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ABBEY MSII U6 > Pharm antivirals > Flashcards

Flashcards in Pharm antivirals Deck (59):
1

are antiretrovirals virustatic or virucidal?

virustatic

2

what are the five major classes of antiretroviral medications?

1. nucleoside reverse transcriptase inhibitors (NRTI's) and nucleotide RTI's (tenofovir))
2. non-nucleoside reverse transcriptase inhibitors (NNRTI's)
3. protease inhibitors
4. entry inhibitors
5. integrase inhibitors

3

what are the NRTI's?

zidovudine, lemivudine, emtricitabine, abacavir, tenofovir

4

what is the mechanism of NRTI's?

viral DNA chain termination via inhibition of viral reverse transcriptase. Tenofovir is a nucleoTide, the others are nucleosides and need to be phosphorylated to be active

5

what does zidovudine mimic? lemivudine? emtricitabine? abacavir? tenofovir?

zidovudine = thymidine.
lemivudine = cytosine.
emtricitabine = cytosine.
abacavir = guanine.
tenofovir = adenosine.

6

which NRTIs can also be used for HBV?

lamivudine, emtricitabine, tenofovir

7

zidovudine side effects

granulocytopenia, anemia, nausea, vomiting

8

lamivudine and emtricitabine side effects

headache, nausea, vomiting, rash, neutropenia, pancreatitis (NOT SERIOUS)

9

abacavir side effects

hypersensitivity reaction - associated with HLA-B5701 mutation

10

tenofovir side effects

nephrotoxicity

11

what are the NNRTI's?

efavirenz, nevirapine, rilpivirine, etravirine

12

NNRTI's mechanism

inhibit reverse transcriptase through direct enzyme inhibition (do not require phosphorylation to be active) - NONCOMPETITIVE!

13

what are NNRTI's and NRTI's used to treat?

HIV

14

NNRTIs side effects

rash and hepatotoxicity - efavirenz also has vivid dreams and CNS symptoms (stop when ax wielding elves appear in dream!), teratogenic, P450 metabolism

15

what are the HIV protease inhibitors?

-navir (NA VIRUS! NO NEW VIRUS!)
ritonavir, fosamprenavir, atazanavir, darunavir, lopinavir

16

HIV protease inhibitors (-navir) mechanism

prevent cleavage of protein chain into functional subunits

17

which HIV protease inhibitor has "good" drug interactions? how?

ritonavir "boosts" other drug concentrations by inhibiting cytochrome P-450

18

HIV protease inhibitors (-navir) side effects

GI intolerance (n/v, diarrhea), metabolic toxicities!! (dyslipidemia, hyperglycemia, lipodystrophy)

19

what are the 3 steps of HIV attachment and fusion?

1. HIV gp120 binds CD4 molecule
2. conformational change occurs in gp120 and then binds the coreceptor CCR5 or CXCR4
3. further conformational changes in gp120 expose gp41 protein which mediates fusion of the viral and cell membranes

20

what are the HIV entry inhibitors?

enfuvitide and maraviroc

21

enfuvirtide mechanism

binds gp41, inhibiting viral entry

22

enfuvirtide side effects

skin reaction at injection sites

23

maraviroc mechanism

binds CCR-5 on surface of Tcells/monocytes, inhibiting interaction with gp120 - TARGET IS ON HOST CELL!

24

maraviroc side effects

hepatotoxicity (rare) - cough, fever, URI, rash, musculoskeletal symptoms, ab pain, dizziness

25

what are the integrase inhibitors?

-tegravir (GRAB the HIV before it integrates!)
raltegravir, elvitegravir, dolutegravir

26

integrase inhibitors mechanism

inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase

27

integrase inhibitors (-tegravir) side effects

myopathy and rhabdo - headache, neausea, diarrhea, pyrexia

28

what are the common HAART regimen combinations?

3 active agents together; typically 2 NRTIs + integrase inhibitor, PI, or NNRTI

29

what is commonly prescribed as initial therapy in HIV? disadvantage of this class?

NNRTI based regimen because of advantage of lower pill burden (preserve PI for later use). disadvantage is only one single mutation is needed to confer resistance and cross resistance develops for entire class

30

what is the preferred NNRTI? exception?

efavirenz - exception pregnancy

31

hepatitis C virus virology

ssRNA virus belonging to Flavivirdae - most common serotypes 1a and 1b

32

what are the old drug classes used for treating HCV?

ribavirin (nucleoside analog - high risk of anemia) and interferon (indirect mechanism - side effects and poor efficacy)

33

what are the newer drug therapies used for HCV?

nucleoside/nucleotide NS5B polymerase inhibitors, NS5A inhibitors, NS3/4A protease inhibitors

34

what are the NS5B polymerase inhibitors?

sofosbuvir and partaprevir

35

what are the NS5B polymerase inhibitors (sofosbuvir and partaprevir) mechanism?

compete with viral nucleotide to cause chain termination - active across all HCV genotypes

36

NS5B polymerase inhibitors (sofosbuvir and partaprevir) side effects

relatively safe - fatigue, headache, GI, anemia

37

what are the NS5A inhibitors?

ledipasvir, daciatasvir, ombitasvir

38

NS5A inhibitors mechanism

inhibits HCB NS5A viral phophoprotein required for viral replication

39

NS5A side effects

relatively safe - fatigue, headache, GI

40

what are the NS3/4A protease inhibitors?

-previr (PROTEASE)
simeprevir, boceprevir, telaprevir

41

NS3/4A protease inhibitors mechanism

prevent viral maturation through the inhibition of protein synthesis

42

NS3/4A side effects

differ slightly depending upon the agent: anemia, rash, itching, GI, drug interactions

43

approach to HVC therapy

combination therapy! esp. simeprevir and sofosbuvir

44

herpes virus virology and life cycle

dsDNA virus - clinical disease appears a few days after initial establishment of infection - viral particles taken up by nerves and transported to nerve cell bodies in dorsal root ganglia of spinal cord where reactivation occurs

45

what drugs are used to treat HSV?

guanosine nucleoside antivirals:
acyclovir, penciclovir, valacyclorvir, famciclovir

46

guanosince nucleoside antivirals (for HSV) mechanism

valacyclovir prodrug fro acyclovir; famciclovir prodrug of penciclovir. after phosphorylation by cellular enzymes, interferes with viral DNA synthesis by competing with DNA analogues to cause viral DNA chain termination

47

acyclovir, penciclovir, valacyclovir, famciclovir side effects

CNS changes and renal dysfunction when used at higher doses

48

what is the DOC for CMV infection?

ganciclovir (purine analog guanine)

49

ganciclovir mechanism

afterphosphorylation, causes viral DNA chain termination

50

ganciclovir side effects

neutropenia, thrombocytopenia (a GANG of cycle running over all the herpes and neutrophils)

51

foscarnet clinical use

CMV retinitis in immunocompromised when ganciclovir fails and acyclovir-resistant HSV

52

foscarnet mechanism

directly inhibits herpesvirus DNA polymerase or HIV reverse transcriptase - does not require any kinase activation so it is active against the purine analog guanine resistant

53

foscarnet side effects

nephrotoxicity (reversible but severe), electrolyte abnormalities leading to seizures (hypo/hyper calcemia, phosphatemia, hypomagnesmia, hypokalemia), myelosuppression

54

best strategy for influenza

vaccination!

55

what is used to treat influenza?

neuraminidase inhibitors (-mivir) = ME most likely to get flu;
oseltamivir, zanamivir, peramivir

56

neuraminidase inhibitors (-mivir for flu) mechanism

prevent viral release from host cells by inhibiting influenza neuraminidase

57

neuraminidase inhibitors side effects

GI, neuropsychiatric (agitation, anxiety, altered mental status)

58

which of the neuraminidase inhibitors for influenza is inhaled therapy? IV formulation only? oral?

zanamivir inhaled; peramivir IV; oseltamivir oral

59

who should receive therapy for influenza?

individuals with severe disease and those at high risk for ocomplications - can also be given as prophylaxis