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antivirals Flashcards

1
Q

what are the categories of respiratory antiviral therapy

A

Neuraminidase inhibitors
Adamantane
Endonuclease inhibitor
Nucleotide Analogue

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2
Q

what medications are neuraminidase inhibitors? what are their administration methods?

A

oseltamivir (VO)
zanamivir (inhaled)
peramivir (IV)

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3
Q

what do neuraminidase inhibitors treat?

A

influenza type A and type B

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4
Q

what’s the mechanism of action of neuraminidase inhibitors?

A

inhibition of neuraminidase → virus unable to cleave connection to sialic acid receptor on host cells → ⭣systemic release of viral progeny

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5
Q

is there any specific instructions of the use of neuraminidase inhibitors

A

reduces symptoms if taken within 48hrs of symptom onset

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6
Q

how does adamantane work?

A

mechanism: inhibition of ion channel (M2 protein) → allowing for proton uptake in virus → ⭣viral uncoating

weak NMDA receptor antagonist

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7
Q

what infection does adamantane target?

A

influenza type A

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8
Q

what are the side effects of adamantane ?

A

orthostatic hipotension, QT interval prolongation

**explained by the weak NMDA receptor antagonist activity

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9
Q

what medication is an endonuclease inhibitor?

A

baloxavir

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10
Q

how does baloxavir work

A

inhibition of endonuclease of viral RNA polymerase → ⭣viral synthesis of RNA

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11
Q

what’s the use of baloxavir

A
  • use: influenza A and B
  • reduces symptoms if taken within 48hrs of symptom onset
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12
Q

what’s the use of nucleotide analogues

A

covid-19

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13
Q

what medication is a nucleotide analogue

A

remdesivir

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14
Q

what’s the mechanism of action of remdesivir

A

incorporation into viral RNA → chain termination → ⭣viral RNA synthesis

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15
Q

is Remdesivir taken alone?

A

sometimes combined with dexamethasone + tocilizumab (inhibitor of IL-6) → this helps to prevent the use of a ventilator

** you’re using two types of immunosuppressants so you have to be careful with superinfections

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16
Q

does Remdesivir have any adverse effects?

A

hepatotoxicity

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17
Q

HSV1 normally causes diseases of …

A

the mouth, face, skin, esophagus or brain

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18
Q

HSV2 usually causes infections of …

A

the genitals, rectum, skin, hands or meninges

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19
Q

what are the categories of herpetic viral therapy

A

HSV-VZV Guanosine Analogues
CMV Guanosine Analogues
Monophosphate Analogue
Pyrophosphate Analogue

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20
Q

what medicines are HSV-VZV guanosine analogues

A

Acyclovir, Valacyclovir, Famciclovir

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21
Q

what’s the difference between Acyclovir and Valacyclovir

A
  • Acyclovir is similar to the acylic guanine nucleoside BUT it lacks 2’ and 3’ parts that are part of the ribose
  • Valacyclovir is an Acyclovir prodrug
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22
Q

what’s the mechanism of action of Acyclovir

A

viral thymidine kinase (HSV TK) phosphorylates drug → incorporation into replicating viral DNA → chain termination = suicide inactivation → ⭣viral replication

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23
Q

do HSV-VZV guanosine analogues work on latent viruses?

A

since this targets viral replication it doesn’t work with latent viruses

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24
Q

which HSV-VZV guanosine analogue has the best bioavailability

A

Valacyclovir

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25
what's the use of Acyclovir and other drugs in their category
primarily = HSV, VZV ** can be used for EBV but with high doses and not commonly
26
when does which type of HSV-VZV guanosine analogue work better?
initial HSV infections > recurrent HSV infections > VZV Valacyclovir > Acyclovir FOR VZV; they are equally effective for HSV
27
adverse effects of Acyclomivir
**obstructive crystal-induced nephropathy** thrombotic thrombocytopenic purpura ** this drug have rapid excretion by the kidneys, and low solubility = obstruction → IV fluids can prevent this
28
which herpetic antivirals need activation by viral kinases
HSV-VZV guanosine analogues CMV guanosine analogues
29
what medicines fall into the CMV guanosine analogue category? what's the difference between them?
Ganciclovir and Valganciclovir - Valganciclovir is the ganciclovir prodrug - Valganciclovir replaced Ganciclovir because the later has a really low oral bioavailability
30
how can you increase the bioavailability of Valganciclovir
food increases the bioavailability of Valganciclovir up to 25%
31
what's the mechanism of action of CMV guanosine analogues
viral UL97 kinase phosphorylates drug → incorporation into replicating viral DNA → chain termination → ⭣viral replication
32
what's the use of CMV guanosine analogues
CMV - can be used as profilaxis with transplant recipients, but you have to be careful with them because they are also immunosuppressed which can cause more risk of bone marrow suppression
33
adverse effects of CMV guanosine analogues
bone marrow suppression (myelosuppression), pancytopenia, nephrotoxicity ** this happens because the viral UL97 kinase is less selective to the tissues it affects it can be phosphorylated by the hosts kinases → typical in sites of high replication
34
which herpetic antiviral uses a viral UL97 kinase to phosphorylate the drug
the CMV guanosine analogues: Ganciclovir and Valganciclovir
35
what medication is a Monophosphate Analogue? what's it form of administration?
Cidofovir → it’s given via IV
36
what's the use of Cidofovir
use: guanosine analogue resistant herpetic infections (HSV, CMV) - it works for acyclovir resistant (TK-deficient or TK-altered HSV and HZV strains) - it works for ganciclovir-resistant CMV strains that have UL97 mutations - it works for some foscarnet-resistant CMV strains ** low oral bioavailability: *IV is better for CMV retinitis *topical gel for mucocutaneous HSV infections
37
whats the mechanism of action of Cidofovir
it’s phosphorylated by CELLULAR enzymes → slows then terminates chain elongation
38
what are the adverse effects of Monophosphate analogues
nephrotoxicity (prevent with probenecid + IV fluids)
39
what medication is a Pyrophosphate Analogue
Foscarnet
40
what's the use of Foscarnet
guanosine analogue resistant herpetic infections (HSV, CMV) ** IV treatment for CMV retinitis, not really used orally because it’s difficult to absorb in aqueous solutions and it has a low bioavailability
41
what's the mechanism of action of Foscarnet
binds reversibly on viral DNA polymerase (+ reverse transcriptase) → chain termination → ⭣viral replication
42
what adverse effects does Foscarnet have?
nephrotoxicity, electrolyte imbalance (seizures), leukopenia
43
what herpetic antiviral has the potential to cause seizures and why?
Foscarnet when the drug is excreted it can take your calcium and magnesium (chelating effect)
44
what are the categories of antivirals for hep. b
nucleoside reverse transcriptase inhibitors (NRTIs) nucleotide reverse transcriptase inhibitors (NtRTIs) Interferon α
45
what medications are nucleoside reverse transcriptase inhibitors
Entecavir, Lamivudine
46
what's the mechanism of action of nucleoside reverse transcriptase inhibitors
lacks 3’-OH → prevents formation of 3’-5’ phosphodiester bond on HBV DNA → termination of DNA chain → prevents viral reverse transcription competitive inhibitors; can inhibit the formation of both the (+) or (-) strand of DNA
47
what can you use Entecavir for
HBV, HIV
48
adverse effects of nucleoside reverse transcriptase inhibitors
lipodystrophy, mitocondrial toxicity (myopathy, neuropathy, lactic acidosis, hepatic steatosis)
49
what medications are considered nucleotide reverse transcriptase inhibitors
Tenofovir, Adefovir
50
mechanism of action of NtRTIs
lacks 3’-OH → prevents formation of 3’-5’ phosphodiester bond of HBV DNA → termination of DNA chain → ⭣viral replication
51
use of NtRTIs
use: HBV, HIV
52
adverse effects of NtRTIs
nephrotoxicity, Fanconi syndrome, osteoporosis
53
what's the name of a medication used as interferon alpha for the treatment of hep. b
pegylated interferon alfa (PEG-INF-α)
54
in which cases do you use PEG-INF-α
HBV + HDV, HCV
55
what are the adverse effects of INT-a
flu-like syndrome, emotional lability, bone marrow suppression, pancytopenia, autoantibody induction
56
apart from INT-a, which are other classes of medications for hep. C
guanosine analogues NS3/4A Protease Inhibitors NS5A Inhibitors NS5B Inhibitors
57
what type of medication is Ribavirin
guanosine analogue
58
how does Ribavirin work
- mechanism: competitive **inhibitor of IMP dehydrogenase** → ⭣guanine nucleoside synthesis - use: HCV
59
adverse effects of ribavirin
adverse effects: hemolytic anemia, teratogenic used to be given with interferon-a in the past, not anymore because of the side effect profile, additionally together they had a lower cure rate
60
what type of medication are: - Simeprevir - Glecaprevir - Grazoprevir - Paritaprevir -PREVIR
NS3/4A Protease Inhibitors
61
mechanism, use, and adverse reactions of NS/3/4A protease inhibitors
- mechanism: inhibition of NS3/4A protease → ⭣viral protein synthesis, ⭣viral replication - use: HCV - adverse effects: photosensitivity/rash (Simeprevir)
62
what type of medications are: - Ledipasvir - Ombitasvir - Elbasvir - Declatasvir - Pibrentasvir Velpatasvir -ASVIR
NS5A Inhibitors
63
how do NS5A Inhibitors work?
- mechanism: inhibition of viral NS5A proteins → ⭣viral replication - use: HCV
64
what type of medications are: - Sofosbuvir - Dasabuvir - BUVIR
NS5B inhibitors
65
how do NS5B inhibitors work?
- mechanism: inhibition of viral NS5B proteins (RNA-dependent RNA polymerase) → ⭣ viral replication - use: HCV
66
Ombitasvir is a ...
NS5A inhibitor for hep C
67
Sofosbuvir is a ...
NS5B inhibitor for hep C
68
Simeprevir is a ------------------, it has a particular adverse effect: -------------
NS3/4A protease inhibitor photosensitivity/rash
69
in a refractory resistant case of HCV you can give triple therapy =
INF-a + Ribavirin + DAA (typically Sofosbuvir)
70
what types of antiretroviral therapy are there
CCR5 antagonist fusion inhibitor nucleoside reverse transcriptase inhibitors (NRTIs) nonnucleoside reverse transcriptase inhibitors (NNRTIs) integrase inhibitors (INIs) protease inhibitors (PIs)
71
how do CCR5 antagonist work? what's their use?
- inhibition of gp120-CD4 complex with CCR5 → prevents viral docking - use: CCR5-tropic (tropism assay)
72
which medication is considered CCR5 antagonist
Maraviroc
73
what's the side effect of a CCR5 antagonist
hepatotoxicity
74
what's the mechanism of action and adverse effect of protease inhibitors
- mechanism: binding to gp41 → prevents viral fusion and entry to host cell - adverse effects: local injection site reaction → subcutaneous injection
75
what's the name of a fusion inhibitor
Enfuvirtide
76
mechanisms and adverse effect of Efurvitide? whats it's use
- binding to gp41 → prevents viral fusion and entry to host cell - adverse effects: local injection site reaction → subcutaneous injection HIV
77
what are the general and specific adverse effects of NRTIs for HIV
general adverse effects: lipodystrophy, mitochondrial toxicity (myopathy, neuropathy, lactic acidosis, hepatic steanosis) - Abacavir → hypersensitivity reaction → avoid in patients carrying the HLA-B*5701 alleles - Didanosine, Stavudine → pancreatitis - Tenofovir → nephrotoxicity, Fanconi syndrome, osteoporosis - Zidovudine → bone marrow suppression (neutropenia, severe anemia), mitocondrial myophaty (”ragged-red fibers”), lactic acidosis
78
one of the medications consider a NRTI for HIV is actually a NtRTI, which med is it
Tenofovir
79
what medications are NNRTIs?
Delavirdine, Doravirine, Efavirenz, Nevirapine, Ripivirine
80
which NNRTI is hepatotoxic
Nevirapine
81
how do NNRTIs work?
binds to reverse transcriptase at allosteric site → conformational change → prevents viral reverse transcription does not require phosphorylation for activity noncomptetitive inhibition (not effective vs HIV-2 RT)
82
what are the general and specific adverse reactions of NNRTIs
hypersensitivity reaction, SJS/TEN, hepatotoxicity - **Efavirenz → vivid dreams**, teratogenic - Delavirdine → teratogenic
83
Bictegravir, Dolutegravir, Elvitegravir, Raltegravir this are example of which type of medication
integrase inhibitors for HIV
84
what's the mechanism of action of integrase inhibitors? what're their adverse effects?
- inhibition of viral integrase → prevents viral dsDNA from integrating into host genome - general adverse effects: Rhabdomyolysis, myositis, myopathy (⭡CK)
85
which medications are protease inhibitors for HIV
*Atazanavir*, Lopinavir, Indinavir, Nelfinavir, *Ritonavir*
86
what are the mechanism and side effects of protease inhibitors for HIV
mechanism: inhibition of viral protease → prevents mature viral protein formation general side effects: lipodystrophy, metabolic abnormalities (**hyperglycemia**, dyslipidemia), nausea, diarrhea - Indinavir → **nephrolithiasis**, nephrotoxicity, hemolytic anemia - Ritonavir → CYP3A4 inhibition

Antimicrobias pharmacology (5 decks)

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