Anti-fungal Agents Flashcards
Mode of action of some antifungal agents
Amphotericin B binds to _____ creating ____
Azoles inhibits _________ in the fungal cell
5FC converts to ______ , incorporated into ____, _______
plasma membrane ; pores
cytochrome P450 enzymes
5FU; RNA; abnormal proteins
Mode of action of some anti fungal agents
Griseofulvin binds _____ proteins, inhibiting ______
Terbinafine is ________ inhibitor useful for ___________
Echinocandins target their action on ______
microtubule; cell wall synthesis
an ergosterol ; systemic mycosis
fungal cell wall
Drugs for systemic fungal infections
Polyene antibiotics
-__________
Pyrimidine antimetabolites
-_______
Antifungal azoles
-_______
-________
-______
Echinocandins
______,______, and _______
Amphotericin B
Flucytosine
Ketoconazole, Fluconazole, Itraconazole
Caspofungin, micafungin, and anidulafungin
Drugs for superficial fungal infections
Systemic drugs
-_______
-_______
Topical drugs
-_______
-______
-_______
-Azoles (______,_____,_____, etc.)
Griseofulvin; Iodide
Nystatin; Haloprogin; Tolnaftate
miconazole, econazole, clotrimazole
Polyenes
are produced from _______
are _______ molecules
Are ______ spectrum
Examples include ____,____,____,____
Streptomyces
Cyclic molecules
Broad spectrum
Natamycin
Nystatin
Amphotericin B
Mepartricin
PHARMACOLOGY OF AMPHOTERICIN B
Chemistry
-Amphotericin B is a _____ antibiotic
Mechanism of action
-Binding to ________ present in the membranes of fungal cells leading to Formation of “ ______ ” in the membrane, Leading to ________________ from the cells
polyene
ergosterol
pores
leaking of small molecules (mainly K+)
polyene: containing _____________
many double bonds
The ultimate effect of amphotericin B is fungistatic?
may be fungicidal or fungistatic depending on the organism and on drug concentration.
Antifungal spectrum and resistance of amphotericin B
-Antifungal spectrum includes:
LOL!
Resistance ?
Histoplasma capsulatus Coccidioides immitis Paracoccidioidoides braziliensis Aspergillus fumigatus Blastomyces dermatitidis Cryptococcus neoformans Candida albicans
Sporothrix schenckii
Mucor and Rhizopus spp
may occur but is very rare
The TI of Amphotericin B is (wide or narrow?)
Very narrow
Adverse effects of Amphotericin B
-Headache, ________ , nausea and vomiting fever and chills, hyperpnea, ____________ (they may appear during IV infusion and may be reduced by concomitant administration of ______ or _______ )
-Malaise, weight loss
-__________
-_______ anemia, likely due to ___________
-_____________
-Delirium, seizures (after intrathecal injection)
arthralgias
shock-like fall in blood pressure; antipyretics or meperidine
Nephrotoxicity
Normocytic; decreased production of
erythropoietin (frequent)
Thrombophlebitis
Amphotericin is the drug of choice for:
-Disseminated _______
-Disseminated and meningeal ______ -Disseminated and meningeal _______
-______
-________
-Mucormycosis
histoplasmosis; coccidioidomycosis; cryptococcosis
Invasive aspergillosis
Deep candidiasis
Amphotericin is an alternative drug for:
- ________
-______________
-Extracutaneous _______
[Amphotericin is preferred when these mycoses are ________, occur in _____ host or involve the _____]
Blastomycosis
Paracoccidioidomycosis
sporotrichosis
rapidly progressive; immunocompromised; CNS
Azole Derivatives
A chemical ______ structure with ___ nitrogen atoms
Water (soluble or insoluble?) except ______
Preferentially inhibit _________
Fungi(static or cidal?)
pentacyclic; 2
Insoluble; fluconazole
cytochrome P450 enzymes
static
fluconazole
Water soluble or insoluble
Soluble
Azole derivatives
First generation Imidazoles:
_______ and ______
Clotrimazole & Miconazole
Clotrimazole
requires (low or high ?) doses
(Well or Poorly?) tolerated
High
Poorly
Parenteral dosages no longer available for _____azole
Micon
CYP is vital to the formation of _____ and _____
cholesterol & steroids
Third generation azoles
Triazole derivatives (contain _____ nitrogen atoms)
three
Third generation azoles
Triazole derivatives
List 5!!
Fluconazole
Itraconazole
Voriconazole
Posaconazole
Revuconazole
Triazoles have a Satisfactory tolerability
T/F
T
Triazoles are not Suitable for systemic use
T/F
F
PHARMACOLOGY OF ANTIFUNGAL AZOLES
Chemistry
-Imidazole derivatives: ____,____,____,_____
-Triazole derivatives: _____,____
ketoconazole, miconazole, econazole,
clotrimazole
itraconazole, fluconazole.
PHARMACOLOGY OF ANTIFUNGAL AZOLES
Mechanism of action
-Inhibition of __________________ , a ________-dependent enzyme (has relative selectivity occurs because the affinity for ________ isozymes is less than that for the ______ isozyme)
sterol 14-alpha-demethylase
cytochrome P450
mammalian P450 ; fungal
Mechanism of action of azoles is to block the ______ of _____ in fungal cell membranes
The ultimate effect may be _____ or ______ depending on _______ and _____
Synthesis of ergosterol
fungicidal or fungistatic
the organism and on drug concentration.
____azole has been extensively used for yeast infections
Flucon
Fluconazole is Useful for systemic infections
T/F
T
Absorption of Fluconazole??
Distribution of Fluconazole
It is readily and completely absorbed by gastrointestinal tract
Distributed equally in different organs and tissue
_________ is Intrinsically resistant to fluconazole
Candida krusei
_______azole is used to treat aspergillus infections
Itracon
Itraconazole is not Entirely metabolized in the liver
T/F
F
It is
Voriconazole
is a modified _____
A _____ spectrum antifungal agent
_____ absorption after oral administration
Distributes in tissues and body fluids
Metabolized in the ____
Eliminated in the ______ in _____ form
fluconazole
broad
Rapid
liver
urine in unchanged
Azoles carry some side effects
_________,__________, and _______
______,________ and other hypersensitivity
Hepatotoxicity, gastrointestinal and endocrine toxicity
Skin rash, pruritis
Cross-resistance between azoles is rare
T/F
F
Cross-resistance between azoles is a common finding.
Azoles may inhibit certain mammalian cytochrome P450 isozymes and therefore they may
1) inhibit the synthesis of _______ and ———
2) ______ the effects of several drugs including cyclosporine,
phenytoin, terfenadine, astemizole, tolbutamide and warfarin.
androgens and of corticosteroids
potentiate
Newest class of antifungal agents are the _________
Echinocandins
Echinocandins
Route of administration: ____________
Mechanism of action: inhibiting ___________
Intravenous
the synthesis of (1–3)-glucan
Echinocandins are (poorly or Well?) tolerated
Well
Examples of Echinocandins
List 3
Caspofungin Micafungin Anidulafungin
Caspofungin
synthesized from _________
Glarea lozyensis
Caspofungin
is natural , semisynthetic or synthetic?
semisynthetic
Caspofungin
Appearance is ________, _________ soluble, fungi(static or cidal?)
Whitish powder
water & methanol
cidal
Caspofungin is Fungicidal against, ______,____, and ______
Aspergilli, Candida and P. carinii
Presence of cross resistance to Caspofungin amongst strains resistant to Ampho B or azoles
T/F
F
No cross resistance
Caspofungin is fungicidal against Cryptococcus neoformans, Fusarium & Rhizopus
T/F
F
No activity against Cryptococcus neoformans, Fusarium & Rhizopus
Caspofungin is Effective against Pneumocystis carinii
T/F
T
Micafungin and Anidulafungin are widespread
T/F
F
Micafungin and Anidulafungin – are under investigation
Terbinafine
Has _______ and _____ administrations
Terbinafine inhibits _________
Oral and topical (cream) formulations
ergosterol biosynthesis
Terbinafine belongs to _______, synthetic, highly lipo____
allylamines
philic
Terbinafine
Used to treat _____ mycosis but Also useful against _____ mycosis (yeast & other fungi)
superficial
systemic
Adverse reactions to terbinafine are in general _________ and _____
transient and mild
Based on one video, antifungal agents can be divided into 5
List them
Antibiotics
Azoles
Antimetabolites
Allylamines
Topical agents
List the antibiotics antifungal agents
Polyenes
Echinocandins
Heterocyclic benzofurun
Hamycin is a ______
Polyene
Examples of antimetabolites anti fungal agents?
Flucytosine
The only systemic imidazole is??
Rest are ??
Ketoconazole
Topical
