1.  DNA viruses (herpesviruses, poxviruses, adenoviruses)

2.  RNA viruses (rubella, rhabdoviruses, picornaviruses)

3.  Retroviruses (HIV)

The nucleoside analog incorporates itself in the DNA or RNA of the virus.  Then, it stops elongation of the strand because it does not have a hydroxyl group in its 3' position.  Therefore, it cannot form a nucleotide and it terminates nucleic acid replication. 

most current analogs have modifications to the ribose part of the molecule. 

absorption: taken orally

duration of action: 2-3 hr half life = multiple daily doses

metabolism/excretion:  not metabolized, not substrates for liver P450 enzymes, eliminated in urine (may need to adjust dose for renally-impaired patients)

Acyclovir

1.  type

2.  method of action

3.  uses

4.  Problems with it

1.  guanosine analog with an acyclic group replacing the ribose of the nucleoside

2.  Because of acyclic group, the next nucleotide cannot be added and the chain is terminated.

3.  Herpesvirus drug; used in pregnancy even though it is not FDA approved for pregnancy; effective in near term women with recurrent genital herpes and helps prevent spread to newborn

4.  Resistance is a major problem (viral enzymes mutate and not longer add initial phosphate to drug). 

Note:  alternative therapeutic options are Foscarnet or Cidofovir (esp. for HSV or VZV)

This drug can be administered orally, by IV, or topically.

Famciclovir

Penciclovir

Valacyclovir

Ganciclovir (gang of cycles running over a lot of things)

1.  type

2.  method of action

3.  uses

4.  toxicity

1.  guanine analog

2.  nucleoside analog

3.  drug of choice for CMV infections (life and sight-threatening in AIDS pts). (acyclovir cannot be used for CMV because it doesn't have the rt enzyme).  Can be used phophylactically in transplant patients.

4.  aspermatogenesis; granulocytopenia and thrombocytopenia; carcinogenic and teratogenic in animals; retinal detachment. 

Note:  resistance is associated with persistant infection.  Treat with foscarnet or cidofovir if it is resistant.

Valganciclovir

1.  Type

2.  Method of action

3.  Uses

4.  Toxicity

1.  oral version of ganciclovir

2.  nucleoside analog

3.  has largely replaced IV and oral ganciclovir for pts with CMV retinitis that is not life or sight threatening

Cidofovir

1.  Type

2.  Method of action

3.  Uses

4.  Toxicity

1.  cytosine analog (nucleoside analog)

2.  inhibition of viral DNA polymerase

3.  administered IV to delay progression of CMV retinitis in pts with AIDS

4.  nephotoxicity

Note:  effective against acyclovir-resistant HSV or VZV

1.  varivax (live attenuated virus vaccine)

2.  zostavax (live attenuated virus vaccine)

Varivax

1.  What is it?

2.  Ages of use

1.  VZV vaccine (live attenuated virus vaccine)

2.  children 13 or younger will get two doses of the vaccine.

Zostavax

1.  What is it?

2.  Ages of Use

3.  When not to use it

1.  VZV vaccine (live attenuated) - used to prevent shingles

2.  for people 60 years and older who are immunocompetent

3.  Contraindicated for immunocompromised pts and people with history of anaphylactic shock to gelatin, neomycin or other components of the vaccine

1.  Viral RNA load

2.  CD4+ T-cell counts

Note: if there is an increase in viral load, then resistance is probably developing.

NRTIs (nucleoside reverse transciptase inhibitors)

1.  method of action

2.  general properties

3.  adverse effects

1.  block transcription of viral RNA into DNA by stopping reverse transcriptase

2.  prevent HIV replication in infected cells; do not interact with other drugs

3.  potentially fatal lactic acidosis, peripheral lipoatrophy, central fat accumulation, hyperlipidemia (esp. for stavudine and zidovudine)

Zidovudine
1.  type

2.  uses

3.  adverse effects

1.  NRTI

2.  used to stop mother to child transmission of HIV.  administered with other NRTIs except stavudine. 

3.  bone marrow depression, insomnia, dizziness, hyperpigmentation of oral mucosa and nail beds (see also the NRTI general card)

Didanosine

1.  type

2.  uses

3.  toxicity

1.  NRTI

2.  increase cd4+ cell counts, decr viral load in AIDS related illness; co-administered with AZT and a protease inhibitor

3.  peripheral neuropathy, pancreatitis, GI disturbances

Stavudine

1.  type

2.  uses

3.  toxicity

1.  NRTI

2.  HIV treatment

3.  fatal lactic acidosis

abacavir

1.  type

2.  toxicity

emtricitabine & lamivudine

1.  type

2.  characteristic

1.   Nucleoside reverse transcriptase inhibitors (NRTI)

2.  HIV protease inhibitors (PI)

3.  Non-nucleoside reverse transcriptase inhibitors (NNRTI)

HIV protease inhibitors

1.  Method of action

2.  Metabolism

3.  Toxicity

1.  block the virally-encoded protease that is responsible for generating mature proteins to build new viruses.  this has to do with the capsid that the virus needs. 

2.  all are metabolized by and inhibitors of cytochrome P450 enzymes.  They can interfere with the metabolism of other drugs

3.  hyperglycemia, GI disturbances, fat redistribution (buffalo hump), hyperlipidemia

Indinavir

1.  type

2.  uses

3.  toxicity

1.  HIV protease inhibitor

2.  good for pediatric patients

3.  can cause kidney stones

Saquinavir (do not have to know)

1.  type

2.  notable characteristics

1.  HIV protease inhibitor

2.  better tolerated then idinavir/ritonavir but can cause bleeding in hemophiliacs

lopinavir +ritonavir

These are HIV protease inhibitors.

tipranavir + low dose ritonavir

These are protease inhibitors.

Non-nucleoside RT inhibitors

1.  method of action

2.  metabolism

3.  toxicity

4.  method of admin

1.  binds directly to reverse transcriptase enzyme to block its function

2.  metabolized by P450 enzymes of the liver

3.  serious skin rashes, a lot of resistance quickly so they are not used alone

4.  oral

Enfuvirtide

1.  type

2.  method of action

3.  uses

4.  toxicity

1.  HIV fusion inhibitor

2.  prevents HIV from entering host cell by blocking function of envelope protein gp41

3.  treatment experienced HIV pts with ongoing HIV replication despite taking anti-retroviral drugs

4.  eosinophilia, hypersensitivity

Integrase inhibitors

1.  method of action

2.  names of drugs

1.  block integration of viral DNA into host genome for HIV pts

2.  raltegravir (pts who have failed other regimens); elvitegravir (still in clinical trials)

Maraviroc

1.  method of action

2.  uses

3.  metabolism

1.  block CCR5 receptor which is needed for the virus to get into the T cells. 

2.  combination therapy for treatment experienced adults with CCR5-tropic HIV-1

3.  metabolized by liver

Initial therapy:

-2 NRTIs +efavirenz (NNRTI) OR
2 NRTIs + PI combination (lopinavir/ritonavir)

Advanced disease:
-darunavir or tipranavir+enfuvirtide

How do you prevent a mother with HIV from giving it to her baby during labor or delivery?

What agents are contraindicated in pregnant women?

1.  therapy most effective throughout pregnancy

2.  AZT+NRTI+PI

3.  If she is not on therapy at onset of pregnancy, she should wait until 10-12 weeks of gestation to begin.

4.  AZT - administer to the newborn for 6 weeks

Stavudine and didanosine (fatal lactic acidosis) and enfavirenz (teratogenic) are contraindicated in pregnancy.

What are the two anti-influenza drugs?

oseltamivir (oral, pts 1 year and older),

zanamivir (inhaled, pts 7 years and older)

-children aged 6-59 months

-pregnant women

-people older than 50

-pts 5-49 years of age

-should not be used in pregnant women

-do not use with immunosuppressed pts

-avoid contact with immunocompromised pts for 7 days after you receive the vaccine

1.  tamiflu (oseltamivir)

2.  relenza (zanamivir)

Foscarnet

1.  method of action

2.  uses

3.  toxicity

1.  blocks viral polymerases by binding to pyrophosphate site

2.  acyclovir-resistant HSV in AIDS pts, acyclovir-resistant VZV, CMV retinitis in immunosuppressed pts (alternative to ganciclovir)

3.  renal toxicity

1.  lamivudine

2.  adefovir diprivoxil

3.  interferon alpha

4.  ribavarin

Human interferons

1.  type

2.  method of action

3.  uses

4.  toxicity

1.  human interferons - also interferon alpha is one

2.  this is a glycoprotein secreted by cells in response to a viral infection that promotes an antiviral state in uninfected cells

3. acute hepatitis B and C inf.  for chronic infections use in combination with ribavirin for Hep
C

4.  increased pulse, fever, decrease in WBC, malaise, bone marrow depression. Contraindicated for psychosis, severe depression, neutropenia, smptomatic heart disease, pregnancy

Ribavarin

1.  Type

2.  Uses

3.  Toxicity

1.  analogue of guanosine with multiple mechanisms of actions

2.  in combination with interferon alpha for treating chronic hepatitis C virus; respiratory synctial virus bronchitis and pneumonia in children

3.  decreased respiratory function, anemia, hypotension, cardiac arrest.  contraindicated in pregnant women.  Do not take it for 6 months before you get pregnant.  Pregnant women should avoid being around people who take it.  It can stay in RBCs for months.

Gardasil

1.  type

2.  uses

3.  toxicity

1.  This is a vaccine for HPV

2.  pre-initiation of sexual activity

3.  contraindicated in pregnant women

Rotavirus

What is it?