Antivirals Flashcards

Question

What is the mode of action for ACV?

Answer 1

ACV and guanosine both coastline purine base guanine ACV has acyclic side chain in place of ribose moiety Further elongation of the chain is impossible because ACV mono phosphate lacks the 3' hydroxyl group necessary for the insertion of an additional nucleotide

Answer 2

They are monophosphorylated by viral thymidine kinase, then further phosphorylated by cellular kinase to ACV-PPP Affinity of cellular kinases for ACV is poor but activity of these enzymes in virally infected cells is greatly increased Affinity of cellular DNA polymerase for ACV PPP is 10-30 times lower than herpesvirus DNA polymerase Hence inhibition of DNA synthesis by acyclovir in herpes virus infected cells is much greater

Answer 3

HSv1 >hsv2> VZV

Answer 4

Supportive treatment alone may be sufficient for single ep of orogenital HSV, uncomplicated chickenpox and shingles Antivirals drugs reduce symptoms, duration of illness, viral shedding, reduce complications ALWAYS treated immunocompromised, pneuminitis, encephalitis, eye disease

Answer 5

ACV 5 times a day, double dose in immunocompromised, consider iv if extensive Treat for longer if new lesions appear Prevention of recurrence ACV and vacv

Answer 6

ACV 5 times a day/ vacv In immunocompromised, iv ACV 10mg/kg 8 hourly for 5-7 days HSV encephalitis: iv ACV 10mg/kg 8 hourly for 14-21 days, within 6 hours admission - get nephrotoxicity

Answer 7

Excreted in saliva, urine, breast milk, infection common in childhood, normally self limiting Mononucleosis like illness and hepatitis 15% aged 1-4 years, 80% in those above 65 years Remains latent in monocytic cells (blood and bone marrow), can reactivate in context of immune suppression CMV retinitis rare due to HAART Major pathogen of solid organ and bone marrow not transplant patients - marrow suppression, graft rejection, pneuminitis, encephalitis, adrenalitis

Answer 8

Salivary transmission, infection common in childhood, usually minimally symptomatic and self limiting Classical cause of infectious mononucleosis, glandular fever, kissing disease Associated with lymphoproliferative disease in immunocompromised- ptld, burkitts

Answer 9

Supportive ACV not effective Expert guidance for immunocompromised Reduction of immune suppression

Answer 10

Ganciclovir- monophosphorylated by viral protein kinase Cidofovir- DI and triphosphorylated by cellular enzymes Foscarnet- inhibition of viral DNA polymerase, pyrophosphate analogue

Answer 11

Ganciclovir- iv, valganciclovir are effective , longer intracellular half life 18 hours. Drawback- toxicity, marrow suppression with neutropenia, and thrombocytopenia Foscarnet- iv only, side fx of renal impairment, electrolyte disturbabc Cidofovir- nucleoside analogue, broad activity against DNA viruses, iv or topical. Iv given weekly, nephrotoxic, contraindicated in renal impairment, requires prior iv hydration, co treatment with probenicid all 3 effective against HSV, VZV, EBV, hhv6

Answer 12

Universal prophylaxis- gcv for all transplant patients Pre emptive therapy- treat viraemia, without evidence of end organ disease Some controversy about which strategy is best

Answer 13

Tx divided into induction and and maintenance 1st line- iv gcv, iv gcv or iv fos Choice of initial agent often depends on relative importance of side fx 2nd line- iv cdv, then for maintenance

Answer 14

Seek expert guidance DAA not effective Chemo and surgery may be required Immunotherapy B cell depletion with anti c20 monoclonal antibody, rituximab effective

Answer 15

Pink/red, macular, can be raised patches, non itchy

Answer 16

Cause of exanthem subitum 6th disease, roseola infantum Children under 3 years, high fever, possibly convulsions, coryzal symptoms, sudden rash Self limiting, virus remains latent Can reactivate in immunocompromised- encephalitis, marrow suppression, pneuminitis

Answer 17

``` Integration of viral DNA into host chrosome can occur Frequency is 1 % population Every cell affected Can be inherited from either parent Biological significance unclear ```

Answer 18

Generally supportive- antipyretic Encephalitis- in transplant patients has been treated with fos and gcv Important to distinguish chromosomally integrated hhv6

Answer 19

Multiple raised, red/violet macules | Diffuse plasma cell proliferation

Answer 20

Infection acquired in early life, asymm 2 main malignancies- kaposi, multicentric castlemans Usually detectable in biopsy but not detectable in blood and biopsies Mcd- HHV 8 usually detectable in blood biopsies, but non HHV related forms exist

Answer 21

Classical- Middle aged, Mediterranean men, indolent Endemic- Africa, skin lesions, aggressive form Iatrogenic- immune suppression esp. Calcineurin inhibitors, atypical location AIDS associated- aggressive, widespread lesions

Answer 22

Gcv, fos, cdv all potentially active in vitro No definitive clinical role for DAA Chemo and immunotherapy May approve with HAART if associated with HIV

Answer 23

Mutations in viral TKs, and DNA polymerase, mediates cross resistance to gcv Resistance stains selected out by drug treatment Nearly always occurs in immune suppression-TK deficient strains less virulent

Answer 24

Diagnose with viral culture, phenotypic resistance test-plaque reduction assay- time consuming and requires viable virus to be isolated Characterisation of resistance mutations may permit genotype testing in the future Treat ACV resistance HSV with fos or cdv

Answer 25

Mutations in protein kinase most commone, DNA poly are most rare Most likely to occur in context of prolonged therapy in immunocompromised Difficult to identify- phenotypic tests rely on viral culture and genotypic mutations incompletely characterised Suspect if clinical failure despite appropriate therapy and reduction of immune suppression 2nd line- fos or cdv

Answer 26

Influenza a spring, rsv xmas, rhinovirus

Answer 27

Major surface glyocoproetins haemagluttinin qnd neuramindase. HA facilitates attachment via host cell sialic acid and causes membrane fusion, NA cleaves sialic acid and allows virion to exit host cell HA binding antibodies can neutralise infection and are the focus of current influenza vaccines

Answer 28

Oseltamivr oral, zanamivir- dry powder inhaler Iv and nebulised zanamivir can be used Effective for influenza a and b Indicated if all 3 apply- influenza is circulating, patient is in risk group, within 48 hours of symptom onset (36 hours for zanamivir) Severely unwell should always be treated Vaccination is better than antiviral

Answer 29

Antiparkinsonian drug- also antiviral activity Inhibit influenza A matrix protein M2 Prevent virus uncoating Orally absorbed only effective for influenza a Not currently recommended or used in UK

Answer 30

Commonest cause of severe respiratory tract illness and hospitalisation of infants in the world Associated with subsequent wheeze and asthma diagnosis in later life Elderly, chronic lung disease and immunocompromised

Answer 31

Ribavarin- guanosine analogue Inhibits viral RNA synthesis- exact mechanism unclear, broad activity in vitro Clinical efficacy unclear- effective for Lassa fever, used in combination with interferon for HCV, weak data for nebulised ribavarin for Rsv Can have anaemia and mitochondrial toxicity

Answer 32

Human monoclonal antibody against fusion protein Given prophylactic ally for Rsv, prevents Rsv infection, and reduces later life wheezing but in ineffective for treatment of Rsv Promising drug- given day after rsv detected, oral gs- 5806

Antivirals Flashcards

(56 cards)