Anti-infective drugs 1

• A. Polyene Antifungal
• B. Azole Antifungals

• 1. Amphotericin B
• 2. Nystatin

• IV for serious and life threatening infections
• Aspergillus, Candida, Cryptococcus, Histoplasma

Bindsto ergosterol

• Dose dependant
• Nephrotoxic
• Hypokalemia
• Normochromic normocytic anemia
• Infusion dependant
• Flu-like symptoms
• Premedicate patients with antipyretic, antihistaminic and antiemetic agents

• Low penetration into CSF
• No BBB crossing  (Given intrathecally)

• synergistic with fluocytosine
• Rx of resistant Cryptococcus and candidiasis
• Resistance: Decreased ergosterol levels

• Used topically for Rx of candidiasis
• too toxic for systemic use

• Ketoconazole - Fluconazole - Itraconazole
• Clotrimazole - Miconazole

• Block synthesis of ergosterol by inhibiting
• 14 alpha demethylase in the fungal P450 complex

Decrease intracellular levels of drugs

• Given PO
• Candidiasis and coccidiomycosis
• Paracoccidiomycosis
• Blastomycosis and Histoplasmosis

• topically
• Rx of candida and dermatophytic infections

• Ketoconazole: Gynecomastia and decrease libido
• Menstrual irregularities

• Fluconazole penetrates CSF
• Itraconazole: No CSF
• Absorption increased by food
• Fluconazole & Itraconazole are available IV

• 1. Griseofulvin
• 2. Terbinafine
• 3. Flucytosine

tinea cruris (Jock itch)

Disruption of mitotic spindle by interfering with microtubules

• Increase effects of alcohol
• Contraindicated in intermittent porphyria

inhibits squalene epoxidase

Rx of onychomycosis (nail fungal infection)

Elevated liver function tests

5 FC -fungal cytosine deaminase-> 5 FU --> 5-Fluorodeoxyuridine MP --> inhibits thymidylate synthetase --> dec, thymine

amphotericin B

• Decrease bone marrow
• Leukopenia, thrombocytopenia
• GI: severe enterocolitis, hepatitis

Nephrotoxicity

• 1. Inhibition of viral penetration and uncoating
• 2. Inhibition of Viral DNA Polymerase
• 3. Inhibition of Viral DNA & RNA Polymerase
• 4. Inhibition of viral RNA polymerase
• 5. Inhibition of Viral Reverse Transcriptase
• 6. Inhibition of Viral Aspartate Protease
• 7. Inhibition of viral neuraminidase

Amantadine, Rimantadine

Acyclovir, Gancyclovir, Famcyclovir, Valacyclovir

Foscarnet

Ribavirin

• Zidovudine, didanosine, zalcitabine
• stavudine, lamivudine, nevirapine

• indinavir, ritonavir, saquinavir
• nelfinavir

Zanamivir, oseltamivir

• 1. Amantadine
• 2. Ribavirin
• 3. Acyclovir
• 4. Famciclovir & Valacyclovir
• 5. Ganciclovir
• 6. Foscarnet
• 7. Zanamivir and Oseltamivir

MOA: Interfere with the attachement, penetration and uncoating of the viral particle

• Influenza A
• Parkinson's disease

• Livedo reticularis
• Anticholinergic effects

• MOA: inhibits viral RNA polymerase
• inhibits end capping of viral mRNA

Indication: RSV

Teratogenic

MOA: inhibits viral DNA polymerase

Resistance: Decrease activity to viral thymidilate kinase

• Herpes simplex
• Varicella zoster (Shingles)
• Not effective in CMV infections

• Nephropathy (IV only)
• Neurotoxicity and Crystalluria

• Newly FDA approved for Herpes simplex
• Similar to Acyclovir

CMV

• MOA: similar to Acyclovir
• Viral thymidylate kinase in Herpes
• Phosphotransferase in CMV

• Side effects: Leukopenia, thrombocytopenia
• Seizure in overdose
• Crystalluria

Inhibits DNA polymerase

• As Ganciclovir
• Rx of CMV retinitis in AIDS patients
• Not retinal detachment

Nephrotoxicity

IV pentamidine + Foscarnet --> severe hypocalcemia

Inhibits neuraminidases of influenza A & B

Prophylaxis to Reduce flu symptoms

• InhaledZanamivir cause throat irritation
• Nausea & Vomiting

• 1. Nucleosides Reverse Transcriptase Inhibitors
• 2. NonNucleoside Reverse Transcriptase Inhibitors
• 3. Protease Inhibitors
• 4. Fusion Inhibitors

CD4 cells

• 1. CD4 < 500 normal 600-1200
• 2. Viral load (PCR) > 10,000-20,000 normal <400

• 2+1
• Any 2 Nucleosides inhibitors (AZT, DDI, 3TC,D4T) + 1 Protease inhibitor (indinavir, Ritonavir)

• CD4 > 500 --> No prophylaxis
• Except PPD +ve with any CD4
• 1. if CD4 < 200
• 2. If CD4 < 100
• 3. If CD4 < 75
• 4. If CD4 < 50

• a. Pneumocystis carinii pneumonia (PCP) propylaxis
• b. Pneumococcal vaccine

• Toxoplasmosis Prophylaxis
• Trimethoprim/Sulpha

• Mycobacterium Avium Complex (MAC) prophylaxis
• Azithromycin
• Clarithromycin

• Cytomegalovirus Prophylaxis
• Ganciclovir

• Needle stick: 1:300
• Anal receptive: 1:50-100
• Vaginal: M to F: 1:1000, F to M: 1:2000-3000
• Pregnant mom to baby: 25%
• Pregnant taking AZT: 8%

• 1. Stuck with a needle of HIV+ve patient?
• 2. Patient had sex one time with an HIV+ve?
• 3. 27y/old female  CD4 >500 and PCR <400
• 4. 27 y/old female pregnant CD4 >500 and PCR <200
• 5. 27 y/old female pregnant CD4 1 and PCR 700,000

2 + 1 for 4 weeks

2 + 1 for 4 weeks

Nothing

• AZT to prevent transmission
• reduce risk from mom to baby:  25% to 8%

• 2+1
• PCP - MAC - CMV prophylaxis