Drugs Used in Bacterial &

Viral Infections

THE BETA-LACTAM

ANTIBIOTICS

The beta-lactam antibiotics consist of several families of penicillins
and cephalosporins.

The penicillins arę divided into 3 groups on the basis of acid stability,
beta-lactamase resistance, and extended spectrum of activity against
gram-negative organisms.

The cephalosporins arę divided into 3 "generations," which roughly
represent narrow, intermediate, and extended spectrum of activity;
each successive generation has increased activity against gram-
negative rods and decreased activity against gram-positive cocci. All
cephalosporins are ineffective for treatment of enterococcal infection.

THE BETA-LACTAM

ANTIBIOTICS

Antimicrobial action. The beta-lactam antibiotics
(penicillins and cephalosporins) act primarily by
inhibiting a step in the synthesis of the bacterial cell
wall (not the cell membrane) that results in
spontaneous cell lysis. This critical step is the
transpeptidation reaction required to synthesize
special mucopolypeptides (peptidoglycans) and occurs
only in actively growing organisms. These products are
unique to bacteria and are necessary to maintain the
cell wall structure.
Because animal cells lack walls, they are unaffected by
the transpeptidase inhibitors.

THE BETA-LACTAM ANTIBIOTICS

Resistance. Resistance to the beta-lactam drugs occurs
through several mechanisms. The most important
mechanism is the presence of beta-lacta-mases in some
bacteria.
These enzymes hydrolyze the beta-lactam ring of the
antibiotic. Subgroups of the beta-lactam antibiotics with
increased resis tance to these enzymes have been
developed; these antibiotics are more effectiye against the
beta-lactamase-producing strains of bacteria. Other agents
are available (eg, clavulanic acid, sulbactam) that lack direct
antibacterial action of their own but bind some beta-
lactamases and prevent their action on coadministered beta-
lactam antibiotics.

Other mechanisms of resistance include genetic
modifications in the penicillin-binding proteins that are the
bacterial receptors for the beta-lactam drugs. A few species
are resistant because their cell walls are so impermeable
that the drugs cannot reach their receptors.

THE BETA-LACTAM

ANTIBIOTICS

Pharmacokinetics
A.Absorption. Some penicillins (eg, penicillin G,
methicillin) are susceptible to hydrolysis by
stomach acid and should not be taken by mouth.
The acid-stable penicillins are bound by food in the
gut and should be given between meals to
maximize absorption. Many cephalosporins are
poorly absorbed from the gastrointestinal tract and
must be administered parenterally. These
cephalosporins are usually given intravenously
because intramuscular injection is painful

.

THE BETA-LACTAM

ANTIBIOTICS

Pharmacokinetics

B. Distribution. Distribution of the beta-lactams
varies markedly, especially in the levels achieved in
the central nenrous system when the blood-brain
barrier is intact. In meningitis, this barrier is more
permeable, and bacterial meningitis can often be
treated successfully with these drugs. Some of the
newer third-generation cephalosporins achieve high
levels in the central nervous system. They are
particularly useful in the treatment of gram-negative
meningitis

.

THE BETA-LACTAM

ANTIBIOTICS

Pharmacokinetics

C. Elimination. Most of the penicillins and
cephalosporins are excreted rapidly by renal tubular
secretion. Their half-lives are relatively short, often
1-2 hours. Ampicillin is excreted more slowly, while
nafcillin is excreted primarily by biliary excretion.
Cefoperazone is excreted primarily by renal
mechanisms, but it is excreted through the biliary
tract by patients with moderate renal failure.
Cefotaxime and ceftriaxone also reach high
concentrations in the bile.

THE BETA-LACTAM

ANTIBIOTICS

Contraindications and warnings
Hypersensitivity. Hypersensitivity is a
contraindication. All of the penicillins share cross-
allergenicity, as do the cephalosporins. These 2
groups of antibiotics have limited cross-reactivity
with each other (incidence of cross-sensitivity is
estimated to be 5-16%). Most allergic responses
to the beta-lactams (even after parenteral
administration) consist of skin rashes or fever.
However, severe reactions, including anaphylaxis,
can occur. A history of hypersensitivity, although
often unreliable, is usually sufficient reason to
select a drug from another family of antibiotics.

THE BETA-LACTAM

ANTIBIOTICS

Contraindications and warnings

Bleeding abnormalities. When given in high
dosage, the extended-spectrum penicillins and
cephalosporins may cause increases in bleeding
time, prothrombin time, and platelet aggregation
time. The effect is usually, but not always, rapidly
reversible upon removal of the drug, and may be
prevented by administration of supplemental
vitamin K.

THE BETA-LACTAM

ANTIBIOTICS

Contraindications and warnings

Development of resistance. Improper use
(eg, subtherapeutic doses, combination with
bacteriostatic agents) may lead to selection of
more resistant organisms.

THE BETA-LACTAM

ANTIBIOTICS

Adverse effects

A. Allergic reactions. Anaphylactic reactions
(angioedema, bronchospasm, hypotension, shock) are
rare (< 0.1% of cases), but the use of penicillin is the
second most common cause of anaphylaxis in the USA. A
history of an anaphylactic reaction to any beta-lactam
agent warrants avoidance of this entire class of drugs
(both penicillins and cephalosporins) if at all possible.
Other non-life-threatening reactions (fever, skin rash,
phlebitis, elevated liver function tests) are observed
much more frequently than true anaphy laxis, but may
also require discontinuation of the antibiotic.

THE BETA-LACTAM

ANTIBIOTICS

Adverse effects

B. Superinfection. When given over long periods,
or when given to patients with inadequate immune
defenses, antibiotic use may result in superinfection
with resistant organisms. This is particularły
common with prolonged oral use. Antibiotic-
associated pseudomembranous colitis may also
occur;
when caused by Clostridium difficile, a toxin-
producing organism, it may be treated with oral
vancomycin, bacitracin, or metronidazole

THE BETA-LACTAM

ANTIBIOTICS

Adverse effects

C. Gl effects. The oral use of beta-lactams, especially
the cephalosporins, is sometimes associated with
diarrhea, nausea, and vomiting
D. Tissue inflammation and damage. Intramuscular
injection often causes pain and tissue damage at the site
of injection. When large doses must be given parenterally,
the intravenous route is preferred. Phlebitis may occur
with administration of some beta-lactams (nafcillin,
oxacillin) through peripheral veins
E. CNS effects. Neurotoxicity may occur in patients
treated with high doses of the beta-lactams, especially if
the blood-brain barrier has been disrupted and antibiotic
penetration enhanced and renal function is impaired,
resulting in very high serum and CNS drug
concentrations. Clinical signs include lethargy,
hallucinations, convulsions, and coma

THE BETA-LACTAM

ANTIBIOTICS

Adverse effects
F. Electrolyte effects. Large parenteral doses of
potassium salts of penicillins (eg, penicillin G) can
result in hyperkalemia. Similarly, large doses of the
sodium salts of the beta-lactams may result in
sodium overload, with
exacerbation of congestive heart failure.
G. Renal effects. A few beta-lactams, notably
methicillin and cefalothin, have been associated with
a reversible allergic interstitial nephritis. Because of
the risk of nephrotoxidty, patients with impaired renal
function (creatinine clearance < 50 mL/min/1.73 m2)
should be carefully monitored while receiving
cephalosporins and are often given reduced doses.

THE BETA-LACTAM

ANTIBIOTICS

Adverse effects

H. Overdose toxicity. Because their primary action
is on a biochemical process that does not exist in
mammals, the beta-lactams are extraordinarily
nontoxic even at very high doses, except for the
allergic reactions

.

THE BETA-LACTAM

ANTIBIOTICS

Drug interactions

A. Aminoglycosides. Aminoglycosides and beta-lactam
agents may have additive or synergistic effects against
many organisms, especially entero-cocci and gram-
negative organisms. However, these 2 classes of
antibiotics should not be mixed in the same intravenous
bottles or syringes, because they are physically
incompatible.
B. Probenecid and other weak acids. These agents
compete with the beta-lactams for the renal tubular acid
secretory carrier. Coadministration increases the
antibiotic half-life but often decreases the peak urinary
con-centration.
C. Bacteriostatic antibiotics. Coadministration of
bacteriostatic agents (eg, tetracyclines) may reduce the
effectiveness of beta-lactam agents

because the latter

require actively growing bacterial cells for maximum
effect.

Drug

Recommended

Dosage

Acld

Stability

Beta-

Lactamase
Resistance

Amdinocillin
IV or IM (0.5,1 g vials)

700 mg IV or
IM q6h

NA"

Partial

Amoxicillin Oral (125, 250 mg chewable tabs; 250,
500 mg

caps; powder for solution)

250-500 mg
PO q8h

Yes

No

Amoxicillin and Potassium CIauulanate Oral

(125,250, 500 mg tabs)

250-500 mg PO q8h

Yes

No

Ampicillin

oral (250,500 mg caps; powder for solution) IV or IM
(125, 250, 500 mg powder;

500-1000 mg PO, l V,

or
IM q6h

Yes

No

Azlocillin
IV (2,3,4 g vials and piggyback vials)

2000-3000 mg IV q4-
6h

NA'

No

Bacampicillin
Oral (400 mg tabs [equivalent to 280 mg ampicillin])

400-800 mg PO q12h

Yes

No

Benzathine Penicillin G
IM (0.3,0.6,1.2, 2.4 MU per dose in single- dose

syringes)

1.2-3.6 MU IM q1-
4wk

NA'

No

Carbenicillin

Oral (382 mg tabs)
IV or lM 1, 2, 5,10 g vials

and piggyback vials)

300-5000 mg PO, IV,

or
IM q4-6h

Yes

No

Cloxacillin
Oral (250, 500 mg caps; powder for solution)

500-1000 mg PO q6h

Yes

Yes

Cyclacillin
Oral (250, 500 mg tabs; powder for solution)

250-500 mg PO q6h

Yes

No

Dicloxacillin Oral(125, 250,500 mg caps; powder for

solution)

250-500 mg PO q6h

Yes

Yes

CLINICAL PHARMACOKINETICS ANO DOSAGES OF PENICILLINS

NA = not applicable (not used by the oral route).

Methlcillin
IVorlM(1,4,6gvials; IV piggyback vials)

1000-2000 mg IV or
IM q4-6h

NA'

Yes

Mezlocillin
IV or IM (1, 2, 3,4 g vials and piggyback

vials)

1500-4000 mg IV or
IM q4-6h

NA'

No

Nafcillm

Oral (250 mg caps; 500 mg tabs; powder
for solution) IV or IM (0.5,1,2 g vials; 1,2,4

g IV piggyback vials)

500-1000 mg PO, IV,

or IM q4-6h

Yes

Yes

Oxaclllin

Oral (250,500 mg caps)
IV or IM (0.25,0.5,1,2,4 g vials; 1, 2 g IV

500-1000 mg PO, IV,

or IM q4-6h
piggyback vials)

Yes

Yes

Penicillin G

Oral (0.2,0.25, 0.4,0.5, 0.8 MU tabs)
IV (0.2, 0.5,1,2, 5 MU 'powder)

0.4-0.8 MU (250-500

mg) PO q6h 1-6 MU
IV q4-6h

No

No

Penicillin V
Oral (125, 250,500 mg tabs; powder for

solution [125,250mg/5mL])

250-500 mg PO q6h

Yes

No

Piperacillin IV or IM (2, 3,4 g vials)

) 2000-4000 mg IV or
IM q4-6h

NA"

No

Drug

Recommended

Dosage

Acld

Stability

Beta-

Lactamase
Resistance

Cefaclor
Oral(250, 500 mg caps; powder for

suspension)

250-1000 mg PO q8h

Yes

No

Cefadroxil
Oral (500 mg caps; 1 g tabs,

powder for suspension
for suspension

500-1000 mg PO
q12h

Yes

No

Cefazolin) IV or IM (0.25, 0.5,1, 5 g vials,

piggy back vials)

250-1000 mg IV or

IM
q6-12h

Na

No

Cephalexin
Oral (250, 500 mg caps; 1 g tabs;125,

250 mg/5 mL suspension)

250-1000 mg PO q6h

Yes

No

Cephalothin

(IVorlM(0.5,1,2,4gvials,infusion packs)

500-1000 mg IV or

IM q6h

Na

Yes

Cephapirin
IV or lM (0.5,1,2,4gvials,piggyback vials)

500-1000 mg IV or
IM
q6h

Na

Yes

Cephradine
Oral (250, 500 mg caps; powder for

suspension
IV or IM 0,25. 0,5. 1, 2, 4g

250-1000 PO, IV, or
IM

q6-12h

Yes

No

NARROW-SPECTRUM (FIRST-GENERATION) CEPHALOSPORINS
Spectrum: active against gram-positive organisms; also active against
some gram-negatives, including E coli, Klebsiella, Haemophilus, and
Proteus mirabilis

Cefamandole
IVorlM(0.5,1,2,10gvials)

500-1000 mg IV or IM
q4-8h

NA"

Partial

Cefonicid

IV or lM (0.5, 1, 10g vials)

1000-2000 mg IV or IM

q24h

NA"

Yes

Ceforanide

IV o rlM (0.5,1,10gvials)

500-1000 mg IV or IM

q12h

NA"

Yes

Cefotetan
IVorlM(1,2gvials)

1000-2000 mg IV or IM
q12h

NA''

Yes

Cefoxitin
IV or lM (1,2,10 gvials)

1000-2000 IV or IM
q6-8h

NA'

1

Yes

Cefuroxime
Oral (axetil: 125, 250, 500 mg tabs)

IV or IM (sodium: 0.75,1.5 g vials,
infusion

packs)

125-500 mg PO q12h
750-1500 mg IV or IM

q8h

Yes
NA"

Yes
Yes

INTERMEDIATE-SPECTRUM (SECOND-GENERATION)
CEPHALOSPORINS Spectrum: active against gram-positive organisms; also
active against some gram Klebsiella, Haemophilus, and some species of
Proteus, Providencia, and Enterobacter

BROAD-SPECTRUM (THIRD-GENERATION) CEPHALOSPORINS

(Spectrum: less activity against gram-positive organisms; active against many

gram-negatiyes, including E coli, Klebsiella, Haemophilus, and some species of

Proteus, Proyidencia, Enterobacter, Salmonella, Shigella, and Serratia: also

active against some anaerobic bacteria and Pseudomonas)

Drug

Recommended Dosage

Acld

Stabili

ty

Beta-Lactamase

Resistance

Cetixime

Oral (200,400 mg tabs)

200-400 mg PO q12-24h

Yes

Yes

Cefoperazone

IV or IM (1,2 g vials)

1000-2000 mg IV or IM

q12-24h

NA

Yes

Cetotaxime

IV or lM (1,2,10gvials)

1000-2000 mg IV or IM

q12h

NA

Yes

Celtazillime IV or lM (0,5, 1, 2, 6g vials)

500-2000 mg IV or IM

q8-12h

Na

Yes

Ceftizoxime IVorlM(1,2gvials)

1000-2000 mg IV or IM

q8-12h

NA

Yes

Ceftriaxone IV or lM (0.25, 0.5, 1, 2g vials)

1000-2000 mg IV or IM

q12-24h

NA

Yes

Moxalactam IV or lM (1,2,10g vials)

500-2000 mg IV or IM

q8-12h

NA

Yes

THE TETRACYCLINES & CHLORAMPHENICOL

Mechanisms
A. Antimicrobial action. The tetracyclines and
chloramphenicol are bacterio-static agents that act by
inhibiting protein synthesis in both gram-positive and
gram-negative microorganisms. The selective action of
the tetracyclines results from an active process that
concentrates these agents in microorganisms but not in
mammalian cells. Chloramphenicol binds to a separate
receptor and blocks a different step in protein
synthesis. Chloramphenicol is less selective than the
tetracyclines, and it reduces pro tein synthesis in
mammalian hematopoietic cells as well as in bacteria.
Both groups of drugs have a broad spectrum of
antibacterial effects. The tetracyclines remain among
the most heavily prescribed antibiotics.

THE TETRACYCLINES &

CHLORAMPHENICOL

Resistance. Bacterial resistance to the
tetracyclines occurs as the result of a loss of
the active concentrating mechanism for the
antibiotic. Passive permeability to the drugs
may also decrease in resistant organisms.
Extensive use of these agents in animal feeds
has resulted in widespread develop-ment of
bacterial resistance. Resistance to
chloramphenicol is plasmid-mediated and
results in the production of an enzyme that
inactivates the antibiotic.

TETRACYCLINES

Pharmacokinetics
A. Absorption and distribution.
Absorption of the tetracyclines from the
gastrointestinal tract is variable and is
impaired by calcium-containing foods such
as milk products. Distribution is widespread,
but central nervous sys tem penetration is
poor. Because they chelate calcium, the
tetracyclines are bound to bones and teeth
and can interfere with the normal growth
and development of these tissues.

TETRACYCLINES

B. Elimination.

Tetracyclines are excreted in both the bile
and the urine. An
exception is doxycycline, which is not
excreted by the kidneys

TETRACYCLINES

Contraindications and warnings

A. Hypersensitivity. Hypersensitiyity to
any tetracycline is a contraindication.
B. Pregnancy. Pregnancy is a
contraindication, unless there is no other
adequate drug for a life-threatening
infection.
C. Pediatrie usage. Tetracyclines should
not be used in children under 8 years of
age because of potential damage to their
teeth.

TETRACYCLINES

Adverse effects

A. Gl effects. Gastrointestinal effects are the most
common adverse reactions and include nausea,
epigastric distress, vomiting, steatorrhea, and
diarrhea.
B. Skin effects. Skin rashes and photosensitization
are frequent. Loss of nails (onycholysis) occasionally
follows photosensitmty reactions. Exfoliative
dermatitis occurs rarey. Blue-gray pigmentation may
occur, especially with prolonged minocycline
treatment.

TETRACYCLINES

Adverse effects

C. Renal effect. Nephrogenic diabetes
insipidus, especially with demeclocycline, is
a possible reaction.
D. Hematologie effects. Blood dyscrasias
are rare with the tetracyclines.
E. Overdose toxicity. Overdose toxicity
results in worsening of the above adverse
effects.

TETRACYCLINES

Interactions

A. Food and antacids. Substances that contain
large amounts of divalent cations (calcium,
magnesium, etc) reduce the absorption of most
tetracy clines.
B. Drug interactions. Hepatic drug-metabolizing
enzyme inducers (eg, barbiturates,
carbamazepine, phenytoin) may decrease the half-
life of doxycycline. The tetracyclines and other
bacteriostatic antibiotics can theoretically interfere
with the beta-lactam and other bactericidal
antibiotics that require active bacterial growth for
maximum effectiveness.

CHLORAMPHENICOL

Pharmacokinetics
A. Absorption and distribution.
Chloramphenicol is readiiy absorbed. It is
widely distributed in the body, including the
central nervous system and bonę.
B. Elimination. Most of the drug is
inactivated by conjugation with glucuronic
acid, a process that is deficient in neonates.
The metabolites are excreted almost
entirely in the urine.

CHLORAMPHENICOL

Contraindications and warnings
A. Hypersensitivity. Hypersensitivity is a
contraindication.
B. Hematologic toxicity. Chloramphenicol
may cause serious bonę marrow
C. Pregnancy. The safety of chloramphenicol
in pregnancy has not been established, but
the drug crosses the placenia and can induce
serious toxicity in the fetus (gray baby
syndrome)
D. Neonates. The drug may induce the gray
baby syndrome in neonates

CHLORAMPHENICOL

Adverse effects
A. Hematologie effects. Chloramphenicol is
associated with 2 different blood disorders. The more
common is a reversible, dose-dependent, and
predictable depression of the bone marrow.
Reticulocytopenia, leukopenia, thrombocytopenia,
and anemia are commoniy observed when large
doses must be used over long periods (peak blood
levels > 25 µg/mL and trough levels > 10 ug/mL).
The less common, but more serious, adverse effect
(estimated incidence 1:40,000-1:200,000) is an
irreversible and non-dose-dependent aplastic anemia
that is usually fatal. It is essential, therefore, that
frequent blood studies be carried out on any patient
receiving this antibiotic.

CHLORAMPHENICOL

Adverse effects
B. Superinfection. This may occur with
prolonged use of this agent.
C. Gray baby syndrome. Gray baby
syndrome (abdominal distention, pallid
cyanosiś, vasomotor collapse, and death)
may occur in neonates receiving this drug. It
can be prevented by appropriate adjustment
of dosage for the reduced ability of the
neonatal liver to conjugate the drug with
glucuronic acid.
D. Overdose toxicity. Overdose results in
exacerbation effects.

CHLORAMPHENICOL

Drug interactions. Chloramphenicol
inhibits the metabolism and prolongs the
half-lives of dicumarol, phenytoin,
phenobarbital, tolbutamide, chlorpropamide,
and cyclophosphamide. There is some
evidence that acetaminophen may inhibit the
metabolism of Chloramphenicol.

Drug

Recommended

Dosage

Durati

on

Demeclocycline Oral (150 mg caps;

150,300 mg tabs)

150-300 mg PO q6h

……

Doxycycline
Oral (50,100 mg caps, tabs; 25, 50

mg/5mLsuspension) IV(100,200mgvials)

100-200 mg PO or IV
q12-24h

24h

Methacycline
Oral(150,300 mg caps)

150-300 mg PO q6-12h

12-24 h

Minocycline
Oral (50,100 mg caps, tabs; 50 mg/5 mL

suspension)
IV(100mg vial)

100-200 mg PO or IV q6-
12h

12-24 h

Oxytetracycline

Oral 250 mg caps, tabs
IV: 250, 500 mg vials

IM: 50,125 m g/m L

250-300 mg PO, IV, or

IM q8-24h

12-24 h

Tetracycline
Oral (100,250,500 mg caps; 125 mg/ 5 mL

suspension) IV or IM(100,250 mg vials)

250-500 mg PO, IV,
orlMq6-12h

12-24 h

Tetracycline anil Amphotericin B
Oral (each capsule contains 250 mg of

tetracycline and 50 mg of amphotericin B)

1 or 2 capsules PO q6-
12h

……

CHLORAMPHENICOL

Oral (250,500 mg caps; 150 mg/5 mL
suspension)

IV(100mg/mL

6 mg/kg PO or IV q6h for

infants under 2 wk of
age and children with

immature metabolic
processes;

12.5 mg/kg PO or IV q6h
for adults and all other

infants and children

6-8h

CLINICAL PHARMACOKINETICS AND DOSAGES OF THE TETRACYCLINES ANO CHLORAMPHENICOL

THE AMINOGlYCOSIDES &

POLYMYXINS

The aminoglycosides and the polymyxins are
bactericidal agents that are useful in the
treatment of serious gram-negative infections
and, as topical agents, in the management of
superficial infections.

AMINOGLYCOSIDES

Mechanisms
A. Antimicrobial action. The
aminoglycoside antibiotics act by irreversibly
inhibiting microbial protein synthesis. They
apparently enter the bacterial cell through
both active and passive processes, but the
latter process may be enhanced by
concurrent treatment with beta-lactam
antibiotics.

AMINOGLYCOSIDES

Mechanisms

B. Resistance. Resistance to the
aminoglycosides occurs through several
mechanisms: deletion of the active uptake
process required to concentrate the drug
inside the microbial celi; alteration of the
receptor protein inside the cell that mediates
the inhibition of protein synthesis; and
development of enzymes that metabolize the
antibiotic molecule.

AMINOGLYCOSIDES

Major indications
A. Gram-negative infections. Because these
agents are not absorbed from the gastrointestinal
tract, they are used primarily for serious gram-
negative infections that require parenteral therapy.
They are also used orally o reduce the number of
intestinal organisms in preoperative bowel prepars
tion.
B. Penicillin-resistant gonorrhea. Spectinomycin
is a related aminocyclitol agent that is used almost
exclusively for the treatment of penicillin-resistant
gonorrhea

AMINOGLYCOSIDES

Pharmacokinetics
A. Absorption and distribution. The
aminoglycosides are not absorbed after oral
administration and must be given parenterally for
systemic effect. The are usually given
intramuscularly or intravenously. They do not
permeate lipid barriers.
B. Elimination. These drugs are excreted
primarily by glomerular filtration and have a
longer than normal half-life in patients with
impaired renal function. Since excessive levels can
produce renal and otologic toxicities, it is essential
to monitor serum levels when the aminoglycosides
are used in high-risk patients.

AMINOGLYCOSIDES

Contraindications and warnings.
Because of their toxicity, (especially renal
and ototoxicity), close monitoring of these
agents is recommended with long term
use. Neomycin is no longer used
systemically because of its severe renal
and ototoxicity.

AMINOGLYCOSIDES

Adverse effects.
Renal damage.
High serum levels of aminoglycosides
predictably result in renal impairment
(manifested by proteinuria, hematuria, white
cell casts, and azotemia). Renal function
should be monitored in all patients, especially
those with preexisting renal disease. Relative
renal toxicity appears to be as follows:
neomycin > kanamycin, amikacin, gentamicin,
netilmicin > tobramycin > streptomycin.

AMINOGLYCOSIDES

Adverse effects.
Ototoxicity.
Aminoglycosides should be used for the
shortest time required, with serum level
monitoring to ensure that levels are not
excessive. Relative ototoxicity appears to be
graded in the following order: neomycin >
streptomycin > kanamycin > amikacin,
gentamicin, tobramycin, netiimicin.

AMINOGLYCOSIDES

Overdose toxicity
A. Renal and otologic effects. Overdose
results in worsening of the above adverse
effects.
B. CNS effects. Confusion, disorientation,
depression, lethargy, respiratory depression,
and delirium (with tobramycin) may occur.
C. Neurologic effects. Paresthesias,
tremor, weakness, and muscle paralysis
may result.
D. Gl effects. Nausea and vomiting are
possible reactions

AMINOGLYCOSIDES

Drug interactions.
Beta-lactams. The aminoglycosides have
additive or synergistic effects with these
antibiotics against many difficult-to-treat
organisms, especially gram-negatives and
enterococci. However, these 2 classes of
compounds should not be mixed before
administration because they are physically
incompatible.

AMINOGLYCOSIDES

Loop diuretics. The effect of
aminoglycosides on the eighth cranial nerve is
potentiated by other ototoxic drugs.
Neuromuscular blockade. The
aminoglycosides potentiate neuromuscular
blocking agents, especially those of the curare
type. In addition, respiratory depression or
paralysis has followed the use of these agents
during or after general anesthesia, and in
patients with myasthenia gravis,
parkinsonism, and botulism.

DOSAGES OF AMINOGLYCOSIDES ANO RELATED ANTIBIOTICS USED
IN THE TREATMENT OF SYSTEMIC INFECTIONS

Drug

Recommended
Dosage

Half-
Life

Amikacin IV or IM (100,500,1000 mg yials

15 mg/kg/d IV or IM,

2.3 h)
usually given as 2 or 3

divided doses

2,3h

Gentamicin IV or IM (60, 80,100 mg

piggyback units;10,40
mg/mL); Intrathecal (2 mg/mL)

3-4.5 mg/kg/d IV, IM,

or intrathecally, usu ally
given as 3 divided doses

2-3 h

Kanamycin IV or lM (500,1000mg vials)

15 mg/kg/d IV or IM,
usually given as 3 or 4

divided doses

2.1 h

Netilmicin IV or lM (150mg vials)

3-4 mg/kg/d IV or IM,

usually given as 3 or 4
divided doses

2,3h

Spectinomycin IM (2,4 g vials)

2000 mg IM, given as

2-3 h single dose

2-3h

Streptomycin IM (400 mg vials)

14-28 mg/kg/d IM,
usually given as 3 or 4

divided doses

5.3 h

Tobramycin IV or IM (60,80 mg vials)

3-5 mg/kg/d IV or IM,
usually given as 3

or4divided doses

2,2h

Kanamycin Oral (500 mg caps)

4000 mg/d PO usually

given as 4 divided doses

…..

Neomycin Ora (500 mg tabs)

4000 mg/d PO, usually

given as 4 divided doses

….

Paromomycin Oral (250 mg caps)

4000 mg/d PO, usually
given as 4 divided doses

……

POLYMYXINS

Mechanisms. Polymyxins are large
polypeptide antibiotics that interfere with
bacterial cell membrane transport
mechanisms and osmotic regulation. They
are bactericidal. Three formulations from this
family are currently available: colistin
(polymyxin E), colistimethate (the
methanesulfonate derivative of colistin), and
polymyxin B. Resistance in gram-negative
organisms is rare.

POLYMYXINS

Pharmacokinetics.
Absorption and distribution.
Polymyxins are not absorbed from the
gastrointestinal tract and must be given
parenterally for systemic effect. They are
slowly and incompletely distributed to the
tissues and do not reach bactericidal
levels in the central nervous system or
intracellular compartments. Colistin
(polymyxin E sulfate) is available only for
oral use, whereas the other agents may
be given parenterally.

POLYMYXINS

Elimination. Polymyxins are eliminated by
the kidneys. The drugs accumulate rapidly
in renal failure

POLYMYXINS

Indications. Polymyxins have been used to
treat serious enteric infections
with susceptible gram-negative organisms
(pathogenic E coli, Shigella,
Enterobacter, Klebsiella, and Pseudomonas,
but not Proteus).
However, less toxic drugs are now available for
all these organisms, and the polymyxins
should probably never be used.

POLYMYXINS

Adverse effects
A. Neurologic effects. Adequate systemic
concentrations of any polymyxin may result in
paresthesias, vertigo, and loss of coordination.
B. Renal effect. Nephrotoxicity (manifested by
proteinuria, cylindruria, and azotemia) is a dose-
dependent effect of systemically administered
polymyxins. It is usually reversible, but fatal
reactions have occurred.
Drug interactions
A. Neuromuscular blocking drugs. Effects of
these drugs are potentiated or increased by the
polymyxins. Calcium gluconate may be tried as an
antidote if rapid reversal is needed.
B. Other nephrotoxic drugs. These should be
avoided during use of polymyxins.

THE OUINOLONES

This is a group of fluorinated antimicrobial
drugs deriyed from nalidixic acid.

Mechanisms
Antimicrobial action. The quinolones
block DNA synthesis in bacteria by
inhibiting DNA gyrase (type II
topoisomerase). Other mechanisms may
also play a role.

THE OUINOLONES

Resistance. Resistance to the quinolones
has been observed and most often involves
a mutation in the target DNA gyrase
system. Multidrug resistance involving a
decrease in drug permeation into the
microorganism may include resistance to
fluoroquinolones

THE OUINOLONES

Major indications
A.Urinary tract infections. These drugs

are excreted in the urine in high
concentration, and are effective against
most of the common urinary tract
pathogens. Norfloxacin is used almost
exclusively for urinary tract infec tions
(UTIs),urethral gonorrhea

B. Other infections. Ciprofloxacin is used

for a variety of lung, bone and joint, and
urinary infections involving K pneumoniae,
E coli, Proteus, Pseudomonas, Serratia,
Shigella, and Staphylococcus spp

THE OUINOLONES

Pharmacokinetics
A. Absorption and distribution. Although the
bioavailability of Ciprofloxacin (70%) is much greater
than that of norfloxacin (30-40%), both drugs are
well absorbed after oral administration.
Ciprofloxacin, unlike norfloxacin, is well distributed
to peripheral tissues. However, the concentration of
Ciprofloxacin in the cerebrospinal fluid (CSF) is only
about 10% of the peak serum concentration.
B. Elimination. Both drugs are excreted in high
therapeutic concentrations in the urine, with about
30% of Ciprofloxacin and as much as 50% of
norfloxacin unchanged. Half-lives of both
compounds, normally 3.5-4 hours, are prolonged in
patients with impaired renal function

.

THE OUINOLONES

Contraindications and warnings
A. Hypersensitivity. Hypersensitivity to any
quinolone drug is a contraindication.
B. Pregnancy. Although both drugs are
classified as pregnancy category C, their
manufacturers state that they should not be
used in pregnant women because of animal
embryotoxicity.
C. Use in children. The use of quinolones is
contraindicated because of evidence of
arthropathy in immature animals.

THE OUINOLONES

Adverse effects
A. Gl effects. Nausea and vomiting occur in 3-6%
of patients.
B. CNS effects. Headache, dizziness, and
lightheadedness occur in 1-3% of patients. Seizures
have occurred rarely with both drugs.
C. Skin effects. Rash, erythema, and pruritus
occur in 0.3-1% of patients. Stevens-Johnson
syndrome has occurred after the use of norfloxacin.
D. Miscellaneous effects. Elevations of liver
enzymes, eosinophilia,.
E. Treatment of overdose. Ciprofloxacin can be
removed by hemodialysis.

BACITRACIN

Mechanisms.
Bacitracin interferes with cell wall synthesis
by a mechanism completely different from
that of the beta-lactams. Therefore, there is
no cross-resistance with the latter group.
Because of serious nephrotoxicity, it is rarely
used systemically. It is stiII extensively used
for surface infections.

BACITRACIN

Indications. Bacitracin is used to treat
surface infections of the skin, wounds, and
mucous membranes . It is effective against
most gram-positive organisms. It is used
rarely in infants with pneumonia or
empyema caused by susceptible strains of
Staphylococcus aureus

BACITRACIN

Pharmacokinetics
A. Absorption and distribution. Topical
application (the usual route) results in very
little absorption. Even intrapleural
administration does not result in dangerous
blood levels. After intramuscular injection,
the drug is rapidly absorbed and widely
distributed in the body.
B. Elimination. Elimination (after
systemic administration) is by glomerular
filtration into the urine.

BACITRACIN

Adverse effects
Topical use. Skin rashes occur but are
uncommon.
Systemic administration. Nephrotoxicity
is not uncommon and may be severe. It is
manifested initially by proteinuria,
hematuria, and azotemia

BACITRACIN

Drug interactions. If systemic use is
considered, other nephrotoxic agents should
be avoided. Neuromuscular blockade by
curarelike agents and other drugs with
neuromuscular effects, eg, aminogłycosides,
is potentiated by sys temic bacitracin

CLINDAMYCIN &

LINCOMYCIN

Mechanisms. These agents act by inhibiting
protein synthesis in gram-positive organisms
and in Bacteroides and many other
anaerobes. Resistance occurs slowly.
Lincomycin is rarely used.

CLINDAMYCIN &

LINCOMYCIN

Indications. Bacteroides fragilis and mixed
anaerobic infections are indications for the
use of these drugs. Clindamycin is also
useful as a second-line agent in gram-
positive infections and, because of excellent
bone penetration, is advocated in
osteomyelitis due to susceptible organisms

CLINDAMYCIN &

LINCOMYCIN

Pharmacokinetics
A. Absorption and distribution.
Clindamycin is well absorbed and distrib
uted, except to the central nervous
system.
B. Excretion. Elimination is by way of the
liver and the kidneys.

CLINDAMYCIN &

LINCOMYCIN

Contraindications and warnings.
Hypersensitivity to either agent is a con
traindication.
These drugs should not be used in minor
infections.

CLINDAMYCIN &

LINCOMYCIN

Adverse effects
Gl effects. Severe diarrhea occurs in 3-
30% of patients and may produce
antibiotic-associated colitis involving
toxigenic Clostridium difficile.
Hepatic effects. Jaundice and abnormal
liver function tests have been reported

Drug interactions.
The action of neuromuscular-blocking
drugs is enhanced by these antibiotics

ERYTHROMYCIN

Mechanisms.
Erythromycin inhibits microbial protein
synthesis. The drug may
be bacteriostatic or bactericidal, depending on
dosage.
Indications. Erythromycin is indicated in the
treatment of streptococcal or staphylococcal
infections as a substitute for beta-lactam
agents when the latter cannot be used for any
reason. It is also used to treat Legionella
infections and
Chlamydia infections, especially in pregnancy
and in newborns.

ERYTHROMYCIN

Pharmacokinetics
A. Absorption and distribution.
Erythromycin base is not acid-stable, so
salts are used for oral administration. Once
absorbed, the drug is well distributed except
to the central nervous system.
B. Elimination. Excretion is by way of the
liver into the bile

ERYTHROMYCIN

Contraindications
A. Hypersensitivity. Hypersensitivity to
any erythromycin is a contraindication.
B. Preexisting liver disease. This is a
contraindication to the use of ery thromycin.

ERYTHROMYCIN

Adverse effects
Hepatic effects. Cholestatic jaundice has
been reported with all forms of
erythromycin, but especially with the
estolate salt.
Gl effects. Epigastric distress may be
severe, but it is usually transient.

Drug interactions. Erythromycin probably
inhibits the hepatic metabolism of
carbamazepine and theophylline

METRONIDAZOLE

Mechanisms. Though originally introduced
for the treatment of protozoal dis ease
(especially Trichomonas vaginalis infections),
metronidazole also has striking bactericidal
activity against most anaerobic bacteria. The
drug is apparently activated by redox
processes in an anaerobic environment within
the microorganism.
Indications. Protozoal infections and
anaerobic infections, especially those due to
B fragilis, Gardnerella, and Clostridium

METRONIDAZOLE

Pharmacokinetics
A. Absorption and distribution. The drug is
readily absorbed and widely distributed to all
tissues, including the central nervous system,
bone, and even abscesses.
B. Elimination. Metronidazole is metabolized
in the liver, but the parent compound and
metabolites are excreted in the urine.

METRONIDAZOLE

Contraindications and warnings
Hypersensitivity. Hypersensitivity to the
drug or to other nitroimidazole
derivatives is a contraindication.
Pregnancy, first trimester. Although no
fetal abnormalities have been reported in
humans, metronidazole is a teratogen in
mice.

METRONIDAZOLE

Adverse effects. At therapeutic doses,
metronidazole is relatively free of untoward
effects. Minor reactions include metallic
taste, glossitis, anorexia, and other
gastrointestinal effects. Overdosage has
been associated with nausea, vomiting,
ataxia, and, rarely, seizures.

Drug interactions. nausea, vomiting,
flushing, headache, and hypotension when
alcohol (ethanol) is consumed

VANCOMYCIN

Mechanisms. The mechanism of action
involves inhibition of cell wall synthesis.
Resistance is rare and develops slowly. There
is no cross resistance with other antibiotics.

VANCOMYCIN

Indications
Enterocolitis. Oral administration is effective
therapy only for enterocolitis due to gut
overgrowth with Clostridium difficile.
Systemic infections. Vancomycin is
indicated only for serious infections due to
gram-positive organisms (Staphylococcus,
Streptococcus, diphtheroids) when other
agents are contraindicated or ineffective. It is
the only agent available with good efficacy
against methicillin-resistant Staphylococcus.

VANCOMYCIN

Pharmacokinetics
Absorption and distribution. Vancomycin
is not absorbed after oral administration. It
is useful as an oral agent only in intestinal
infections. After
intravenous administration, it is well
distributed to tissues, including good
penetration into the CNS.

Elimination. After oral administration, the
drug is eliminated entirely in the feces.
Parenteral administration results in renal
excretion. The drug is noteffectively
removed by hemodialysis.

VANCOMYCIN

Adverse effects
Thrombophlebitis. Thrombophlebitis may
occur at the site of intravenous
administration.
Allergic reactions. Fever, chills, and rashes
have been observed
Direct toxicity. Ototoxicity and
nephrotoxicity rarely occur
Histamine release. Histamine release with
a sudden fall in blood pressure and a
maculopapular rash on the upper half of the
body ("red neck syndrome") may occur after
rapid intravenous infusion.

VANCOMYCIN

Drug interactions. There is possible
additive toxicity with other ototoxic and
nephrotoxic drugs.

Acyclovir

Mechanism of Action:
Acyclovir is converted to acyclovir
monophosphate by virus-specific thymidine
kinase then further converted to acyclovir
triphosphate by other cellular enzymes.
Acyclovir triphosphate inhibits DNA
synthesis and viral replication by competing
with deoxyguanosine triphosphate for viral
DNA polymerase and being incorporated into
viral DNA.

Acyclovir

Pharmacodynamics/Kinetics
Absorption: Oral: 15% to 30%
Distribution: Widely (ie, brain, kidney, lungs, liver,
spleen, muscle, uterus, vagina)

Bioavailability: Oral: 10% to 20% with normal renal
function (bioavailability decreases with increased
dose)
Half-life elimination: Terminal: Neonates: 4 hours;
Children 1-12 years: 2-3 hours; Adults: 3 hours
Time to peak, serum: Oral: Within 1.5-2 hours
Excretion: Urine (62% to 90% as unchanged drug and
metabolite)

Acyclovir

Use:

Treatment of genital herpes simplex virus
(HSV), Herpes labialis (cold sores),
Herpes zoster (shingles),
HSV encephalitis,
Neonatal HSV,
Mucocutaneous HSV,
Varicella-zoster (chickenpox)

Acyclovir

Pregnancy Implications:
Teratogenic effects were not observed in
animal studies. Acyclovir has been shown
to cross the human placenta.

Lactation:
Enters breast milk/use with caution

Acyclovir

Contraindications:
Hypersensitivity to acyclovir,
valacyclovir, or any component of the
formulation

Acyclovir

Warnings/Precautions
Use caution in the elderly, pre-existing renal disease or
in those receiving other nephrotoxic drugs. Maintain
adequate hydration during I.V. therapy. Use I.V.
preparation with caution in patients with underlying
neurologic abnormalities, serious hepatic or electrolyte
abnormalities, or substantial hypoxia.

Chickenpox: Treatment should begin within 24 hours of
appearance of rash; oral route not recommended for
routine use in otherwise healthy children with
varicella, but may be effective in patients at increased
risk of moderate to severe infection (>12 years of age,
chronic cutaneous or pulmonary disorders

,

long-term

salicylate therapy, corticosteroid therapy).

Acyclovir

Warnings/Precautions

Genital herpes: Physical contact should be
avoided when lesions are present; transmission
may also occur in the absence of symptoms.
Treatment should begin with the first signs or
symptoms.
Herpes labialis: For external use only to the lips
and face; do not apply to eye or inside the
mouth or nose. Treatment should begin with
the first signs or symptoms.
Herpes zoster: Acyclovir should be started
within 72 hours of appearance of rash to be
effective.

Acyclovir

Adverse Reactions
Systemic: Oral:

Central nervous system: Lightheadedness, headache
Gastrointestinal: Diarrhea, nausea, vomiting, abdominal pain

Systemic: Parenteral:

Central nervous system: Lightheadedness
Gastrointestinal: Anorexia
Dermatologic: Hives, itching, rash
Gastrointestinal: Nausea, vomiting
Hepatic: Liver function tests increased
Local: Inflammation at injection site or phlebitis
Renal: Acute renal failure, BUN increased, creatinine increased

Acyclovir

Overdosage/Toxicology
Symptoms of overdose include seizures, somnolence,
confusion, elevated serum creatinine, and renal failure.
In the event of overdose, sufficient urine flow must be
maintained to avoid drug precipitation within renal
tubules. Hemodialysis has resulted in up to 60%
reduction in serum acyclovir levels.

Drug Interactions
Increased CNS side effects with zidovudine and
probenecid

Oseltamivir

Mechanism of Action
Oseltamivir, a prodrug, is hydrolyzed to the
active form, oseltamivir carboxylate. It is
thought to inhibit influenza virus
neuraminidase, with the possibility of
alteration of virus particle aggregation and
release. In clinical studies of the influenza
virus, 1.3% of post-treatment isolates had
decreased neuraminidase susceptibility to
oseltamivir carboxylate.

Oseltamivir

Use
Treatment of uncomplicated acute illness due
to influenza (A or B) infection in adults and
children >1 year of age who have been
symptomatic for no more than 2 days;
prophylaxis against influenza (A or B) infection
in adults and adolescents 13 years of age

Oseltamivir

Pregnancy Implications
There are insufficient human data to
determine the risk to a pregnant woman or
developing fetus.

Lactation
Excretion in breast milk unknown/not
recommended

Oseltamivir

Contraindications
Hypersensitivity to oseltamivir or any component of
the formulation

Warnings/Precautions
Oseltamivir is not a substitute for the flu shot.
Dosage adjustment is required for creatinine
clearance between 10-30 mL/minute. Safety and
efficacy in children (<1 year of age) have not been
established for treatment regimens. Safety and
efficacy have not been established for prophylactic
use in patients <13 years of age.

Oseltamivir

Adverse Reactions
As seen with treatment doses:
Central nervous system: Insomnia , vertigo
Gastrointestinal: Nausea (adults 10%), vomiting
,abdominal pain
Ocular: Conjunctivitis
Otic: Ear disorder
Respiratory: Epistaxis
Similar adverse effects were seen in prophylactic use,
however, the incidence was generally less. The following
reactions were seen more commonly with prophylactic
use: Headache (20%), fatigue (8%), diarrhea (3%)

Oseltamivir

Pharmacodynamics/Kinetics
Absorption: Well absorbed
Metabolism: Hepatic (90%) to oseltamivir
carboxylate; Bioavailability: 75% reaches systemic
circulation in active form
Half-life elimination: Oseltamivir carboxylate: 6-10
hours; similar in geriatrics (68-78 years)

Excretion: Urine (as carboxylate metabolite)

Oseltamivir

Dosage
Oral: Treatment: Initiate treatment within 2
days of onset of symptoms; duration of
treatment: 5 days:
Children: 1-12 years:
15 kg: 30 mg twice daily
>15 kg - 23 kg: 45 mg twice daily
>23 kg - 40 kg: 60 mg twice daily
>40 kg: 75 mg twice daily
Adolescents 13 years and Adults: 75 mg twice
daily

Amantadine

Mechanism of Action
As an antiviral, blocks the uncoating of
influenza A virus preventing penetration of
virus into host; antiparkinsonian activity
may be due to its blocking the reuptake of
dopamine into presynaptic neurons or by
increasing dopamine release from
presynaptic fibers

Amantadine

Pharmacodynamics/Kinetics
Onset of action: Antidyskinetic: Within 48 hours
Absorption: Well absorbed

Metabolism: Not appreciable; small amounts of an
acetyl metabolite identified
Bioavailability: 86% to 90%
Half-life elimination: Normal renal function: 16 ± 6
hours (9-31 hours); End-stage renal disease: 7-10
days
Excretion: Urine (80% to 90% unchanged) by
glomerular filtration and tubular secretion
Total clearance: 2.5-10.5 L/hour

Amantadine

Use
Prophylaxis and treatment of influenza A viral
infection; treatment of parkinsonism;
treatment of drug-induced extrapyramidal
symptoms

Amantadine

Pregnancy Implications
Teratogenic effects were observed in
animal studies; limited data in humans.

Lactation
Enters breast milk/not recommended

Amantadine

Contraindications
Hypersensitivity to amantadine or any
component of the formulation

Warnings/Precautions
Use with caution in patients with liver
disease, history of recurrent and eczematoid
dermatitis, uncontrolled psychosis or severe
psychoneurosis, seizures, and in those
receiving CNS stimulant drugs; reduce dose
in renal disease. When treating Parkinson's
disease, do not discontinue abruptly.

Amantadine

Adverse Reactions

Cardiovascular: Orthostatic hypotension, peripheral
edema
Central nervous system: Insomnia, depression, anxiety,
irritability, dizziness, hallucinations, ataxia, headache,
somnolence, nervousness, dream abnormality, agitation,
fatigue, confusion
Dermatologic: Livedo reticularis
Gastrointestinal: Nausea, anorexia, constipation,
diarrhea, Respiratory: Dry nose

Amantadine

Drug Interactions
Anticholinergics may potentiate CNS side effects of amantadine;
monitor for altered response. Includes benztropine and
trihexyphenidyl, as well as agents with anticholinergic activity
such as quinidine, tricyclics, and antihistamines.
Thiazide diuretics: Hydrochlorothiazide has been reported to
increase the potential for toxicity with amantadine (limited
documentation); monitor response
Triamterene: Has been reported to increase the potential for
toxicity with amantadine (limited documentation); monitor
response
Trimethoprim: Has been reported to increase the potential for
toxicity with amantadine (limited documentation); monitor for
acute confusion

Amantadine

Overdosage/Toxicology
Symptoms of overdose include nausea,
vomiting, slurred speech, blurred vision,
lethargy, hallucinations, seizures, and
myoclonic jerking. Acute toxicity may be
primarily due to anticholinergic effects.

Amantadine

Dosage
Oral: Children:
Influenza A treatment:
1-9 years: 5 mg/kg/day in 2 divided doses
10 years and <40 kg: 5 mg/kg/day; maximum dose: 150
mg/day
10-12 years and 40 kg: 100 mg twice daily.
13 years: Refer to Adults dosing
Note: Initiate within 24-48 hours after onset of
symptoms; discontinue as soon as possible based on
clinical response (generally within 3-5 days or within 24-
48 hours after symptoms disappear)

Amantadine

Adults:
Drug-induced extrapyramidal symptoms: 100 mg
twice daily; may increase to 300-400 mg/day, if
needed
Parkinson's disease 100 mg twice daily as sole
therapy; may increase to 400 mg/day if needed with
close monitoring; initial dose: 100 mg/day if with
other serious illness or with high doses of other anti-
Parkinson drugs
Influenza A viral infection: 100 mg twice daily; initiate
within 24-48 hours after onset of symptoms;
discontinue as soon as possible based on clinical
response (generally within 3-5 days or within 24-48
hours after symptoms disappear)
Influenza A prophylaxis: 100 mg twice daily

GANCICLOVIR

Mechanism of Action: Ganciclovir is an
acyclic nucleoside analogue of 2'-
deoxyguanosine that inhibits replication of
herpes viruses. Ganciclovir has been shown
to be active against cytomegalovirus (CMV)
and herpes simplex virus (HSV) in human
clinical studies

GANCICLOVIR

Indication:
Active CMV- radiculopathy, encephalitis,
GI ulcerations, CMV retinitis.

Oral form also used for prevention of CMV
disease in advanced AIDS for patients at
high risk

GANCICLOVIR

SIDE EFFECTS: Diarrhea, nausea, stomach
upset, loss of appetite, headache, dizziness,
confusion, nervousness, vivid dreams,
tremor, weakness, swelling of the feet or
ankles and pain or irritation at the injection
site have been reported.
Ganciclovir may cause significant bone
suppression

GANCICLOVIR

Use in Pregnancy:
Risk to fetus cannot be ruled out. Consider use
if benefit outweighs potential risk.

GANCICLOVIR

Drug Interactions: ZDV may potentiate
ganciclovir's bone marrow toxicity;
nephrotoxic and bone marrow depressant
drugs should be administered with caution
due to possible additive effects.

RIBAVIRIN

Ribavirin is an anti-viral drug active against a
number of DNA and RNA viruses. It is a member of
the nucleoside antimetabolite drugs that interfere
with duplication of the viral genetic material. The
drug inhibits the activity of the enzyme RNA
dependent RNA polymerase, due to it's resemblence
to building blocks of the RNA molecules. The oral
form is used in the treatment of hepatitis C, in
combination with interferon drugs. The aerosol form
is used to treat respiratory syncytial virus-related
diseases in children. The primary serious adverse
effect of ribavirin is hemolytic anemia

,

which may

worsen preexisting cardiac disease.

RIBAVIRIN

Mechanism of Action

Ribavirin is readily phosphorylated intracellularly by
adenosine kinase to ribavirin mono-, di-, and
triphosphate metabolites. Ribavirin triphosphate
(RTP) is a potent competitive inhibitor of inosine
monophosphate (IMP) dehydrogenase, viral RNA
polymerase and messenger RNA (mRNA)
guanylyltransferase (viral). Guanylyltranserase
inhibition stops the capping of mRNA. These diverse
effects result in a marked reduction of intracellular
guanosine triphosphate (GTP) pools and inhibition of
viral RNA and protein synthesis. Ribavirin is also
incorporated into the viral genome causing lethal
mutagenesis and a subsequent decrease in specific
viral infectivity.

RIBAVIRIN

Absorption

Rapidly and extensively absorbed following
oral administration. However, due to first-
pass metabolism, the absolute bioavailability
averages 64%.

Half Life: 9.5 hours

Side effects include "flu-like" symptoms, such
as headache, fatigue, myalgia, and fever

RIBAVIRIN

Ribavirin is contraindicated in:
· Patients with known hypersensitivity to any
component of the tablet.
· Women who are pregnant.
· Men whose female partners are pregnant.
· Patients with hemoglobinopathies (e.g., thalassemia
major or sickle-cell anemia).

Combination therapy is contraindicated in patients
with:
·Autoimmune hepatitis.
·Hepatic decompensation