Anti-viral drug comparison; tinable ko lng ang drugs dun sa Cor tranx, double checked na din with Katzung

11th ed by: Miu

Drug Characteristics MOA Pharmacokinetic Pharmacokinetic Pharmacokinetic Pharmacokinetic Adverse Effect
Absorption Distribution Metabolism Excretion
Acyclovir  A cyclic guanosine Activated and Formulation: Well distributed T ½: 3-4 hrs if Glomerular Generally well tolerated
derivative converted by Oral, even to CSF; normal renal filtration &
thymidine intravenous, CSF function; tubular Nausea, diarrhea and
 High specificity to kinase to topical concentration is secretion headache have
HSV-1 and HSV-2 and monophosphate 50% of serum T1/2: 20 hrs if occasionally been
VZV  converted by Oral: level anuric patient Probenecid and reported (katzung)
host kinase to 20-30% cimetidine dec
 DNA Polymerase  diphosphate bioavailability; acy clearance Principal dose-limiting;
Inhibitors  triphosphate Unaffected by and inc renal insufficiency
inhibits viral food exposure
 Against HSV & VSV DNA If IV admin:
polymerase by: - Reversible
Resist thru: renal
a) Absence or partial a.) Competition dysfunction
production of viral with - Neurologic
thymidine kinase deoxyGTP for toxicity such
b) Atletered thymidine the viral DNA as tremors,
kinase substrate polymerase delirium,
specificity  binding to serizures
c) Altered viral DNA DNA
polymerase template as High doses:
d) Clinically resistant an Chromosomomal dagae
infection have been irreversible and testicular atrophy
reposted in comlex in rats
immunocompromise b.) Chain
d host termination
ff
incorporatio
n to viral
DNA
Anti-Retrovirals A. Nucleosid/tide
Reverse
Transcriptase
Inhibitors (NRTI)
B. Non-NRTI

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 Anti-viral drug comparison; tinable ko lng ang drugs dun sa Cor tranx, double checked na din with Katzung 11th ed by: Miu

A. zidovudine NRTIs  Competitive o Well Well distributed T ½= 1 hr Renal excretion Should be suspended
inhibition of absorbed – to most body int the setting of:
 Incorporated into HIV-1 63% trissues and Intracellular half-life 20% active form  Rapidly rising
growing viral DNA reverse fluids including of the PO4 excreted in the aminotransferase
chain to cause transcriptase o Usually co- the CSF: 60-65% compound = 3-7 hrs urine levels
termination (RNA- admin with of serum level  Progressive
dependent lamivudine Glucoronidation in Cleance is hepatomegaly
 Requires DNA the liver  metab reduced by 50%  Metabolic acidosis of
intracytoplasmic Polymerase) o Increase into inactive in uremic uknown cause
activation via serum levels glucoronide patients
PO4rylation by with the ff May be assoc with
cellular enzyme to by inhibiting toxicity may incrase Adverse effect mitochondrial toxicity
the triPO4 form. the first pass in patients with (cont) sorry d n probably due to
effect or dec advance hepatic kaxa sa kabila eh inhibition of
 Deoxythymidine clearance: insufficiency hahaha. mitochondrial DNA
analog o Probenicid 1. polymerase gamma
o Phenytoin Myelosuppres- resulting to:
Resistance: o Methadone sion resulting - Increased risk
Generally seen in o Fluconazole in macrocytic of lactic
strains with three or o Atovaquone anemia (1-4%) acidosis with
more of the five most o Valproic aid or neutropenia hepatic
common mutation: o Lamvudin (2-8%) steatosis 
1. M41L 2. GIT fatal
2. D67N o Zidovudine intolerance - Disorders of
3. K70R decreases 3. Headache lipid metab
4. T215F phenytoin 4. Insomnia
5. K219Q level naman 5. Thrombocyto- Hematologic toxicity
hahaha penia may be increased when
6. Hyperpigmen- given with other
tation of nails myelosupp like
7. myopathy ganciclovir and
cytotoxic agents
B1. Nevirapine - Non-NRTI Binds directly to o 90% 60% protein Metab by CYP450 Urine Severe life threatening
- Compete with the enzyme’s bioavailability bound and CYP3A skin rashes
nucleoside triPO4 (HIV-reverse o Not food o Steven Johnson
- Doesn’t require PO4 transcriptase) dependent T ½: 25-30 hrs Induces CYP3A4 o Toxic epidermal
to be active active site  o Highly thus decreases necrolysis
blocking RNA lipophilic some antiviral

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 Anti-viral drug comparison; tinable ko lng ang drugs dun sa Cor tranx, double checked na din with Katzung 11th ed by: Miu

and DNA agents Hepatoxicity:

Resistance: dependent DNA - Occur more
Occurs rapidly with Polymerase Let’s clear things frequently in
monotherapy and can activity out katzung 11th ed those with
be due to single higher pre-
mutation of: Page 861, therapy CD4
- K103N “a further limitation cell counts, in
- T181C to use of NNRTI women and in
agent as a patients with
Drug interaction with component of Hepatitis B or C
niverapine, maxado HAART is their co-infection
mahaba. Tignan nio n metab by CYP450
lng sa tranx ni kate. system….” Fulmitant hepatitis –
Thank you! Same page… rare
“…all NNRTI agents
are substrates for Fever, nausea,
CYP3A4 and can act headache, somnolence
as inducer
(nevirapine)…”

Page 862,
“…extensive
metabolized by the
CYP3A isoform to
hydroxylated
metabolites…”
Same page
“…moderate
inducer of CYP3a4
metabolism,
resulting in dec
levels….”
Protease 1. Saquinavir Effective against
Inhibitor 2. Ritonavir HIV-1 and HIV2
and does not
need
intracellular
activation

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 Anti-viral drug comparison; tinable ko lng ang drugs dun sa Cor tranx, double checked na din with Katzung 11th ed by: Miu

st
1. Saquinavir Drug interaction: nhibited Formulation: 98% protein Extensive 1 pass feces 1. GIT discomfort
Pls refer to kate’s tranx cleavage of the Hard gel capsule bound metabolism (common in soft
translated (originally) but CYP3A4 and func as gel)
protein (Gag has poor Large vol inhibitor too and  Nausea
and Gag-pol bioavail of 4% distribution substrate.  Diarrhea
polyproteins) and should be CSF penetration  Abdo
into func and taken within 2 is negligible discomfort
structural hrs after fatty  Dyspepsia
protein  meal
production of 2. Rhinitis
immature and Now:
non-infectious Soft gel capsule
viral particles with 3x better
absorption,
Block viral increases when
maturalation taken with food
therefore active
in both acutely
and chronically
infected cells
Ritonavir Inhibitor of High bioavail og 98% protein CYP3A4 and CYP2D6 Feces o GIT disturbances
HIV1-HIV2 75% and bound isoforms o Parathesias
proteases increases when o Elevated serum
taken with food T1/2: 3-5 hours aminotransferases
o Altered taste
o Headache
o Hypertriglyceridemi
a
o Hyperchole
o Elevation in serum
creatine kinase
(katzung)

During 1st few wks of

therapy:
1. Nausea
2. Vomiting
3. Diarrhea

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 Anti-viral drug comparison; tinable ko lng ang drugs dun sa Cor tranx, double checked na din with Katzung 11th ed by: Miu

4. Abdominal
pain

Entry 1. Enfuvirtide Fusion inhibitors

Inhibitors 2. Maraviroc that blocks the
3. Vicriviro entry of the
virus into the
cell
1. Enfurvitide Formerly called as T-20 Binds to gp41 Subcutaneously Proteolytic T ½: 3.8 hrs From katzung (but not
subunit of viral hydrolysis w.o discussed by doc)
Synthetic 36 amino acid envelope involvement of
peptide fusion inhibitor glycoprotein, CYP450 1. Local injection site
preventing the rxn
Only effective for HIV-1 conformational 2. Eosinophilia
changes
Resistance: required for the
1. Mutation to gp41 fusion of the
viral and cellular
membranes
Integrase 1. Raltegravir Combination of
Inhibitors 2. Elvitegravir multiple agents
is
recommended
for HIV infected
individuals to
a. Inc potency
b. Delay
emergence of
resistance

E.g
Elvucitabine
(NRTI) +
Vicriviroc (entry
inhibitor) +

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 Anti-viral drug comparison; tinable ko lng ang drugs dun sa Cor tranx, double checked na din with Katzung 11th ed by: Miu

Elvitegravir
(integrase
inhibitor)

Anti- A. Ganiciclovir Cmv infection

Cytomegalo- B. Valganciclovir occur primarily
virus C. Foscarnet in the setting of
D. Cidofivir advanced
immunosuppres
sion and are
typically due to
reactivation of
latent infection
Antihepatitis Effective against HBV
and HCV;
More of suppressive
rather than curative
1. Anti-Hepa- o IFN-a2b Enhance
B o Pegylated IFN-a2b specific T-cell
mediated
immune
response

Direct antiviral
effect:
 Degredation
of viral mRNA
 Inhibition of
proteinsynth
esis
 iii.Prevents
infection of
new cell
2. Anti- o IFN-a2b same
Hepa C o Pegylated IFN-a2a
o Pegylated IFN-a2b
o IFN-alfacon-1

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 Anti-viral drug comparison; tinable ko lng ang drugs dun sa Cor tranx, double checked na din with Katzung 11th ed by: Miu

Anti- a. Amantidine
influenza b. Rimantidine
agents c. Oseltamivir
d. zanamivir
a. amantidine  Approved by DA in o inhibits the Well absorbed 67% protein T ½: 12-18 hours 90% excreted 1. Low toxicity at
1976 to treat uncoating of orally and bound and varies by unchanged w.o therapeutic levels
Influenza A the viral crosses BBB creatinine clearance metabolic 2. GIT
 Targets early stages genome products - Nausea
of infection o specifically - Anorexia
 1-aminoadamante targets a 3. CNS
HCL protein called - Nervousness
 Alpha-methyl M2 (an ion - Diffutly in
derivative of channel) concentrating
rimantidine, thereby - Insomnia
 Tricyclick amins of inhibiting the - Light-
adamantane family uncoating of headedness
the viral DNA
o infective to
influenza B
because it
lacks M2
b. rimantidine Same with Same with Same with 40% protein T ½: 24-36 hours Urinary Same but CNS
amantidine amantidine amantidine bound excretion toxicity is less
Undergoes frequent
extensive
metabolism by
hydroxylation,
conjugation and
glucoronidation
Immuno- 1. normal Ig
globulin 2. prophylaxis
Therapy 3. hyper-Ig serum
1. Normal Ig Pooled product from
serum of normal
donorsl contain low
titers of Ab to a wide
range of human viruses

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 Anti-viral drug comparison; tinable ko lng ang drugs dun sa Cor tranx, double checked na din with Katzung 11th ed by: Miu

2. Prophylaxis Vs:
Heap-B
Parovirus

3. Hyper-Ig e.g
serum of zoster immune globulin
selected human rabies Ig
individuals Hepa-B Ig
with high
titers of Ab to
a particular
dse
Viral vaccine Vaccination- most cost a. Killed virus
effective method of vaccine
prevention of serious (influenza,
viral infection rabies
b. Attenuated
live vaccine
(MMR(
c. Future
genetic
manipulation
(?)
Warning:
th
1) table form lng po ito but na-double checked ko na using katzung 11 ed
2) for drug interaction, pls refer to cor’s tranx. Kasi kung lalagay ko ditto maxado na mahaba
3) pls pls refer to cor’s tranx explanation for viral replication, kasi ung mga drugs will act on certain phase of viral replication, like acyclovir sa DNA
polymerase inhibitor  halt DNA synthesis, etc

I STRONGLY SUGGEST TO READ YOUR BOOKS  AND NEXT TIME PAG C DOC DEO NAGLLECTURE, SUNDAN NIO LNG SIYA SA BOOK, KATZUNG LNG LAGI ANG
REFERENCE NIA 

HAPPY CRAMMING! 2014

SEMBREAK….SOOOO NEAR YET SOOO FAR