PHARMACOLOGY

PART 1 Chemotherapeutic Agents

1. Introduction to Cell Physiology

 Chemotherapeutic drugs are used to
destroy both organisms that invade the
body (e.g., bacteria, viruses, parasites,
protozoa, fungi) and abnormal cells within
the body (e.g., neoplasms, cancers).
 The Cell - is the basic structural unit of the
body. The cells that make up living
organisms, which are arranged into
tissues and organs, all have the same
basic structure. Each cell has a nucleus, a
cell membrane, and cytoplasm, which
contains a variety of organelles.
o The cell is composed of a nucleus,
which contains genetic material
and controls the production of proteins by the cell; a cell membrane, which separates the
inside of the cell from the outside environment; and a cytoplasm, which contains various
organelles important to cell function.
o The cell membrane functions as a fluid barrier made of lipids and proteins. The
arrangement of the lipoprotein membrane controls what enters and leaves the cell.
o Proteins on the cell membrane surface can act either as receptor sites for specific
substances or as histocompatibility markers that identify the cell as a self-cell (i.e., a cell
belonging to that individual).
o Channels or pores in the cell membrane allow for easier movement of specific substances
needed by the cell for normal functioning.
o Mitochondria are rod-shaped organelles that produce energy in the form of ATP for use by
cells.
o Ribosomes are sites of protein production within the cell cytoplasm. The specific proteins
produced by a cell are determined by the genetic material within the cell nucleus.
o The Golgi apparatus packages particular substances for removal from the cell (e.g.,
neurotransmitters, hormones).
o Lysosomes are packets of digestive enzymes located in the cell cytoplasm. These enzymes
are responsible for destroying injured or nonfunctioning parts of the cell and for promoting
cellular disintegration when the cell dies.

 Cell Properties
o Endocytosis is the process of moving substances into a cell by extending the cell
membrane around the substance and engulfing it. Pinocytosis refers to the engulfing of
necessary materials, and phagocytosis refers to the engulfing and destroying of bacteria
or other proteins by white blood cells.
o Exocytosis is the process of removing substances from a cell by moving them toward the
cell membrane and then changing the cell membrane to allow passage of the substance
out of the cell
o Cells maintain homeostasis by regulating the movement of solutes and water into and

out of the cell.

 Passive transport happens without the expenditure of energy and can occur across
any semipermeable membrane.
 Diffusion is the movement of a substance from a region of higher
concentration to a region of lower concentration.
 Osmosis, a special form of diffusion, is the movement of water across a

semipermeable membrane from an area that is low in dissolved solutes to

one that is high in dissolved solutes. The water is attempting to equalize the
dilution of the solutes.
 Sometimes a substance cannot move freely on its own in or out of a cell.
Such a substance may attach to another molecule, called a carrier, to be
diffused. This form of diffusion, known as facilitated diffusion, does not
require energy, just the presence of the carrier. Carriers may be hormones,
enzymes, or proteins
o Active Transport - Sometimes a cell requires a substance in greater concentration
than is found in the environment around it or needs to maintain its cytoplasm in a
 situation that would normally allow chemicals to leave the cell. When this happens,
the cell must move substances against the concentration gradient using active
transport, which requires energy. One of the best-known systems of active transport
is the sodium–potassium pump.
 Cell Cycle - Most cells have the ability to reproduce themselves through the process of mitosis. The
genetic makeup of a particular cell determines the rate at which that cell can multiply.
o G0 Phase, the resting phase
o G1 Phase, which involves the production of proteins for DNA synthesis
o S Phase, which involves the synthesis of DNA
o G2 Phase, which involves manufacture of the materials needed for mitotic spindle
production
o M Phase, the mitotic phase, in which the cell splits to form two identical daughter
cells.

1. Anti-Infective Agents

 Anti-infectives are drugs designed to act on foreign organisms that have invaded and infected the
human host with selective toxicity, which means that they affect biological systems or structures
found in the invading organisms but not in the host.
 Anti-infectives include antibiotics, antivirals, antifungals, antiprotozoals, and anthelmintic agents.
 The goal of anti-infective therapy is interference with the normal function of invading organisms to
prevent them from reproducing and promotion of cell death without negative effects on the host
cells. The infection should be eradicated with the least toxicity to the host and the least likelihood
for development of resistance.
 Anti-infectives can work by altering the cell membrane of the pathogen, by interfering with protein
synthesis, or by interfering with the ability of the pathogen to obtain needed nutrients.
 Anti-infectives also work to kill invading organisms or to prevent them from reproducing, thus
depleting the size of the invasion to one that can be dealt with by the human immune system.
 Pathogens can develop resistance to the effects of anti-infectives over time when:
o mutant organisms that do not respond to the anti-infective become the majority
of the pathogen population;
 o the pathogen develops enzymes to block the anti-infectives or alternative routes
to obtain nutrients or maintain the cell membrane.
 An important aspect of clinical care involving anti-infective agents is preventing or delaying the
development of resistance. This can be done by ensuring that the particular anti-infective agent is
the drug of choice for the specific pathogen involved and that it is given in high enough doses for
sufficiently long periods to rid the body of the pathogen.
 Culture and sensitivity testing of a suspected infection ensures that the correct drug is being used
to treat the infection effectively. Culture and sensitivity testing should be performed before an
anti-infective agent is prescribed.
 Anti-infectives can have several adverse effects on the human host, including renal toxicity,
multiple GI effects, neurotoxicity, hypersensitivity reactions, and superinfections.
 Some anti-infectives are used as a means of prophylaxis when patients expect to be in situations
that will expose them to a known pathogen, such as travel to an area where malaria is endemic, or
oral or invasive GI surgery in a person who is susceptible to subacute bacterial endocarditis.

2. Antibiotics

 Antibiotics work by disrupting protein or enzyme systems within a bacterium, causing cell death
(bactericidal) or preventing multiplication (bacteriostatic).
 The proteins or enzyme systems affected by antibiotics are more likely to be found or used in
bacteria than in human cells.
 The primary therapeutic use of each antibiotic is determined by the bacterial species that are
sensitive to that drug, the clinical condition of the patient receiving the drug, and the benefit-to-
risk ratio for the patient.
 The longer an antibiotic has been available, the more likely it is that mutant bacterial strains
resistant to the mechanisms of antibiotic activity will have developed.
 The most common adverse effects of antibiotic therapy involve the GI tract (nausea, vomiting,
diarrhea, anorexia, abdominal pain) and superinfections (invasion of the body by normally
occurring microorganisms that are usually kept in check by the normal flora).
 To prevent or contain the growing threat of drug resistant strains of bacteria, it is very important to
use antibiotics cautiously, to complete the full course of an antibiotic prescription, and to avoid
saving antibiotics for self-medication in the future. A patient and family teaching program should
address these issues, as well as the proper dosing procedure for the drug (even if the patient feels
better) and the importance of keeping a record of any reactions to antibiotics.

TERMS
o aerobic: bacteria that depend on oxygen for survival
o anaerobic: bacteria that survive without oxygen, which are often seen when blood flow is
cut off to an area of the body
o gram-negative: bacteria that accept a negative stain and are frequently associated with
infections of the genitourinary or GI tract
o gram-positive: bacteria that take a positive stain and are frequently associated with
infections of the respiratory tract and soft tissues
o synergistic: drugs that work together to increase drug effectiveness
3. Antiviral Agents
 TERMS
o acquired immunodeficiency syndrome (AIDS): collection of opportunistic infections and
cancers that occurs when the immune system is severely depressed by a decrease in the
number of functioning helper T cells; caused by infection with human immunodeficiency
virus (HIV)
 o AIDS-related complex (ARC): collection of less serious opportunistic infections with HIV
infection; the decrease in the number of helper T cells is less severe than in fully developed
AIDS
o CCR5 coreceptor antagonist: a drug that blocks the receptor site the HIV virus needs to
interact with in order to enter the cell
o cytomegalovirus (CMV): DNA virus that accounts for many respiratory, ophthalmic, and liver
infections
o fusion inhibitor: a drug that prevents the fusion of the HIV-1 virus with the human cellular
membrane, preventing it from entering the cell.
o herpes: DNA virus that accounts for many diseases, including shingles, cold sores, genital
herpes, and encephalitis
o human immunodeficiency virus (HIV): retrovirus that attacks helper T cells, leading to a
decrease in immune function and AIDS or ARC
o influenza A: RNA virus that invades tissues of the respiratory tract, causing the signs and
symptoms of the common cold or “flu”
o integrase inhibitor: a drug that inhibits the activity of the virus-specific enzyme integrase, an
encoded enzyme needed for viral replication; blocking this enzyme prevents the formation
of the HIV-1 provirus
o interferon: tissue hormone that is released in response to viral invasion; blocks viral
replication
o nonnucleoside reverse transcriptase inhibitors: drugs that bind to sites on the reverse
transcriptase, preventing RNA- and DNA-dependent DNA polymerase activities needed to
carry out the viral DNA synthesis; prevents the transfer of information that allows the virus
to replicate and survive
o nucleoside reverse transcriptase inhibitors: drugs that prevent the growth of the viral DNA
chain, preventing it from inserting into the host DNA, so viral replication cannot occur
o protease inhibitors: drugs that block the activity of the enzyme protease in HIV; protease is
essential for the maturation of infectious virus, and its absence leads to the formation of an
immature and noninfective HIV particle
o virus: particle of DNA or RNA surrounded by a protein coat that survives by invading a cell to
alter its functioning
 Viruses are particles of DNA or RNA surrounded by a protein coat that survive by injecting their
own DNA or RNA into a healthy cell and taking over its functioning.
 Because viruses are contained within human cells, it has been difficult to develop drugs that are
effective antivirals and yet do not destroy human cells. Antiviral agents are available that are
effective against only a few types of viruses.
 Influenza A and respiratory viruses cause the signs and symptoms of the common cold or “flu.”
The drugs that are available to prevent the replication of these viruses are used for prophylaxis
against these diseases during peak seasons and to treat disease when it occurs.
 Herpes viruses and CMV are DNA viruses that cause a multitude of problems, including cold
sores, encephalitis, infections of the eye and liver, and genital herpes.
 Helper T cells are essential for maintaining a vigilant, effective immune system. When these cells
are decreased in number or effectiveness, opportunistic infections occur. AIDS and ARC are
syndromes of opportunistic infections that occur when the immune system is depressed.
 HIV, which specifically attacks helper T cells, may remain dormant in these cells for long periods
and has been known to mutate easily.
 Antiviral agents that are effective against HIV and AIDS include nonnucleoside and NRTIs,
protease inhibitors, fusion inhibitors, CCR5 coreceptor antagonists, and integrase inhibitors, all
 of which affect the way the virus communicates, replicates, or matures within the cell. These
drugs are known as antiretroviral agents. They are given in combination to most effectively
destroy the HIV virus and prevent mutation.
 Recently three drugs have been approved to treat hepatitis B infection: adefovir, entecavir, and
telbivudine.
 Some antivirals are available only for the local treatment of viral infections, including warts and
eye infections. These drugs are not absorbed systemically.
 4. Antifungal Agents
 A fungus is a cellular organism with a hard cell wall that contains chitin and polysaccharides and a
cell membrane that contains ergosterols.
 Any infection with a fungus is called a mycosis. Systemic fungal infections, which can be life
threatening, are increasing with the rise in the number of immunocompromised patients.
 Systemic antifungals alter the cell permeability, leading to leakage of cellular components. This
causes prevention of cell replication and cell death.
 Because systemic antifungals can be very toxic, patients should be monitored closely while receiving
them. Adverse effects may include hepatic and renal failure.
 Local fungal infections include vaginal and oral yeast infections (Candida) and a variety of tinea
infections, including athlete’s foot and jock itch.
 Topical antifungals are agents that are too toxic to be used systemically but are effective in the
treatment of local fungal infections.
 Proper administration of topical antifungals improves their effectiveness. They should not be used
near open wounds or lesions.
 Topical antifungals can cause serious local irritation, burning, and pain. The drug should be stopped
if these conditions occur.
 5. Antiprotozoal Agents

 A protozoan is a parasitic cellular organism. Its life cycle includes a parasitic phase inside human
tissues or cells.
 Malaria is caused by Plasmodium protozoa, which must go through a cycle in the Anopheles
mosquito before being passed to humans by the mosquito bite. Once inside a human, the protozoa
invade red blood cells.
 The characteristic cyclic chills and fever of malaria occur when red blood cells burst, releasing more
protozoa into the bloodstream.
 Malaria is treated with a combination of drugs that attack the protozoan at various stages in its life
cycle.
 Amebiasis is caused by the protozoan E. histolytica, which invades human intestinal tissue after
being passed to humans through unsanitary food or water. It is best treated with metronidazole or
tinidazole.
 Leishmaniasis, a protozoan-caused disease, can result in serious lesions in the mucosa, viscera, and
skin. It is treated with systemic pentamidine.
 Trypanosomiasis, which is caused by infection with a Trypanosoma parasite, may assume two forms.
African sleeping sickness leads to inflammation of the CNS, and Chagas’ disease results in serious
cardiomyopathy. These diseases can be treated with systemic pentamidine.
 Trichomoniasis is caused by T. vaginalis. This common cause of vaginitis results in no signs or
symptoms in men but serious vaginal inflammation in women. It is treated with metronidazole and
tinidazole.
 Giardiasis, which is caused by G. lamblia, is the most commonly diagnosed intestinal parasite in the
United States. This disease may lead to serious malnutrition when the pathogen invades intestinal
mucosa. It is treated with nitazoxanide, metronidazole, and tinidazole.
 Pneumocystis jiroveci is an endemic protozoan that does not usually cause illness in humans unless
they become immunosuppressed. This is the most common opportunistic infection seen in AIDS
patients. It is treated with inhaled pentamidine and oral atovaquone.
 Patients receiving antiprotozoal agents should be monitored regularly to detect any serious adverse
effects, including loss of vision, liver toxicity, and so on.
 6. Anthelmintic Agents

 Helminths are worms that cause disease by invading the human body. Helminths that affect humans
include nematodes (round-shaped worms) such as pinworms, hookworms, threadworms,
whipworms, and roundworms; and platyhelminths (flatworms), which include tapeworms and
flukes.
 Pinworms are the most frequent cause of helminth infection in the United States, and roundworms
called Ascaris are the most frequent cause of helminth infections throughout the world.
 Some helminths invade body tissues and can seriously damage lymphatic tissue, lungs, CNS, heart,
liver, and so on. These include trichinosis-causing tapeworms, which are found in undercooked pork;
filariae, which occur when thread-like worm embryos clog up vascular spaces; and schistosomiasis-
causing flukes. Schistosomiasis is a common problem in many tropical areas where the snail that is
necessary in the life cycle of the fluke lives.
 Anthelmintic drugs affect metabolic processes that are either different in worms than in human
hosts or are not found in humans. These agents all cause death of the worm by interfering with
normal functioning.
 Prevention is a very important part of the treatment of helminths. Thorough hand washing;
laundering of bed linens, pajamas, and underwear to destroy ova that are shed during the night; and
disinfection of toilet facilities at least daily and of bathroom floors periodically help to stop the
spread of these diseases. In addition, proper sanitation and hygiene in food preparation and storage
is essential for reducing the incidence of these infestations.
 Patient teaching is important for decreasing the stress and anxiety that may occur when individuals
 are diagnosed with a worm infestation.
7. Antineoplastic Agents

 Cancers arise from a single abnormal cell that multiplies and grows.
 Cancers can manifest as diseases of the blood and lymph tissue or as growth of tumors arising from
epithelial cells (carcinomas) or from mesenchymal cells and connective tissue (sarcomas).
 Cancer cells lose their normal function (anaplasia), develop characteristics that allow them to grow
in an uninhibited way (autonomy), have the ability to travel to other sites in the body that are
conducive to their growth (metastasis), and can stimulate the production of blood vessels to bring
nutrients to the growing tumor (angiogenesis).
 Antineoplastic drugs affect both normal cells and cancer cells by disrupting cell function and division
at various points in the cell cycle; new drugs are being developed, such as protein kinase inhibitors,
to target cancer cell–specific functions.
 Cancer drugs are usually most effective against cells that multiply rapidly (i.e., proceed through the
cell cycle quickly). These cells include most neoplasms, bone marrow cells, cells in the GI tract, and
cells in the skin or hair follicles.
 The goal of cancer chemotherapy is to decrease the size of the neoplasm so that the human
immune system can deal with it.
 Antineoplastic drugs are often given in combination so that they can affect cells in various stages of
the cell cycle, including cells that are emerging from rest or moving to a phase of the cycle that is
disrupted by these drugs.
 Adverse effects associated with antineoplastic therapy include effects caused by damage to the
rapidly multiplying cells, such as bone marrow suppression, which may limit the drug use; GI toxicity,
with nausea, vomiting, mouth sores, and diarrhea; and alopecia (hair loss).
 Chemotherapeutic agents should not be used during pregnancy or lactation because they may result
in potentially serious adverse effects on the rapidly multiplying cells of the fetus and neonate.
 The newest drugs developed as antineoplastic agents target very specific enzyme systems or
processes used by the cancer cells but not by healthy human cells. These drugs are not as toxic to
the patient as traditional antineoplastic drugs.
Reference:
Karch, A. M. (2013). Focus on nursing pharmacology. Sixth edition. Philadelphia: Wolters Kluwer.