Fungal infection

High incidence of fungal infection is brought by:

1. A dvances in surgery
2. Cancer treatment
3. Critical care accompanied by increase in the
use of broad spectrum anti-microbial.
4. HIV epidemic

Fungal infection can either be

PHARMACOKINETICS
o Superficial
• Because it is nearly insoluble in water it is
o Mucocutaneous
prepared as
o Systemic
o colloidal suspension of amphotericin B
o sodium desoxycholate
Fungal cell wall composition
o lipid associated delivery system (liposomal
• Fungal cell wall contains CHITIN
amphotericin B)
• Cell membrane composed of ERGOSTEROL
▪ Amphotericin B lipid complex
• Cell membrane of human is made up of (abelcet)
CHOLESTEROL – some anti-fungal drug binds to ▪ Amphotericin B cholesterol sulfate
human membrane sterols owing to drug toxicity. complex (amphotec)
▪ Liposomal amphotericin B
1. SYSTEMIC MYCOSES (ambisome)
a. Amphotericin B – amphoteric (associates its self to
• Poorly absorbed from the GI tract
either lipid or water) polyene, (double bonds)
• NO dose adjustment for hepatic & renal
macrolide (lactone ring)
impairment and dialysis
• Amphotericin A & B is obtained from
Streptomyces nodosus
Antifungal activity
• Amphotericin A has no clinical use
• BroadSigest spectrum of action
• Fungicidal

ADVERSE EFFECTS
• INFUSION RELATED TOXICITY
o Fever, chills, muscle spasm, vomiting, HA
and hypotension
Amphotericiin B
o Infusion related toxicity can be
ameliorated by SLOWING THE INFUSION
Chemistry
RATE or DECREASING THE DAILY DOSE
▪ Hydrocortisone 10-50mg in
MOA: binds to ergosterol found in the cell membrane
infusion – prevent infusion related
of fungi to form pores or channels →increase
reactions
permeability and permitting leakage of intracellular
▪ Paracetamol, Antihistamine
contents.
▪ Meperidine 25-50mg – for muscle
spasm
o To prevent this, single test dose should be
given before the administration of larger

ANTI-FUNGAL AGENTS | 1
 dose. (1mg in 20ml 5% dextrose) • in libido
administered for 20-30 minutes II. Itraconazole (sporanox)
• CUMULATIVE TOXICITY • DOC for blastomycoses
o Renal damage • Penetrates poorly in the CNS
o Electrolyte abnormalities (hypoK, hypoMg,
and hypoCa) III. Fluconazole (Diflucan)
• Higher oral BA than keto & itra
b. Flucytosine (5-FC) • CYP-450 inhibition is less common
• Pyrimidine analog related to the • Because of this, it is the azole that has
chemotherapeutic agent 5-FU the widest therapeutic index
• MOA: 5-FC enters the cell → converted to 5-FU → • Good CSF penetration
incorporated to fungal RNA → inhibits protein • DOC & secondary prophylaxis to
synthesis cryptococcal meningitis
• For the treatment of Cryptococcus neoformans IV. Voriconazole (Vfend)
o Never used alone; added with • Inhibition of CYP-450 is low
amphotericin B → SYNERGISM • S/E: visual disturbance – blurring and
• S/E: bone marrow toxicity due to 5-FU changes in color vision and brightness

c. Azoles d. Echinocandins (IV only)

• Imidazoles – ketoconazole, miconazole, • Newest class of antifungals
clotrimazole • Caspofungin (Cancidas), micafungin, &
• Triazoles – itraconazole, fluconazole, voriconazole anidulafungin (Eraxis)
• IMIDAZOLES exhibit a lesser degree of specificity • MOA: inhibits the synthesis of β(1-3)glucan →
than TRIAZOLES disruption of fungal cell wall → death
• Imidazoles have higher incidence of drug • Active for candida and aspergillus but not
interaction. Cryptococcus neoformans

MOA: reduction of ergosterol synthesis by inhibition Caspofungin

of fungal CYP-450 • LD: 70mg; daily dose 50mg
Anidulafungin
Clinical use: • LD: 100mg; daily dose 50mg
• Broad spectrum 2. SYSTEMIC ANTIFUNGALS FOR SUPERFICIAL
• All candida species, Cryptococcus neoformans, MYCOSES
dermatophytes and Aspergillus infection a. Griseofulvin
• Derived from Penicillium griseofulvum
S/E: GI upset, liver enzymes abnormalities • MOA: interact with the microtubules within
I. Ketoconazole the fungus to disrupt the mitotic spindle and
• 1st oral azole introduced inhibit mitosis.
• Inhibition of mammalian CYP-450
is GREATER – it’s an enzyme
inhibitor
• Used for systemic and
mucocutaneous mycoses
• Penetrates poorly in the CNS
• S/E: gynecomastia and decrease

ANTI-FUNGAL AGENTS | 2
 • Use for the treatment of systemic
dermatophytosis
• ↑ absorption when given with fatty foods
• Ultra-fine crystalline preparations are
absorbed adequately in the GI
• Other usesdrugs
o Used to treat gout
o Possesses vasodilatory effect and may
be used in raynaud’s disease –
vasospastic disorder causing
discoloration of fingers and toes
b. Terbinafine (Lamisil)
• MOA: inhibits squalene monooxygenase
→ disruption of fungal sterol
3. TOPICAL ANTIFUNGALS THERAPY
a. Nystatin (Mycostatin)
• A polyene macrolide
• Resembles amphotericin B
• Too toxic for parenteral administration
• Administered as oral agent (“swish & swallow)
for the treatment of oral candidiasis
• SAME MOA with amphotericin B
b. Clotrimazole (Canesten)
c. Miconazole (Monistat)
• Tinea, vaginal candidiasis
d. Tioconazole (Trosyd)
• For C. albicans
e. Tolnaftate (Tinactin)
• Used for dermatophytoses and Tinea
versicolor or Pityriasis versicolor.
f. Naftifine

Tinea pedis – athlete’s foot

Tinea unguium – nail fungus
Tinea cruris – jock itch
Tinea corporis – ringworm
Tinea capitis – scalp ring worm

ANTI-FUNGAL AGENTS | 3