Antiviral Agent Flashcards
How do viruses work
- Binding and fusion of virus w/ host cell
- Penetration-uncoating and release of genetic material
- Insertion into host genome via integrase
- Genome replication
- Expression of viral proteins and protein processing
- Assembly of virus in host cell
- Release of virus from host
Viruses are obligate intracellular pathogens
Types of viral genome replication
Examples of each
DNA→DNA→mRNA
DNA pol
Herpes, CMV, varicella
DNA→RNA→DRNA
DNA pol, RNA dep DNA pol
HBV
+RNA→mRNA
HCV, HAV
-RNA→mRNA, +RNA template
RNA dep RNA pol
RSV, ebola
+RNA→DNA→+RNA
Reverse transcriptase
HIV
Viral infections
Many not life threatening
Some only show up when damage has been done-untreatable until damage is done (polio, resp. viruses)
Best tx for preventing/limiting viral inf is immunization (polio, MMR, smallpox, HPV)
Chronic viral inf. that can be treated:
- Herpes
- Varicella zoster
- CMV
- RSV
- Influenza
- HIV
What drugs are used to treat herpes infections?
Ciclovirs
Cyclovirs
Cidofovir
Foscarnet
Acyclovir
Antiviral drug
Tx: Herpes simplex and zoster
Mech: Incorporated into DNA and inh. viral DNA pol
Prodrug-must be phosphorylated by viral kinase
Only occurs in active cells
Much higher affinity for viral DNA pol
Route: IV and oral (not well absorbed though)
SE:
- GI upset
- Renal damage
- CNS problems
- Delerium when given IV
Valacyclovir
Antiviral drug
Tx: Herpes simplex and zoster
Mech: Prodrug converted to acyclovir
Must be given orally-prodrug metab. by 1st pass metab.
Famciclovir
Antiviral agent
Tx: herpes simplex and zoster
Mech: prodrug converted to acyclovir analog
Ganciclovir
Antiviral agent
Tx: CMV (herpes virus)
CMV→retinitis+ blindness
Mech: Inhibits viral DNA pol
Prodrug-activated by viral kinase
SE:
- Neutropenia
- Thrombocytopenia
- Teratogen
Valganciclovir
Antiviral agent
Tx: CMV (herpes virus)
CMV→retinitis+ blindness
Mech: Inhibits viral DNA pol
Prodrug-converted to ganciclovir by viral kinase
Cidofovir
Antiviral agent
Tx: CMV (herpes virus)
CMV→retinitis+ blindness
Mech: Inhibits viral DNA pol
Prodrug-converted by host kinase
Used if resistance has occured so that host cells convert prodrug
SE: Renal damage
Foscarnet
Antiviral agent
Tx: CMV (herpes virus)
CMV→retinitis+ blindness
Mech: Inhibits viral DNA pol
Not a prodrug–directly inh. DNA pol
Route: IV 3x/day
SE: Renal damage
Agents used to treat Hep B
Names and mech
LATTE:
Lamivudine
Adefovir
Telbivudine
Tenofovir
Entecavir
Mech: Inh. Hep B reverse transcriptase
- I HRT LATTE*
- Inh. hep B rev. trans.–LATTE*
Lamivudine
Antiviral agent
Tx: Hep B
Mech: Inh. Hep B reverse transcriptase
Discontinuation→Increase hepatitis symptoms
Adefovir
Antiviral agent
Tx: Hep B
Mech: Inh. Hep B reverse transcriptase
SE: Liver and renal damage
Discontinuation→Increase hepatitis symptoms
Telbivudine
Antiviral agent
Tx: Hep B
Mech: Inh. Hep B reverse transcriptase
SE:
- Lactic acidosis
- Hepatomegaly
Discontinuation→Increase hepatitis symptoms
Tenofovir
Antiviral agent
Tx: Hep B
Mech: Inh. Hep B reverse transcriptase
SE:
- Lactic acidosis
- Hepatomegaly
Discontinuation→Increase hepatitis symptoms
Entecavir
Antiviral agent
Tx: Hep B
Mech: Inh. Hep B reverse transcriptase
SE:
- Lactic acidosis
- Hepatomegaly
Discontinuation→Increase hepatitis symptoms
Ribavirin
Antiviral agent
Tx: RNA virus (RSV)
Only for severe lower resp inf.
Mech: Inh RNA dep DNA pol
Phosphorylated in cell.
SE:
- Preg cat X
- Hemolytic anemia
- Decrease pulmonary fxn in infants
- Cardiac arrest
Not used much anymore. Very expensive
Palivizumab
Antiviral agent
Tx: RNA virus (RSV)
Mech: vs antigenic site of RSV–blocks fusion of virus w/ target
Only used prophylactically
Amantadine
Antiviral agent
Tx: RNA virus (Influenza A virus)
Virus taken up by cell endosome→opens channel in endosome→H enters→virus can release genes
Mech: Blocks process by which H channel forms in endosome
Blocks transporter or ion channel
Used proph. or very early
SE:
- Renal failure
- Teratogen
- CNS fx
- Dizziness
- Slurred speech
- Confusion
- Seizures
- Nausea
Rimantadine
Antiviral agent
Tx: RNA virus (Influenza A virus)
Virus taken up by cell endosome→opens channel in endosome→H enters→virus can release genes
Mech: Blocks process by which H channel forms in endosome
Blocks transporter or ion channel
Used proph. or very early
Widespread resistance
SE: Fewer than amantidine but similar SE
- Renal failure
- Teratogen
- CNS fx
- Dizziness
- Slurred speech
- Confusion
- Seizures
- Nausea
-amivir
Zanamivir
Oseltamivir
Antiviral agent
Tx: Influenza A+B virus (RNA virus)
Virus leaves cell and is attached by tether of neuraminic acid
Release of virus requires neuraminidase
Mech: Neuraminidase inh.
So virus cannot be released from cell and spread
SE:
- Nausea
- Diarrhea
- Psychosis
- Hallucinations
- Zanamivir is a powder that must be inhaled so asthma issues
Only shorten influenza by about a day
Recombinant interferon alpha
Antiviral agent
Tx: Hepatitis virus (esp Hep C)
Cytokine w/ multiple mech
Mech:
- Immunostimulant
- Inh. mRNA processing
- Decrese viral synth
SE:
- Fatigue
- Flu-like symptoms
- Depression
- Hypertensino
- Retinopathy
- Myelosuppression→fewer platelets, granulocytes, etc.
-previr
Boceprevir
Telaprevir
Simeprevir
Antiviral agent
Tx: Hepatitis virus (esp Hep C)
Mech: HCV protease inh.
Virus makes proteins but cannot be processed to final stage
Used in comb. w/ interferon
Sofosbuvir
Antiviral agent
Tx: Hepatitis virus (esp Hep C)
Mech: Inh HCV RNA dep RNA pol
Ledipasvir+Sofosbuvir=harvoni
Ledipasvir
Antiviral agent
Tx: Hepatitis virus (esp Hep C)
Mech: Binds to and inh. protein thats necessary for HCV replication
Ledipasvir+Sofosbuvir=harvoni
Harvoni
DOC for HCV
Ledipasvir+sofosbuvir
Nucleoside analog reverse transcriptase inh (NRTIs)
DAZLES T
Didanosine
Abacavir
Zidovudine
Lamivudine
Emtricitabine
Stavudine
Telbivudine
(Tenefovir=nucleoTide analog of RT inh)
**Nucleotides do not have to be processed like nucleosides* *
Tx: HIV
Mech: Inh reverse transcriptase
Nucleoside analog–competetive inh.
Phosphorylated in cell
SE:
- Life threatening hepatomegaly
- Systemic lactic acidosis
- Anemia
- Myopathy
- Pancreatitis
- Some neuropathy
- Daves got flow*
- DAVE PHLOA*
Didanosine
Abacavir
Vudine
Emtricitabine
Pancreatitis
Hepatomegaly
Lactic acidosis
-Opathy (retin- +my-)
Anemia
Non nucleoside analog reverse transcriptase inh (NNRTIs)
1st gen
Nevirapine
Delavirdine
Efavirenz
Tx: HIV
Mech: Bind to non-active sites on reverse trans.
Non competetive inh.
Non nucleoside analog reverse transcriptase inh (NNRTIs)
2nd gen
Etravirine
Rilpivirine
Tx: HIV
Mech: Bind to non-active sites on reverse trans.
Non competetive inh.
Differ from 1st gen:
- Higher potency
- Longer T1/2
- Fewer SE
Nevirapine
Antiviral agent
Tx: HIV
Mech: bind to non active sites and Inh reverse trans
Not competetive inh.
1st gen NNRTI
SE
- Hepatotoxicity
- Stevens Johnson syndrome
Delavirdine
Antiviral agent
Tx: HIV
Mech: bind to non active sites and Inh reverse trans
Not competetive inh.
Not as effective
1st gen NNRTI
SE
- Hepatotoxicity
- Stevens Johnson syndrome
- P450 inh.
Efavirenz
Antiviral agent
Tx: HIV
Mech: bind to non active sites and Inh reverse trans
Not competetive inh.
1st gen NNRTI
SE
- CNS- so some people crush it up and smoke it
- hallucinations
- memory loss
- Rash
- Smoke EFavirenz to get EFfed up*
- hallucinations and mem loss*
-virine
Etravirine
Rilpivirine
Antiviral agent
Tx: HIV
Mech: bind to non active sites and Inh reverse trans
Not competetive inh.
2nd gen NNRTI
Differ from first gen:
- Higher potency
- Longer T1/2
- Fewer SE
-navir
Antiviral agent
Tx: HIV
Mech: Protease inh.
Prevent formation of active viral proteins from their peptide precursor
Most inh. P450
Some are absorbed poorly via oral route and 18 capsules must be taken/day
Ritonavir is most potent known P450 inh so it is given w/ the poorly absorbed protease inh to avoid taking so many
Ritonavir given w/: SALTD
- Saquinavir
- Atazanavir
- Lopinavir
- Tipranavir
- Darunavir
SE:
- Alter fat distribution
- Loss of fat in face and limbs
- Gain fait in gut, chest, and back
- Increase diabetes
- Some have sulfur groups→allergies
- Tipranavir
- Fosamprenavir
Enfuvirtide
Tx: HIV
Mech: binds to specific site on virus that binds to target
Fusion inhibitor
SE: Insomnia
Maraviroc
Tx: HIV
Mech: Blocks binding site on macrophage preventing entry of virus
Fusion inhibitor
SE:
- Hepatotoxicity
- Allergies
- Increase MI
-gravir
Tx: HIV
Mech: Inh. HIV-1 integrase
Inh. insertion of viral genome into human
Prevents propagation
HAART
Highly Active Anti Retroviral Therapy
Protease inh
NRTI
NNRTI
