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Pharmacology > antiviral agents > Flashcards

antiviral agents Flashcards

1
Q

what do antivirals target?

A

viral replication

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2
Q

what are good potential antiviral drugs?

A

Molecules that are virus encoded ofer potential virus-specific targets. This is notably the
case with viruses that have large genomes and code for their own replicative enzymes.

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3
Q

what is the main issue with using antivirals?

A

Therefore the most severe constraint limiting the use of antiviral drugs is not the lack of eficacy but he toxicity to the mammalian cel (por selective toxicity).
-viral replication is intimately associated with host replication

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4
Q

what defines a good antivirals

A

1.) successful antiviral drug should interfere with a virus-specific function (either because the function is unique to the virus or the similarhost function is much less
susceptible to the drug). Virus specific enzymes include proteases, mRNA caping enzyme, neuraminidases, ribonucleases, kinases, integrases, and uncoating enzymes

2.) successful antiviral drug should interfere with a virus-specific function (either because the function is unique to the virus or the similar host function is much less
susceptible to the drug). Virus specific enzymes include proteases, mRNA caping enzyme, neuraminidases, ribonucleases, kinases, integrases, and `uncoating enzymes

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5
Q

target therapeutic index

A

100-1000
- ratio of the minimum dose that is toxic to
host cels over the minimum dose that is toxic to the virus

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6
Q

ideally antiviral should

A

should be stable in the blood stream and easily taken by cells.
-They should also have as low toxicity as posible

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7
Q

successful antivirals

A

interferes with virus specific function or with a function for which the host target is less susceptible to the drug

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8
Q

what is virostatic

A

doesn’t kill virus

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9
Q

what does it mean that antivirals are virostatic?

A

must have an intact immune system to maintain the suppression of many viral infections

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10
Q

potential targets of drugs

A
  1. ) prevention of entry into host cells
  2. ) inhibition of virus uncoating
  3. ) integrase inhibitors
  4. ) duplication of viral genome
  5. ) mRNA transcription and processing
  6. ) protein translation
  7. ) post-translational modification of proteins
  8. ) assembly of molecular components into whole virus, maturation
    - CCR5 co-receptor antagonist maraviroe
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11
Q

prevention of entry into host cells

A
  • CCR5 co-receptor antagonist maraviroc
  • can be used to treat in CCR5 tropic patients
  • adjust dosage if combined with drugs that influence CYP enzymes
  • one of the drugs being considered for preventive treatment against HIV infection
  • exist non-competitive resistance by HIV: uses drug-bound form of CCR5 as a co-receptor
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12
Q

fusion inhibitors

A

Enfuvirtide

  • inhibits HIV-specific gp-41 transmembrane glycoprotein
  • used for patients not responding to current therapy
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13
Q

uncoating of virus consist of

A

loss of nucleocapside

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14
Q

what is noncompetitive resistance

A

when a virus learns to use a drug-bound form of receptor -example: maraviroc

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15
Q

when is un-coating pH-dependent?

A

at low pH, at level of endosomes or lysosomes

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16
Q

when is un-coating pH-independent?

A

when fusion with the plasma membrane

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17
Q

what is the best class of selective drugs available?

A

duplication of viral genome (RNA, DNA)

  • act on duplication of viral genome, polymerases
  • these drugs are mainly nucleoside analogs
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18
Q

why makes duplication drugs so selective?

A
  1. ) virus may use its own enzymes to activate the drug

2. ) viral polymerases are much more sensitive to drug than the corresponding host enzyme

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19
Q

what activates drugs in the duplication of viral genome class?

A

thymidine kinase encoded by some viruses-> used for synthesis of their DNA

  • can activate certain drugs of this class
  • leads to SELECTIVITY for infected cells only
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20
Q

what does the lack of selectivity for viral thymidine kinase allow?

A

allows nucleoside-analog drugs to be phosphorlyated like endogenous nucleosides
-enzyme of host cell have much greater specificity and it often does not phosphorylate the drug

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21
Q

why can nucleoside analogs enter the cell?

A

viral thymidine kinase can phosphorylate the nucleoside analogs permitting administration of drug in nonpohosphorylated form-> can enter cell better

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22
Q

how do nucleoside analog drugs cause chain termination?

A

-once the nucleoside analog is phosphorylated by thymidine kinase-> then by host cell’s enzymatic machinery-> formed into triphosphate compound-> incorporated into the growing nucleic acid chain-> leads to an irreversible association with viral polymerase and chain termination

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23
Q

nucleoside analog drugs

A

idoxuridine, cytarabine, vidarabine, ribavirin, acyclovir, ganciclovir, azidothimide

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24
Q

integrase inhibitor drugs

A

elvitegravir, dolutegravir, raltegravir (used to treat AIDS)

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25
Q

integrase inhibitors MOA

A

prevent insertion of virus genetic code into the DNA of infected cells by inhibiting the viral integrase
-Integrase strand transfer inhibitors-> used to treat AIDS

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26
Q

inhibition of un-coating drugs

A

arildone, plecoranil, amatidine, rimantidine

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27
Q

mRNA transcription and processing drug MOA

A

act on polyadenylation, methylation, capping and splicing of viral RNA
-can act as guanosine analogs and inhibit 5’ capping

28
Q

mRNA transcription and processing drugs

A

ribavirin (inhibits DNA/RNA replication) , interferon

29
Q

what are riboenzymes? what class of drugs do they belong with?

A
  • RNA molecules that induce specifically the cleavage of nucleic acids (heptazyme-> cleave hep C RNA)
  • mRNA transcription and processing drugs
30
Q

post translational drugs

A

interferons

31
Q

post-translational modification drugs MOA

A
  • interfere w/ glycosylation, phosphorylation, fatty acylation
  • Neuraminidase (NA) or sialidase helps spread infleunza from cell to cell by removing sialic acid from surface of infected cells ->viral particles can escape
32
Q

post-translation modification drugs

A

zanamivir (inhibitor of NA), oseltamivir (inhibitor of NA, activated in gut and liver)
-N&V side effect

33
Q

what does zanamivir require?

A

aerosol delivery to respiratory tract

34
Q

protease inhibitor need to know

A

indinavir

35
Q

Amantadine MOA

A

inhibits un-coating of viral RNA of influenza

  • lysosomotropic
  • maybe act on Golgi-network
  • real action: maturation of influenza HA glycoprotein-> decreases infective potential of virus progeny
  • eliminated in urine unchanged
36
Q

use for amantadine

A

oral prophylaxis against influenza A

-alternate vaccine in IC’s and elderly

37
Q

side effects of Amantadine

A

GI intolerance, CNS complaints

38
Q

better drug than amantadine

A

rimantadine

-less toxic

39
Q

first generation antiviral nucleoside analog

A

idoxuridine

-pyrimidine analog

40
Q

MOA of idoxuridine

A

inhibits viral DNA synthesis after activation by phosphoylation by thymidine kinase
-active against herpes and pox viruses

41
Q

why is idoxuridine so toxic? How is it ONLY use?

A

lacks specificity

  • inhibits host DNA polymerase as well as virus
  • used topically, for epithelial herpetic keratitis
42
Q

acyclovir is

A

VERY SELECTIVE

-one of better antivirals

43
Q

why is acyclovir so selective?

A

nontoxic to noninfected cells because is not activated by these cells

44
Q

MOA of acyclovir

A

activated by herpes virus thymidine kinase-> activation converts to monophosphate-> rate of conversion very fast in infected cells-> binds with high affinity to viral enzymes more than host-> second and third PO3 preformed by host

45
Q

Acyclovir is what kind of analog?

A

purine analog

  • competes with dGTP
  • once phosphorylated and incorporated into DNA-> blocks DNA synthesis by binding to active site of DNA polymerase and inhibits it.
  • also acts as chain terminator (triPO3)-> remains bound to polymerase-> polymerase inhibition
46
Q

administration of acyclovir

A

IV, topically, per os

47
Q

what is major consideration when administering acyclovir IV?

A

tissue irritation if extravasation occurs

-N&V otherwise side effect

48
Q

how is acyclovir clear?

A

kidneys

-dosage adjustment if renal impairment

49
Q

use for acyclovir

A

EBV, herpes simplex keratitis, chicken pox, HSV, fever blisters, genital herpes, CMV

50
Q

azidothymidine (AZT) drug classification

A

chain terminator

-prodrug

51
Q

what kind of viruses is AZT used for?

A
  • phosphorylated by cells kinase-> used against viruses that do not have their own kinase
  • phosphorylation required to become active
52
Q

what accounts for AZT specificity?

A

reverse transcriptase is more sensitive to drug than DNA dependent DNA polymerase

53
Q

what enhances AZT use?

A

acyclovir and interferon

54
Q

side effects of AZT

A 
hematologic-> anemia
GI disturbances
paresthesia
skin rash
fever
abnormal liver function
myopathy
55
Q

why shouldn’t AZT be taken with aspirin, acetaminophen or indomethacin?

A

if used with a drug that interacts with the glucuronyl transferase pathway

56
Q

use of AZT

A

HIV treatment

57
Q

antivirals used in treatment for HIV

A

Indinavir, AZT, maraviroc, saquinavir, ritonavir, amprenavir, darnavir

58
Q

different classes of interferons?

A

alpha, beta, gamma

59
Q

alpha and beta interferons MOA

A

cytokines that secreted by virus infected cells

  • bind specific receptors on adjacent cells and protect them from viral infection
  • enhance expression of class I and class II MHC molecules on surface of infected cells-> enhances phenomenon of presentation of viral antigens to specific immune cells
60
Q

gamma interferons MOA

A

cytokine secreted only by T-cells in response to antigen

-enhances specific T cell mediated immune response

61
Q

what do interferons do to RNA and DNA virus replication?

A
  1. ) enhance specific immune responses
  2. ) direct antiviral effects including viral penetration or uncoating, stimulation of degradation of viral mRNA, inhibition of synthesis or methylation or mRNA and inhibition of protein synthesis
62
Q

how must interferons by administered?

A

IV or IM

-not active if given orally

63
Q

examples of pre-exposure prophylaxis

A

Truvada
amantadine
rimantadine
NA inhibitors: zanamivir and oseltamivir

64
Q

pre-exposure prophylaxis

A

PrEP
-only used in individuals who are HIV negative
used in combination with protective sex practices

65
Q

influenza PrEP

A

osetlamivir (tamiflu) (1 year old)

Zanamivir (5 years old)-> not be used with people with underlying respiratory disease

Pharmacology (14 decks)

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