Term
| What will be disscussed in this sectionÉ |
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Definition
| The following viruses: HSV, VZV, CMV, Hepitis & Influenza, along wé their MOA & AéEs; in addition we`ll talk abt resistance and Rx-Rx interactions |
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Term
| What Rxs will be disscussedÉ |
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Definition
A) Influenza + RSV - Neuraminidase Inhibitors (-amivir), Viral uncoating Inhibitors (-mantadine), G analogue (Ribavirin)
B) Hepatitis - Interferons (Interferon alpha, beta, gamma); Nucleotideé nucleoside anaolugues (Lamivudine, Adefovir, Entecavir, Telbivudine; NB that they need to be phosphorylated to be active form)
C) Herpes - Purineé Pyrimidine analogs (-ovir + Vidarabine & Trifluridine); Fomivirsen; Foscarnet |
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Term
| How do the Neuraminidase Inhibitors workÉ |
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Definition
| Oseltamivir & Zanamivir are sialic acid analogs and thats what hemagglutinin on the virion need to be cleaved off of for release. NB that its mainly prophylasis use for Influenza A & B |
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Term
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Definition
Oral proRx thats hydrolysed in the liver, after that eliminated unchanged in urine.
GI discomfort and nausea but alleviated when taken wé food |
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Term
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Definition
Inhaled, eliminated unchanged in urine.
Because of airway irritation avoid in severe asthma and COPD |
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Term
| How do the ion channel blockers workÉ |
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Definition
| Amantadine and Rimantadine block the viral membrane protein M2 which is a H+ channel, this prevents fusion and thus no uncoating. NB that only Influenza A has this protein but can be used as prophylaxis or Tx |
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Term
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Definition
Oral, Doesnt cross BBB (Amantadine does), metabolized and eliminated by kidney (Amantadine, not so much).
Amantadine causes CNS probs like insomnia, dizziness, ataxia -. hallucinations, seizures thus watch out in crazy pts. epileptics, renally impaired pts and in cerebral atherosclerosis; in addition both cause GI intolerance. Also it FDA C and cross-resistance can occur in 50% |
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Term
| How does the G analog workÉ |
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Definition
Ribavirin is active against RSV, HCV (É), Lassa fever, it works by converting to ribavirin-triphosphate -. to inhibit GTP formation thus viral mRNA is not capped -. inhibits RNA-dependent RNA polymerase
Can be given orally, IV or aerosolized but increased with a fatty meal (L), Rx retension seen everywhere but the brain, Rx and metabolites eliminated in urine.
AéEs - dose-dependent transient anemia (can bind to RBC) elevate bilirubin.
NB that its FDA X thus have to be off it 4 mos before pregnancy |
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Term
| How do the Interferons workÉ |
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Definition
Induce PKR that inhibits RNA & DNA synthesis; given IV, subcutaneously, intralesionally, there is lil left in plasma as cells take it up and so does the liver and kidney (but there is no renal eliminationÉÉÉ); pegylated to improve PKs (made bigger to increase T1é2).
AéEs - flu-like (fever, chills, myalgias + GI distrubances); fatigue + mental depression; may cause toxic levels of theophylline by interfering with hepatic metabolism; may potentiate myelosuppression caused by zidovudine |
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Term
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Definition
| HCV, HBV, condyloma acuminata, hairy-cell leukemia, kaposi`s sarcoma |
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Term
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Definition
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Term
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Definition
Competitively inhibits HBV DNA polymerase, Well absorbed orally + widely distributed (t1/2~9h),
70% excreted unchanged in urine,
Well tolerated (headache, dizziness) |
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Term
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Definition
| Incorporated in viral DNA |
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Term
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Definition
Competes with deoxyguanosine triphosphate for viral reverse transcriptase,
Effective against lamivudine-resistant strains of HBV,
Very little metabolized,
Renal function must be assessed and drugs with renal toxicity avoided,
Monitor after discontinuation |
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Term
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Definition
Not effective against HIV or other viruses,
Either competes with endogenous thymidine triphosphate or, incorporates into viral DNA |
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Term
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Definition
Prototypic antiherpetic therapeutic agent.
Herpes simplex virus (HSV) Types 1 and 2, varicella-zoster virus (VZV) + some Epstein-Barr (HSV4) infections.
TREATMENT OF CHOICE IN HSV ENCEPHALITIS.
Commonly used for genital herpes infections + prophylactically in immunocompromised and transplant
patients.
MOA:
Guanosine analog - monophosphorylated by herpes virus-encoded enzyme (thymidine kinase) |
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Term
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Definition
HSV, adenovirus + CMV-induced retinitis in HIV/AIDS,
Not phosphorylated by viral kinases,
Requires activation by host cell kinases,
Effective against HSV + Ganciclovir resistant organisms.
MOA:
DNA chain terminator + DNA polymerase inhibitor.
Pharmacokinetics:
IV, intravitreal + topical,
Must be co-administered with probenecid (blocks renal tubular secretion).
May cause nephrotoxicity. And resistance is due to mutation in viral DNA polymerase |
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Term
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Definition
Valganciclovir (pro-drug with greater oral bioavailability).
Analog of acyclovir (8-20 x activity against CMV),
Drug of choice for CMV retinitis + CMV prophylaxis in immunocompromised.
MOA:
Phosphorylated by viral (UL97) and cell kinases,
DNA chain terminator + DNA polymerase inhibitor.
Pharmacokinetics:
IV, well distributed (including CSF),
Excretion in urine via glomerular + tubular secretion,
Valganciclovir undergoes rapid hydrolysis in intestine +
liver |
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Term
| Famciclovir & Penciclovir |
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Definition
Famciclovir - pro-drug of penciclovir,
Active against HSV-1, 2 and VZV.
MOA:
Inhibit HSV DNA polymerase / chain terminator.
Pharmacokinetics:
Penciclovir – only topical (t1/2 – 20-30 x acyclovir triphosphate),
Famiclovir – oral.
Adverse Effects:
Headaches, nausea, diarrhea.
Resistance:
Low occurrence clinically |
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Term
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Definition
Adenine analog,
Effective against HSV, CMV and VZV.
Limited to treatment of immunocompromised patients with
herpetic and vaccinal keratitis + HSV keratoconjunctivitis.
MOA:
Inhibits viral DNA synthesis after conversion to triphosphate
Pharmacokinetics: Ophthalmic ointment
Adverse Effects:
Superficial punctate keratitis, pain, photophobia |
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Term
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Definition
Thymidine analog,
Effective against HSV-1, 2, and vaccina virus.
Drug of choice for HSV keratoconjunctivitis and recurrent
epithelial keratitis.
MOA:
Incorporated into viral DNA causing fragmentation.
Pharmacokinetics:
Ophthalmic ointment (triphosphate can incorporate into cellular DNA.
Adverse Effects:
Transient irritation of eye + palpebral (eyelid) edema |
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Term
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Definition
Antisense oligonucleotide,
Used when other therapies for CMV retinitis fail.
MOA:
Binds to CMV mRNA inhibiting CMV protein synthesis.
Pharmacokinetics:
Intravitreally; t1/2 ~55h.
Adverse Effects:
Iritis (25%), vitritis, changes in vision + increases in intraocular pressure (15-20%) |
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Term
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Definition
Organic analog of inorganic pyrophosphate (does NOT require phosphorylation).
Used for CMV retinitis in immunocompromised patients,
acyclovir-resistant HSV + CMV retinitis, ganciclovir-resistant CMV + VZV.
MOA:
Selectively inhibits virus-specific DNA polymerase + reverse transcriptase.
Pharmacokinetics:
IV (poor oral absorption),
Widely distributed including CNS.
Adverse Effects:
Nephrotoxicity(!), hypocalcemia(!), anemia, nausea + fever,
CNS: hallucinations, seizures, headache (25%)
Resistance: Point mutation in polymerase |
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Term
| Summary of Respiratory Anti-viral Rxs |
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Definition
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Term
| Summary of Hepatic Anti-viral Rxs |
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Definition
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Term
| Summary of Herpes Anti-viral Rxs |
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Definition
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