Lesson: Antibiotics, Antifungals, and

Antivirals
INTRODUCTION
Obviously, pharmacists and pharmacy technicians work with drugs on a daily
Lesson
basis. Some of the most commonly prescribed medications are antibiotics, ANTIBIOTICS,
antifungals, and antiviral drugs. Consequently, pharmacy technicians must be
familiar with these drug classes and develop methods for recognizing the names ANTIFUNGALS,
of the drugs in various classes and/or categories. They must also understand the
approach and mechanism of actions of these agents. This lesson provides an
AND ANTIVIRALS
overview of these subjects and offers examples of the different types of drugs
that are encountered in the pharmacy.

OBJECTIVES
After completing this lesson, you should be able to

Understand the differences among antibiotics, antifungals, and antivirals

Identify typical drugs in each class

Understand when and why to use drugs to treat various infections

Explain the advantages and risks of using chemotherapeutic agents

ANTIBIOTICS
Antibiotics are a class of drugs that inhibit the growth of bacteria without
harming the human host. This selective toxicity is a key concept with this class of
drugs, which are typified by the penicillins and the tetracyclines.

History of Antibiotics
Antibiotics were discovered in 1929 by Alexander Fleming when he first identified
penicillin as a chemical with antibiotic properties (Figure 1). This discovery
ushered in the era of antibiotics, and it has revolutionized modern medicine.
Since the initial discovery of penicillin, many additional classes of antibacterial
antibiotics have been discovered, and these drugs are now classified based on
their mechanism of action, their chemical structure, or their spectrum of activity.

PHARMACOLOGY 1
 FIGURE 1Antibiotics were discovered in 1929 by Alexander Fleming, when he
first identified penicillin as a chemical with antibiotic properties.

Gram-Positive and Gram-Negative Bacteria

Certain drugs are denoted as being effective against Gram-positive or Gram-
negative bacteria. Gram-positive bacteria are those that create a positive result in
the Gram stain test for bacteria. Gram-negative bacteria give a negative result on
the test.

Bactericidal vs. Bacteriostatic

The suffix -cidal means to kill or have killing power, whereas the suffix -static
pertains to stopping or controlling. Thus, bactericidal antibiotics typically kill the
bacteria, and bacteriostatic antibiotics merely stop their growth and replication.
With bacteriostatic antibiotics, the patients immune system must complete the
task of clearing the body of the invading bacterial species.

2 PHARMACOLOGY
Antibiotic Mechanism of Action
Certain antibiotic compounds work by 1) inhibiting cell-wall synthesis,
2) inhibiting protein synthesis, and 3) interfering with essential bacterial
enzymes.

Classes of Antibiotics
Penicillins, cephalosporins, vancomycin, imipenem, and aztreonam all work by
inhibiting the bacterial cell-wall synthesis. These medications can be subdivided
into b-lactams (penicillins and cephalosporins, along with carbapenems and
monobactams) and other cell-wall inhibitors without a b-lactam structure.

b-lactams
A b-lactam is a molecular component that works by interfering with the
enzymesspecifically penicillin-binding proteinsthat the bacteria use to build
its cell wall. This results in the formation of a weakened cell wall, which ultimately
kills the bacteria.

While this is a very effective mechanism to thwart the growth of bacteria, some
bacteria have developed resistance to b-lactams. They do this through the use of
an enzyme called a b-lactamase. In these cases, the b-lactamase can react with
the b-lactam in the antibiotic, thereby inactivating it. Penicillinase is a b-lactamase
that specifically inactivates penicillin (Figure 2).

FIGURE 2Penicillinase is a b-lactamase that specifically inactivates penicillin.

One way around the issue of penicillin inactivation is to give a b-lactamase

inhibitor, such as clavulanic acid or sulbactam. The use of these b-lactamase
inhibitors increases the effectiveness of the antibiotics. Another approach is to
chemically modify the b-lactam structure, which then makes it more difficult for
the enzyme to open the b-lactam ring, which is the four-atom chemical structure
of b-lactam.

The b-lactam class of medications include penicillins, cephalosporins,

carbapenems, and monobactams.

PHARMACOLOGY 3
 Penicillins

Penicillins are a group of antibiotics discovered in the late 1920s and are derived
from the Penicillium fungi. Thus, the natural penicillins are made by this mold, or
fungi, to kill off invading bacteria. Other penicillins have since been developed
through chemical modification of the structures. These modifications have been
made in attempts to improve the bacterial spectrum and to improve resistance to
the penicillinase enzymes, such as the b-lactamase just discussed. The suffix -cillin
makes drugs in this class easy to identify. Penicillins are typically categorized into
four groups as shown in Figure 3.
Type Spectrum
Natural Narrow Spectrum
(Gram-positive)
penicillin G
penicillin V
benzathine pen G
Penicillinase/b-lactamase resistant Narrow Spectrum
(Gram-positive)
methicillin
cloxacillin
dicloxacillin
nafcillin
oxacillin
Aminopenicillin Broad spectrum (some
Gram-negative and
amoxicillin Gram-positive)
ampicillin
Extended spectrum Active against pseudomonas;
ineffective against
azlocillin Gram-positive
carbenicillin
mezlocillin
piperacillin
ticarcillin

FIGURE 3List of -cillin Drugs

All of the penicillins have the potential to create allergic reactions. Therefore, its
very important to understand a patients sensitivity and history. Some individu-
als are extremely sensitive to penicillins, and the reactions can be fatal. They can
manifest immediately, occurring within 20 minutes. Other reactions can appear
hoursor even days or weeksafter administration.

4 PHARMACOLOGY
Allergic reactions can include the following:

Itching

Paresthesia (numbness and tingling)

Wheezing

Choking

Fever (Figure 4)

Swelling

Generalized urticarial (hives)

FIGURE 4Symptoms of allergic reaction to penicillins can include fever.

The use of IgE antibodies can help mediate hypersensitive reactions to penicillins.

Cephalosporins

Like penicillins, cephalosporins are b-lactams that were derived from a fungus
originally known as cephalosporium. All of the drugs in this class begin with
the prefix ceph- or cef-. Theyre classified by their generationfor example,
first-, second-, third- or fourth-generation cephalosporins. First-generation
cephalosporins are primarily used against Gram-positive bacteria, whereas
later generations are useful against Gram-positive and Gram-negative bacteria.
Cephalosporin drugs are typically given orally.

PHARMACOLOGY 5
 Carbapenems

The carbapenem class of antibiotics includes drugs such as doripenem,

ertapenem, imipenem, and meropenem. They have a broad spectrum of
activity anddue to their chemical designtheyre highly resistant to most
b-lactamases. Unfortunately, theyre not very soluble. They also have poor oral
bioavailabilty, which means that when given in an oral dosage, theyre difficult
to absorb into the body and become effective. Therefore, carbapenems are
delivered via intravenous administration in a hospital setting. Due to their
activity, theyre often used for serious infections as an antibiotic of last resort.

Monobactams

Aztreonam is the only currently available drug in the class of monobactam drugs.
Aztreonam only works against Gram-negative bacteria and is highly resistant to
b-lactamases.

WIN (Whats Important Now!)

Antibiotic Resistance

According to the CDC [antibiotic] drugs have been used so widely and
for so long that the infectious organisms the antibiotics are designed to
kill have adapted to them, making the drugs less effective.

Each year in the United States, at least 2 million people who become
infected with bacteria are resistant to antibiotics. At least 23,000 people
die each year as a direct result of these infections.

Because of this increased resistance to antibiotics, medical

professionals are urged to use judicious care in prescribing antibiotics.
In the case of a viral infection, antibiotics arent effective and, in fact,
merely worsens the problem of antibiotic resistance. Meanwhile, drug
companies are working diligently to create the next generation of
antibiotics to help combat this troubling issue.

Other Inhibitors of Cell-Wall Synthesis

In addition to the b-lactam antibiotics, there are a few additional drugs that work
in a similar manner, but they dont contain a b-lactam. These medications include
vancomycin, bacitracin, fosfomycin, and daptomycin. Each one of these drugs is
different both in terms of its structure and its mechanism for preventing cell-wall
synthesis.

6 PHARMACOLOGY
Vancomycin, for example, is a glycopeptide that prevents the microbial cell-wall
polymerization process. While its is a powerful antibiotic, it also can cause dose-
related ototoxicity (toxicity in the ears) leading to potential tinnitus (ringing in
the ears), high-tone deafness, hearing loss, and possible deafness. Thus, its very
important to understand the need for and administration of this drug.

Protein-Synthesis Inhibitors
Unlike the compounds previously discussed, which work by inhibiting the cell-
wall synthesis of bacteria, another group of drugs works by preventing protein
synthesis in bacteria (Figure 5). Remember that a key to successful antibiotics is
their ability to selectively target the bacteria without harming the host (humans).
While humans also need protein synthesis to live, the process by which bacteria
synthesize proteins is somewhat different from the process that occurs in human
beings. This difference makes inhibiting protein synthesis a viable way to target
bacteria with antibiotics.

FIGURE 5Antibiotics work by a variety of mechanisms, including inhibiting

protein synthesis.

This group of antibacterial drugs can be classified into three main categories:
aminoglycosides, tetracyclines, and macrolides. Some newer drugs may also be
included in this drug class.

PHARMACOLOGY 7
 Aminoglycosides

Aminoglycoside drugs all end in the suffix -mycin and include kanamycin A,
tobramycin, and neomycins B and Cto name a few of the drugs. These are
broad-spectrum antibiotics, but theyre poorly absorbed from the GI tract.
Therefore, theyre typically administered intravenously or parenterally. Its
important to note that these drugs have ototoxicity, nephrotoxicity (poisonous
to the kidneys), and neuromuscular toxicity (toxic to nerves and muscles). In
addition, the safety margin is small; that is, the toxic concentration is only slightly
higher than the therapeutic concentration. So great care has to be taken when
administering aminoglycosides.

Tetracyclines

Tetracyclines all end in the suffix -cycline and include tetracycline, doxycycline,
minocycline, and oxytetracycline. These are broad-spectrum antibiotics useful for
treating both Gram-positive and Gram-negative microbes. These drugs can be
delivered orally, although food impairs their absorption, with the exceptions of
doxycline and minocycline. The major side effect of these drugs relates to the
incorporation into teeth and bone since they form insoluble chelates, or a kind of
bond, with calcium. Teeth can be discolored and bone growth can be inhibited.
As such, -cycline drugs shouldnt be used with children or pregnant women.

Macrolides

Like the aminoglycosides, some macrolides end in the suffix -mycin. However,
most macrolides end in -thromycin, which can be useful in differentiating them
from aminoglycosides. Drugs in this class include erythromycin, azithromycin,
and clarithromycin. These drugs are particularly useful in treating mycoplasma
infections, pneumonia, Legionnaires disease, diphtheria, and pertussis. These
drugs can be delivered orally, and they have relatively few side effects.

Other Antibiotics
In addition to cell-wall synthesis inhibitors and protein-synthesis inhibitors, a
relatively new class of antibiotics is the quinolone class. These drugs work by
inhibiting DNA synthesisspecifically acting on the DNA gyrase enzyme, which
is an enzyme that relieves strain while double-stranded DNA is being unwound .
Quinolones are used primarily to treat urinary tract infections and typically end in
the suffix -oxacin. Drugs include ciprofloxacin, gemifloxacin, and levofloxacinto
name just a few. Theyre broad-spectrum antibiotics and can be used orally.

8 PHARMACOLOGY
ANTIFUNGALS
Antifungals are used to treat fungal infections. These infections typically occur in
the tissues with poor circulation or in the upper layers of the skin, nails, and hair
(Figure 6). These infections are classified as superficial fungal infections. Fungi can
also infect the human host systemically, causing diseases such as disseminated
blastomycosis and coccidiomycosis. These infections are classified as systemic
infections.

FIGURE 6Fungal infections typically occur in the upper layer of the skin, nails,
and hair.

In the case of bacteria, antibiotics often take advantage of targeting the

cell-division process, which is rapid in bacteria. In contrast, fungi divide much
more slowly, making the treatment of fungal infection more difficult. Moreover,
antifungals in general are poorly soluble drugs, making distribution to the site of
action problematic.

Therefore, antifungal agents typically work to assist the human hosts immune
system to fight against the infection. Like antibiotics, these drugs need to be
selective in targeting the invading organism rather than the human host.
Nevertheless, these drugs are useful for the treatment of a variety of
fungal diseases.

PHARMACOLOGY 9
 Classes of Antifungals
The main classes of antifungals are polyene antifungals, azole antifungals, and
echinocandins.

Polyene Antifungals
The term polyene refers to the chemical structure that makes up this group of
antifungals. The most popular drug in this class is amphotericin B, which works
by binding to sterols in the fungal cell membranewhich, in turn, ultimately
disrupts the membrane function, causing electrolytes to leak from the cell. This
process ultimately leads to cell death for the fungus. As with other successful
drugs, its important to selectively target the invading organism, not the host.
In the case of polyene ampotericin B, the sterol thats targeted by the polyene
antifungals (ergosterol) is found in the cell membrane of fungi and protozoa
but not in animals and humans. The most common toxicity associated with
amphotericin B is nephrotoxicity. Finally, this drug isnt absorbed from the GI
tract, so it must be given intravenously or topically (Figure 7).

FIGURE 7Some antifungals are nephrotoxic, so they must be given

intravenously or topically.

10 PHARMACOLOGY
Azole Antifungals
Like the polyene class of drugs, the azole class is so named because the chemical
structures in this class contain an azole chemical structure. Drugs in this class
work by inhibiting an enzyme that fungi use to make the sterol ergosterol. As with
polyene antifungals, this inhibiting leads to cell death through the disruption
of the cell membrane. Drugs include ketoconazole, bifonazole (both imidazoles),
albaconazole, fluconazole (triazoles), and abafungin (thiazole).

Echinocandins
This class of antifungals works through the disruption of the cell-wall production
by fungi, but it does so by inhibiting the synthesis of glucan, a polysaccharide
sugar. Caspofungin, anidulafungin, and micafungin are the three drugs in this
class. Theyre typically given by injection since theyre poorly absorbed orally.
Echinocandins are used to treat candida and the mold aspergillus.

Terbinafine
Terbinafine is another antifungal drug thats used for superficial fungal infections.
It targets poorly vascularized tissues such as the hair, skin, and nails. Its
administered topically.

ANTIVIRALS
Antivirals are used to treat viral infections through selective targeting of the
viral-development cycle. Vaccination is the traditional and typical method
for targeting viral disease. Its a preventive strategy whereby a vaccine is
administered to promote the immune system to develop adaptive immunity to a
pathogen or virus.

Antiviral chemotherapeutics have also been developed as an additional

treatment strategy. In fact, antivirals have been successful in treating diseases
such as the human immunodeficiency virus (HIV), which is the causative virus of
AIDS (Figure 8). In addition to targeting HIV, antivirals are now available to treat
the herpes virus, hepatitis B and C, and influenza A and B.

PHARMACOLOGY 11
 FIGURE 8Antivirals have been successful in treating the human immunodefi-
ciency virus (HIV), the causative virus of AIDS.

Like other antimicrobials and antifungals, antivirals need to selectively target

the virus without harming the host. This is particularly challenging in the area of
antiviral development since the viruses typically use the hosts cells to replicate.
Nevertheless, some effective strategies have surfaced that target the viruss life
cycle steps.

Anti-HIV
HIV is the causative virus for AIDS (acquired immune deficiency syndrome). Drugs
in this category work by a variety of mechanisms. Often, multiple drugs targeting
different mechanisms are given as a cocktail to HIV patients. This group of drugs
target an enzyme called reverse transcriptase. Therefore, the drugs in this cocktail
are called reverse transcriptase inhibitors (RTIs), which may be further divided
into nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleotide reverse
transcriptase inhibitors (NNRTIs). The cocktails for treating HIV typically include
one NNRTI and two NRTIs used in combination. A list of typical NRTIs and NNRTIs
are shown in Figure 9. These drugs typically end in the suffix -ine.

12 PHARMACOLOGY
 NRTIs NNRTIs
abacavir delavirdine
emtricitabine efavirenz
didanosine etravirine
lamivudine nevirapine
stavudine
FIGURE 9Reverse Transcriptase Inhibitors

In addition to RTIs, another group of antivirals falls into the category of protease
inhibitors (PIs). These work by interfering with the processing of viral proteins
and, therefore, prevent the formation of new viral particles. Some drugs in this
category include atazanavir, darunavir, fosamprenavir, and nelfinavir. Note that all
of these antivirals end in the suffix -vir. When used in combination, typically two
PIs are used with two NRTIs.

Influenza Drugs
While vaccination has been the standard approach toward treating influenza,
drugs have recently been developed as an alternative treatment option. As with
all antivirals, these drugs work by targeting the development cycle of a virus and
work to stop its replication. Oseltamivir is a typical drug used to treat influenza
A. If treatment is started within 48 hours of the onset of the illness, oseltamivir
shortens the duration of symptoms by about one half.

Other Antivirals
Other antivirals have been developed to treat herpes (e.g., acyclovir, valacyclovir),
respiratory syncytial virus (e.g., ribavirin), and hepatitis B (e.g., adefovir). They all
work by targeting the development cycle of the virus in a variety of ways.

PHARMACOLOGY 13
 CHECK YOUR LEARNING 1
Complete the following questions to test your knowledge.
Do not send the answers to the school.

Match the terms on the left with the definitions on the right.

_____ 1. antibiotics a. drugs used to treat viral infections

_____ 2. antifungals b. antibiotics that kill bacterial

_____ 3. antivirals c. antibiotics that stop the growth and rep-

lication of bacteria but dont have killing
_____ 4. bactericidal power

_____ 5. bacteriostatic d. polyene antifungal drug

_____ 6. penicillin e. broad-spectrum antibiotic with a major

side effect of being incorporated into the
_____ 7. tetracycline teeth and bone

_____ 8. amphotericin B f. class of drugs that inhibit the growth of

bacteria without harming the host
_____ 9. HIV
g. causative virus for AIDS
_____ 10. abacavir
h. common antiviral drug belonging to the
nucleotide reverse transcriptase inhibitor
(NRTI) class

i. common b-lactam antibiotic

j. class of drugs used to treat fungal

infections

Check your answers with those found at the end of this learning guide.
If you are accessing this lesson online, click on Check Your Learning
Answers in the left-hand menu of this lesson group.

14 PHARMACOLOGY