AntiHerpes Flashcards
Acyclovir structure
deoxyguanosine analogue- side chain which usually consists of a ribose cyclic base is replaced by acyclic side chain which lacks 3’OH end
Acyclovir vs Valacyclovir
Valacyclovir is the L-valyl ester of acyclovir
Less frequent doses
Spectrum of acyclovir
HSV > VZV > CMV, EBV
Mechanism of action of acyclovir
Taken up by cells, activated by viral thymidine kinase to monophosphate.. triphosphate by cellular kinases.. this competitively inhibits dna poly and chain termination
Tenofovir- what analogue, moa, approved for, use in hsv
adenosine monoP analogue - inhibits DNA poly (comp inh, chain termination), approved for HIV, HBV; conflicting results in trials for hsv with and without emtricitabine- concentration differences
Foscarnet- moa,
Inorganic pyrophosphate analogue, directly inhibits dna poly and hiv reverse transcriptase- will not undergo any cellular activation- non competitively inhibits
Foscarnet- spectrum, main use,
hiv, hbv, cmv, ebv, hsv, vzv
approved for cmv retinits in hiv, acyclovir resitant mucocutaneous hsv
also useful in: cmv encephalitits, hhv 6, 8, hbv, hsv and vzv retinal necrosis
Foscarnet - mech of resisstance, main problem (7)
mutation in DNA poly (CMV- ul54)
1/3rd have to stop due to side effects:
1) nephrotoxicity- 33%: second week of Rx, reversible
2) hemorrhagic cystitis, genital ulcer
3) neurotoxicity (dystonia, tremors - 1/4th pts)
4) heart blocks
5) metabolic( chelator- hypoca, hypop, hypomg)
6) anemia
Secondary resistance in 37% of pts
Cidofovir - MOA
deoxycytidine monophosphate analogue - DNA poly and chain termination
Cidofovir - spectrum
hsv, ebv, cmv, hhv;
papiloma, polyoma, adeno
pox
Cidofovir - mech of resistance
UL 54
cidofovir - mode of administration
iv weekly dose for 2 weeks 5 mg/kg then once in two weeks
topical
intravesical
cidofovir - main problem
nephrotoxic - organic anion transporter in proximal tubules- apoptosis induced.. overcome by oral probenicid and iv saline
neutropenia
local reactions
cidofovir uses
Approved for cmv retinitis in aids
also used in: cmv preemp and prophy in sot and hsct
adenovirus pulmonary early treatment and viremia
refractory bk van and hgic cystitis(intravesical too)
hhv 8
recurrent papiloomatosis
recurrent anogenital herpes
recurrent molluscum
recurrent ebv nasopharyngeal carcinoma
brincidofovir
increased cellular uptake
better action on pox virus
oral
no nephrotoxicity
ul 54 confers resistance to
foscarnet and cidofovir
synergism between antivirals
foscarnet syner with cyclovirs and cido and lamivudine
cido with fos and cyclovirs
acyclovir resistance
MC and cross resistance: low or absent viral TK,
non cross: altered tk substrate specificity and altered viral dna poly
Vidarabine - MOA, spectrum
Adenosine analogue, chain termination and DNA poly inhibition; additionally has activity on 3:
S- adenosylhomocysteine hydrolase
ribonucleoside reductase
RNA polyadenylation
herpesvirus, poxvirus, rhabdovirus, adeno
Vidarabine - Use, MOR, issues
idoxuridine resistant and acyclovir resistant HSV keratitis
HSV encephalitis or neonatal HSV
Adenovirus in immunocomp
Chronic EBV
no resistance
mutagenic; discontinued in US
Brivudin- MOA, Use approval, main issue
Thymidine analogue
Herpes zoster in European countries (reduces pain, postherpetic neuralgia, accelerates healing of existing lesions, prevents formation of new lesions)
drug interaction; 5 FU; acyclovir cross resistance
Idoxuridine - MOA, spectrum, main issue, use
thymidine analogue, herpesvirus and poxvirus, local irritation and inflammation
US- herpes keratitis
UK- herpes labialis, herpes genitalis, herpes zoster
Trifluridine - MOA, spectrum, main issue, use
thymidine analogue, herpesvirus, adeno, pox
topical inflammation and irritation and mutagenic
Topical trifluridine and acyclovir better that idoxuridine and vidarabine for HSV keratitis
also useful for cutaneous lesions
