Chemotherapeutic Agents

 These are drugs that are used to destroy both organisms that invade the body and abnormal cells within
the body.
 They affect cells by altering cellular function or disrupting cellular integrity, causing cell death, or by
preventing cellular reproduction, eventually leading to cell death.
 Most of them do not possess complete selective toxicity, they also affect the normal cells of patients.

Anti-Infective Agents
 Target foreign organism that have invaded and infected the body of a human host.
 They do not possess selective toxicity - the ability to affect certain proteins or enzyme systems used only
by the the infecting organism but not by human cells.
 No anti-infective drug has yet been developed that does not affect the host.

1. Antibiotics 
2. Antivirals
3. Antifungals 
4. Antiprotozoals
5. Anthelmintics 

Therapeutic Actions
 They may act on the cells of invading organisms in several
different ways.
 The goal is interference with the normal function of the
invading organism to prevent it from reproducing and to
cause cell death without affecting host cells.
a. Interference with biosynthesis of pathogen cell wall
(penicillins)
b. Prevention of invading organism from using substances for
their growth and development (sulfonamides) 
c. Interference with the steps involved in protein synthesis
d. Interference with DNA synthesis
e. Alteration of the permeability of the cell membrane 

Anti-Infective Activity
 Narrow spectrum - selective in their action that they are
effective against only a few microorganisms.
 Broad spectrum - interfere with biochemical reactions in may different kinds of microorganisms.
 Bactericidal - causes death of cells they affect
 Bacteriostatic - not aggressive, interfere with the ability of the cells to reproduce or divide
 Several drugs are both bactericidal and bacteriostatic

Resistance - can be natural or acquired, and refers to the ability over time to adapt to an anti-infective drug and
produce cells that are no longer affected by a particular drug. 
a. Natural or innate - microorganisms are not affected by a particular anti-infective drug because the drugs
act on specific enzyme systems or biological processes.
b. Acquired - microorganisms develop resistance to anti-infective drugs

Acquired Resistance
a. Producing an enzyme that deactivates the drug
 Penicillinase - enzyme inactivating penicillin 
b. Changing cellular permeability to prevent the drug from entering the cell or altering transport systems to
exclude the drug from active transport into the cell
c. Altering binding sites on the membranes or ribosomes, which then no longer accept the drug
d. Producing a chemical that acts as an antagonist to the drug
 e. Cells that remain may be somewhat resistant to the effects of the drug, and, with time, these cells form
the majority in the population.
f. Other microbes develop resistance through actual genetic mutation

Preventing Resistance
1. Limit the use of antimicrobial agents
2. Drug dosing - dose should be high enough and duration long enough to eradicate even slightly resistant
microorganisms
3. Healthcare providers should be cautious about the indiscriminate use of anti-infectives

Prophylaxis - prevent infection before they occur.

 Antimalarial drugs for those who will travel to areas where malaria is endemic.
 Antibiotics for those who are undergoing GI or GU surgery

Adverse Reactions
 Because anti-infective agents affect cells, it is always possible that the host cells will also be damaged.
 No anti-infective agent has been developed that is completely free of adverse effects.
a. Kidney damage - drugs that are metabolized by the kidney and then eliminated in the urine. Patients should
be well hydrated throughout the course of the therapy.
b. GI toxicity - direct toxic effects on the cells lining the GI tract, causing nausea, vomiting, stomach upset,
diarrhea. Dead microorganisms release chemicals and toxins into the body which can stimulate the CTZ and
induce nausea and vomiting.
c. Liver toxicity - hepatitis and liver failure. Patients should be monitored closely, drug should be stopped at any
sign of liver dysfunction. 
d. Neurotoxicity - damage and interfere with the function of nerve tissue, usually in areas where drug drugs
tend to accumulate in high concentrations. 
e. Hypersensitivity reactions - agents are able to induce antibody formation in susceptible people, with the next
exposure to the drugs, allergic responses may occur. anaphylaxis can occur which can be life-threatening
f. Superinfections - infections that occur when opportunistic pathogens that were kept in check by the normal
flora bacteria have the opportunity to invade tissues.

Antibiotics
 Goal is to decrease the population of invading bacteria to a point at which the immune system can
effectively deal with the invader.
 To determine which antibiotic will effectively interfere with the specific proteins or enzyme systems,
causative organism must be identified through a culture. 
 Sensitivity testing is also done to determine the antibiotic to which the particular organism is most
sensitive.
 Gram-positive - resists decolorization with alcohol during culture and sensitivity test. Commonly
associated with infections of the respiratory tract and soft tissues (Streptococcus pneumoniae).
 Gram-negative - decolorized by alcohol. Frequently associated with infections of the GU and GI tract
(Escherichia coli).
Major Classes of Antibiotics:
b. Aminoglycosides
c. Carbapenems
d. Cephalosporins
e. Fluoroquinolones
f. Penicillins
g. Penicillinase-resistant drugs
h. Sulfonamides
i. Tetracyclines
j. Disease-specific antimycobacterials (antitubercular and leprostatic drugs)

Antiviral Agents
 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.
  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.

HIV and AIDS

 No CURE only treatment
 Treatment has been difficult for these reasons:
1. The length of time the virus can remain dormant within the T cells
2. The adverse effects of many potent drugs, which may include further depression of the immune system

Antifungal Agents
 Mycosis - infection caused by fungus
 Incidence of fungal infections has increased with the rising number of immunocompromised individuals:
o AIDS and AIDS-related complex
o Patients taking immunosuppressants
o Cancer treatment
o Elderly populations

Antiprotozoal Agents
 Infections caused by protozoa (single-celled organisms).
 Protozoal infections caused by insect bites
Malaria, trypanosomiasis, leishmaniasis
 Ingestion or contact with causal organism
Amebiasis , giardiasis, trichomoniasis

Anthelmintic Agents
Helminthic infections - infections in the GI tract or other tissues due to worm infestation.
Helminths:
a. Nematodes - roundworms
b. platyhelminths – flatworms

Antineoplastic Agents
 Drugs to act on and kill or alter human cells
 Designed to fight neoplasms, or cancers
 Action is intended to target the abnormal cells that compose the neoplasm
or cancer, having a greater impact on them than on normal cells.

Anaplasia - loss of cellular differentiation and organization, which leads to a loss of

their ability to function normally. 
Metastasis - travelling from the place of origin to develop new tumors in other
areas of the body where conditions are favorable for cell growth.

Types of Cancers
1. Solid tumors 
a. Carcinomas - tumors that originate from the epithelial cells (breast, skin)
b. Sarcomas - tumors that originate in the mesenchyme and are made up
of embryonic connective tissue cells (bones, muscles)
2. Hematological malignancies - blood-forming organs of the body, the bone
marrow, and the lymphatic system. These malignancies alter the body’s ability to produce and regulate the cells
found in the blood. (leukemias, lymphomas)

Antineoplastic Drugs
Work by affecting cell survival or by boosting the immune system in its effort to combat the abnormal cells.
 Alkylating agents
 Antimetabolites
 Antineoplastic antibiotics
 Mitotic inhibitors
 Hormones and hormone modulators
 Cancer cell-specific agents
 Protein tyrosine kinase inhibitors

a. Alkylating agents produce their cytotoxic effects by reacting chemically with portions of the RNA, DNA, or
other cellular proteins, being most potent when they bind with cellular DNA.
b. Antimetabolites inhibit DNA production in cells that depend on certain natural metabolites to produce
their DNA.
c. Antineoplastic antibiotics cytotoxic and interfere with cellular DNA synthesis.
d. Mitotic inhibitors kill cells as the process of mitosis begins.
e. Hormones and hormone modulators are receptor-site specific or hormone specific to block the
stimulation of growing cancer cells that are sensitive to the presence of
that hormone.
f. Cancer cell-specific agents don’t have the devastating effects on healthy
cells.
 Protein tyrosine kinase inhibitors - act on specific enzymes that are
needed for protein building by specific tumor cells.
 Epidermal growth factor inhibitor - inhibits cell epidermal growth
factor receptors.
 Protease inhibitor - inhibits proteasome in human cells, a large
complex that works to maintain cell homeostasis and protein
production.