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51 Cards in this Set

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Drugs for herpes
Acyclovir
Gancyclovir
Cidofovir
Foscarnet
Uses for acyclovir
HSV (esp 1 and 2)
HSV encephalitis (decrease mortality by 50%)
prophylaxis against HSV in IC
Prophylaxis against CMV sero+ reactivation in IC
severe VZV (esp of eye) in IC
ADME of acyclovir
15-30% bioavailibility
CSF = 50% of serum
15% metabolize
Renal excretion with T1/2 = 2.5 hours
Adverse effect and interaction with acyclovir
No real side effects unless impaired renal function
Encephalopathy in 1% of IV admin with unexpectedly high levels

Probencid inhibits excretion

Acyc reduces elimination of methotrexate
Use of Gancyclovir
Only approved for CMV

has effect with HSV 1-2
MOA of ganciclovir
like acyclovir but better substrate for host phorphorylation (CMV won't phosphorylate acyclovir)
ADME ganciclovir
IV only
Good CNS penetration
Reneal excretion with T1/2 = 3-4 hours
Adverse effect of ganciclovir
1/3 experience bone marrow suppression and must come off

5-15% CNS toxicity
Cidofovir resistance
Phorphorylated by cellular enzyme so low resistance

No cross-resistance expected
Cidofovir ADME
IV drug
17-65 hour half life (no need for permanent IV)
Adverse effect of cidofovir
1/4 get nephrotoxicity, ocular hypotnia, neutropenia and acidosis
MOA for foscarnet
Inhibits DNA polymerase and reverse transcriptase at different site than other HSV drug so no resistance is seen
Use of Foscarnet
CMV retinitis
CMV prophylaxis
Acyclovir resistant HSV
Gancyclovir resistant CMV
Your AIDS patient get CMV but is resistant to gancylovir tx. What should you use?
Foscarnet

Different site of action so no cross-resistance
ADME of Foscarnet
IV, but poorly soluble so large amounts needed
Renally excreted
Accumulates in bone
Adverse effect of cidofovir
1/4 get nephrotoxicity, ocular hypotnia, neutropenia and acidosis
MOA for foscarnet
Inhibits DNA polymerase and reverse transcriptase at different site than other HSV drug so no resistance is seen
Use of Foscarnet
CMV retinitis
CMV prophylaxis
Acyclovir resistant HSV
Gancyclovir resistant CMV
Your AIDS patient get CMV but is resistant to gancylovir tx. What should you use?
Foscarnet

Different site of action so no cross-resistance
ADME of Foscarnet
IV, but poorly soluble so large amounts needed
Renally excreted
Accumulates in bone
Adverse effects of Foscarnet
Causes nephrotoxicity and hypocalcemia
anemia
CNS toxicity

w/ AMP-B is particularly nephrotoxic
w/ Pentamidine is particualrly bad for hypocalcemia
Drugs used for HIV Tx
Zidovudine
Lamivudine
Didanosine
Nevirapine
Tenofovir
Ritonavir
Indinavir
Which two drugs has phosphonate diesters
Cidofovir
Tenofovir
Zidovudine
AZT
RT inhibitor (nucleoside analog)

Recommended only for HIV
ADME Zidovudine
Oral absorbed
Good distribution
Some renal, mostly hepatic
T1/2 = 1 hour, give every 4
Side effect of Zidovudine
Granulocytopenia
Anemia

50% of people
Dose dependent, limiting
Drug interaction with Zidovudine
Bone marrow supression with Ampho B and TMP/SMX (glucourondiation)

Nephrotoxic (and probenicid may inhibit clearance)
Didanosine
nucleoside analog RT inhibito

for kids or adults in whom Zidovudine isn't working
Adverse effects and SE of Didanosine
30% peripheral neuropathy
10% pancreatitis

GI symptoms
Lamivudine
Use with Zidovudine for Ping-Pong resistance, better serum HIV lowering and few additional side effects

Pancreatitis rare additional side effect of Lamivudine
Side effects of Lamivudine vs Zidovudine
Lam has the same ones, but less frequently and not additive when used together

Pancreatitis is rare additional side effect
Unusual use for lamviduine
Hepatitis B
HIV drug also useful in Hep B
Lamivudine
Tenofuvir
Nevirapine
NON-nucleoside analog whose use remains to be determined

May cause severe rash
Tenofuvir
Nucleotide analog RT inhibitor
Given once daily and does not require phorphorylation
Side effects of Tenofuvir
Fanconi's syndrome (nephrotoxicity)

Not for kids or pregnant
Ritonavir
PI with ton's of drug interactions!
Ritonavir ADME and interactions
Give twie daily with meal in ethyl alcohol solution (disufuram and metronidazole are a problem)

Interacts adversly with any drug metabolized by the P450 3A system
Side of effect of Ritonaivr
Circumoral paresthesia
Elevates liver enzymes, CK's and TG's
Use of Ritonavir
With RT inhibitors for HIV
ADME of Indinavir
Take every 8 hours, not three times a day, while fasting

Effects P450, but 20% renal excreted

Use with Didanosine inhibits abosorption, use 1 hous apart
Indinavir Drug interactions
Ketoconazole interferes with metabolism

Didanosine inhibits its absorption

Effects any drug metabolized by P450, though not as badly as Ritonavir
Side Effect of Indinavir
Renal stones (drink 1.5 L of water)

Gi Distress

Elevated Bilirubin
Elevates Bilirubin, but not as a sign of hepatitis
Indinavir
Causes nephrolithiasis
Indinavir
Enfuravirtide
SC injected fusion inhibitor. Expensive, complicated, and in short supply

but it works!
Amantadine for flu prophylaxis
5 weeks alone
2 weeks with vaccination
ADME Amantadine
Oral

Not metabolized, renal excretion
12-18 hour half life
Side effect of Amantadine
CNS toxicity at high dose. Releases dompamine, which inhibits ACh (used for parkinson's). Anticholinergics make it even worse
Rimanatdine
Amantadine but metabolized by liver. Used for Renal imparied patients
Oseltamavir and Zanamavir
Neuraminidase inhibitors

Zanamavir make cause brochospasm in asthmatics