HSV, VZV, CMV Pharm
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| Drug List ? | * Acyclovir = HSV and VZV...... * Foscarnet = HSV, VZV, CMV ......* Ganciclovir = CMV
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| MOA of these drugs ? | * Most drugs used are nucleoside analogs --> triphosphate inhibits DNA polymerase and can cause strand breaks
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| 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
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| Acyclovir uses ? | * HSV 1 and 2 recurrent or primary.... VZV ...... HSV-1 encephalitis
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| 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
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| Acyclovir MOA ? | * Phosphorylated by viral thymidine kinase --> inhibits viral DNA synthesis, which terminates the chain
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| 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
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| 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
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| Ganciclovir MOA ? | * Similar to acyclovir --
CMV phosphotransferase (viral enzyme) responsible for initial phosphorylation of GCV
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| Ganciclovir SEs ? | * Dose Limiting Toxicities: BMD, CNS ..... * don't use Zidovudine with it
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| 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
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| Foscarnet MOA ? | * NOT a nucleoside analog - Does NOT require activation by kinases.......... * Blocks the pyrophosphate binding site & Inhibits viral DNA polymerase
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| Foscarnet SEs ? | * Pretty Toxic Drug ....... * Dose Limiting CNS Tox, Hypocalcemia, Nephrotoxicity, and electrolyte imbalances
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| 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
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| 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
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| Why we get a recurrent infection in the same spot ? | * viral miRNAi/siRNA’s expressed that block neuronal apoptosis
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| 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
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| 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
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| Most ppl with HSV ? | * present with CxSx, but have no clue they have herpes
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| 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
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| 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
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| Differential diagnosis when you see genital ulcerations ? | * syphilis and chancroid (H. ducreyi)
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| 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
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| 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
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| Initial infections with HSV ages ? | * kids = HSV-1.... * Adolescents/Adults = HSV-2
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| HSV TmT/Prevention ? | * Abstinence, condoms, education, possibly drug prophylaxis
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| PAPILLOMAVIRUSES (HPV) basics ? | * Papilloma viruses cause benign tumors(warts) ....... * Also, responsible for 95% of malignant cervical (and 70% of
anal) carcinoma
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| 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
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| How HPV is spread ? | * sexual contact and most self resolve and go away, unlike HSV which is permanent in the body
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| HPV strains and Cancer ? | * only certain ones cause cancer, not every one of them does..... * all HPV causes cell dysplasia
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| Cells to look at if suspecting HPV infection ? | * koliocytes = cervical cells infected with HPV that cause dysplasia
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| Oncogenic HPV types ? | * 16 and 18 which integrate in to cellular chromosomes ..... *
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| Proteins that are higher in 16 and 18 ? | * E6 and E7, which eliminate p53 and Rb, so we get constant proliferation and no apoptosis
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| Benign HPV types = ? | * 11 and 6
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| HPV epidemiology ? | * 2nd most common cancer in women..... * usu see presence of ABS and - HPV test ..... * seen in lower SEC
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| HPV Dx ? | * VIA : visual inspection with acetic acid enhancement...... * Cytology: PAP to see koliocytes..... * Best = DNA + PAP
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| 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
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