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Anti-Herpes Pharm


Drug List ? * Acyclovir = HSV and VZV...... * Foscarnet = HSV, VZV, CMV ......* Ganciclovir = CMV
MOA of these drugs ? * Most drugs used are nucleoside analogs --> triphosphate inhibits DNA polymerase and can cause strand breaks
What makes these drugs unique ? * the phosphat is not added to these drugs by the host, but rather by the virus itself by a viral kinase...... * after it is a monophosphate, then the host adds the DP and TP
Acyclovir uses ? * HSV 1 and 2 recurrent or primary.... VZV ...... HSV-1 encephalitis
Acyclovir DOC ? * HSV encephalitis ---- neonatal HSV infections ---- serious HSV or VZV infections........ * also safe to use in neonates and for pregnant ppl that are at risk to passing HSV on to their baby
Acyclovir MOA ? * Phosphorylated by viral thymidine kinase --> inhibits viral DNA synthesis, which terminates the chain
Acyclovir SEs ? * not too many due to the first step of the viral enzyme adding the 1st phosphate...... * Big Ones: Acute renal failure and CNS tox (seizures/coma)....... * also watch renal and hydration status, bc if either are low, could cause these SEs
Ganciclovir primary use ? * Prevention and treatment of CMV infection and for Prevention of CMV reactivation in transplant patients ...... * CMV isn't an isue in normal ppl, but in immunocomp individuals it is
Ganciclovir MOA ? * Similar to acyclovir -- CMV phosphotransferase (viral enzyme) responsible for initial phosphorylation of GCV
Ganciclovir SEs ? * Dose Limiting Toxicities: BMD, CNS ..... * don't use Zidovudine with it
Foscarnet use ? * for serious CMV and HSV infections only.... * not a 1st use drug, but one to resort to if mutations are seen or severe
Foscarnet MOA ? * NOT a nucleoside analog - Does NOT require activation by kinases.......... * Blocks the pyrophosphate binding site & Inhibits viral DNA polymerase
Foscarnet SEs ? * Pretty Toxic Drug ....... * Dose Limiting CNS Tox, Hypocalcemia, Nephrotoxicity, and electrolyte imbalances
Latency and/or Recurrent Disease basics ? * Retrograde travel through peripheral nerves after it gets through the skin, where it lay dormant in that particular segment level of nerves
Some things that allow for the virus to lay latent and not seen by our immune system ? * Neuronal methylation silences the virus until activation....... * Neuronal stimulation converts chromatin & tethered viral genome to euchromatic state, where it was in the heterochromatic state before that
Why we get a recurrent infection in the same spot ? * viral miRNAi/siRNA’s expressed that block neuronal apoptosis
Signs and Symptoms, Primary Episode of HSV ? * Can be asymptomatic, mild, or occur with meningitis...... * CxSx last about 2-3 weeks...... * Mean duration of viral shedding approximately 12 days
Recurrent genital herpes ? * occurs even with circulating ABs against it.... * Asymptomatic viral shedding, up to 75% of days! Avg. 17/100 days male, 30/100 female. .... * Complications: meningitis/encephalitis, neonate issues
Most ppl with HSV ? * present with CxSx, but have no clue they have herpes
Neonatal Herpes = ? * TORCH, HSV-2....... * acquired in birth canal..... * Present with : (1) SEM (skin, eyes, mouth); (2) CNS (encephalitis); (3) Disseminated. ..... * usu have neuro issues after tmt
Pregnancy and time you get infected with HSV ? * Increased risk with primary (3rd trimester) maternal infection vs. recurrent disease ( likelihood + severity). Baby get ABs....... * basically, if new infection during 3rd tri = way worse than reactivation
Differential diagnosis when you see genital ulcerations ? * syphilis and chancroid (H. ducreyi)
HSV-2 Diagnosis ? * Viral Culture (“Gold standard”)...... * PCR/DNA (most sensitive, but not routinely available)...... * Point-Of-Care “POCkit”, = sees if type 1 or 2 in office in about 10 minutes
HSV Epidemiology ? * is an endemic throughout the world...... * incidence increases with more sex partners, low SEC, low education, hispanics/blacks....... * sheds in ppl that are asymptomatic--> why it spreads a lot
Initial infections with HSV ages ? * kids = HSV-1.... * Adolescents/Adults = HSV-2
HSV TmT/Prevention ? * Abstinence, condoms, education, possibly drug prophylaxis
PAPILLOMAVIRUSES (HPV) basics ? * Papilloma viruses cause benign tumors(warts) ....... * Also, responsible for 95% of malignant cervical (and 70% of anal) carcinoma
HPV Classification that causes cervical cancer and that is benign and malignant ? * Mucocutaneous - different strands have different outcomes and present differently from person to person
How HPV is spread ? * sexual contact and most self resolve and go away, unlike HSV which is permanent in the body
HPV strains and Cancer ? * only certain ones cause cancer, not every one of them does..... * all HPV causes cell dysplasia
Cells to look at if suspecting HPV infection ? * koliocytes = cervical cells infected with HPV that cause dysplasia
Oncogenic HPV types ? * 16 and 18 which integrate in to cellular chromosomes ..... *
Proteins that are higher in 16 and 18 ? * E6 and E7, which eliminate p53 and Rb, so we get constant proliferation and no apoptosis
Benign HPV types = ? * 11 and 6
HPV epidemiology ? * 2nd most common cancer in women..... * usu see presence of ABS and - HPV test ..... * seen in lower SEC
HPV Dx ? * VIA : visual inspection with acetic acid enhancement...... * Cytology: PAP to see koliocytes..... * Best = DNA + PAP
HPV Vaccines ? * Recombinant HPV L1 (capsid) proteins – assemble into VLP’s (virus-like particles)...... * Gardasil and Cervarix are the top vacs...... * boys are now getting vaccinated for it too bc they help spread it
Created by: thamrick800