Dela Cruz, Christine
MT 3-3
ANTIMICROBIAL AGENTS:
CLASSIFICATI DRUG GENERIC NAME MECHANISM OF
ON NAME ACTION
Clotrimazol Clotrimazole interacts with
ANTIFUNGAL Mycelex e yeast 14- demethylase, a
DRUG Troche cytochrome P-450 enzyme
alevazol
(ANTIMYCOT that converts lanosterol to
antifungal
IC DRUG) ergosterol, an essential
foot
component of the membrane.
In this way, clotrimazole
inhibits ergosterol synthesis,
resulting in increased cellular
permeability. Clotrimazole
may also inhibit endogenous
respiration, interact with
membrane phospholipids,
inhibit the transformation of
yeasts to mycelial forms and
the uptake of purine, impair
triglyceride and/or
phospholipid biosynthesis,
and inhibit the movement of
calcium and potassium ions
across the cell membrane by
blocking the ion transport
pathway known as the Gardos
channel.
PHARMACO KINETICS
Absorption: Absorption is
limited with topical
administration. Absorption
following dissolution of a
lozenge in the mouth not
resolute.
Distribution: Distributed
minimally with local
application.
Metabolism: inhibits
biosynthesis of the sterol and systems bound to the
ergosterol, an important
component of fungal cell
membranes.
Excretion: Feces (as
metabolites)
PHARMACO
DYNAMICS
Clotrimazole, an imidazole
derivative with a broad
spectrum of antimycotic
activity, inhibits
biosynthesis of the sterol
ergostol, an important
component of fungal cell
membranes. Its action leads
to increased membrane
permeability and apparent
disruption of enzyme
membrane. Betamethasone
and clotrimazole are used
together to treat cutaneous
tinea infections. In studies
in fungal cultures, the
minimum fungicidal
concentration of
clotrimazole caused
leakage of intracellular
phosphorous compounds
into the ambient medium
with concomitant
breakdown of cellular
nucleic acids, and
accelerated potassium
etflux. Both of these events
began rapidly and
Dela Cruz, Christine
MT 3-3
ANTIBIOTIC Cipro Ciprofloxacin
DRUG ciloxan The bactericidal action of
ciprofloxacin results from
cipoflaxin
inhibition of the enzymes
topoisomerase II (DNA
gyrase) and topoisomerase IV, approximately 70% with no
which are required for
bacterial DNA replication,
transcription, repair, strand
supercoiling repair, and
recombination
extensively after addition
of the drug to the cultures.
The primary action of
clotrimazole is against
dividing and growing
organisms.
Absorption:Rapidly and Ciprofloxacin is a broad-
well absorbed from the spectrum antiinfective
gastrointestinal tract after agent of the
oral administration. The fluoroquinolone class.
absolute bioavailability is Ciprofloxacin has in
vitro activity against a wide
substantial loss by first pass
metabolism. range of gram-negative and
gram-positive
Volume of distribution:not microorganisms. The
Available mechanism of action of
quinolones, including
ciprofloxacin, is different
Protein binding:20 to 40% from that of other
antimicrobial agents such
Metabolism:Hepatic. Four as beta-lactams,
metabolites have been macrolides, tetracyclines,
identified in human urine or aminoglycosides;
which together account for therefore, organisms
approximately 15% of an
resistant to these drugs may
oral dose. The metabolites
have antimicrobial activity, be susceptible to
but are less active than ciprofloxacin. There is no
unchanged ciprofloxacin. known cross-resistance
between ciprofloxacin and
Route of elimination other classes of
antimicrobials. Notably the
Approximately 40 to 50% of drug has 100 times higher
Dela Cruz, Christine
MT 3-3
ANTIVIRAL Abreva Docosanol
DRUG Docosanol works by
inhibiting fusion between the
human cell plasma membrane
and the herpes simplex virus
(HSV) envelope, thereby
preventing viral entry into
cells and subsequent viral
replication. Unlike other cold-
sore antivirals, docosanol
does not act directly on the
virus, and as such it is
unlikely it will produce drug
resistant mutants of HSV.
an orally administered dose affinity for bacterial DNA
is excreted in the urine as gyrase than for
unchanged drug. mammalian.
Half life
4 hours
Absorption
Topical absorption has been Docosanol is a saturated
shown to be minimal under 22-carbon aliphatic alcohol
conditions reflecting normal which exhibits antiviral
clinical use.
activity against many lipid
Volume of distribution
Not Available
enveloped viruses
including herpes simplex
Protein binding virus (HSV). Docosanol
Not Available speeds the healing of cold
sores and fever blisters on
Metabolism the face or lips. It also
Not Available relieves the accompanying
symptoms, including
Route of elimination tingling, pain, burning, and
Not Available itching. Docosanol cannot,
however, prevent cold
Half life
Not Available
sores or fever blisters from
appearing.
Drug Interactions
No interactions found.
Food Interactions
Not Available
Dela Cruz, Christine
MT 3-3

ANTIHELMENT Albendazole Abzole Absorption

ICS acizole Albendazole causes Poorly absorbed from the Albendazole is a broad-
degenerative alterations in the gastrointestinal tract due to spectrum anthelmintic. The
agroben
tegument and intestinal cells its low aqueous solubility. principal mode of action
AD Dworm of the worm by binding to the Oral bioavailability appears
for albendazole is by its
colchicine-sensitive site of to be enhanced when
tubulin, thus inhibiting its coadministered with a fatty
inhibitory effect on tubulin
polymerization or assembly meal (estimated fat content polymerization which
into microtubules. The loss of 40 g) results in the loss of
the cytoplasmic microtubules cytoplasmic microtubules.
leads to impaired uptake of Volume of distribution
glucose by the larval and Not Available
adult stages of the susceptible
parasites, and depletes their
glycogen stores. Degenerative Protein binding
changes in the endoplasmic
reticulum, the mitochondria 70% bound to plasma
of the germinal layer, and the protein
subsequent release of
lysosomes result in decreased Metabolism
production of adenosine
triphosphate (ATP), which is
Hepatic. Rapidly converted
the energy required for the
in the liver to the primary
survival of the helminth. Due
metabolite, albendazole
to diminished energy
sulfoxide, which is further
production, the parasite is
metabolized to albendazole
immobilized and eventually
sulfone and other primary
dies.
oxidative metabolites that
have been identified in
human urine.

Route of elimination
Albendazole is rapidly
converted in the liver to the
Dela Cruz, Christine
MT 3-3

primary metabolite,
albendazole sulfoxide, which
is further metabolized to
albendazole sulfone and
other primary oxidative
metabolites that have been
identified in human urine.
Urinary excretion of
albendazole sulfoxide is a
minor elimination pathway
with less than 1% of the dose
recovered in the urine.
Biliary elimination
presumably accounts for a
portion of the elimination as
evidenced by biliary
concentrations of
albendazole sulfoxide
similar to those achieved in
plasma.

Half life

Terminal elimination half-

life ranges from 8 to 12
hours (single dose, 400mg).

ANTIPROTOZO Eflornithine vaniqa Absorption Eflornithine irreversibly

AN DRUGS Eflornithine prevents hair Not Available inhibits ornithine
growth by inhibiting the Volume of distribution decarboxylase, an enzyme
anagen phase of hair Not Available involved in the production
production. This occurs by Protein binding of the hair shaft by the hair
Dela Cruz, Christine
MT 3-3
eflornithine irreversibly
binding (also called suicide
inhibition) to ornithine
decarboxylase (ODC) and
physically preventing the
natural substrate ornithine
from accessing the active site.
Not Available follicle. Vaniqa has been
Metabolism shown to reduce the rate of
hair growth. The safety and
Not metabolized efficacy of Vaniqa was
evaluated in two double-
Route of elimination
blind, randomised, vehicle-
controlled clinical trials
Renal involving 596 women of
skin types I-VI (395 on
Half life Vaniqa, 201 on vehicle)
treated for up to 24 weeks.
8 hours Physicians assessed the
Clearance
change from baseline on a
Not Available
Toxicity
4-point scale, 48 hours
Not Available after women had shaved
Affected organisms the treated areas of the
affected areas of the face
Humans and other and under the chin,
mammals considering parameters
Yeast, Molds, such as hair length and
Trypanosomes density, and darkening of
Trypanosoma brucei the skin associated with the
gambiense presence of terminal hair.
Improvement was seen as
early as 8 weeks after
initiation of treatment.
Dela Cruz, Christine
MT 3-3
DRUG NAME GENERIC NAME MECHANISM OF
ACTION
ALKYLATING Alkeran Alkylating agents work by
AGENTS: evomela three different mechanisms:
1) attachment of alkyl groups
melphan
MELPHALAN to DNA bases (primarily at
hydrocloride the N-7 position of guanine
and to a lesser extent, at the
N-3 position of adenine),
forming monoadducts and
resulting in the DNA being
fragmented by repair
enzymes in their attempts to
replace the alkylated bases,
preventing DNA synthesis
and RNA transcription from
the affected DNA, 2) DNA
damage via the formation of
cross-links (bonds between
atoms in the DNA) which
prevents DNA from being
separated for synthesis or
transcription, and 3) the
induction of mispairing of
the nucleotides leading to
mutations.
PHARMACO KINETICS PHARMACO
DYANAMICS
Absorption Melphalan is an
Incomplete, variable, 25- antineoplastic in the class of
89% post oral dose alkylating agents and is used
to treat various forms of
Volume of distribution cancer. Alkylating agents are
0.5 L/kg so named because of their
ability to add alkyl groups to
Protein binding many electronegative groups
Moderate to high (60 to under conditions present in
90%), primarily to albumin cells. They stop tumor
and, to a lesser extent, alpha growth by cross-linking
1-acid glycoprotein. 30% is guanine bases in DNA
irreversibly bound. double-helix strands -
Metabolism directly attacking DNA. This
Melphalan is not actively makes the strands unable to
metabolised, it uncoil and separate. As this
spontaneously degrades to is necessary in DNA
mono and dihydroxy replication, the cells can no
products. longer divide. In addition,
these drugs add methyl or
Route of elimination other alkyl groups onto
The 24-hour urinary molecules where they do not
excretion of parent drug in belong which in turn inhibits
these patients was 10% their correct utilization by
4.5%, suggesting that renal base pairing and causes a
clearance is not a major route miscoding of DNA.
of elimination of parent drug. Alkylating agents are cell
Half life cycle-nonspecific. Alkylating
1.5 (0.83) agents work by three
different mechanisms all of
which achieve the same end
result - disruption of DNA
Dela Cruz, Christine
MT 3-3
ANTIMETABOLITES: Arasid
biobin Cytarabine acts through
CYTARABINE direct DNA damage and
cytabin
incorporation into DNA.
cytarabine Cytarabine is cytotoxic to a
cytarine wide variety of proliferating
oncotar mammalian cells in culture.
It exhibits cell phase
specificity, primarily killing
cells undergoing DNA
synthesis (S-phase) and
under certain conditions
blocking the progression of
cells from the G1 phase to
the S-phase. Although the
mechanism of action is not
completely understood, it
appears that cytarabine acts
through the inhibition of
DNA polymerase. A limited,
but significant, incorporation
of cytarabine into both DNA
and RNA has also been
reported.
Absorption
Less than 20% of the orally
administered dose is
absorbed from the
gastrointestinal tract.
Protein binding
13%
Metabolism
Hepatic.
Route of eliminationt
the primary route of
elimination of cytarabine is
metabolism to the inactive
compound ara-U, followed
by urinary excretion of ara-
U.
Half life
10 minutes
function and cell death.
Cytarabine is an
antineoplastic anti-
metabolite used in the
treatment of several forms of
leukemia including acute
myelogenous leukemia and
meningeal leukemia. Anti-
metabolites masquerade as
purine or pyrimidine - which
become the building blocks
of DNA. They prevent these
substances becoming
incorporated in to DNA
during the "S" phase (of the
cell cycle), stopping normal
development and division.
Cytarabine is metabolized
intracellularly into its active
triphosphate form (cytosine
arabinoside triphosphate).
This metabolite then
damages DNA by multiple
mechanisms, including the
inhibition of alpha-DNA
polymerase, inhibition of
DNA repair through an effect
on beta-DNA polymerase,
and incorporation into DNA.
The latter mechanism is
probably the most important.
Cytotoxicity is highly
specific for the S phase of
the cell cycle.
Dela Cruz, Christine
MT 3-3
ANTIBIOTIC Adriamycin Intercalates and binds to
ANTINEOPLASTIC caelyx DNA, disrupting helical
structure and DNA template;
doxorubicin
DOXORUBICIN inhibits RNA and DNA
hydrocholride polymerases; causes DNA
topoisomerase IImediated
chain scission; generates free
radicals that cause DNA
scission and cell membrane
damage
Absorption Doxorubicin is an
Not Available antineoplastic in the
Volume of distribution anthracycline class. General
The distributive half-life is 5
properties of drugs in this
minutes, which suggests that class include: interaction
doxorubicin is rapidly taken with DNA in a variety of
up by tissue. Steady state different ways including
volume of distribution = 809 intercalation (squeezing
to 1214 L/m2 between the base pairs),
DNA strand breakage and
Protein binding inhibition with the enzyme
Doxorubicin and its major topoisomerase II. Most of
metabolite, doxorubicinol, is these compounds have been
74-76% bound to plasma isolated from natural sources
protein. The extent to and antibiotics. However,
binding is independent of they lack the specificity of
plasma concentration up to the antimicrobial antibiotics
1.1 mcg/mL. Doxorubicin and thus produce significant
does not cross the blood toxicity. The anthracyclines
brain barrier. are among the most
important antitumor drugs
Metabolism available. Doxorubicin is
Doxorubicin is capable of widely used for the treatment
undergoing 3 metabolic of several solid tumors while
routes: one-electron daunorubicin and idarubicin
reduction, two-electron are used exclusively for the
reduction, and treatment of leukemia.
deglycosidation. However, Doxorubicin may also inhibit
approximately half of the polymerase activity, affect
dose is eliminated from the regulation of gene
body unchanged. Two expression, and produce free
electron reduction yields radical damage to DNA.
doxorubicinol, a secondary Doxorubicin possesses an
alcohol. This pathway is antitumor effect against a
considered the primary wide spectrum of tumors,
Dela Cruz, Christine
MT 3-3

metabolic pathway. The one either grafted or

electron reduction is spontaneous. The
facilitated by several anthracyclines are cell cycle-
oxidoreductases to form a nonspecific.
doxirubicin-semiquinone
radical. These enzymes
include mitochondrial and
cystolic NADPH
dehydrogenates, xanthine
oxidase, and nitric oxide
synthases. Deglycosidation is
a minor metabolic pathway
(1-2% of the dose undergoes
this pathway). The resultant
metabolites are
deoxyaglycone or
hydroxyaglycone formed via
reduction or hydrolysis
respectively. Enzymes that
may be involved with this
pathway include xanthine
oxidase, NADPH-
cytochrome P450 reductase,
and cytosolic NADPH
dehydrogenase.
Route of elimination
40% of the dose appears in
bile in 5 days. 5-12% of the
drug and its metabolites
appears in urine during the
same time period. <3% of the
dose recovered in urine was
doxorubicinol.

Half life
Dela Cruz, Christine
MT 3-3
Terminal half life = 20 - 48
hours.
MITOTIC INHIBITOR Marqibo Absorption
oncovin solution Binds to tubulin, leading to Not Available
VINCRISTINE disruption of mitotic spindle
vincristine sulfate
apparatus and arrest of cell Volume of distribution
injection cycle Within 15 to 30 minutes after
vincasar pfs injection, over 90% of the
drug is distributed from the
blood into tissue, where it
remains tightly, but not
irreversibly, bound.
Protein binding
~75%
Metabolism
Hepatic. Cytochrome P450
isoenzymes of the CYP3A
subfamily facilitate the
metabolism of vincristine.
Route of elimination
The liver is the major
excretory organ in humans
and animals. 80% of an
Vincristine is a vinca
alkaloid antineoplastic agent
used as a treatment for
various cancers including
breast cancer, Hodgkin's
disease, Kaposi's sarcoma,
and testicular cancer. The
vinca alkaloids are
structurally similar
compounds comprised of 2
multiringed units, vindoline
and catharanthine. The vinca
alkaloids have become
clinically useful since the
discovery of their antitumour
properties in 1959. Initially,
extracts of the periwinkle
plant (Catharanthus roseus)
were investigated because of
putative hypoglycemic
properties, but were noted to
cause marrow suppression in
rats and antileukemic
effects in vitro. Vincristine
binds to the microtubular
proteins of the mitotic
spindle, leading to
crystallization of the
microtubule and mitotic
Dela Cruz, Christine
MT 3-3

injected dose of vincristine arrest or cell death.

sulfate is excreted via feces. Vincristine has some
10 - 20% is excreted via immunosuppressant effect.
urine. The vinca alkaloids are
considered to be cell cycle
Half life phase-specific.

When intravenously injected

into cancer patients, a
triphasic serum decay patten
was observed. The initial,
middle, and terminal half-
lives are 5 minutes, 2.3
hours, 85 hours respectively.
The range of the terminal
half-life is humans is 19 -
155 hours.

MISCELLANEOUS Cisplan Reacts with proteins and Absorption Cisplatin is an antineoplastic

cisplat nucleic acids; forms cross- Following cisplatin doses of in the class of alkylating
CISPLATIN links between DNA strands 20 to 120 mg/m^2, the agents and is used to treat
cisplatinum
and between DNA and concentrations of platinum various forms of cancer.
platikem protein; disrupts DNA are highest in liver, prostate, Alkylating agents are so
plationco synthesis and kidney; somewhat lower named because of their
plaricis in bladder, muscle, testicle, ability to add alkyl groups to
blastolem pancreas, and spleen; and many electronegative groups
cismax lowest in bowel, adrenal, under conditions present in
heart, lung, cerebrum, and cells. They stop tumor
cerebellum. Platinum is growth by cross-linking
present in tissues for as long guanine bases in DNA
as 180 days after the last double-helix strands -
administration. directly attacking DNA. This
makes the strands unable to
Dela Cruz, Christine
MT 3-3

Volume of distribution uncoil and separate. As this

is necessary in DNA
Volume of distribution at replication, the cells can no
steady state = 11-12 L/m^2 longer divide. In addition,
these drugs add methyl or
Protein binding other alkyl groups onto
molecules where they do not
Cisplatin does not undergo belong which in turn inhibits
instantaneous and reversible their correct utilization by
binding to plasma protein base pairing and causes a
that is characteristic of miscoding of DNA.
normal drug-protein binding. Alkylating agents are cell
However, the platinum itself cycle-nonspecific. Alkylating
is capable of binding to agents work by three
plasma proteins, including different mechanisms all of
albumin, transferrin, and which achieve the same end
gamma globulin. Three hours result - disruption of DNA
after a bolus injection and function and cell death.
two hours after the end of a
three-hour infusion, 90% of
the plasma platinum is
protein bound.

Metabolism
not Available

Route of elimination

The parent compound,

cisplatin, is excreted in the
urine. Although small
amounts of platinum are
present in the bile and large
Dela Cruz, Christine
MT 3-3

intestine after administration

of cisplatin, the fecal
excretion of platinum
appears to be insignificant.

Half life

Cisplatin decays
monoexponentially with a
half life of 20 to 30 minutes
following administrations of
50 or 100 mg/m^2. Cisplatin
has a plasma half-life of 30
minutes. The complexes
between albumin and the
platinum from cisplatin do
not dissociate to a significant
extent and are slowly
eliminated with a minimum
half-life of five days or more.