Antifungal

Question 1

AMPHOTERACIN

Answer 1

Amphotericin B is a naturally occurring polyene
antifungal produced by Streptomyces nodosus

Question 2

MECHANISM OF ACTION
Amphoteracin

Answer 2

Amphotericin B binds to ergosterol in the plasma membranes of fungal cells.
it forms pores
require hydrophobic interactions between the lipophilic
segment of the polyene antifungal and the sterol
pores disrupt membrane function, allowing electrolytes AND small molecules to leak from the cell,
resulting in cell death

Question 3

Spectrum of amphoteracin
static or cidal
unique feature

Answer 3

fungicidal or fungistatic
Candida albicans, Histoplasma capsulatum, Cryptococcus
neoformans, Coccidioides immitis, Blastomyces dermatitidis, and
many strains of Aspergillus

Amphotericin B is also used in
the treatment of the protozoal infection leishmaniasis.

Question 4

KINETICS amphoteracin

Answer 4

IV INFUSION
INSOLUBLE IN WATER
coformulated with sodium deoxycholate (conventional) or artificial lipids to form liposomes.
extensively bound to plasma
proteins and is distributed throughout the body.
ittle of the drug is
found in the cerebrospinal fluid (CSF), vitreous humor, peritoneal
fluid, or synovial fluid.

Question 5

ADRS AMPHOTERACIN

Answer 5

FEVER AND CHILLS/ANTIPYRETIC OR
RENAL TOXICITY
a decrease in glomerular filtration rate and renal tubular function. Serum creatinine may
increase, creatinine clearance can decrease, and potassium
and magnesium are lost.

Sodium loading with infusions of normal saline prior to administration of the conventional formulation or use of the liposomal
amphotericin B products minimize the risk of nephrotoxicity.
SUDDEN DROP IN BLOOD PRESSURE DUE TO IV INFUSION

Question 6

Flucytosine

Answer 6

a synthetic pyrimidine antimetabolite that is often used in combination with other antifungal age

Question 7

mechanism of action FLUCYSTOSINE

Answer 7

5-FC enters the fungal cell via a cytosine-specific permease, an enzyme not found in mammalian cells.
It is subsequently converted to a series of compounds, including 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine 5′-monophosphate,
which disrupt nucleic acid and protein synthesis

Question 8

Spectrum flucystosine

Answer 8

Fungistatic.
effective in combination with itraconazole for treating chromoblastomycosis
combination with amphotericin B for the treatment of
systemic mycoses and meningitis caused by C. neoformans
and C. Albicans.
USED FOR Candida UTI INFECTION WHERE FLUCONAZOLE IS NOT EFFECTIVE.

Question 9

kinetic of flucystosin

Answer 9

well absorbed
disribute and penetrates well
dose adjustment in renal compromised patients

Question 10

ADRS OF FLUCYSTOSINE

Answer 10

NEUTROPENIA
THROMBOCYTOPENIA
BONE MARROW DEPRESSION

Question 11

griseofulvin
why use is stopped
speectrum
absorption
contra indication
ADRS

Answer 11

causes disruption of the mitotic
spindle and inhibition of fungal mitosis
Replaced by terbinafine, still for treatment of onychomycosis, although it is still used for dermatophytosis of the scalp and hair
py is dependent on the rate of replacement of healthy skin and
nails.
Ultrafine crystalline preparations are absorbed adequately from
the gastrointestinal tract, and absorption is enhanced by high-fat .
Griseofulvin induces hepatic CYP450 activity, which increases the
rate of metabolism of a number of drugs, including anticoagulants.
The use of griseofulvin is contraindicated in pregnancy and patients
with porphyria.
meals.

Question 12

. Nystatin
why it is administed parentally
spectrum
absorption
why it is not used parentally
how it resembles to amphoteracin B

Answer 12

Nystatin is a polyene antifungal, and its structure,
chemistry, mechanism of action, and resistance profile resemble
those of amphotericin B. It is used for the treatment of cutaneous
and oral Candida infections. The drug is negligibly absorbed from
the gastrointestinal tract, and it is not used parenterally due to systemic toxicity (acute infusion-related adverse effects and nephrotoxicity). It is administered as an oral agent (“swish and swallow”
or “swish and spit”) for the treatment of oropharyngeal candidiasis
(thrush), intravaginally for vulvovaginal candidiasis, or topically for
cutaneous candidiasis.

Question 13

RESISTANCE TO AMPHOTERACIN AND FLUCYSTOSINE

Answer 13

RARE BUT DUE TO DECREASED ERGOSTEROL CONTENT

ANY OF THE ENZYME IN THE CONVERSION OF 5-FC to 5FU AND OTHER METABOLITES

Question 14

AZOLE ANTIFUNGAL

IMIDAZOLE

TRIAZOLE

Answer 14

Azole antifungals are made up of two different classes of drugs—
imidazoles and triazoles. Although these drugs have similar mechanisms
of action and spectra of activity, their pharmacokinetics and therapeutic uses vary significantly.
imidazoles are applied topically for
cutaneous infections
triazoles are administered systemically
for the treatment or prophylaxis of cutaneous and systemic mycoses

Question 15

MAO AZOLE

Answer 15

Azoles are predominantly fungistatic. They
inhibit 14-α demethylase (a cytochrome P450 [CYP450] enzyme),
thereby blocking the demethylation of lanosterol to ergosterol. The inhibition of ergosterol biosynthesis disrupts
fungal membrane structure and function, which, in turn, inhibits
fungal cell growth

Question 16

RESISTANCE TO AZOLE

Answer 16

Mechanisms
of resistance include mutations in the 14-α demethylase gene that
lead to decreased azole binding and efficacy.

Question 17

CI OF AZOLES

Answer 17

Azoles are considered teratogenic, and they
should be avoided in pregnancy unless the potential benefit outweighs the risk to the fetus.

Question 18

DRUG DRUG INTERACTIONS

Answer 18

CYP450 ISOENZYME INHIBITORS
SO THE concomitant administration of cyp 450 inhibitors such as ritonavir,rifampicin,phenytoin can lead to adverse side effects.

Question 19

FLUCONAZOLE SPECTRUM

Answer 19

Fluconazole was the first triazole antifungal
agent. It is the least active of all triazoles,

It is highly active
against Cryptococcus neoformans and certain species of Candida,
including C. albicans and C. parapsilosis

Question 20

THERAPY OF FLUCONAZOLE

Answer 20

Fluconazole is used for prophylaxis against invasive fungal infections
in recipients of bone marrow transplants.
DOC for
Cryptococcus neoformans after induction therapy with amphotericin
B
flucytosine and is used for the treatment of candidemia and
coccidioidomycosis.
Fluconazole is effective against most forms of
mucocutaneous candidiasis.
It is commonly used as a single-dose oral treatment for vulvovaginal candidiasis

Question 21

KINETICS OF FLUCONAZOLE

Answer 21

Fluconazole is available
in oral and IV dosage formulations. It is well absorbed after oral
administration and distributes widely to body fluids and tissues. The
majority of the drug is excreted unchanged via the urine, and doses
must be reduced in patients with renal dysfunctio

Question 22

ADRS OF FLUCONAZOLE

Answer 22

most common adverse effects with fluconazole are nausea, vomiting, headache, and skin rash

Question 23

SEQUELENE EPOXIDE INHIBITORS

Answer 23

These agents act by inhibiting squalene epoxidase, thereby blocking
the biosynthesis of ergosterol, an essential component of the fungal cell membrane

Question 24

TERBINAFINE SPECTRUM

Answer 24

Terbinafine is active against
Trichophyton. It may also be effective against Candida,
Epidermophyton, and Scopulariopsis,

Question 25

ADRS TERBINAFINE

Answer 25

Common adverse effects include diarrhea,
dyspepsia, nausea, headache, and rash. Taste and visual disturbances have been reported, as well as elevations in serum
hepatic transaminases

Question 26

KINETICS TERBINAFINE

Answer 26

e bioavailability after oral administration
is only 40% due to first-pass metabolism. Terbinafine is highly
protein bound and is deposited in the skin, nails, and adipose
tissue.

half-life of 200 to 400 hours may
reflect the slow release from these tissues.
Oral terbinafine
is extensively metabolized by several CYP450 isoenzymes
and is excreted mainly via the urine The drug
should be avoided IN renal
impairment or hepatic dysfunction. Terbinafine is an inhibitor of the CYP450 2D6 isoenzyme, and concomitant use with
substrates of CYP450 2D6 may result in an increased risk of
adverse effects with those agents

Question 27

effective sepctrum terbinafine

Answer 27

Oral terbinafine is DOC for treating dermatophyte onychomycoses (fungal infections of nails).
It is better tolerated, requires a shorter duration
of therapy, and is more effective than either itraconazole or griseofulvin for Trichophyton. Therapy is prolonged (usually about 3 months) but considerably shorter than that with griseofulvin

Oral terbinafine may also be used for tinea capitis (infection of
the scalp).
Note: Oral antifungal therapy (griseofulvin, terbinafine,
itraconazole) is needed for tinea capitis. Topical antifungals are
ineffective.]
Topical terbinafine (1% cream, gel or solution) is used
to treat tinea pedis, tinea corporis (ringworm), tinea cruris (infection of the groin), and tinea versicolor due to Malessezia furfur.
The duration of treatment is usually 1 week.