Miscellaneous Quiz / Anti-hepatitis Agents

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Can you name the Anti-hepatitis Agents?

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Group MOA: 3 major enzymes are activated by IFN-JNK/STAT signaling pathway: (1) 2',5' oligo A synthase: produces 2'5' oligo A.
P-kinetics: Higher rate of complete response & less resistance vs. adefovir
Group MOA: Competively inhibit HBV DNA polymerase +/- incorporate into viral DNA causing chain termination. Phosphorylated to active forms intracellularly by cellular kinases.
Use: HBV: Safer for pts w/ decompensated liver dz. For both adults & peds
Group MOA cont. (2) Ribonuclease L (activated by 2'5' oligo A): degrades mRNA.
Use: HBV treatment adults only
P-kinetics: Natural. SC or IM
SE: HA, fatigue, nausea. Potential mitochondrial toxicity (lactic acidosis & hepatic steatosis)
IFN α-2b Class
Tenofovir Class
SE: Dose-dependent hemolytic anemia. Depression, fatigue, irritability, nausea, insomnia.
Telbivudine (Tyzeka) Class
IFN alfacon-1 class
Drug MOA: PEG = polyethylene glycol
Use: Lamivudine-resistant HBV. Adults only
Group P-kinetics: Pills once a day for a year or longer
MOA: An adenosine analogue. Structurally similar to adefovir.
Lamivudine (3TC, Heptovir) Class
Use: Effective suppression of HBV DNA, normalization of ALT & reducing HBeAg. Adults only
Group MOA cont: Associated with mitochondrial DNA toxicity (by inhibiting DNA polymerase gamma)
PEG-IFN α-2a Class
SE: Increased pancreatitis in HIV/HBV pts. Emergence of resistance (mutations of DNA polymerase)
MOA: A guanisine analog. Inhibits all 3 functions of HBV RNA-dependent DNA polymerase (base priming, reverse transcription of the -strand, synthesis of the + strand of HBV DNA.
SE: Flu-like symptoms (fever, chills, myalgias, malaise). Neurotoxicity, myelosuppression, fatigue (chronic use). Transient hepatic enzyme elevation.
Group MOA cont. (3) Protein kinase (activated by dsRNA): phosphorylates/inhibits eIF-2, therefore blocking PRO synthesis
HintAnswer
P-kinetics: Oral bioavailability increased with high-fat meal, decreased with antacid.
Boceprevir Class
Entecavir (Baraclude) Class
Use: The most potent anti-HBV agent. Adults only
P-kinetics: Clinical resistance is rare. Oral bioavailability decreased by food (taken w/ empty stomach). Renal elimination (serum concentration increased w/ altered kidney activit
P-kinetics: Lipophilic (pivoxil) moiety enhances oral bioavailability.
MOA: A prodrug (a guanosine nucleoside analogue). Phosphorylated by host cell enzymes; inhibits viral RNA-dependent polymerases.
Use: Improve therapeutic response in pts (>18 yo) w/ HCV genotype 1 when combined w/ IFN/ribavirin
IFN α-2a/2b class
MOA: A cytosine analogue
Contraindications: Hepatic decompensation, autoimmune dz, cardiac arrhythmia, pregnancy
MOA: A prodrug of adefovir (adenosine analogue). Slows suppression of HBV DNA; least seroconversion
Contraindications: Pts w/ uncorrected anemia, ESRD, preggo. Teratogenic: avoid pregnancy for > 6 mos thereafter
P-kinetics: Slower clearance (less frequent dosing). Dosage adjustment is needed in renal dysfunction
MOA: Serine protease inhibitors. Bind to inhibit HCV non-structural protein NS3
P-kinetics: Prolonged intracellular half-life in HBV (than in HIV). Rapid oral absorption; eliminated unchanged. Used at lower doses for hepatitis than for AIDS.
Adefovir dipivoxil (Hepsera) Class
P-kinetics: Oral (TID). P450 substrates (potential rx interactions)
PEG-IFN α-2a/2b class
Telaprevir Class
MOA: A thymidine analog
P-kinetics: Synthetic (consensus). SC
SE: Anemia, neutropenia, dysgeusia, skin rash (esp. telaprevir), increased QT intervals (telaprevir)
SE: Nephrotoxicity (at high doses). Potential mitochondrial DNA toxicity
P-kinetics:Oral bioavailability not affected by food. Emergence of resistance in long term use.

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