ANTIFUNGAL AGENTS - has antifungal activity against Cryptococcus
neoformans, some candida species, and
I. Polyenes
A. Amphotericin B – PO, IV
- binds to the fungal cell membrane, forming open
channels that increase cell permeability and leakage of
intracellular components
- not absorbed in the GI tract
- drug of choice for treating severe systemic fungal
infections
- antifungal agent with the broadest spectrum of action
- Adverse reactions include flush, fever, chills, nausea,
vomiting, hypotension, paresthesias, thrombophlebitis,
nephrotoxicity, hypokalemia, and hypomagnesemia
B. Nystatin – PO, topical
- increases the permeability of the fungal cell membrane
- poorly absorbed in the GIT
- excreted unchanged in the feces
- oral preparations are used for intestinal candidiasis
II. Azoles
- inhibit cytochrome P450 in fungal cells, interfering with
the formation of ergosterol
A. Fluconazole – PO, IV
- good CSF penetration
- high oral bioavailability
- least effect on hepatic microsomal enzymes among the
azoles
- widest therapeutic index among the azoles
- drug of choice in the treatment and secondary
prophylaxis of cryptococcal meningitis
- can be used in the treatment of candidemia,
mucocutaneous candidiasis, coccidioidal diseases
B. Itraconazole – PO, IV
- oral absorption is increased by food and low gastric pH
- azole of choice for the treatment histoplasmosis,
blastomycoses, and sporotrichosis
- also used in treating dermatophytoses and
onychomycoses
C. Voriconazole – PO, IV
- well absorbed orally
- azole of choice for aspergillosis
- causes rash, elevated liver enzymes, and visual
disturbances
D. Ketoconazole – PO, IV
- not used systemically because it has greater propensity
to inhibit mammalian cytochrome P450
- inhibits steroid biosynthesis
E. Miconazole – Topical
F. Clotrimazole – Topical, troches (alternative for
Nystatin in treating oral thrush)
III. Antimetabolite
A. Flucytosine – PO
- converted to metabolites that inhibit DNA and RNA
synthesis
- well absorbed after oral administration
- penetrates well into all body fluid compartments,
including CSF
chromoblastomycosis
- excreted by glomerular filtration
- Adverse effects include bone marrow toxicity,
derangement in liver enzymes, and a form of toxic
enterocolitis
IV. Echinocandins
- inhibit the synthesis of β(1-3) glucan, causing
disruption of the cell wall
- used to treat Aspergillus and Candida infections
- not absorbed orally
- excreted by the kidneys and GIT
- Adverse effects include GI disturbances and elevation
of liver enzymes
A. Caspofungin - IV
ANTIVIRAL AGENTS
I. Anti-Influenza Agents
A. Amantadine
- inhibit replication of Influenza A
- reduces the duration of fever and systemic complaints
by 1-2 days when started 1-2 days after the onset of
clinical symptoms
- excreted unmetabolized in the urine
B. Rimantadine
- inhibit replication of Influenza A
- more active than Amantadine
- reduces the duration of fever and systemic complaints
by 1-2 days when started 1-2 days after the onset of
clinical symptoms
- undergoes metabolism before excreted in the urine
- adverse effects include GI intolerance and CNS
complaints (nervousness, lightheadedness, difficulty in
concentrating)
C. Neuraminidase inhibitors
- shortens the severity and duration of illness and may
decrease the incidence of respiratory complications
when given within 36-48 hours after the onset of
symptoms
- have activity against both Influenza A and B
1. Zanamavir
- poor oral bioavailability
- may cause nasal and throat discomfort as well as
bronchospasm
2. Oseltamivir
- a prodrug activated in the gut and liver
- excreted primarily in the urine
- may be used as a prophylaxis for influenza
- adverse effects include nausea and vomiting
II. Agents to Treat VZV and HSV Infections
1. Acyclovir
- inhibits viral DNA synthesis
- can diffuse into most tissues and body fluids including
CSF
- effective against HSV1, HSV2, VZV, and CMV
infections
- cleared by glomerular filtration and tubular secretion
- well tolerated causing only nausea, diarrhea, and - Toxicities include GI irritation, skin rash, headaches,
headache peripheral neuropathy, myocardial depression, retinal
2. Valacyclovir damage, auditory impairment, and psychosis
- prodrug of Acyclovir 2. Mefloquine
- unknown mechanism of action
III. Agents to Treat CMV Infections - first-line drug for prophylaxis of P falciparum in
1. Gancyclovir chloroquine-resistant areas
- inhibits DNA polymerase causing termination of viral - toxicities include GI distress, skin rash, headache,
DNA elongation dizziness, cardiac conduction defects, psychiatric
- poor oral bioavailability disorders, neurologic symptoms, and seizures
- penetrates most body tissues and fluids including CSF 3. Primaquine
and vitreous - complete absorption after oral administration
- eliminated through the kidneys - tissue schizonticide and gametocide
- Adverse effects include myelosuppression - eradicates liver stages of of P vivax and P ovale
(neutropenia) , CNS toxicity (headache, seizure, - should be used with a blood schizonticide
changes in mental status) (Chloroquine)
2. Valgancyclovir - Toxicities include GI distress, pruritus, headaches,
- prodrug of Gancyclovir methemoglobinemia, and hemolysis in G6PD-deficient
patients
IV. Antiretroviral Agents 4. Quinine
A. Nucleoside Reverse Transcriptase Inhibitors - complexes with dsDNA blocking replication and
1. Zidovudine transcription
2. Didanosine - blood schizonticide
3. Lamivudine - rapidly absorbed orally
4. Zalcitabine - excreted through the kidneys
5. Stavudine - used in the treatment of chloroquine-resistant P.
6. Abacavir falciparum
- can be given intravenously in severe falciparum
B. Nucleotide Inhibitors malaria
1. Tenofovir - toxicities include GI distress, headache, vertigo, blurred
vision, tinnitus, disturbances in cardiac conduction, and
C. Nonnucleoside Reverse Transcriptase Inhibitors hemolysis in G6PD-deficient patiens
1. Nevirapine 5. Doxycycline
2. Delavirdine - prophylaxis for areas with chloroquine- and mefloquine-
3. Efavirenz resistant P falciparum

D. Protease Inhibitors II. Amebiasis

1. Saquinavir 1. Metronidazole (see previous lecture)
2. Ritonavir 2. Diloxanide Furoate
3. Lopinavir/Ritonavir - used as a sole agent for the treatment of asymptomatic
4. Indinavir amebiasis
5. Nelfinavir - causes GI distress
6. Amprenavir
ANTHELMINTIC DRUGS
E. Fusion Inhibitors
1. Enfuvirtide 1. Albendazole
- blocks the entry of the virus into the cell - blocks glucose uptake to parasites leading to
- administered subcutaneously decreased formation of ATP; inhibit microtubule
assembly
- primary drug for ascariasis, hookworm, pinworm, and
ANTIPROTOZOAL DRUGS whipworm
- alternative drug for threadworm, filariasis, visceral and
I. Antimalarial Agents cutaneous larva migrans, hydatid disease, and pork
1. Chloroquine tapeworm
- prevents polymerization of the heme into hemozoin - Toxicities include leukopenia, alopecia, elevation of
- blood schizonticide liver enzymes
- rapidly absorbed when given orally 2. Mebendazole
- oral absorption is decreased by antacids - inhibit microtubule synthesis and glucose uptake
- excreted unchanged in the urine - less than 10% of the drug is absorbed orally
- drug of choice for nanfalciparum and sensitive - primary drug for ascariasis, pinworm, and whipworm
falciparum malaria, and chemoprophylaxis - alternative drug in visceral larval migrans
- Toxicities include GI irritation and embryotoxicity
3. Diethylcarbamazine
- unknown mechanism of action
- drug of choice for loa loa
- rapidly absorbed from the gut and excreted in the urine
- Toxicities include headache, malaise, weakness, and
anorexia
4. Praziquantel
- increases membrane permeability to calcium causing
contractions initially and then paralysis
- drug of choice in schistosomiasis, clonorchiasis, and
paragonimiasis, cysticercosis
- absorbed for the gut rapidly
- Adverse effects include headache, dizziness, malaise,
GI irritation, skin rashes, and fever
5. Ivermectin
- intensifies GABA-mediated neurotransmission causing
immobilization of the parasites
- drug of choice for onchocerciasis, cutaneous larva
migrans, strongyloidiasis, and most forms of filariasis
- Adverse effects include headache, dizziness, rashes,
pruritus, tachycardia, hypotension, myalgia, arthralgia

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