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ID > Non HIV Drugs Med chem > Flashcards

Non HIV Drugs Med chem Flashcards

1
Q

viral entry, replication and possible site for anti viral

A

viral attachment
cell entry
transcription
translation
viral assembly

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2
Q

what is a dominant factor for infectious disease

A

aging

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3
Q

what kind of analogs are antivirals

A

purines or pyrimidine

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4
Q

what kind of drugs are antivirals and how do they become active?

A

prodrugs

must be phosphorylated by viral or cellular enzymes

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5
Q

what do antivirals inhibit?

A

active replication so the viral growth resumes after drug removal

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6
Q

anti-viral agents do not eliminate

A

non replicating or latent virus

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7
Q

what is important for the prevention of and recovery from a number of viral infections

A

effective host immune response

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8
Q

what are herpes virial infection and disease structure

A

a linear double stranded virus, all similar and known to cause latent infections

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9
Q

herpes simplex virus 1

A

infections above the waist, gingivostamatitis, herpes labialis, encephalitis

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10
Q

herpes simple virus 2

A

infection below the waist, herpes genitals

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11
Q

varicella zoster virus

A

causes varicella (chickenpox) or zoster (shingles)

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12
Q

epstein barr virus

A

infectious mononucleosis and development of nasopharyngeal carcinoma

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13
Q

cytomegalovirus

A

congenital infections, mononucleosis

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14
Q

human herpes virus type 8

A

kasposi sarcoma

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15
Q

oral agents for herpes virus

A

acyclovir
valacyclovir
famciclovir

MOA: inhibition of viral synthesis of DNA

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16
Q

topical agents for herpes

A

acyclovir
dococanol
peniciclovir

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17
Q

ophthalmic agents for herpes

A

trifluridine

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18
Q

Acyclovir MOA

A

uptake of infected cell
-thymidine kinase phosphorylates to acyclovir monophosphate
-converted to acyclovir triphosphate

completes with deoxygusnosine triphosphate for viral DNA polymerase
-lacks 3 hydroxyl group –> chain termination
-inactivates the viral DNA polymerase-guanosine analog

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19
Q

acyclovir fomulations and spectrums

A

-oral, topical, IV formulas
-spectrum: Herpes simplex 1 and 2, varicella , possibly the epstein barr virus

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20
Q

valacyclovir

A

-L-valyl ester prodrug
-rapidly and almost converted to acyclovir
-spectrum: Herpes simplex 1 and 2, varicella , possibly the epstein barr virus
- oral only

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21
Q

what are three basic resistance mechanisms of acyclovir resistance

A

reduced or absent thymidine kinase
altered TK substrate specificity
alterations in DNA polymerase

cross resistance to famciclovir& valacyclovir

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22
Q

famciclovir

A

-cyclic adenine analog
-converted to penciclovir in the liver and intestine
-oral only
-spectrum: Herpes simplex 1 and 2, varicella ,epstein barr virus (less)
-AE: HA, GI

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23
Q

famciclovir resistance

A

-mutations in viral TK or DNA polymerase
-cross resistance w acyclovir in TK negative strain
-may still have activity in TK altered strains

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24
Q

topical agents for orolabial herpes

A

Penciclovir
-inhibit DNA synthesis
-topical guanine analog similar to acyclovir*
-apply every 2 hrs

Docosanol
-active against a broad range of lipid envelop virus **
-MOA: interferes with viral fusion to host *

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25
Q

HSV ocular keratoconjuctivitis

A

Trifluridine
inhibits dna synthesis

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26
Q

anti-cmv agents

A

ganciclovir
valganciclovir
foscarnet
cidofovir

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27
Q

ganciclovir MOA

A

inhibits DNA polymerase
-complets with deoxyguanosin triphosphate
-viral encoded phosphotransferase converts to ganciclovir
-more effective than acyclovir

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28
Q

ganciclovir formulation and spectrum

A

oral, IV, Intraocular

CMV
EBV
HSV/VZV

very effective in treating CMV retinitis in AIDS patients

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29
Q

Valganciclovir MOA

A

Inhibition of viral synthesis of DNA
L-valyl prodrug of ganciclovir

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30
Q

Valganciclovir formula and spectrum

A

available orally only

CMV
EBV
HSV/VZV

31
Q

valganciclovir resistance

A

-mutation in the viral protein kinase responsible for monophosphrylation

-responsible for monophosphorylation
–confers resistance to ganciclovir alone

-mutation in the viral polymerase gene
–may show cross resistance to similar antivirals

32
Q

foscarnet MOA

A

Inhibition of viral synthesis of DNA

does not require thymine kinase
– works on HSV strains deficient in this enzyme

selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerase

noncompetitive inhibitor

does not affect cellular DNA polymerse

33
Q

resistance of foscarnet

A

not caused by thymidine kinase alterations

34
Q

Foscarnet formulation and spectrum

A

IV only - controlled infusions

CMV including ganciclovire strains
acyclovir resistant HSV or VZV, EBV

35
Q

Foscarnet structure

A

phosphonomethanoic acid

36
Q

Cidofovir structure

A

cytosine analog

37
Q

Cidofovir MOA

A

Inhibition of viral synthesis of DNA
-acyclic nucleoside phosphonate derivative
-phosphorylation not dependent on viral kinase
-may enhance activity to TK deficient strains

38
Q

Cidofovir formula

A

IV only

39
Q

Cidofovir must be avoided in

A

preexisting renal impairment

40
Q

Cidofovir AE

A

nephrotoxicity (dose-limiting), neutropenia, metabolic acidosis

41
Q

cidofovir resistance

A

mutation in viral DNA polymerase in CMV, pox, and adenovirus

confers resistance to CMV

Foscarnet activity not affected by cidofovir resistance

42
Q

what is shingles ( herpes zoster) caused by ?

A

reactivation of varicella zoster (VZV), initial infection causes chicken pox

effective vaccine available

43
Q

Antiviral therapy for Shingles (herpees zoster)

A

acyclovir, famciclovir, and valaciclovir

reduces severity of shingles in Administration begins within 72hours of beginning of symptoms

44
Q

Zoster Immune globin

A

useful for prevention of chickenpox and shingles but typically not for treatment

45
Q

Human Papilloma virus

A

non enveloped double stranded DNA virus

associated with the development of carcinoma, cervix, anus, and penis

46
Q

What can human papilloma cause

A

cervical, vaginal, vulvar cancers in women

penile cancer in men

anal and throat cancer, and genital warts in both men and women

47
Q

papillomavirus treatment options

A

no specific treatment available

Imiquimod*
Podofilox
Trichloroacetic acid*

48
Q

imiquimod

A

Immunomodulator*
- activates immune cells (monocytes, macrophages, NK cells)

produces antiviral cytokines

indirectly activates antigen presenting cells including langerhan cells and T helper cells

49
Q

Podofilox

A

AKA podophyllotoxin
main ingredient in podophyllin
exact mechanism not known

50
Q

trichloroacetic acid

A

keratolytic agent
given topically
crypto therapy

burning off HPV wart with liquid nitrogen

51
Q

lopinavir

A

experimental for HPV but approved for HIV as a protease inhibitor

52
Q

vaccines against HPV

A

Gardasil- against types 6,11,16, and 18

Cervarix- against types 16 and 18

both non living vaccines

53
Q

influenza vireuses

A

majority respiratory virus that can cause considerable mortality and in some cases mortality

converted with 2 different type of spikes
- neuraminidase
-hemagglutinin

54
Q

influenza agents

A

oseltamivir
zanamivir
amantadine
rimantadine

55
Q

what are the two large glycoproteins on the outside of the viral particles

A

neuraminidase (NA)
hemagglutinin( HA)

56
Q

hemagglutinin (HA)

A

a lectin that mediates binding of the virus to target cells and entry of the viral genome into the target cell

57
Q

neuraminidase (NA)

A

involved in the release of progeny virus from infected cells by cleaving sugars that bind the mature viral particles

58
Q

oseltamivir MOA

A

oral neuraminidase inhibitor *

cleaves terminal sialic acid residues on glycoconjugates and destroys receptors

newly formed virions adhere to cell surface and limit spread

59
Q

Oseltamivir spectrum and AE

A

Influenza A and B
avian influenza
H5N1 disease

AE: HA, N/V

60
Q

zanamivir MOA

A

Neuraminidase inhibitor
given inhalation

61
Q

zanamivir spectrum and AE

A

Uncomplicated influenza A and B
some strains of avian influenza
possible effective fo H5N1

AE: nasal and throat discomfort, btanchospasm

62
Q

Amantadine and Rimantadine MOA

A

prevents the release of viral nucleic acid into host cell

blocks M2 protein channel (type A only)

disrupts hydrogen transport, viral uncaring in host cell and therefore viral RNA transcription

not currently used in US

63
Q

Amantadine and Rimantadine spectrum and AE

A

Influenza A (not influenza B) , resistance is frequent

AE: Seizures, anticholinergic , CNS, edema , blurry vision

64
Q

Influenza Vaccines (best way to control flu infections)

A

-inactivated or recombinant (conventional)
—-IM
—-Trivalent or Quadrivalent*

-LAIV- live attenuated prep –FLUMIST
—-administered intranasally
—-not recommended due to lack of efficacy

65
Q

moneypox

A

viral zoonosis and symptoms are similar to small pox patients

66
Q

viral structure of of monkeypox

A

-double stranded DNA virus
-belongs to the orthopoxvirus genus of the poxvirdae family
-central african and west african cascade

67
Q

Central african strain

A

more transmissible
more severe

68
Q

west african strain

A

only sporadic cases

hypothesis- may be little propensity for human to human transmission

69
Q

what are the natural host for monkey pox

A

exact natural reservoir unknown

rodents ( dormice, squirrels, and rats)

eating inadequately cooked meals from infected animals

70
Q

transmission of monkeypox

A

human close contact with infected animal or human

person to person through lesions, bodily fluid, respiratory droplets, contaminated material (beddings)

71
Q

symptoms of monkey pox

A

invasion period: fever, chills, HA, backache ( last 0-5 days )

skin eruption: development of rash including lesions and pustules (begin 1-3 days, most contagious)

symptoms last 2-4 weeks

72
Q

diagnosis of monkey pox

A

Polymerase chain reaction (PCR)
-samples from skin lesions, liquid from pustules or dry crust

biopsy

73
Q

treatment for monkeypox

A

no treatment same as small pox and cytomegalovirus

Tercovirimat ( not FDA approved)
-limited to pts who are at risk for severe disease such as immunocompromised conditions and younger than 8 yo

74
Q

what is the vaccines available for monkey pox

A

ACAM2000
-replication competent vaccine that protects against smallpox
-contain the vaccinia virus which is live and infectious

JYNNEOS
-live virus and is replication-deficient vaccine
-18 or older and with immune deficiencies can receive the vaccine

ID (27 decks)

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