Antimicrobials part 5

Antimicrobials part 5 Antiviral Agents I: Drugs for Non-HIV Viral Infections Antiviral Therapy: Our ability to treat viral infections remains limited; Viruses use biochemical machinery of host cells to reproduceDifficult to suppress viral replication without doing significant harm to the host; Antivirals suppress biochemical processes unique to viral reproduction Acyclovir [Zovirax]: Active only against members of the herpesvirus family; Agent of first choice for herpes simplex virus (HSV) or varicella-zoster virus (VZV) infection; more frequently than the valacyclovir and famciclovir simply because it's less expensive Effect Against: -Herpes simplex genitalis, Mucocutaneous herpes simplex infection, VZV infections Herpes virus develops resistance to acyclovir: Decreased thymidine production, Alteration in thymidine kinase, Alteration of viral DNA polymerase Pharmacokinetics: the oral bile availability is low ranging from about 15 to 30%, no significant absorption occurs with topical use. When in the blood, acyclovir distributed widely to the body fluids and tissueslevels achieved in the cerebral spinal fluid or about 50% of those in the plasma. All the elimination is renal and primarily as an unchanged drug. In patients with normal kidney function, it has a half life of 2.5 hours, but this is prolonged with renal impairment reaching up to 20 hours in some patients. REDUCED DOSING WITH KIDNEY DISORDERS Adverse Effects Intravenous therapy: Phlebitis, Reversible nephrotoxicity, Neurotoxicity Oral therapy: Gastrointestinal, Vertigo; Capsules up 200 milligrams, 400 milligrams, 800 milligrams and a suspension of 200 milligrams per 5 mils. Dosing: compliance is bad because of dosing Genital Herpes: 400 mg TID for 7-10 days Episodic Recurrences Of Genital Herpes: about 400 mg TID for 5 days Long Term Suppressive Therapy: 400 mg BID for up to 12 months Herpes Zoster: 800mg 5X/day at 4 intervals for 7-10 days Topical therapy: Stinging sensations, 5% cream and it is applied five times per day Valacyclovir [Valtrex]: Prodrug form of acyclovir, Valacyclovir represents a more efficient way of getting acyclovir into the body Uses: Herpes zoster (shingles), Herpes simplex genitalis (genital herpes), Herpes labialis (cold sores), Varicella (chickenpox), Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) Oral Valcyclovir: undergoes rapid absorption followed by rapid and essentially complete conversion to acyclovir When acyclovir itself is given orally, the bioavailability is only 15 to 30% but when valacyclovir is given, the bioavailability goes up to 55%. Dosing: 500 and 1000 milligram oral capsules and can be done without regard to meals; *don’t expect us to know dosages Herpes Zoster: 1000mg TID for 7 days, start as soon as sx begin Genital Herpes: 1G BID for 10 days for initial, 500mg BID TID for 3 days for recurrent, and 500-1000mg daily for suppressive Immunocompetent Children 2-18 yrs: 20mg/kg up max of 1000mg TID Famciclovir [Famvir]: Prodrug used to treat acute herpes zoster or genital herpes infection, Benefits are equivalent to those of acyclovir; Adverse effects are minimal Pharmokinetics: undergoes rapid absorption from the GI tract. All that enzymatic conversion to penciclovir in its active form and food does decrease the rate of absorption, but not to an extent and as a result, the amount of penciclovir produced is the same whenever famciclovir is taken with or without food. Penciclovir is excreted in the urine.