Antiviral I Flashcards Preview

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Flashcards in Antiviral I Deck (88)
1

Viruses are Obligate intracellular parasites... Enter living cells and take over cell’s synthetic machinery.
________core surrounded by protein sheath or lipid-protein envelope.

Nucleic acid

2

Viral latency—

some can integrate into host chromosome allowing for recurrence of
clinical infection without re-exposure to viral agent.

3

After virus is absorbed or penetrates, it has to

uncoat proteins from nucleic acids

4

Main point of attack for antivirals

Any of the stages of the viral life cycle, so long as agent is nontoxic/ adequately specific

5

In many viral infections viral replication is at maximum when

viral replication reaches a maximum near the time clinical symptoms first appear (influenza, poxviruses)

6

Drugs are most effective if administered

before onset of symptoms, except herpes bc replication continues after appearance of clinical signs

7

Key issues of viral infections

side effects/toxicity
occurance of resistant strains
latent (dormant form) and recurrent infections
carcinogenicty
need to have competent host immune system

8

Uses of passive immunization

injection of immune globulin will block viral penetration before disease
can modify course of disease if given early enough IV or IM

9

Viral replication rate is reduced by blocking viral entry into cells; may allow for
active immunity to develop.

passive immunization

10

Prophylaxis against influenza A but not influenza B

Amantidine
~ works about 70% time

11

Amantidine is given to pts w/ influenza A and will

Reduces fever in 50% of patients and illness
duration by 1-2 days if given within first 2 days of illness

12

Issue we've seen with amantidine in the past few years

influenzas have been resistant

13

Mech for amantidine

Blocks viral uncoating by interfering with influenza A M2 protein (an ion
channel

14

Blocks viral uncoating by interfering with influenza A M2 protein (an ion
channel

Amantidine

15

Metabolism and excretion in amantidine

90% excreated unchaged in urine and REDUCE dose in RENAL disease

16

Toxicity of Amantidine

CNS effects
(slurred speech, anxiety, confusion, depression, headache)

17

inactive prodrug ...converted to active competitive inhibitor of influenza neuraminidases;

Oseltamivir

18

Oseltamivir is a prodrug that will inhibit neuramidase.. this is effective because

it interferes with viral release
from infected cells and viral penetration into respiratory epithelium

19

treatment of uncomplicated influenza A and B in patients ≥1 year old and prophy

Oseltamivir

20

Admin of Oseltamivir

2x day for 5 days with renal elimination

21

side effects in Oseltamivir

bronchitis, vomit, diahrrhea

22

decreases risk of serious influenza in 71% of adults and decrease chance of pnemonia in children

Oseltamivir

23

Interferes with DNA synthesis; thymidine analog.

Trifluridine

24

Trifluridine mech

interferes with DNA synthesis, thymidine analog

25

Uses of trifluridine

Ophthalmic herpes type 1 and 2 but not useful prophylactically

26

Ophthalmic herpes type 1 and 2 but not useful prophylactically

Trifluridine

27

guanosine derivative; inhibits DNA polymerase.
Phosphorylated form is produced 40-100x faster in infected cells by herpes thymidine kinase;
inhibits herpes DNA polymerase 10-30x more than host cell DNA polymerase; acts as a competitive inhibitor of dGTP and as a DNA chain terminator.

Acyclovir

28

acts as a competitive inhibitor of dGTP and as a DNA chain terminator

Acyclovir

29

Acyclovir mech

inhibits DNA polymerase by activing like a competitive inhibitor of dGTP and as DNA chain terminator

30

IV Drug of choice for serious systemic herpes simplex virus (HSV), including HSV encephalitis

Acyclovir

31

IV, acyclovir is used for

Drug of choice for serious systemic herpes simplex virus (HSV), including HSV encephalitis and severe initial genital herpes

32

Oral drug to tx Primary herpetic gingivostomatosis

Acyclovir

33

______ used to tx primary genital herpes

acyclovir

34

Approved for chickenpox in children

Acyclovir

35

Side of Acyclovir

IG, well tolerated, rash, itch, nasuea
can be nephrotoxic or cause thrombophleibits

36

Similar to acyclovir; prodrug that is converted to penciclovir which is then phosphorylated—this is what inhibits viral DNA polymerase.

Famciclovir

37

Mech of Famciclovir

Similar to acyclovir; prodrug that is converted to penciclovir which is then phosphorylated—this is what inhibits viral DNA polymerase.

38

recurrent genital herpes and herpes zoster within 3 days of onset

Famciclovir

39

Oral; prodrug absorbed better than acyclovir
- less frequent dosing than acyclovir; renal elimination.

Famciclovir

40

Famciclovir sides:

Generally well-tolerated. - Rash, itching, nausea, vomiting, headache, fatigue

41

Penciclovir mech

simular to acyclovir

42

used for recurrent herpes of lips and face as topical cream

Penciclovir

43

similar to acyclovir, except the monophosphorylation is catalyzed byCMV protein kinase; virustatic.

Ganciclovir

44

Mech of ganciclovir

similar to acyclovir, except the monophosphorylation is catalyzed byCMV protein kinase; virustatic.

45

Used to tx CMV retinitis in AIDS and CMV prophy for transplant pts

Ganciclovir

46

Use of Ganciclovir

Used to tx CMV retinitis in AIDS and CMV prophy for transplant pts

47

Admin and exreation of Ganciclovir

IV or oral
unchanged in urine

48

Sides of Ganciclovir

Bone marrow suppression, leukopenia, thrombocytopenia, anemia.
- May enhance bone marrow suppression when given with zidovudine (AZT)

49

Bone marrow suppression, leukopenia, thrombocytopenia, anemia. - May enhance bone marrow suppression when given with zidovudine (AZT)

Ganciclovir

50

inhibits CMV DNA polymerase by binding to its pyrophosphate-binding site; this blocks viral DNA synthesis
- Does not require conversion to triphosphate form to be active.

Foscarnet

51

Mech of Foscarnet

inhibits CMV DNA polymerase by bindint to pyrophostape binding ste to block viral DNA synthesis

52

Use of Foscarnet

AIDS patients with CMV (cytomegalovirus) retinitis and
acyclovir-resistant herpes simplex.

53

Drug to tx AIDS patients with CMV (cytomegalovirus) retinitis andacyclovir-resistant herpes simplex.

Foscarnet

54

Side effects of Foscarnet

Renal damage (30–50%), reversible (enhanced with amphotericin B).
- Electrolyte imbalances
- seizures

55

Nucleoside analog inhibitor of the reverse transcriptase domain of the hepatitis B DNA polymerase; must be phosphorylated by cell enzymes to be active.

Lamivudine

56

Mech of Lamivudine

Nucleoside analog inhibitor of the reverse transcriptase domain of the hepatitis B DNA polymerase; must be phosphorylated by cell enzymes to be active.

57

used to tx hep B

Lamivudine and Tenofovir

58

Use of Lamivudine and admin

Hep B and oral with 85% bioavailable

59

Side of Lamivudine

nausuea and diarrhea

60

esterified adenosine monophosphate analog phosphorylated by cell enzymes to the
active nucleotide
- inhibits the reverse transcriptase domain of the hepatitis B DNA polymerase

Tenofovir

61

Tenofovir ultimately will

inhibits the reverse transcriptase domain of the hepatitis B DNA polymerase

62

Tenofovir is for and it's admin

Hep B
25% oral bioavailable

63

Sides of Tenofovir

GI upset

64

Mech of Ribavirin

interferes with viral mRNA synthesis
Mono-P form will inhibit inosine 5'P DH thus inhibits GTP synthesis

65

Tri-P form will inhibit:
(for Ribivarin)

Tri-P form inhibits GTP-dependent capping of viral mRNA

66

Mono-P form inhibits_________ and thus GTP synthesis

inosine-5’-P dehydrogenase

67

aerosol use in carefully selected infants and young children with documented severe
lower respiratory syncytial virus (RSV) infections

Ribivarin

68

USed to tx Hepatitis C (oral) in combination with interferon-α

Ribivarin

69

Use of Ribavirin

aerosol use in carefully selected infants and young children with documented severe
lower respiratory syncytial virus (RSV) infections
• Hepatitis C (oral) in combination with interferon-α

70

used to tx Lower RSV infections

Ribavirin

71

Metabolsim of Ribavirin

hepatic metabolism; very slow clearance from blood; some metabolites and
unmetabolized drug excreted in urine

72

Toxicity of Ribavirin in aerosol form

In aerosol form: Exercise caution with assisted ventilation (requires special aerosol equipment as drug may precipitate in and clog respiratory equipment)

73

CAn cause Pulmonary function deterioration (respiratory depression, lung inflammation) in aerosol use

Ribavirin

74

In IV form, Ribavirin can cause:

anemia and bone marrow suppresion

75

Induce host cells to produce enzymes that block translation of viral mRNA.

Interferon

76

Host produced proteins
Exert virus-nonspecific antiviral activities; active only in species in which they are produced

Interferon

77

EnZ induced by Interferons:

Protein kinase—phosphorylates elongation factor. Oligoisoadenylate synthetase—activates RNase that degrades viral mRNA.
Phosphodiesterase—degrades terminal nucleotides of tRNA.

78

Treatment of hairy cell leukemia and AIDS-related Kaposi’s sarcoma

Interferon

79

2nd line for Condyloma acuminata (venereal warts)

Interferon alpha

80

Hepatitis B and C (improves disease course in 40–50%

Interferon alpha

81

PEG-alfa-2a and PEG-alfa-2b interferons in combination with ribavirin are specifically useful for

hepatitis C

82

Toxicity for interferon alpha

Flu-like syndrome. Leukopenia, bone marrow suppression. Neurotoxicity, myalgia.

83

Toxicity: Flu-like syndrome. Leukopenia, bone marrow suppression. Neurotoxicity, myalgia

Interferon A

84

reversible inhibitor of hepatitis C NS3 protease, thus blocking formation of infectious
virus particles

Boceprevir

85

Boceprevir mech

reversible inhibitor of Hep C NS3 protease to block formation of infectious virus particles

86

Boceprevir works by reversible inhibitor of hepatitis C ______, thus blocking formation of infectious
virus particles

NS3 protease

87

Uses of Boceprevir

hepatitis C genotype 1, in combination with PEG-interferon + ribavirin

88

Admin and elimiatino of Boceprevir

oral 3x day and metabolized by CYP3A