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Pharm 2 - Exam 4 > Lecture 6 - AntiViral > Flashcards

Lecture 6 - AntiViral Flashcards

1
Q

Nucleoside vs nucleotide?

A

Nucleoside = sugar + base

Nucleotide = sugar + base + phosphate

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2
Q

All antivirals are ____ - no action against latent virus

A

virustatic

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3
Q

What is the MOA of anti-herpes drugs?

A

inhibit viral DNA polymerase

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4
Q

Acyclovir

A

topical, PO, IV

Indications: 
effective against HSV >> VZV
shortens duration of HSV if given early 
IV First line: 
herpes simplex encephalitis 
neonatal HSV 
severe HSV
VZV infection 
ADME: 
acyclic guanasine derivative 
metabolically activated by 3 phosphorylations (the first one done by viral thymidine kinase) 
acyclovir triphosphate = active form 
renal clearance

SE:
N/D/HA

Toxicities:
renal toxic, neurotoxic

Resistance:
viral thymidine kinase mutation
can be treated with agents not requiring viral phosphorylation like Foscarnet

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5
Q

What are the indications for acyclovir?

A

topical, PO, IV

Indications: 
effective against HSV >> VZV
shortens duration of HSV if given early 
IV First line: 
herpes simplex encephalitis 
neonatal HSV 
severe HSV
VZV infection
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6
Q

What is the ADME of acyclovir?

A 
ADME: 
acyclic guanasine derivative 
metabolically activated by 3 phosphorylations (the first one done by viral thymidine kinase) 
acyclovir triphosphate = active form 
renal clearance
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7
Q

What are the SE and toxicities of acyclovir?

A

SE:
N/D/HA

Toxicities:
renal toxic, neurotoxic

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8
Q

What resistance is present with acyclovir?

A

Resistance:
viral thymidine kinase mutation
can be treated with agents not requiring viral phosphorylation like Foscarnet

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9
Q

What is the MOA of acyclovir?

A

inhibit viral DNA polymerase

needs to be activated by 3 phosphorylations fist - the first one being done by the virus thymidine kinase

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10
Q

CMV meds

A

anti-cytomegalovirus drugs:
ganciclovir
foscarnet

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11
Q

When are CMV infections common?

A

HIV and organ transplant pts

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12
Q

Ganciclovir

A

Indications:
CMV infections
treatment/prophylaxis for CMV post-transplantation

MOA:
inhibit viral DNA polymerase, but first it must be activated by 3 polymerizations, the first one done by CMV kinase

ADME:
acyclic guanosine analog (same as acyclovir)
requires 3 phosphorylations (similar to acyclovir)
first phosphorylation done by CMV kinase

SE: toxicity: myelosuppression (major)

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13
Q

What are the indications for ganciclovir?

A

Indications:
CMV infections
treatment/prophylaxis for CMV post-transplantation

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14
Q

What is the MOA of ganciclovir?

A

MOA:

inhibit viral DNA polymerase, but first it must be activated by 3 polymerizations, the first one done by CMV kinase

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15
Q

What are the SE/toxicities for ganciclovir?

A

SE: toxicity: myelosuppression (major)

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16
Q

What is the ADME for ganciclovir?

A

ADME:
acyclic guanosine analog (same as acyclovir)
requires 3 phosphorylations (similar to acyclovir)
first phosphorylation done by CMV kinase

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17
Q

Foscarnet

A

IV only

Indications:
CMV
useful in strains resistant to acyclovir

MOA:
inhibits viral DNA polymerase, RNA polymerase, HIV RT
- no activation required
useful in strains resistant to acyclovir

SE/toxicity:
renal toxicity
hyperphosatemia, hypokalemia/calcemia/magnesemia

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18
Q

What are the indications for foscarnet?

A

IV only

Indications:
CMV
useful in strains resistant to acyclovir

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19
Q

What is the MOA for foscarnet?

A

MOA:
inhibits viral DNA polymerase, RNA polymerase, HIV RT
- no activation required
useful in strains resistant to acyclovir

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20
Q

What are the SE and toxicities seen with foscarnet?

A

SE/toxicity:
renal toxicity
hyperphosatemia, hypokalemia/calcemia/magnesemia

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21
Q

Which influenza causes mass infection?

A

only influenza A

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22
Q

When must anti-influenza medications be given in order to effective?

A

quickly after onset of sxs (~48hours)

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23
Q

What agents are available for anti-influenza?

A

amantidine
oseltamivir (tamiflu)
zanamivir (relenza)

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24
Q

Oseltamivir

A

(tamiflu, oral)
same for zanamivir (relenza, inhalation)

Indications:
influenza A, quickly given within 48 hours of symptom onset (activity against influenza B too)
Zanamivir is useful against oseltamivir - resistant strains

MOA:
neuraminidase inhibitors

25
Q

What are the indications for oseltamivir?

A

(tamiflu, oral)
same for zanamivir (relenza, inhalation)

Indications:
influenza A, quickly given within 48 hours of symptom onset (activity against influenza B too)
Zanamivir is useful against oseltamivir - resistant strains

26
Q

What are the indications for Zanamivir?

A

Zanamivir is useful against oseltamivir - resistant strains

influenza A, quickly given within 48 hours of symptom onset (activity against influenza B too)

27
Q

What is the MOA of oseltamivir and zanamivir?

A

neuraminidase inhibitors

28
Q

Why is there so much resistance seen with HIV drugs?

A

retroviral replication is ERROR PRONE which means a lot of mutations which means more resistance

29
Q

NRTIs

A

nucleoSIde reverse transcriptase inhibitors

Abacavir
Lamivudine/Emtricitabine

(not on drug list: Zidovudine/AZT)

30
Q

What is the MOA of NRTIs?

A

resembles nucleoside competitive inhibitor of RT –incorporates into DNA

31
Q

What resistance is seen with NRTIs?

A

mutations in viral RT

32
Q

What toxicities are seen with NRTIs?

A

lactic acidosis with hepatic steatosis

D/t NRTI mediated inhibition of mitochondrial function –build up of triglycerides –> hepatic steatosis

33
Q

Abacavir

A

NRTI

ADME:
guanosine analog
administered in combo with lamivudine (or emtricitabine)

MOA: nucleoside analog (guanosine) competitive inhibitor of RT –incorporates into DNA

unique toxicities:
myocardial infarction
(caution in CV disease)
hypersensitivity reactions associated with HLAb5701 (Can be fatal)

Resistance:
slow. requires 2-3 RT mutations

34
Q

What is the MOA of abacavir?

A

NRTI

ADME:
guanosine analog
administered in combo with lamivudine (or emtricitabine)

MOA: nucleoside analog (guanosine) competitive inhibitor of RT –incorporates into DNA

35
Q

What toxicities are seen with abacavir?

A

Unique toxicities:
myocardial infarction
(caution in CV disease)
hypersensitivity reactions associated with HLAb5701 (Can be fatal)
in addition to the overall class toxicity of lactic acidosis with hepatic steatosis

36
Q

What resistance is seen with abacavir?

A

Resistance:

slow. requires 2-3 RT mutations

37
Q

Lamivudine

A

NRTI

Emtricitabine is a fluorinated form of lamivudine –making it have a longer half life (once daily dosing)

MOA: 
nucleoside analog (cystine) competitive inhibitor of RT --incorporates into DNA

Indications:
HIV combo (administered with tenofovir called truvada)
HBV (inhibits HBV RT)

38
Q

What are the indications for lamivudine/emtrictabine?

A

Indications:
HIV combo (administered with tenofovir called truvada)
HBV (inhibits HBV RT)

39
Q

What is the difference between lamivudine and emtricitabine?

A

Emtricitabine is a fluorinated form of lamivudine –making it have a longer half life (once daily dosing)

40
Q

What is the MOA of lamivudine/emtricitabine?

A 
MOA: 
nucleoside analog (cystine) competitive inhibitor of RT --incorporates into DNA
41
Q

NtRTIs

A

nucleoTide reverse transcriptase inhibitors

tenofovir

42
Q

Tenofovir

A

NtRTI

ADME:
acyclic nucleoTide analog of adenosine
given as a pro-drug: disoproxil fumarate (DF) or alafenamide (AF)

MOA:
competitive inhibitor of HIV RT = chain termination after incorporation into DNA

Indication:
first line RTI therapy when combined with emtricitabine

Toxicities:
renal accumulation: tubular necrosis, renal failure, Fanconi’s syndrome (less with AF)

43
Q

What is the MOA of tenofovir?

A

NtRTI

ADME:
acyclic nucleoTide analog of adenosine
given as a pro-drug: disoproxil fumarate (DF) or alafenamide (AF)

MOA:
competitive inhibitor of HIV RT = chain termination after incorporation into DNA

44
Q

What is the indication for tenofovir?

A

Indication:

first line RTI therapy when combined with emtricitabine

45
Q

What toxicities are seen with tenofovir?

A

Toxicities:

renal accumulation: tubular necrosis, renal failure, Fanconi’s syndrome (less with AF)

46
Q

NNRTIs

A

non-nucleoside reverse transcriptase inhibitors

efavirenz

47
Q

Efavirenz

A

NNRTI

MOA:
binds directly to HIV1 reverse transcriptase and inhibit RNA and DNA dependent DNA polymerase activity
no phosphorylation needed since it’s not a nucleoside
binding site of NNRTIs is distinct from that of NRTIs (allosteric)

Drug-drug interactions:
Extensive metabolism/induction via CYP3A4 pathway

Resistance: can occur rapidly with single mutation in RT

Toxicity: nightmares/psychiatric disturbances (at start of therapy, then resolve)

48
Q

What is the MOA of efavirenz?

A

NNRTI

MOA:
binds directly to HIV1 reverse transcriptase and inhibit RNA and DNA dependent DNA polymerase activity
no phosphorylation needed since it’s not a nucleoside
binding site of NNRTIs is distinct from that of NRTIs (allosteric)

49
Q

What drug drug interaction are present with efavirenz?

A

Drug-drug interactions:

Extensive metabolism/induction via CYP3A4 pathway

50
Q

What toxicities are present with efavirenz?

A

Toxicity: nightmares/psychiatric disturbances (at start of therapy, then resolve)

51
Q

What resistance is present with efavirenz?

A

Resistance: can occur rapidly with single mutation in RT

52
Q

HIV protease inhibitors

A

Ritonavir
Darunavir
Atazanvir

ADME:
Pepitdomimetics

MOA:
Inhibits proteolytic cleavage of Gag and Gag-pol in HIV 1 and 2

Drug-drug interactions:
Metabolized by, inhibitors of CYP3A4

Toxicities as a class:
Redistribution and accumulation of body fat (lipodystrophy)
Increase triglycerides/LDL

53
Q

Ritonavir

A

HIV Protease Inhibitor

Inhibitor of CYP3A4 — used with other PIs to increase their serum levels
Less frequent dosing (BOOSTER)
Taken with food

Toxicities:
Increase triglycerides/LDL
Elevated serum aminotransferase levels

54
Q

Atazanavir

A

HIV protease inhibitor

Toxicities: 
Hyperbilirubinemia 
Rash 
Kidney stones
Cholelithiasis

Only available as a fixed dose combo with ritonavir since ritonavir inhibits CYP3A4 and increases blood levels

55
Q

Maraviroc

A

CCR5 receptor antagonist/Entry inhibitor

Not first line therapy

Binds selectively to CCR5 - one of the two co-receptors necessary for entrance of HIV into CD4+ cells

56
Q

Enfuvirtide

A

Fusion inhibitors

Binds to gp41 subunit of the viral envelope glycoprotein, preventing the conformational changes required for the fusion of the viral and cellular membranes
NOT for HIV2

SubQ injection (peptide—long change)

Only for treatment experienced HIV pts with ongoing HIV replication

57
Q

Dolutegravir

A

Integrase strand transfer inhibitors (INSTIs)

Inhibits viral DNA strang integration in host genome

Toxicities:
Hypersensitivity
Elevated liver enzymes with HCV/HBV co-infection

58
Q

What is the latest recommendation for PEP?

A

Pre/pst exposure prophylaxis

Raltegravir/dolutegravir + TDF/emtricitabine for PEP

TDF/emtricitabine for pre-exposure

Pharm 2 - Exam 4 (9 decks)

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