acid-reducing medications because absorption of iron will be decreased.

Vitamin C increases iron absorption.

Iron supplements should not be taken with tetracycline or fluoroquinolones – binding occurs,
reducing effectiveness.

Iron dextran is associated with severe allergic reactions.

Hematopoietic Agents
Darbepoetin (Aranesp) and erythropoietin (Epogen, Procrit) are used to treat anemia associated
with kidney disease. Sometimes used when cancer chemotherapy causes bone marrow suppression
and affects blood cell production. Used in combination with iron supplements.

Side Effects and Contraindications:

Side effects include: headache, fatigue, fever, muscle or joint pain, edema, diarrhea, nausea, and
vomiting; high blood pressure, clotting, and rapid heart rate.

Contraindicated for patients with uncontrolled high blood pressure and pure red blood cell aplasia
(decline of red blood cells produced by bone marrow) Not to be used in neonates, infants, pregnant
and nursing women.
Patients with hemoglobin levels greater than 11 g/dL are at increased risk for serious cardiovascular
events, thromboembolic events, stroke, and mortality.

Cautions and Considerations:

Laboratory tests are used to monitor patients taking hematopoietic agents, including reticulocyte
count, which is a measure of newly formed red blood cells released from bone marrow into the
bloodstream.

These products should be refrigerated, and should not be shaken or diluted during preparation.

Some erythropoietin products have a limited shelf life and must be discarded after 21 days if not
used.

Darbepoetin should be protected from light, covered with a light resistant, often amber colored bag,
over the IV.
Stroke and Clotting Disorders

Stroke or cerebrovascular accident (CVA) is an interruption in oxygen supply to the brain. When
oxygen cannot reach parts of the brain, it takes only minutes for a patient to lose consciousness and
for tissue damage to occur.

Ischemic stroke results from blood flow obstruction.

Transient ischemic attack (TIA) is a result of a brief block in blood flow.

Hemorrhagic stroke results from a rupture in blood vessels that supplies an area of the brain.

Aneurysm is a thin-walled protrusion in an artery wall that can easily burst.

Clotting disorders involve hypercoagulation (over production of clots) and hemophilia (inability to
produce clots).

The majority of clotting disorders are linked to genetics. Other clotting disorders include von
Willebrand factor, protein C, protein S, factor V Leiden, and liver disease.

Deep-vein thrombosis (DVT) is a clot that forms in an extremity, like the lower leg or calf.

Pulmonary embolism (PE) is a clot in the lungs.

Risk factors for DVT include over 40 years of age, estrogen therapy (birth control), smoking, obesity,
surgery, trauma, prolonged immobility, hip replacement, and varicose veins.

Treatment for DVT and PE may last for 3-6 months to prevent emboli as the body dissolves the clot.

Embolus is a piece of the clot that can dislodge and travel to the heart, brain, or lungs.
Drug Regimens and Treatments for Strokes
Stroke drug therapy is aimed at prevention, with anticoagulant therapy starting after a stroke or TIA.

Treatment and prevention of unwanted clots, employs anticoagulants, antiplatelet agents, and
thrombolytics.

Patients using these therapies should be regularly monitored by laboratory tests:

o Partial thromboplastin time (PTT) – measuring the function of the intrinsic and
common pathways of the coagulation cascade.

o Prothrombin time (PT) – measuring the function of the extrinsic and common
pathways of the coagulation cascade.

o International normalized ratio (INR) – reference for coagulation involving the

extrinsic and common pathways of the coagulation cascade.
Anticoagulant Agents
Anticoagulants can be used to treat already formed blood clots, by halting growth and keeping
emboli from forming as the body reabsorbs the clot on its own.

(1) Heparin via IV is usually the first for treatment. Heparin works by inhibiting clotting factors in the
coagulation cascade and inactivating thrombin and factor Xa (activated factor X). It does not affect
an existing clot but prevents emboli from forming while the body slowly dissolves and absorbs a
clot.

Heparin is used to flush IV lines and subcutaneously as a prophylactic in patients at high risk for
developing clots. It can be used during pregnancy because it does not cross the placenta barrier.

(2) Low-molecular-weight heparin (LMWH) works similar to heparin, but affects factor Xa more than
thrombin. This product can be injected subcutaneously, with a longer half-life than heparin. LMWH is
more convenient because it can be given once or twice a day by self-injection. Preferred for pregnant
patients and are used to bridge therapy from IV heparin to oral warfarin.

(3) Warfarin (Coumadin) works by inhibiting the production of vitamin K-dependent clotting factors
in the liver. Onset is five days or more for full effect.
Side Effects and Contraindications

Heparin: bruising, bleeding due to excessive anticoagulation, and thrombocytopenia (low platelet
count). Not to be used in patients with severe thrombocytopenia or uncontrolled active bleeding.

LMWHs: bruising, bleeding due to excessive anticoagulation, fever, pain at injection site, and
thrombocytopenia.
Not to be used in patients with a history of HIT, hypersensitivity to heparin or pork products, and
active major bleeding.

Warfarin: bleeding due to excessive anticoagulation, hair loss, skin lesions, and purple/blue toe s

Cautions and Considerations:

Heparin is not to be given IM.

Dose adjustments are required in patients with impaired renal function for LMWHs and direct
thrombin inhibitors.

Warfarin interacts with many OTC and prescription medications. Warfarin is also affected by certain
foods; foods high in vitamin K (green, leafy vegetables).

Alcohol increases warfarin’s effects; moderate alcohol intake (1-2 drinks a day) does not affect
anticoagulation therapy.

Anticoagulants are considered high-risk medications.

Anticoagulant Antagonists
Anticoagulant antagonists like vitamin K and protamine are used to treat coagulation problems.

Vitamin K is used in the body to make clotting factors; it is also used to reverse warfarin effects
when signs of bleeding are present.

Protamine is used to reverse heparin effects; it works by combining with heparin to form a complex
that is no longer able to exert anticoagulant effects.

Side effects of vitamin K include flushing, changes in taste, dizziness, sweating, rapid pulse, and
difficulty breathing; pain at the injection site; administered under supervision to monitor for side
effects and signs of anaphylaxis.

There are no contraindications. Vitamin K is administered subcutaneously when possible, IM or IV if

unavoidable – though administered very slowly (1 mg a minute); it should be mixed in preservative-
free normal saline or dextrose 5% in water.

Antiplatelet Agents
Antiplatelet agents are used to decrease the risk of stroke, DVT, and clotting associated with
cardiovascular blockage. Typically administered to patients who have already had a cardiovascular
blockage in order to prevent further clotting.

Low-dose aspirin (81-325 mg/day) is used to prevent clots associated with stroke and heart attack.

Aspirin can be used during a heart attack to keep clots from completing occluding blood vessels in
the heart.
Side Effects, Contraindications & Cautions, and Considerations

Side effects include bleeding due to excessive anticoagulation, upset stomach, headache, dizziness,
and skin rash.

Aspirin should not be used in patients with hypersensitivity to other salicylates or NSAIDs; patients
with asthma, rhinitis, nasal polyps, or bleeding disorders; for treatment of viral infections in children.

Patients with active pathologic bleeding (peptic ulcer) or intracranial hemorrhage should not take
clopidogrel (Plavix)

Patients with a history of ulcers should avoid or use caution with antiplatelets; patients taking
NSAIDs should not take along with antiplatelet or anticoagulation therapy.

Complete blood count (CBC) is used to monitor drops in platelet or white blood cell count; liver
function tests are also tracked. Antiplatelets work best when taken with food.
Thrombolytic Agents
Thrombolytic agents are used to dissolve and shrink already formed clots. Use of these medications
is limited to select situations, yielding dramatic lifesaving results when administered within hours to
days of the event to be effective. These agents work through a variety of mechanisms, breaking up
clots that have already formed.

Cost and potential serious side effects must be weighed against the benefits of these medications.

Side effects include bleeding, bruising, slow heart rate, decreased blood pressure, arrhythmias, fever,
and allergic reactions.

Contraindications, Cautions & Considerations

Not to be used in patients with active bleeding or internal bleeding; a history of CVA; recent
intracranial or intraspinal surgery or trauma; intracranial neoplasm, arteriovenous malformations, or
aneurysm; known bleeding diathesis; severe uncontrolled high blood pressure; ischemic stroke
within 3 months; prior intracranial hemorrhage; suspected aortic dissection; and significant closed
head or facial trauma within the preceding 3 months.

Tenecteplase (TNKase) should not be shaken during reconstitution; it should be mixed with only
sterile water, and allowed to sit for a few minutes.

Reteplase (Retavase) must be refrigerated and protected from light.

Hemophilia Agents
These drugs replace specific missing clotting factors in patients with hemophilia, which allows the
coagulation cascade to function, restoring normal coagulation.

Hemophilia agents are injectable and include factors VIIa, VIII, and IX, as well as von Willebrand
factor.

Side effects include allergic reactions, mild chills, nausea, and irritation at the injection site;
infectious diseases can be passed on to recipients of these products.

Factor VIIa has no contraindications; Factor VIII should not be used in patients with a
hypersensitivity to the drug; Factor IX does not have contraindications.

Hemophilia agents are expensive and are dispensed from a specialty pharmacy.

Herbal and Alternative Therapies

Few herbal or dietary supplements besides iron, folic acid, and vitamin B12 are used to treat blood
disorders.

Vitamin C is often prescribed along iron supplements to boost absorption.

There are no OTC products to treat coagulation and clotting disorders.

Warfarin and antiplatelet agents interact with numerous herbal/dietary and nutritional supplements
including cranberry juice, dong quai, Feverfew, ginger, garlic, ginkgo biloba, green tea, St. John’s wort,
and vitamin E.
 The Respiratory System and Drug Therapy
Asthma
Asthma – a disease in which inflammation (irritation of the lungs) causes the patient’s airways to
tighten.

Occurring in intermittent attacks, involving reversible airway obstruction, it is precipitated by specific

triggering events that vary in severity from patient to patient. In asthma & COPD, less oxygen is
available to exchange with carbon dioxide, or the amount of surface exchange is limited. Most
commonly classified as allergic (35-55%), exercise induced, or nonallergic. More sensitive and
responds to lower doses of allergen; studies support the concept of genetic predisposition for
asthma development.

Asthma characteristics: reversible small-airway obstruction, progressive airway inflammation, and

increased airway responsiveness to a variety of endo- and exogenous stimuli. Recurrent episodes of
wheezing (a whistling respiratory sound), dyspnea (labored or difficult breathing), and cough that
have both acute (short, severe course) and chronic (persisting for a long time).

Bronchospasms – spasmodic contraction of the smooth muscle of the bronchioles, or small

airways.

Apparent failure of normal dilator muscle systems, excessive production of mucus – plugging the
airway, presence of sometimes severe long-term inflammatory reactions – may lead to patchy
shedding of the lining of small airways.
The Asthmatic Response
Cells activated by immunoglobulin E (IgE), air inhalation during exercise, cold weather, and allergens.

Activation of these cells leads to airway obstruction caused by smooth-muscle contractions,

increased secretion of mucus, and increased vascular permeability.

Asthma attacks have two phases or responses:

1. Triggered by an antigen antibody reaction; characterized by degranulation of the

mast cells, which release histamine and other mediators, resulting in immediate
bronchospasm and increased production of mucus; resulting in the release of
mediators: histamine, chemotactic factor, platelet-activating factor, brandykinin,
prostaglandins, and leukotrienes.

2. Bronchoconstriction with delayed, sustained reactions, including epithelial damage;

making airway more sensitive to further challenge, even weeks after exposure; late
response causes self-sustaining inflammation. Peak flow meter – an instrument
used to assess severity of asthma; measuring peak expiratory flow rate (PEFR).
Patient blow into the peak flow meter, and PEFR is recorded in L/min. A
measurement below 50% indicated medical alert; immediate treatment with a
bronchodilator and anti-inflammatory agent is needed.
Goals of Asthma Care and Management of the Disease
Goals of asthma care are:

Sleep well every night; go to work or school every day; free from wheezing all day; maintain
control of cough; continue with activities and exercise; tolerate medicines well.

The patient must learn to manage the disease and its complications and to limit the amount of
exposure to irritants.

Patients need to learn what triggers asthma attacks and how to control those triggers.

Avoid smoke, dust mites, and obtain a yearly flu vaccination.

Peak flow meter should be used twice a day, recording results; simple adjustments to asthma
medication based on peak flow readings helps manage asthma effectively.

Status asthmaticus – potentially life-threatening condition; begins like a normal asthma attack, but
does not respond to normal management; patients experience increasing difficulty in breathing and
exhibits blue lips and nail beds; patients may lose consciousness; this constitutes a medical
emergency, requiring prompt attention.
Asthma Drug Therapy
Drug therapy is the mainstay of asthma management, with appropriate therapy depending on the
persistence of the asthma attacks. Attacks can begin intermittent, progressing to mild-to-severe,
persistent symptoms.

Metered dose inhaler (MDI) – “puffer,” contains medication and compressed gas; delivering a
specific amount of medication with each actuation; suspending the medication in particles that are
fine enough to penetrate the deepest parts of the lungs.

Spacer – often prescribed with a MDI; recommended to decrease the amount of spray deposited on
the back of the throat and swallowed. The spacer holds the drug mist until the patient is ready to
breathe; allowing the patient to breathe the mist in a slower, more effective rate, providing better
penetration of the drug into the lungs; extremely useful for children and the elderly. Side effects are
reduced because the drug is delivered to lower portions of the lungs with fewer particles left in the
mouth and throat.

Chlorofluorocarbons (CFCs) were the propellant of MDIs; banned in the 1980s; 2008, the FDA
required all MDIs to convert to hydrofluoroalkane (HFA) as the propellant; produces a finer mist.

Dry-powder inhalers are another alternative to CFC-propelled inhalers; a pellet is placed in the inhaler,
crushed, and activated when the user inhales.
MDIs need to be primed before first use (shaken for 5 seconds); should be shaken before each use.

Steps for using an HFA MDI:

1. Remove cap and shake inhaler

2. Breathe out all the way

3. Place mouthpiece between lips

4. Press down inhaler, hold for a few seconds, then breathe slowly

5. Hold breath and count to 10

6. Breath out slowly

Steps for dry-powder inhaler:

o Activate the inhaler

o Breathe out all the way

o Put the mouthpiece to your lips and breath quickly

o Hold breath and count to 10

o Breathe out slowly

If a second puff is prescribed, wait approximately 1 minute, then start at step 1; if another inhaler is
prescribed, wait 5 minutes before using. Clean the mouthpiece after each use and rinse the mouth if
a corticosteroid is used.

Treatment should be reviewed every 3-6 months.

Nebulizer – a device in which a stream of air flows past a liquid and creates a fine mist that the
patient inhales while breathing normally through a mouthpiece or mask. Resulting in a higher
likelihood of the drug being deposited farther into the lungs; should be cleaned, because it could be a
source of bronchitis and infections.

Long-term control: cromolyn sodium, nedocromil, inhaled steroids, theophylline, long-acting beta-2
agonists, and leukotriene antagonists.

Quick relief: short-acting beta-2 agonists, systemic corticosteroids, and ipratropium.

A more aggressive initial approach has supporting evidence.

Long-term and rescue medications are needed to treat asthma and control exacerbations. Inhaled
corticosteroids are most effective medications for long-term needs; bronchodilators should be
always used first when using different medications.

Beta blockers should not be used in patients with asthma, because they can constrict bronchial
tubes.

Many asthmatics are sensitive to aspirin and other NSAIDs, penicillin, cephalosporin, and sulfa
drugs.
Bronchodilators
Bronchodilator – an agent that relaxes smooth-muscle cells of the bronchioles; airway diameter
increases, improving the movement of gases into and out of the lungs.

Albuterol inhalers, rescue inhalers, the bronchodilator of choice, used most often for acute attacks.

For a life-threatening attack, epinephrine (Epi-Pen) sub-q is used; self-administered, usually in the
thigh; side effects: alpha agonist actions - risk of angina, aortic rupture, and cerebral hemorrhage
due to vasoconstriction; beta-1 agonist – palpitation, tachycardia, and arrhythmias; beta-2 agonist –
CNS stimulation (nervousness, tremor, anxiety, nausea, vomiting), relaxation of uterine muscles, and
dry mouth.

Potential for overdependence on short-acting beta-2 agonists; more than 1 canister per month; sign
that the patient’s asthma is not be adequately controlled.

Albuterol (Proventil HFA, Ventolin HFA, ProAir HFA) – bronchodilator used in cases of airway
obstruction, such as asthma or COPD; relaxes bronchial smooth muscle by acting on pulmonary
beta-2 receptors with little effect on heart rate.

Albuterol is administered by inhalation or orally for relief of bronchospasms; duration 3-6 hours.

Proventil HFA and ProAir HFA, both albuterol inhalers, but cannot be interchanged.

Any three brands may be used if a physician writes a prescription for albuterol. Side effects include
tremor and nervousness.
Xanthine Derivatives
Xanthine derivative – structurally similar to caffeine and causes relaxation of airway smooth
muscle; leads to airway dilation and better air movement.

Theophylline – phosphodiesterase inhibitor that reverses early bronchospasm associated with

antigens or irritants; improves the contractibility of the fatigued diaphragm; used as a bronchodilator
in reversible airway obstruction due to asthma, chronic bronchitis, or emphysema; many interactions,
and blood levels can become elevated quickly; used only in lung disease unresponsive to other
drugs; can be used for the neonatal (first 4 weeks after birth) apnea and bradycardia.

Leukotriene Inhibitors
Metabolized from arachidonic acid – responsible for forming prostaglandins; increase accumulation
of mucus and fluid in the spaces between cells; increase vascular permeability, permitting substance
to pass through the blood vessels; 100 – 1,000 times more potent than histamine.

Leukotriene inhibitor – blocks either the synthesis of, or the body’s inflammatory response to
leukotrienes; blocks tissue inflammatory responses.

Montelukast (Singulair) – indicated for prophylaxis and chronic treatment of asthma; shown to
reduce incidence of daytime asthma and nocturnal awakenings due to asthma attacks; can
decrease the need for beta-adrenergic agonists; should not be used to treat acute attacks. It can be
prescribed for use in children over 12 months; once a day dosing; common side effect is headache;
approved to treat seasonal allergic rhinitis (inflammation of the nasal membrane); asthma and hay
fever are treated with the same dose.
Corticosteroids
Corticosteriods – resemble certain chemicals naturally produced by the adrenal gland; they inhibit
inflammatory cells by stimulating adenylate cyclase; acting as an anti-inflammatory agent to
suppress the immune system; inhaled corticosteroids may be successful when other drugs are not.

Persons with asthma don’t use inhaled corticosteroids because of potential side effects. Primary
side effects of inhaled corticosteroids is oral candidiasis (thrush), irritation and burning of the nasal
mucosa, hoarseness, and dry mouth – possibly leading to coughing episodes. Patients should be
advised to rinse the mouth after the use of corticosteroid inhaler.

Corticosteroids taken orally for long periods in a dose exceeding 10mg/day, can cause growth of
facial hair in females, breast development in males, “buffalo hump,” “moon face,” edema, weight
gain, and easy bruising.

Corticosteroids may stunt a child’s growth; inhaled steroids do not affect long-term growth in kids –
possible slowdown of ½ an inch in the first year, but eventually children grow to normal adult
height. Controlling asthma is more important to achieving normal growth and development.

Patient should use the lowest effective dose; beta-2 agonist, such as salmeterol (Servent) should be
added to inhaled corticosteroids if needed to decrease the steroid dose necessary for control.

Beta-2 agonist help to open the airway, allowing more of the inhaled steroid to reach the site of
action in the lungs.

Steroids include: prednisone (Deltasone), hydrocortisone (Solu-Cortef), methylprednisolone (Medrol

Dose Pack, Solu-Medrol), dexamethasone (Decadron), prednisolone (Orapred, Pediapred),
triamcinolone (Azmacort, Nasacort AQ), and flunisolide (AeroBid).
Mast cell stabilizer – protects mast cell membranes from rupture cause by antigenic substances;
resulting in less histamine, leukotrienes, and prostaglandins released in airway tissue.

Monoclonal antibody – an antibody produced in a laboratory from an isolated specific lymphocyte

that produces a pure antibody against a known specific agent.

Combination Drugs
Pairing a short-acting drug with a long-acting drug; designed for maintenance therapy and work
better than monotherapy to decrease exacerbations and control symptoms; efficacy is similar to
using the two drugs separately.

(1) Budesonide-formoterol (Symbicort) – maintenance therapy for asthma; approved for acute
symptoms in Canada but not the U.S.; the inhaler must be primed, and patients are directed to take
two puffs twice daily, rinsing mouth afterwards.

(2)Fluticasone-salmeterol (Advair Diskus) – anti-inflammatory and beta-2 adrenergic agonist used

for maintenance treatment of asthma and COPD; for patients older than 12; a powder for inhalation;
fluticasone – corticosteroid, potent vasoconstrictor and anti-inflammatory; salmeterol – relaxes
bronchial smooth muscle with little effect on heart rate; the drugs work synergistically to improve
pulmonary function, more than either alone; should not be used with a spacer.
COPD and Other Lung Diseases
Chronic Obstructive Pulmonary Disorder (COPD)

Chronic obstructive pulmonary disorder (COPD) – encompasses emphysema and chronic

bronchitis.

Emphysema – destruction of the tiny alveoli, or air sacs, on the lungs resulting in air accumulation in
tissues and organs; air spaces distal (farther away from) to the terminal bronchioles are enlarged;
inflammation destroys these air sacs, losing their ability to expand and contract as well as pass
oxygen into the blood and remove carbon dioxide.

Early stages include shortness of breath only after heavy exercise; as the disease progresses,
walking even a short distance can cause the patient to gasp for air.
Patients with emphysema have tachypnea – very rapid respiration, giving them a flushed
appearance.
Risk factors are cigarette smoking, occupational exposure, air pollution, and genetic factors.

Bronchitis – the lining of the bronchial airways becomes inflamed, causing the patient to experience
obstruction of air flow on expiration. It is characterized by a cough that produces sputum (phlegm)
that may be purulent (contain pus), green, or blood streaked.

Acute bronchitis may be caused by infection, usually viral; runs a brief course, with the aid of
antibiotics, generally not to return.

Chronic bronchitis is a serious disease, defined as excessive production of tracheobronchial mucus

sufficient to cause cough with expectoration of at least 30 mL of sputum/ 24 hours for 3 months of
the year for more than 2 years, consecutive.

Patients are typically overweight, have a barrel chest, and retain carbon dioxide; most have morning
cough resulting from irritation to the lungs. Contributing factors include cigarette smoking; exposure
to occupational dust, fumes, and environmental pollution; and bacterial infection.
Drug Treatments of COPD
The lungs’ defense system:

o Ciliary carpet

o Goble cells

o Clara cells

o Epithelial cells

o Type I pneumocytes

o Type II pneumocytes

Pharmacological treatment for emphysema and chronic bronchitis is similar. Pharmacological

management of emphysema and bronchitis is still largely empirical, with methylxanthines,
coriticosteroids, beta agonists, and ipratropium forming the foundation. Oxygen administration and
physiotherapy are important in treating both lung diseases.

Antibiotic therapy is sometimes necessary if sputum changes from yellow to green or a fever is
present.

Expectorants are sometimes used, stimulating irritation and coughing; water is the expectorant of
choice, drinking large amounts of water helps to break up mucus and enables the patient to cough
up secretions.

COPD patients should be encouraged to get annual flu and pneumonia vaccines.
Other Lung Diseases
Measures can be taken to prevent and control lung disease, not smoking, avoiding secondhand
smoke and air pollution. The flu and pneumococcal pneumonia can be prevented with vaccination.
Most infections occur when people come in contact with fluids, sneezes, and coughs that contain
bacteria, viruses, or fungi. Hand contact is the most frequent cause in respiratory infections.
Frequent hand washing and avoiding close contact with an infected host are some of the best
defenses.

Pneumonia
Pneumonia – common lung infection, affecting persons of all ages.

Microorganisms that cause pneumonia gain access to the lower respiratory tract by one of the
following routes:

o Inhalation as aerosolized particles

o Entry through the blood stream

o Aspiration in oropharyngeal contents

Aspiration – involves inhalation of fluids from the mouth and throat, common occurrence during
sleep by both healthy and ill persons; the major way by which pulmonary pathogens gain access to
the normally sterile lower airways and alveoli. Treated with antibiotics, depending on the causative
organism.
Cyctic Fibrosis
Cystic fibrosis (CF) – hereditary disease that involves the GI and pulmonary systems; a fatal
disease, but some patients survive into early adulthood.

Disorders in the pulmonary system are associated with morbidity and mortality; GI system is
increased viscosity of secreted mucus, causing bile duct blockage, and a relative deficiency of
pancreatic digestive enzymes. Patients experience hypoxia (lack of adequate oxygen), and resultant
cyanosis and digital clubbing (enlarged fingertips with loss of normal angle at the nailbed).

Respiratory status is cyclical, moving from a state of relative well-being to one of acute pulmonary
deterioration.

Management of the pulmonary aspect is broken down into two areas: respiratory therapy and
antibiotic therapy.

Percussion – a tapping movement to induce cough and expectoration of sputum from the lungs, is
the cornerstone of respiratory therapy. Usually proceeded by nebulizer therapy, during which sterile
water or normal saline is breathed to liquefy pulmonary secretions; bronchodilators or acetylcysteine
may be added to prevent bronchospasm and further liquefy the secretions.

Oral Mucomyst has an unpleasant taste and odor, and many patients prefer not to use it.

Asthmatic bronchodilators is appropriate for CF; theophylline may benefit, however theophylline
clearance in CF patients may differ from asthmatics. Acetylcholine and dornase alfa are most
commonly used agents for CF.

Patients with CF should get annual flu shots. Pulmonary exacerbations can be treated with
antibiotics, though this is controversial because microorganisms may develop resistance to the
antibiotic.
Respiratory Distress Syndrome
Respiratory distress syndrome (RDS) – occurs in newborns during the first few hours of life. It is
characterized by inadequate production of pulmonary surfactant – a fluid that, like a soap bubble,
lowers the surface tension between the air and alveoli surfaces; lack of surfactant leads to collapse
of the alveoli along with acute asphyxia with hypoxia and acidosis. Two known causes of RDS is
prematurity and diabetes.

If RDS occurs, a replacement surfactant is administered.

Tuberculosis
Tuberculosis (TB) – caused by the bacterium Mycobacterium tuberculosis; commonly affects the
lungs, but can infect other body tissues and organs.

TB is transmitted by inhaling respiratory droplets; droplets are produced by TB infected persons in

cough, sneeze, speak, kiss, or spit; suspended in the air, the droplets descend under the influence of
gravity at a rate of 1-2 inches/hour. The bacterium spreads throughout the body in the bloodstream
and in lymphatic fluids; the bacterium thrives in areas of high oxygen (lung, bone and kidney
tissue). Seen primarily in alcoholics, prison population, immunocompromised, and the elderly.

Two groups of TB patients are recognized:

1. Exposed but no disease.

2. Exposed and having active organism.

TB test is purified protein derivative (PPD) from killed bacteria; injected intradermally; persons who
have been exposed or have the disease show a circular area of hardened tissue (induration) at the
injection site within 48-72 hours; a patient should have a chest X-ray if the reading is positive, to
check for lung shadow.

TB develops slowly and may take as long as 20 years to develop from time of exposure; highest
incidence of infection occurs 1-2 years after exposure. Patients have a continued risk of reactivity all
their life; the organism can remain dormant for years, until the immune system is depressed, then it
will reemerge as an active infection.

TB therapy goals are to initiate treatment promptly, convert the sputum culture from positive to
negative, achieve cure without relapse, and prevent emergence of drug-resistant strains. Primary
agents are isoniazid (INH), rifampin - highly effective when used in combination, ethambutol,
streptomycin – recommended as a third drug because it can be injected twice weekly, and
pyrazinamide. Treatment depends on symptoms.

MDR-TB, multidrug-resistant tuberculosis, a new strain of M. tuberculosis that is highly resistant to

currently used drugs, and is difficult to treat. Successful treatment may last 18-24 months.

First line therapy includes capreomycin and cycloserine; patients are given isoniazid, however if
resistance develops they are given rifampin. For resistance to both these agents the following
combinations are recommended: pyrazinamide + ethambutol (Myambutol); pyrazinamide +
ciprofloxacin (Cipro) or ofloxacin (Floxin).

Compliance is a major problem in treating TB. Patients being treated for TB should avoid alcohol.
Histoplasmosis
Histoplasmosis – caused by a fungus that most commonly occurs in accumulated droppings from
chickens, pigeons, starlings, and other birds, and bats. The fungus, when inhaled, spores are
transported to the bronchial tubes; lymph tissue reacts and sensitivity develops and tissue becomes
inflamed. Most prevalent in the valleys of the Missouri and Ohio Rivers.

Often referred to as the summer flu, producing flu-like symptoms; with most patients recovering on
their own.

Serious if only high levels of fungi are present, however in the disseminated form, it can be fatal
without treatment

Amphotericin B and itraconazole appear to be the only effective drugs for the disseminated form.

Surgery may be indicated.

Cough, Cold, and Allergy
The common cold - a mild self-limited viral infection, is the most prevalent form of respiratory tract
infection.

Symptoms can include mild malaise, rhinorrhea (runny nose), sneezing, scratchy throat, and fever.

Bacterial sinusitis and otitis media are frequent complications and may require antimicrobial
therapy; antibiotics and antivirals are sometimes used. Viruses are the most common cause of
respiratory infections.

Allergy symptoms are the same as colds – runny nose and itchy eyes – sometimes mistaken for a
cold. Allergies are a result of hypersensitivity induced by exposure to a particular antigen. Colds and
allergies may be treated with the same medications. People often seek self-treatment to alleviate
symptoms and to prevent complications associated with colds.

The common cold and cough are treated with four groups of drugs, either together or individually:
antitussives, expectorants, decongestants, and antihistamines. Because most of these drugs are
OTCs, technicians can assist patients, putting their drug knowledge to use. Technicians cannot
make recommendations, but can make the patient aware of the proper uses and side effects of
these drugs. Tavist (clemastine), an antihistamine, is the only drug approved by the FDA for the
treatment of colds.

Colds are transmitted (1) directly and (2) indirectly. Colds can be avoided, for the most part, if simple
precautions are taken.
Antitussives

Coughing is a mechanism for clearing the airways; intense, frequent coughing with lack of sputum,
can be annoying. Antitussive is an agent that suppresses coughing and is indicated when cough
frequency needs to be reduced, especially when the cough is dry and unproductive.

Narcotic and non-narcotic antitussives affect intensity and frequency of cough depending on the
principal site of action: (1) CNS depression of the cough center in the medulla (cough reflex) or (2)
suppression of the nerve receptors in the respiratory tract.

Cough reflex involves two receptors, when stimulated can initiate events that lead to a cough:

o Stretch receptor – elongation of muscle.

o Irritant receptor – course particles and chemicals.

Antitussives are formulated to work on one or more events, helping to stop the cough reflex.
Different antitussives:
(1) Codeine – “gold standard” of antitussive therapy; average adult dose is 15 mg every 4-6
hours. On its own codeine is C-II, but in combination with other drugs can have other control
schedules. It is a CNS depressant, not to be combined with other CNS depressants like
alcohol. Most common side effects are nausea, drowsiness, lightheadedness, and constipation;
should be taken with food to decrease upset stomach.

Codeine has the possibility for dependency, even when used at the recommended dose; however,
because of frequent misuse, stringent controls have been enacted regarding its dispensing.

In some states, codeine containing cough syrups can be purchased without a prescription, but it
must be signed for, by an adult with identification. These products can only be dispensed by the
pharmacist, because the pharmacist is required to sign their name by the patient’s signature.

(2) Diphenhydramine (Benadryl) – antitussive and antihistamine; usual adult dose 25mg every 4
hours; main side effect is drowsiness.

(3) Benzonatate (Tessalon) – used for nonproductive cough; local anesthetic on stretch receptors in
the airway, lungs, and pleura (membrane that lines the thoracic cavity); does not affect the
respiratory center; capsules should not be chewed – results are unpleasant effect with pronounced
salivation; fluid intake is encouraged to liquefy sputum; main side effects are sedation, headache,
and dizziness.

(4) Dextromethorphan (Delsym) – equivalent to codeine, without its analgesic properties, and does
not depress respiration; acts on the same receptors as codeine; nonopioid derivative of morphine;
acts on the cough center to suppress the cough reflex; average adult dose is 10-20 mg every 4
hours; interacts with MAOIs; consumption of large quantities can cause hallucinations, “robo-
tripping;” purchasers must provide proof they are over the age of 18, because of the potential for
misuse.
Expectorants
Expectorants – enable the patient to rid the lungs and airway of mucus when coughing; decreasing
the thickness and viscosity (stickiness) of mucus so a cough will eject mucus and other fluids from
the bronchi – a productive cough; also used for dry, and unproductive coughs. For a well hydrated
patient, coughing up mucus is not a problem; fluid intake and adequate humidity are important to
liquefy mucus in the respiratory tract.

Guaifenesin – OTC expectorant; available in caplet, capsule, liquid, syrup, tablet (Mucinex), and
sustained-release forms; often combined with other drugs; derived from tree bark extract; loosens
phlegm (mucus) and thins bronchial secretions, making coughs more productive; side effects
include vomiting, nausea, GI upset, and drowsiness.
Decongestants
Swelling and stuffiness is a result of fluids leaking into these tissues due to vasodilation of blood
vessels in the nasal mucosa. Decongestant stimulates alpha-adrenergic receptors of the vascular
smooth muscle, constricting the dilated arteriolar network within the nasal mucosa; constriction
shrinks the engorged mucus membranes, promoting draining, improving nasal ventilation, and
relieving the feeling of stuffiness; also permitting the sinus cavity to drain. Topical agents have more
immediate effects, but are short-acting to systemic agents. Sympathetic nervous system
stimulation, increased heart rate and blood pressure, and heightened CNS stimulation can occur with
the use of decongestants.

Often combined with antihistamines to offset the drowsiness caused by antihistamines, most are
available OTC.

Following directions regarding frequency and duration of use is very important. Topical nasal
application of these drugs over long periods of time is often followed by rhinitis medicamentosa;
duration of therapy should be limited to 3-5 days
Therapeutic Use of Decongestants
Used for temporary symptomatic relief of nasal congestion due to the common cold, upper
respiratory allergies, and sinusitis.

Promoting nasal drainage, and is useful in providing vascular constriction of blood vessels in the
nasal mucosa.
Constriction of vessels allows excess tissue fluids to be carried away in circulation, reducing
swelling, opening airways, and allowing the patient to breathe.

Side Effects and Issues dispensing Decongestants

Patients taking other sympathomimetic drugs should not take decongestants. They should also be
avoided for the following conditions: Diabetes, heart disease, uncontrolled hypertension,
hyperthyroidism, prostatic hypertrophy, Tourette syndrome.

Pseudoephedrine (Sudafed) – most used and most effective decongestant; may be combined with
many other drugs; if hypertension is controlled, pseudoephedrine is not contraindicated; works best
when combined with an antihistamine; strong abuse potential, can be made into methamphetamine;
limitations exist on how much a consumer may purchase at one time.

Phenylephrine (Sudafed PE) – used over the counter to treat symptoms of cold and allergies and
itchy, watery eyes; replaced pseudoephedrine because it cannot be made into methamphetamine;
significantly less effective than pseudoephedrine; works well in combination with an antihistamine;
used extensively IV to treat hypotension because of arterial vasoconstriction; also used in eye drops
– allergy treatments, and nasal sprays – no longer than 3 days in a row
Antihistamines
Histamine is found in all body tissue; inducing capillary dilation and increasing capillary permeability,
both help to decrease blood pressure; contracts smooth muscle, increases gastric activity, increases
heart rate, and mediates hypersensitivity. Antihistamines block H1 receptors in the upper respiratory
system; H2 blockers, affect cells in the gastrointestinal tract. Antihistamines are well absorbed and
widely distributed across the blood-brain barrier and placenta; sedation occurs when the drug
penetrates the blood-brain barrier.

Pregnant mothers are warned against the use of antihistamines; possible adverse effects to the
fetus.

Therapeutic Uses of Antihistamines

H1 blockers provide symptomatic relief by acting on the H1 receptors to prevent histamine binding.

Antihistamines also:

o Treatment of allergies & rashes, insomnia, symptomatic relief of urticarial lesions

(rash), edema, and hay fever, control of cough, alleviation of vertigo

o Alleviation of nausea and vomiting, relief of serum sickness, control of venom

reactions, mitigation of extrapyramidal side effects of antipsychotics

o Prophylaxis for certain drug reactions & for certain drug allergies

Can be used in the treatment of hypersensitive reactions. Promethazine (Phenergan) and meclizine
(Antivert) are antihistamines used most frequently for nausea and motion sickness.
The side effects are the same with a wide range of varying degree between the different drugs. More
useful in prevention of some allergic reactions than in reversing actions once they have taken place.

2nd generation antihistamines produce less drowsiness, this includes: cetirizine, clemastine,
desloratidine, fexofenadine, levocetirizine, and loratidine.

Cetirizine and levocetirizine lean more towards sedation than other 2nd generations. Levocetirizine
(Xyzal) is promoted for faster-onset and longer-acting than the other drugs; first-line for itching and
rashes; approved for allergies.

Side Effects and Dispensing Issues of Antihistamines

Most common side effects include anticholinergic responses, hyperactivity (children), sedation –
effect is synergistic with alcohol use, and dizziness. Anticholinergic responses include atropine-like
dry mouth, drying of the mucosa of the upper respiratory tract, blurred vision, constipation and
urinary retention.

Some antihistamines are prescribed for sleep induction; almost every OTC sleeping pill contains
diphenhydramine.

Very versatile drugs, used for many different reasons; some better than others.
 o Azelstine (Astelin, Optivar): seasonal allergies

o Brompheniramine: runny noses

o Cetirizine (Zyrtec): allergies

o Chlorpheniramine: upper respiratory symptoms

o Clemastine (Tavist): common cold

o Desloratadine (Clarinex): allergies

o Diphenhydramine (Benadryl): allergic reactions & sleep promotion

o Fexofenadine (Allegra): allergies

o Levocetirizine (Xyzal): rashes & itching

o Loratadine (Claritin): allergies

o Meclizine (Antivert): motion sickness

o Olopatadine (Pataday, Patanase, Patanol): allergic rhinitis

Fexofenadine (Allegra) – not as sedating; no arrhythmias reported or other serious reactions.

Loratadine (Claritin) – OTC since 2002; Desloratadine (Clarinex) does require a prescription.
Desloratadine is a long-acting metabolite of loratadine, with additional anti-inflammatory properties;
should not be given with erythromycin or ketoconazole.

Olopatadine (Pataday, Patanase, Patanol) – antihistamine spray for allergic rhinitis in patients 6 and
older; comes in nasal and ophthalmic forms; should be used as rescue therapy for allergy
symptoms; can cause bitter taste and sleepiness.
Nasal Corticosteroids

Nasel corticosteroids are used to treat allergies; used daily for maximum benefit. It can cause nasal
irritation and bleeding; directed away from the septum to avoid this. Local infections, Candida
albicans, may occur in patients using nasal steroids long-term.

Most effective monotherapy for allergic rhinitis; some value in the treatment of otitis media
(earaches) in children.

Most Commonly Prescribed Nasal Corticosteroids:

o Flonase (fluticasone) OTC

o Nasacort (triamcinolone) OTC

Fluticasone is in two forms Veramyst – stronger binding affinity than Flonase (OTC), and the device
is easier to use.

Mometasone (Nasonex) – depresses the release of endogenous chemical mediators (kinin,

histamine, and prostaglandins) of inflammation; reverses dilation and permeability of vessels in the
area and decreases access to cells to the site of injury; may be used in children over the age of 12 to
prevent symptoms of allergic rhinitis.
Smoking Cessation

Smokers live approximately 15 years less than non-smokers. Cigarette smoke contains more than
4,000 identified chemical compounds, 43 are known carcinogens.

Lung cancer, leukemia, cancers of the mouth, larynx, pharynx, esophagus, pancreas, cervix, kidney,
and bladder are associated with smoking; link with ovarian, uterine, and prostate cancers. Tobacco
is the single largest cause of preventable death. It increases the risk of heart disease, COPD, and
stroke; acute risks include shortness of breath, aggravation of asthma, impotence, infertility, and
increased serum carbon monoxide concentration.

Secondhand (environmental) smoke poses substantial health threat because it contains all the
carcinogens and toxins in inhaled cigarette smoke. Children in a household with smokers have a
higher risk of respiratory infections, asthma, and middle-ear infections; birth defects may be related
to smoking while pregnant.

Smoking cessation has physical benefits of a longer life and better health.
Nicotine – the addictive component of tobacco, is readily absorbed in the lungs from inhaled smoke;
from smokeless tobacco, chewing tobacco and snuff, is absorbed across the oral or nasal
mucosa. Nicotine is extensively metabolized in the liver and to a lesser extent in the kidneys and
lungs.

Cotinine – a urinary metabolite, has a longer half-life (15-20 hours) and a tenfold higher
concentration than nicotine.
Nicotine and polycyclic aromatic hydrocarbons induce production of hepatic (liver) enzymes
responsible for metabolizing caffeine, theophylline, imipramine, and other drugs.

Increasing plasma cortisol and catecholamine concentrations, affecting treatment with adrenergic
agonist and adrenergic-blocking agents. Nicotine is a ganglionic cholinergic-receptor agonist.

Pharmacological effects include central and peripheral nervous system stimulation and depression,
respiratory stimulation, skeletal muscle relaxation, catecholamine release by the adrenal medulla,
peripheral vasoconstriction, and increase in blood pressure, heart rate, cardiac output, and oxygen
consumption.

Chronic ingestion leads to physical and psychological dependence. Smoking cessation leads to
withdrawal symptoms, usually within 24 hours.
Planning to Stop Smoking

Nicotine has behavior reinforcing properties, including relaxation, increased alertness, decreased
fatigue, improved cognitive performance, and “reward” effect (pleasure or euphoria).

Smoking cessation treatment involves three main elements: training in general problem-solving
skills, social support from the clinician, and nicotine replacement therapy – recommended as first-
line pharmacotherapy.

Nicotine replacement therapy is not a substitute for behavior modification and success is the
greatest when two modes of therapy are used concomitantly.

Counseling, individual or group, is highly recommended.

Total abstinence is the key to smoking cessation; rewards should be given for abstaining and
avoiding situations that serve as smoking triggers. Reduced alcohol consumption or abstinence is
suggested during the quitting process.

Smokers have a fear of weight gain as they quit; weight gain does occur, however it is less than 10
lbs.; weight gain is caused by increased caloric intake and metabolic adjustments; it can happen
even if caloric intake doesn’t change or is restricted.
Smoking Cessation Drug Therapy

Patients who continue to smoke when initiating nicotine replacement therapy, may show signs of
nicotine excess.

Symptoms of Nicotine Excess:

o Overlap with withdrawal symptoms; dizziness, perspiration, anxiety, depression, and

irritability

Nicotine nasal spray and inhalant (Nicotrol), varenicline (Chantix), and buproprion (Wellbutrin SR,
Zyban) are not approved for OTC drug use. The nasal spray mimics the effects of cigarette smoking
more closely than transdermal or chewing gum. Nasal spray adverse effects include nasal irritation,
runny nose, throat irritation, watering eyes, sneezing, and cough; regular use during the first week
may help patients adapt to these effects.

Nicotine lozenge is based on “time” of the first cigarette, rather than number per day; should not be
chewed; full dose released as it is sucked on, dissolving completely; daily cost is the same to a pack
of cigarettes.

Nicotine gum is recommended for smokeless tobacco users; adverse effects include mouth
soreness, hiccups, dyspepsia, and jaw ache.

Transdermal nicotine doubles abstinence rates at 6-12 months after initiation of therapy; apply to a
clean, dry, hair-free site on the upper body or outer arm; rotation of application site may prevent skin
reactions.
The key points from this module are:

Cardiovascular system – heart and blood vessels, circulates blood through the body, bringing
oxygen and nutrients to tissues, carrying away carbon dioxide and toxic by-products. Cardiac muscle
fibers make up the hearts four chambers: right and left atria and right and left ventricles. The atria
receive blood brought into the heart, the ventricles push blood out.

Blood pressure is the force of blood that fills the circulatory system. Hypertension (HTN), or high
blood pressure can cause damage to vital organs such as the heart, kidneys, eyes, and brain.

Heart failure is characterized by weakness, fatigue, severe fluid retention, and difficulty breathing
due to pulmonary edema.

High blood pressure and coronary blockage, over time, can cause the heart to no longer work
properly, resulting in enlargement and weakening. With the heart unable to pump sufficiently vital
organs will shut down due to lack of blood supply. Lowering cholesterol levels has been found to
significantly reduce the risk of a heart attack. Hyperlipidemia drugs are either used to prevent a first
heart attack or subsequent heart attacks. A finger-stick test can test for lipids.

Blood serves several functions, supplying the cells of the body with oxygen and nutrients, carrying
hormones and enzymes that control bodily functions and regulating body temperature. Blood is cells
suspended in plasma. Plasma contains water, protein (albumin and immunoglobulins), and a variety
of dissolved substances.

Blood type is determined by specific antigen proteins on the surface of red blood cells. Blood types
are categorized as A, B, AB, and O.
Anemia is a chronic illness characterized by lower-than-normal number of health red blood cells that
contain functional hemoglobin in the blood. Anemia can be caused by inadequate production of red
blood cells, rapid destruction of red blood cells, or blood loss. Iron, folic acid (folate), and vitamin
B12 are supplements used to treat anemia caused by nutrient deficiency.

Asthma is a disease in which inflammation (irritation of the lungs) causes the patient’s airways to
tighten. Occurring in intermittent attacks, involving reversible airway obstruction, it is precipitated by
specific triggering events that varying in severity from patient to patient. Nebulizer is a device in
which a stream of air flows past a liquid and creates a fine mist that the patient inhales while
breathing normally through a mouthpiece or mask.

The common cold - a mild self-limited viral infection, is the most prevalent form of respiratory tract
infection. Symptoms can include mild malaise, rhinorrhea (runny nose), sneezing, scratchy throat,
and fever. The common cold and cough are treated with four groups of drugs, either together or
individually: antitussives, expectorants, decongestants, and antihistamines. Because most of these
drugs are OTCs, technicians can assist patients, putting their drug knowledge to use.

Smokers live approximately 15 years less than non-smokers. Cigarette smoke contains more than
4,000 identified chemical compounds, 43 are known carcinogens. Secondhand (environmental)
smoke poses substantial health threat because it contains all the carcinogens and toxins in inhaled
cigarette smoke. Total abstinence is the key to smoking cessation; rewards should be given for
abstaining and avoiding situations that serve as smoking triggers.
Anatomy and Physiology of the GI System

Gastrointestinal (GI) system is the system of organs that processes food and liquids.

Digestion – breakdown of large food molecules to smaller ones.

Absorption – uptake of essential nutrients into the bloodstream.

GI tract also known as the alimentary tract includes:

o Mouth

o Esophagus

o Stomach

o Small intestine

o Colon

o Rectum
Digestive Process in the Upper GI System
Food is propelled via the esophagus to the stomach.

Peristalsis – process of coordinated muscle contraction; moving food particles through the GI tract.

Gastrin – a hormone that stimulates acid secretion is released when the walls of the stomach
stretch in response to food; stimulates the release of histamine.

Parietal cells – line the walls of the stomach; produce acid from proton pumps.

pH – scale of acidity.

A low pH helps digestion of food particles, protects the stomach, killing a majority of bacteria that
are ingested, and is critical for absorption of certain drugs.

Digestive Process in the Lower GI System

Small intestine – where most digestion and nutrient absorption occurs.

GI motility – movement of food through the intestines.

Increased GI motility can result in diarrhea; decreased GI motility can result in constipation.

Large intestine includes: ascending colon, transverse colon, descending colon, and sigmoid colon.

The GI tract absorbs all carbohydrates, fats, and proteins; non-absorbable substances, like fiber and
bacteria, remain as waste material – stool.

Waste material exits the body through the rectum and anus via defecation – bowel movement.
Common GI System Disorders

Diarrhea – excessive (greater than 250 g or larger number of bowel movements), soft, or watery
stools.

Acute diarrhea is a common condition that can be caused by infections such as traveler’s
diarrhea and food poisoning.

Common causes of diarrhea include: Salmonella, Escherichia coli (E. coli), Giardia, and Norovirus.

Chronic diarrhea can be caused by irritable bowel syndrome (IBS), ulcerative colitis, or Crohn’s
disease.

Drug Regimens and Treatments

Antidiarrheal medications – slow the transit of food through the GI tract or decrease secretions into
it, reducing stool volume and makes stool less watery.

These medications help to relieve symptoms of diarrhea, not the underlying cause.

Opiate derivatives – poorly absorbed and do not reach the brain in high concentrations; they work by
inhibiting peristalsis and slowing the progression of food through the GI tract; they also reduce the
liquid content of stool.

Loperamide (Imodium) – OTC; side effects – dizziness and constipation; avoid in children under 2
years and patients with abdominal pain without diarrhea.

Diphenoxylate/atropine (Lomotil) – C-V; side effects – dizziness and drowsiness; blurred vision, dry
mouth, and difficulty urinating. It is contraindicated in children under 2 years, patients with
obstructive jaundice and diarrhea associated with pseudomembranous enterocolitis or enterotoxin-
producing bacteria. It has potential for abuse; caution while driving.
Bismuth Subsalicylate
Bismuth subsalicylate (Pepto-Bismol) can be used to treat acute diarrhea. It has both antibacterial
and antisecretory action; beneficial in the treatment of Helicobacter pylori (H. pylori) infection and
traveler’s diarrhea.

May be used in small children, but may require specialized doses.

Side effects include constipation, nausea, vomiting, and darkening of the tongue and/or stools; rare
is tinnitus (ringing in the ears), confusion, and weakness.

Should not be used in patients with a history of severe GI bleeding or coagulation problems; patients
with an aspirin hypersensitivity should avoid because it may trigger an allergic-like reaction.

Tongue and stools may darken; if patients experience confusion, dizziness, or vision changes
bismuth subsalicylate should be stopped; may decrease the effectiveness of tetracycline antibiotics.

Children and adolescents are at risk of Reye syndrome, a potentially life-threatening disorder caused
by salicylate use for viral infections.
Constipation
Constipation – the opposite of diarrhea; infrequent bowel movements, small stool size, hard stools,
or the feeling of incomplete bowel evacuation.

Constipation could be related to a diet low in fiber or fluid intake; certain foods or drugs; and stress.

Drug Regimens and Treatments

Dietary and lifestyle changes should accompany treatment of constipation.

Adequate intake of fiber – fruits, vegetables, and cereals – and regular exercise.

Laxatives – are used to relieve constipation, only as needed on a short-term basis. Laxatives are
available in oral forms, as well as suppositories and enemas.

A suppository is useful for patients in a hospital setting who are unable to swallow oral laxatives.

Enemas are liquid solutions delivered directly to the rectum.

Types of Laxatives
(1)Bulk-forming laxatives can be used to treat mild constipation. They are poorly absorbed and
remain in the GI tract, drawing water and other electrolytes into the GI system. They work best to
prevent constipation rather than acute treatment.

Side effects include obstruction of the esophagus or bowels.

Contraindicated in patients with impaired intestinal motility and intestinal stenosis.

Bulk-forming laxatives should be used with caution in patients with esophageal strictures, ulcers,
intestinal adhesions, or difficulty swallowing; patients should separate doses of laxatives with other
medications by at least 2 hours to ensure proper absorption.

(2)Emollient laxatives (stool softeners) are used for patients at risk of becoming constipated; taken
typically on a regular or daily basis. Stool softeners work by increasing water and electrolyte
secretions in the GI tract, making stools softer and easier to pass.

Side effects include throat irritation, abdominal pain, diarrhea, and intestinal obstruction.

Docusate (Colace) is contraindicated in patients with intestinal obstruction, acute abdominal pain,
nausea, or vomiting; should not be used at the same time as mineral oil.

The syrup has a bitter taste; taking with milk or juice can mask the taste.

Drink plenty of fluids to enhance the effect; long-term use can lead to electrolyte imbalance.

(3)Stimulant laxatives treat acute constipation, by stimulating parasympathetic neurons that control
bowel muscles, enhancing peristalsis and GI motility. Taken only as needed on a short-term basis.

Commonly prescribed to treat opiate induced constipation.

Side effects include mild abdominal pain, nausea, vomiting, and rectal burning; best taken at
bedtime; serious electrolyte abnormalities are rare.

Bisacodyl is contraindicated in patients with abdominal pain or obstruction, nausea, or vomiting.

Senna should be avoided in patients with intestinal obstruction, acute intestinal inflammation, colitis,
ulcerative colitis, appendicitis, and abdominal pain of unknown origin.
Bisacodyl should be taken with a full glass of water on an empty stomach; dairy products and
antacids can decrease the effects.

Bowel evacuation may be required prior to surgery or a diagnostic procedure; for clearing poisons or
parasitic worms from the GI tract and for treating bowel impaction.

(4)Bowel preparation (“prep”) laxatives work by drawing water and electrolytes into the GI tract.

Magnesium citrate and sodium phosphate are available OTC.

Polyethylene glycol (MiraLax) is available OTC and by prescription (GlycoLax, GoLytely).

Side effects include abdominal pain, diarrhea, and electrolyte loss or imbalance.

Polyethylene can cause anal irritation, bloating, nausea, and vomiting.

Sodium phosphate has contraindications based on its route of administration; magnesium citrate
and polyethylene glycol have no contraindications.

Patients with congestive heart failure should use caution with products that contain magnesium or
sodium; caution should be used for patients with kidney problems and children under 2 years.

(5) Misc Laxatives

Milk of magnesia an OTC item used for mild constipation.

Glycerin suppositories are used in children with occasional constipation.

Lactulose used for patients with ammonia toxicity and delirium in end-stage liver failure; pulling
ammonia from the bloodstream to the GI tract, where diarrhea is stimulated to eliminate the
ammonia rapidly.
Heartburn and Ulcers

Gastroesophageal reflux disease (GERD) aka heartburn is a common patient complaint.

An estimated 10% of the people in the U.S. get heartburn every week. It is characterized by a burning
or sensation of warmth starting in the gut or chest that may radiate to the neck. The lower
esophageal sphincter allows stomach contents to move up into the esophagus, where acidic juices
can cause tissue damage and pain.

Chronic exposure to acid can change to cells of the esophageal lining; these changes have been
linked to narrowing of the esophagus (esophageal stricture) and esophageal cancers.

Long-term treatment involves reducing the acidity of the stomach contents to limit damage to the
esophagus.

Ulcers occur when the lining of the GI tract is worn away and bleeding occurs.

They are patches of dead tissue along the walls of the GI tract.

H. pylori is the most common cause of peptic ulcer disease (PUD), or ulcers in the stomach.

H. pylori is a spiral-shaped, gram-negative organism that attaches to the lining of the stomach;
releasing chemicals that cause inflammation and damage stomach lining, leading to ulcer
formation.

Duodenal ulcers occur in the small intestine just below the stomach; caused by hyperacidity, not
usually H. pylori.

Stress ulcers occur in critically ill patients who are bedridden; it is thought that serious illness,
stress, and trauma lead to a decrease in the protective mucous layer of the stomach and an increase
in acid secretion.

Non-steroidal anti-inflammatory drugs (NSAIDs) – ibuprofen and aspirin, can cause ulcers; these
drugs irritate and erode GI tissue, and inhibit production of prostaglandins – which protect the lining
of the stomach from acid secretion.

GI bleed – when an ulceration erodes into a blood vessel.

Drug Regimens and Treatments
Drug treatment for GERD and GI ulcers do not directly fix the problem, rather, antacids, proton pump
inhibitors (PPIs), and H2 blockers relieve symptoms by decreasing acid production.

(1)Antacids – contain special ions that react with hydrogen ions in the stomach and neutralize acid;
only effective for a few hours, and are available OTC.

Side effects include constipation, diarrhea, stomach pain, nausea, and vomiting.

There are no contraindications but continuous use of calcium-containing antacids can cause acid
hypersecretion; they can also bind to oral drugs, decreasing their absorption.
Patients with renal failure must use caution with antacids because aluminum and magnesium can
accumulate in the blood.

(2)Proton pump inhibitors (PPIs) can be used to treat GERD, PUD, and H. pylori. They work by
binding to proton pumps in the stomach lining, rendering them inactive, producing less stomach
acid. PPIs are long-acting, lasting approximately 24 hours; most effective when taken on an empty
stomach. Infants can be prescribed liquid forms of PPIs that need to be specially compounded to
meet the needs of the patient.

Side effects include headache, nausea, vomiting, and diarrhea.

Hypersensitivity to one PPI contraindicates use in all PPIs.

DR capsules or tablets cannot be chewed or crushed; PPIs may decrease absorption of drugs that
need an acidic environment; PPIs seem to decrease the effectiveness of clopidogrel (Plavix).
(3)H2 blockers treat GERD and PUD, working to block type 2 histamine receptors in the stomach
which decreases proton pump activity and limits acid secretion. Effects last approximately 8 hours;
can be taken daily or PRN.

Side effects include: headache, diarrhea, and occasionally dizziness; temporary confusion is rare;
increased risk of developing certain infections, such as respiratory tract infections.

Patients with hepatitis should not take ranitidine (Zantac) – rare are reports of liver failure and
death.

Cimetidine (Tagamet) interacts with several other drugs; H2 blockers decrease absorption of drugs
that require an acidic environment.

(4)Sucralfate coats the walls of the stomach and small intestine; taken 4 times a day on an empty
stomach 1 hour before or 2 hours after a meal.

Side effects include: constipation, diarrhea, headache, GI discomfort, and indigestion.

There are no contraindications.

Sucralfate interacts with many other medications because it coats the lining of the stomach,
forming a barrier, preventing absorption.

(5)Misoprostol is approved for prevention of NSAID-induced ulcers; a prostaglandin analog and

replaces prostaglandins reduced or inhibited by NSAIDs; taken 4 times a day with food.

Side effects include: diarrhea and abdominal pain; flatulence, dyspepsia, and uterine contractions.

Hypersensitivity to prostaglandins and pregnancy contraindicates the use of misoprostol.

Only used to treat patients with high risk for gastric ulcers; when used in pregnancy, may cause
abortion, birth defects, or premature birth.
Regimens for H. pylori:

A patient with PUD that is H. pylori positive is prescribed a multidrug regimen.

These drugs treat the ulcer, reduce symptoms, and kill H. pylori in the GI tract simultaneously.

A PPI is used to heal the ulcer, an antibiotic is used to destroy the bacteria.
Nausea – the feeling of the need to vomit.

Vomiting – the expulsion of stomach contents out of the mouth; a defense mechanism to protect
the body from harmful substances that may have been consumed.

Reverse peristalsis – coordinated muscle contractions along the upper GI tract.

Chemoreceptor trigger zone (CTZ) and vomiting center in the medulla receive input from the
cerebral cortex, hypothalamus, GI tract, and blood-borne stimuli to cause nausea and vomiting.
Nausea and vomiting are symptoms caused by a variety of diseases and conditions; intestinal
infections are a common cause.

Morning sickness is nausea and vomiting within the first weeks of pregnancy, related to hormonal
changes.

Motion sickness is nausea and vomiting following movement; related to vestibular responses in the
inner ear.

Anesthesia is also associated with nausea and vomiting. It can be drug induced; drugs have the
potential to trigger stomach irritation, nausea, and vomiting.

Chemotherapy agents are most commonly associated with nausea and vomiting; along with
radiation treatments.

Drug Regimens and Treatments

Emesis – the act of vomiting.

Antiemetics – drugs used for the prevention of vomiting.

Nausea and vomiting due to heartburn, antacids, and H2 blockers can be used.

For motion sickness, OTC anticholinergic agents can be used.

For moderate-to-severe nausea and vomiting, more potent antiemetics are needed.

Anticholinergic antiemetics are similar in chemical structure to antihistamines; used for mild motion
sickness.

They work by blocking histamine and acetylcholine.

Side effects include: drowsiness, dry mouth, and urinary retention; in some children it can have a
paradoxical effect.
Anticholinergic antiemetics should not be given to infants or mothers breast-feeding; patients with
glaucoma or taking MAOIs should also not take these agents.

Patients with high blood pressure or heart problems should talk with their doctors prior to using
anticholinergic antiemetics.

General antiemetics include:

Metoclopramide (Reglan) – increases GI motility, allows food to pass quickly, preventing vomiting

Promethazine (Phenergan) – blocks histamine (H1) receptors

Phenothiazines – block dopamine; 1st generation antipsychotics when used in higher doses.

o Chlorpromazine (Thorazine)

o Prochlorperazine (Compazine)

Side effects include: drowsiness and sedation; extrapyramidal symptoms (EPS) or EPS side
effects – movement disorders (tardive dyskinesia and dystonia) are possible with phenothiazines.

Contraindications are drug specific.

Patients should use caution when taking due to sedative effects; alcohol may make it worse; EPS
risk can be increased in patients with liver problems.

Serotonin type 3 receptor antagonist work to block serotonin type 3 (5-HT3) receptors in the brain
and GI tract.

Blocking these receptors stops nausea signals from traveling from the brain to the stomach.

Side effects include: headache, fatigue, drowsiness, constipation, and muscle weakness; rare is
anaphylaxis, hypotension, or swelling of the throat or tongue.
Dolasetron (Anzemet) is contraindicated via IV route; granisetron (Kytril), ondansetron (Zofran), and
palonosetron (Aloxi) do not have contraindications.

Patients should be advised that activities such as driving may not be safe while taking these
medications.

Dronabinol (Marinol, C-III) is the active substance in Cannabis sativa (marijuana).

Effects the sympathetic nervous system, influencing appetite.
Used to treat nausea and vomiting associated with chemotherapy and appetite stimulation in
patients with AIDS.
Side effects can be psychoactive including easy laughing, elation or euphoria, heightened
awareness, anxiety, hallucinations, confusion, and paranoia; dizziness, sleepiness, heart palpitations,
and flushing.
Withdrawal effects can include irritability, insomnia, restlessness, hot flashes, sweating, runny nose,
loose stools, and hiccups.
This is contraindicated in patients with hypersensitivity to cannabinoids, sesame oil, and marijuana.
Psychiatric monitoring is needed in patients who suffer with depression, mania, or schizophrenia.

Neurokinin-1 receptor antagonists (neurokinin-1 inhibitors) Emend (aprepitant [oral] & fosprepitant
[IV]) are used to prevent nausea and vomiting induced by chemotherapy drugs or anesthesia.
They work by blocking NK1 receptors, preventing substance P – a neuropeptide involved in
mediating responses such as pain, pleasure, thirst, and hunger – from stimulating nausea; stopping
the nausea signal as it travels from the brain to the GI tract.
Side effects include fatigue, muscle weakness, and constipation; hypotension, slow heart rate,
diarrhea, GI pain, kidney and liver dysfunction, and blood abnormalities are rare.
Hemorrhoids

There are two sphincters in the anus that control defecation.

Hemorrhoidal cushion protects the anal sphincters from damage.

Straining and hard stools, can force blood vessels from the hemorrhoidal cushion into the anal
cavity, where they are at risk of rupturing.

Hemorrhoids are displaced blood vessels, similar to varicose veins.

Hemorrhoid disease is bleeding and irritation when a blood vessels ruptures.

Drug Regimens and Treatments

Fiber such as a bulk-forming laxative can be used for mild hemorrhoids, making the passing of
stools easier and resolving symptoms.

Topical hemorrhoid agents decrease symptoms of itching and pain caused by hemorrhoids.

Witch hazel an astringent that may stop bleeding.

Pramoxine (Anusol) is a local anesthetic.

Side effects include mild itching and burning; rarely Pramoxine can cause swelling of the tongue.

Hydrocortisone rectal enemas are contraindicated in systemic fungal infections and ileocolostomy.

None of these products should be used for long periods.

Other GI System Disorders
Irritable bowel syndrome (IBS) – a chronic disease that features frequent and painful constipation
or diarrhea without any structural or dietary problems.

Three types of IBS: constipation-predominant (IBS-C), diarrhea-predominant (IBS-D), and mixed IBS.

IBS-C: increased fiber and polyethylene glycol (PEG); linaclotide and lubiprostone.

IBS-D: loperamide, bile acid sequestrants, alosetron, and antispasmodic agents.

Side effects for agents used to treat IBS-C and IBS-D is diarrhea; antispasmodics can cause dry
mouth and eyes, blurred vision, reduced urination, and constipation.

Patients with a history of bowel obstruction or suspected of having this condition all agents for IBS
are contraindicated. Patients with heart disease or an enlarged prostate should use caution with
antispasmodics.

Ulcerative colitis – excessive inflammation of the GI tract, causing ulcers; damage causes
abdominal pain and weight loss as well as diarrhea. Damage can be limited to specific portions of
the colon or large intestines; surgical removal of the affected portion can be a cure for some.

Crohn’s disease – inflammation of the GI tract and causes chronic diarrhea; an autoimmune disease
in which the immune system malfunctions and attacks tissue lining of the entire GI tract; surgery is
not a cure.
Drug Treatments and Regimens

Immunosuppressants and anti-inflammatory medications are 1st line therapy for ulcerative colitis
and Crohn’s disease. Corticosteriods like prednisone, methylprednisolone, hydrocortisone, and
budesonide are used.

Aminosalicylates are used for induction and maintenance of remission in patients with
Crohn’s disease and ulcerative colitis.

Side effects include upset stomach, headache, arthralgia, and pharyngitis. Patients with sulfa
allergies should avoid sulfasalazine. Reports of cardiac hypersensitivity in patients using
aminosalicylates; along with hepatic failure.

Corticosteroids are used for their anti-inflammatory and immunosuppressant properties.

Side effects include headache, dizziness, insomnia, and hunger; long-term use can affect
metabolism in the body and cause facial swelling, significant weight gain, fluid retention, and
fat redistribution to the back and shoulders; high blood pressure, loss of bone mass,
electrolyte imbalance, cataracts and glaucoma, and insulin resistance.

Prednisone and methylprednisolone are contraindicated in systemic fungal infections.

Patients are an increased risk of infection because of suppression to the immune system.

Immunosuppressants suppress the immune system; may induce response and remission in patients
with ulcerative colitis and Crohn’s disease.

Side effects include sore throat, cough, dizziness, nausea, muscle aches, fever, chills, itching,
and headache; rare side effects include changes in heart rhythm or blood pressure, chest
pain, unusual bleeding, bruising, anemia, and hyperlipidemia.

Azathioprine (Imuran) is contraindicated in pregnancy and patients with RA and a history of

treatment with alkylating agents; Cyclosporine (Neoral, Sandimmune) is contraindicated in
patients with a hypersensitivity to polyoxyethylated castor oil. Patients are at increased risk
for infection.
Herbal and Alternative Therapies
Ginger can be used to reduce nausea associated with vertigo, surgery, and motion sickness. It may
exert it effects by inhibition of serotonin receptors. It may cause heartburn, gas, bloating, mouth and
throat irritation, and diarrhea and should be avoided in patients taking aspirin, warfarin, or other
anticoagulants.

Probiotics contain live cultures of yeast or bacteria. They are used as non-pharmacological
adjunctive treatment for diarrhea, constipation, H. pylori, and antibiotic induced diarrhea.

Lactobacilli gram-positive bacteria that are normal flora of the human GI tract; side effects include
gas and bloating.

Saccharomyces boulardii (S. boulardii) a yeast organism that lives in the human GI tract; side
effects include gas, bloating, and constipation.

Bifidobacteria may be effective for diarrhea associated with a variety of causes; potential to cause
gas and bloating.
Nutrition and Drugs for Metabolism
Nutritional Needs of the Body

Micronutrients – vitamins and minerals that are essential for the growth of a living organism;
playing a key role in metabolic processes; range of intake between inadequate and excess.

The US Department of Agriculture (USDA) and the Institute of Medicine publish dietary reference
intakes (DRIs) provide information on sufficient intake of micronutrients and macronutrients.

DRIs include: estimated average requirements, recommended dietary allowances (RDAs), adequate
intakes (AIs), and tolerable upper intake levels.

Micronutrients are often reported in mass, mg or mcg; some may list in international units (IUs).

Vitamins

Vitamin – an organic substance that is required in the diet in small amounts for the maintenance of
normal metabolic integrity.

Vitamin deficiency can cause disease only restored by adequate physiological levels of that
vitamin. Vitamins don’t generally have contraindications, except in the case of hypersensitivity and
evidence of vitamin toxicity.

Fat-soluble vitamins – absorbed with dietary fats and are maintained in stores in the body.
Vitamin A – family of compounds referred to as retinoic acids or retinoids. Found in two forms:
provitamin A carotenoids (beta-carotene) and preformed vitamin A (retinol, retinal, retinoic acid, and
retinyl esters).

Provitamin A can be found in green, leafy vegetables; sweet potatoes; and carrots. Excessive intake
of provitamin A is unlikely to cause toxicity.
Preformed Vitamin A is found in liver, kidney, egg yolk, and butter. Toxicity can occur if excessive
quantities are ingested.

Keratomalacia – softening and ulceration of the cornea of the eye may result from Vitamin A
deficiency.
Other deficiencies include: poor bone growth, dermatologic problems, and impairment of the
immune system.
Used in the treatment of cataracts and reducing complications of HIV, measles, and malaria.
Excessive intake of preformed Vitamin A may cause toxicity. Symptoms include nausea, vomiting,
vertigo, blurry vision, hair loss, headache, irritability, skin peeling, and bone and liver problems. Can
be teratogenic, in the 1st trimester of pregnancy, leading to spontaneous abortions and fetal
malformations.

Vitamin D, or calciferol – identified as a vitamin in the 20th century and now recognized as a
hormone.

Vitamin D plays an important role in maintaining calcium and phosphate levels in the body; evidence
suggests that it also plays a role in insulin resistance, obesity, metabolic syndrome, and various
cancers.

Two major forms of Vitamin D: ergocalciferol (Vitamin D2) and cholecalciferol (Vitamin D3).

Ergocalciferol is human-made and added to foods.

Cholecalciferol is synthesized in the skin in response to sunlight (80-90%) and can be consumed in
the diet through the intake of animal-based foods.

Naturally occurring Vitamin D sources include fatty fish, fish liver oil, and egg yolks.

Rickets – childhood disease where lack of Vitamin D results in bone softening and muscle
weakness; bowlegs.

Osteomalacia – disorder of bone that is manifested by bone pain, muscle weakness, difficult
walking, and fracture, can be treated with Vitamin D.
Excessive intake of Vitamin D can lead to toxicity. Symptoms include high blood calcium levels,
kidney stones, nausea, vomiting, thirst, increased urination, muscle weakness, and bone pain.

Vitamin E, or tocopherol, physiological role is still being defined; thought to be used as an

antioxidant.

Found in food products including oils; meat; eggs; and green, leafy vegetables.

Best known for its role in human health is alpha-tocopherol, is abundant in olive oil and sunflower oil;
gamma-tocopherol can be found in soybean oil and corn oil.

Vitamin E deficiency is rare, except in cases of specific genetic or malabsorption disorders.

Deficiency can cause neuromuscular disorders, fragile red blood cells, and hemolysis.

Vitamin E is used in the treatment of macular degeneration and Alzheimer’s disease; has shown to
reduce the risk of some cancers and dementia and to improve immune system function; diabetic
retinopathy and cardiovascular disease; topically it can improve skin health, healing, and hydration.

Very high doses may result in bleeding or stroke.

Vitamin K (phytonadione) functions as a coenzyme for the hepatic production of blood-clotting

factors and for bone metabolism.

Vitamin K dietary forms include phylloquinone and phytonadione, which can be found in green leafy
vegetables like spinach, broccoli, and Brussels sprouts, and in fats such as plant oils and margarine.

Vitamin K deficiency is rare in healthy adults. Symptoms of deficiency are associated with impaired
coagulation which includes easy bruising, mucosal bleeding, melena, and hematuria.

Administered where blood clotting is desired and in cases of deficiency caused by drug therapy;
injection may be administered to neonates.

Toxicity is rare; signs include anemia and jaundice.