ANTI-VIRAL DRUGS Flashcards
OSELTAMIVIR
ZANAMIVIR
NEURAMINIDASE INHIBITORS
- Effective against BOTH Type A and Type B Influenza
- Administered prior to exposure as prophylaxis
- Administered within 24 - 48h after infection drugs have modest effect on symptoms
2015-2016 Influenza Season
• Oseltamivir & zanamivir are the only TWO agents recommended for use
MOA: inhibit the RELEASE of virus by inhibiting SIALIC ACID SUBSTRATE
NEURAMINDIASE INHIBITORS
PK/AE
Resistance
- Oseltamivir: orally active prodrug (hydrolyzed in liver)
- Zanamivir: NOT orally active (inhaled, intranasal)
Adverse Effects
- Oseltamivir: GI discomfort, nausea (alleviated when taken with food)
- Zanamivir: airway irritation (avoid in severe asthma, COPD)
RESISTANCE:
• Less infective & virulent neuraminidase mutations identified
AMANTADINE
RIMANTADINE
ION CHANNEL BLOCKERS
- _EXCLUSIVELY ACTIVE ON *INFLUENZA A* VIRUS*****_
- Equally effective in prophylaxis and treatment (70-90%)
• Since 2006 not recommended as first-line treatments due to resistance
2015-2016 Influenza Season
• Amantadine & rimantadine are NOT effective for the treatment or prevention of the currently circulating strains of influenza A.
MOA: BLOCKS VIRAL M2 PROTEIN THEREBY INHIBITING FUSION/UNCOATING
- Block viral membrane protein, M2 (H+ channel)
- Channel is required for fusion of viral with cell membrane to endosome (requirement for viral uncoating)
PK:
- Oral
- Amantadine is widely distributed & crosses BBB (Rimantadine is NOT), not extensively metabolized & excreted into urine where it may accumulate (b/c a MAN = STRONG –> goes everywhere and can cross any barrier)
- Rimantadine IS metabolized before elimination in urine
AMANTADINE
RIMANTADINE
adverse effects + contraindications + resistance
AE
- Amantadine: CNS (~10%) (insomnia, dizziness, ataxia leading to hallucinations, seizures)
- Rimantadine: fewer problems
- Both: GI intolerance
CONTRAINDICATIONS:
- Amantadine should be monitored in psychiatric patients, cerebral atherosclerosis, renal impairment, epilepsy (b/c A MAN = MORE LIKELY TO BE CRAZY!)
- Pregnancy, nursing (FDA Category C)
RESISTANCE:
- Up to 50% individuals are naturally resistant
- Cross-resistance between drugs occurs
RIBAVIRIN
SYNTHETIC GUANOSINE ANALOG
RIB-A-VIRIN –> RIB A LIVIN with your girl. Think of going out for ribs with your GIRL (guanosine analog). She’s a sweet girl so she likes any food –> broad spectrum (RNA + DNA) –> and has many flavors Regular (RSV), Hot (HCV), and LAVA hot (lassa fever)
–> if you choose the Hot (HCV) means you’re the ALPHA male (IFN-alpha used for HCV)
NOTE: at the restaurant you CANNOT WEAR A CAP!!! (b/c it’s fancy) –> prevents RNA capping!!!
–> also inhibits RNA dependent RNA pol (RRRRR for Ribs)
• Active against broad spectrum of RNA & DNA viruses
–> (eg, RSV, HCV, Lassa fever)
• Commonly used in combination with interferon alpha for the treatment of HCV
MOA:
1) Converted to ribavirin-triphosphate which inhibits guanosine triphosphate formation and PREVENTS VIRAL mRNA CAPPING!!!
2) Inhibits RNA-dependent RNA polymerase resulting in INHIBITION OF VIRAL PROTEIN SYNTHESIS
RIBAVIRIN
PK/AE + CONTRAINDICATIONS
Eat 16-40 wings –> means the dinner will be PROLONGED and DISTRUBUTED
–> WINGS are so hot they are toxic to the baby, so ***DON’T GIVE TO PREGNANT GF***
–> WINGS so hot they can cause HEMOLYTIC ANEMIA
- Oral, IV, & aerosolized
- Distribution significantly prolonged in RBC (16-40 days)
Adverse Effects
• Dose-dependent transient anemia (can bind to RBC)
- GI (nausea, anorexia)
- CNS (fatigue, headache, insomnia)
CONTRAINDICATIONS:
• Pregnancy (FDA Category X)
• Negative pregnancy tests required before treatment and monthly during treatment of female patients or female partners of male patients
TREATMENT OF HEPATIC VIRAL INFECTIONS
Hepatitis A, B, C, D & E
• HBV and HCV are most common causes of chronic hepatitis, cirrhosis & hepatocellular carcinoma
A) Interferon
–> INTERFERON ALPHA
B) Nucleotide / Nucleoside Analogs
–> Lamivudine, Entecavir, Ribavirin
C) Protease Inhibitors
–> Boceprevir, Telaprevir
INTERFERON ALPHA
ALPHA = _A_RRESTS RNA/DNA synthesis by ACTIVATING protein expression that inhibits viral infection
• Naturally occurring, inducible glycoproteins / cytokines
• alpha and beta produced by many cell types
–> gamma by immune cells (T cells)
MOA
- Use innate immune response.
- DO NOT target viral gene products directly
- Inhibit RNA & DNA synthesis by activating / inducing protein expression that inhibit virus infection eg, PKR
PK:
• Not orally active (IV, subcutaneously, intralesionally)
- Cellular uptake and metabolism by liver & kidney
- Usually pegylated to improve PK profile
Adverse Effects
- Flu-like (fever, chills, myalgias & GI disturbances)
- Fatigue & mental depression
INTERFERON ALPHA
DRUG INTERACTIONS
CLINICAL APPLICATIONS
ALPHA –> the alpha male THEOPHYLLUS (theophylline) gets angry and accumulates!!!!
–> think of theophyllus as a WARTY, HBV/HCV DRUG user that has KAPOSI dots everywhere, and is HAIRY!!! (hairy cell leukemia)
• Interferes with hepatic drug metabolism.
–> Can cause _toxic accumulation of theophylline.****_
• May potentiate zidovudine induced myelosuppression
Clinical Applications
- HCV (in combination with ribavirin)
- HBV, condyloma acuminata, hairy-cell leukemia, Kaposi’s sarcoma
LAMIVUDINE
ENTECAVIR
NUCLEOSIDE/NUCLEOTIDE ANALOGUES
LAMB DINING ENTErs-CAVE –> he’s just going into cave because can’t do much else ie he is just SUPRESSING what is actually going to happen (ie not curative)
–> must be PHOSPHORLYATED to ACTIVE form
- Must be phosphorylated by cellular enzymes to triphosphate (active) form
- Actions are suppressive rather than curative
LAMIVUDINE
NUCLEOTIDE/NUCLEOSIDE ANALOG
LAMB DINING –> lamB dining for hep B, also HIV. Is what you get for getting a little LAMB on the SIDE (nucleotide/nucleoside analog)
- MONO –> gets incorporated into DNA
- TRI –> inhibits reverse transcriptase
• Effective against hepatitis B and HIV
• Triphosphate form inhibits HBV and HIV reverse transcriptase
- Monophosphate form is incorporated into DNA (by HBV polymerase) resulting in chain termination
- Well tolerated (headache, dizziness, GI complaints)
ENTECAVIR
NUCLEOTIDE/NUCLEOSIDE ANALOG
ENTER CAVE from the SIDE to avoid the TIDE (analogs)
Effective against lamivudine-resistant strains of HBV & HIV
Phosphorylated form competes with natural substrates for viral polymerase.
Subsequent inhibition of polymerase blocks reverse transcriptase activity
Monitor after discontinuation in case of exacerbation of severe hepatitis
BOCEPREVIR
TELAPREVIR
PROTEASE INHIBITORS = “PREVIR”
TELA BOCCE PREVIR —> tell a bocce player to BIND RIVERSIBLY to the NS3 serine protease –> inhibits HCV for NS3
- Used in the treatment of HCV in adult patients who have been previously untreated or failed treatment with interferon and ribavirin
- Administered in combination with 1) interferon and 2) ribavirin
MOA
• Bind reversibly to nonstructural protein 3 (NS3) serine protease and inhibit replication of HCV
AE:
The most commonly reported adverse reactions in adult subjects are:
- fatigue
- anemia
- nausea
- headache
• dysgeusia: is an abnormal taste or change in taste that won’t go away. It can be described as bad, metallic, salty, foul or rancid.
TREATMENT OF HERPES VIRAL INFECTIONS
eg, cold sores, viral encephalitis, genital infections etc
• Herpes can form latent infection. Available drugs are for replicating virus only.
• Purine / Pyrimidine Analogs
Acyclovir, Valacyclovir, Cidofovir, Ganciclovir, Valganciclovir, Penciclovir, Trifluridine
• Foscarnet
ACYCLOVIR
PURINE/PYRIMIDINE ANALOG
KNOW THIS SLIDE WELL
- Prototypic antiherpetic therapeutic agent
- Activity against: herpes simplex virus (HSV) Types 1 and 2, varicella-zoster virus (VZV) & some Epstein- Barr (HSV4) infections
- _TREATMENT OF CHOICE IN HSV ENCEPHALITIS*****_
- Commonly used for genital herpes infections & prophylactically in immunocompromised and transplant patients
