Antivirals

Question 1

primary HSV infection

Answer 1

in a susceptible host, usually asymptomatic
no antibodies or specific T-cells against HSV
positive serotypes are susceptible to superinfections and autoinfections
clinical disease lasts 1-3 weeks with the infectious virions in the saliva for 7-10 days
virus dormant in sensory ganglion of inoculation site

Question 2

HSV reactivation:

Answer 2

triggered by emotional stress, transient hyperthermia, menstruation, fever, radiation
requires immune suppression (deficient humoral and cytotoxic HSV specific T-cell)

Question 3

indications for HSV tx:

Answer 3

pt is immunocompromised or has frequent reactivations
must be initiated shortly after infection to be effective
topical tx used to shorten the duration of the disease

Question 4

Anti HSV drugs:

Answer 4

thymidine kinase dependent: need to be phosphorylated by viral TK then act as thymidine analogues to end DNA synthesis
Acyclovir (Zovirax)
Valacyclovir (Valtrex)
Famciclovir (Famvir)
Ganciclovir (Cytovene) (use limited to CMV retinitis in HIV pts and CMV prophylaxis in transplant pts)

TK independent: directly inhibit viral DNA polymerase. mostly for CMV prophylaxis
Foscovir
Cidofovir

acyclovir and penciclovir come in topical form
lysine can shorten an HSV outbreak (as do most OTC preps)
prosurX: topical homeopathic antiviral prep. shown to shorten an HSV outbreak

Question 5

prevention of herpes labialis:

Answer 5

use sunscreen on lips

Question 6

HZV Tx:

Answer 6

same meds as HSV but in higher doses

Question 7

NRTIs

Answer 7

no complex food requirements
easy dosing schedule
backbone of combination therapy
few drug interactions

serious side effects like lactic acidosis

Question 8

PIs:

Answer 8

high genetic threshold

complex food requirements
CYP3A4 substrate and inhibitor
metabolic issues
cross resistance

Question 9

NNRTIs:

Answer 9

less lipid toxicity
impressive long term results
leaves PIs for future use
low toxicity

cross resistance
CYP450 inhibitor
low genetic barrier

Question 10

INSTIs

Answer 10

impressive long term results
first line therapy
well tolerated

mutations and resistance is possible, esp. with first gen
cross resistance common in 1st gen
potential CYP450 drug interactions

Question 11

NRTI side effects

Answer 11

pancreatitis 
lipodystrophy
peripheral neuropathy
hepatic adiposis
myopathy cardimyopathy myositis 
BM suppression 
lactic acidosis

Question 12

PI side effects

Answer 12

lipodistrophy
hyperlipidemia 
increased bleeding in hemophiliacs 
insulin resistance 
osteonecrosis and osteoporosis 
hepatotoxicity 
drug interactions

Question 13

NRTI side effects

Answer 13

rash
drug interactions
Nevirapine: rash including Steven Johnson syndrome. hepatotoxicity
Efavirenz: neuropsychiatric. teratogenic

Question 14

INSTI side effects

Answer 14

rash
allergy
hepatotoxicity

Question 15

lypodystrophy

Answer 15

peripheral fat wasting w/ NRTIs
central fat accumulation with PIs
associated with dyslipidemia 
polymer injections could help
switch to other class of meds