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Drugs 2 Flashcards

1
Q

Amantadine

A

Anti-influenza drug

MOA=uncoating agent

Widespread resistance, so rarely used

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2
Q

Amphotericin B

A

Amphipathic macrolide that binds to ergosterol in fungal cell membrane, forming pores that allow ions to leak out of cell

Broad anti-fungal spectrum

Given for life threatening systemic infections

Insoluble in water, so suspended in deoxycholate

Poorly absorbed by GI tract–>only given orally if problem is in GI tract

Intrinsic resistance in candida lusitaniae and pseudallescheria boydii

Causes bad side effects
Acute/infusion related toxicity=fever, chills, hypotension
Slower toxicity=kidney damage

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3
Q

Imidazoles

A

2N azoles

Older, less potent

Ketoconazole, clotrimazole, miconazole

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4
Q

Dasabuvir

A

HCV RNA polymerase inhibitor

In Viekira Pak

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5
Q

Triazoles

A

3N azoles

Itraconazole, voriconazole, and fluconazole

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6
Q

Griseofulvin

A

Anti-fungal that interferes with microtubules

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6
Q

Itraconazole

A

Most potent triazole

Wide spectrum of action

Widely distributed

Lipid soluble; absorption increased by gastric acid

Toxicity=GI distress, teratogenic

Drug interactions: H2 and proton pump blockers decrease gastric acidity, metabolized by P450 enzymes

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7
Q

5-Fluorocytosine

A

Anti-fungal nucleoside analog that inhibits DNA and RNA synthesis

Soluble in water so can be taken orally with rapid absorption from GI tract

Water soluble–>taken orally and easily absorbed in GI tract

Narrow spectrum

Given in drug combo to avoid resistance

Adverse effects: decrease function of bone marrow, rash, GI effects, renal toxicity

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10
Q

Oseltamivir

A

Anti-influenza drug

MOA=neuraminidase inhibitor

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11
Q

Capsofungin

A

Echinocandins that inhibit beta-glucan synthesis

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13
Q

Fluconazole

A

Triazole

As compared to itraconazole, absorption is not impaired by stomach acid, it has fewer P450 drug interactions, and is widely distributed to include CNS

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14
Q

Echinocandins

A

Anti-fungals that blocks cell wall synthesis by inhibiting beta (1,3)-glucan synthase

Caspofungin

Used for candida, invasive aspergillosis that is resistant to amphotericin B

Minor adverse effects

Resistance from mutation in FKS1 (gene encoding for beta 1,3 glucan synthase)

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15
Q

Zanamivir

A

Anti-influenza drug

MOA=neuraminidase inhibitor

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16
Q

Rimantidine

A

Anti-influenza drug

MOA=uncoating agent

Widespread resistance, so rarely used

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17
Q

Acyclovir

A

Nucleoside analog for herpes and CMV

Guanosine derivative

First phosphorylation by the viral enzyme; second and third by host enzymes

Outcompetes guanosine and is a chain terminator

Oral, topical, IV that is well tolerated

Resistance from HSV thymidine kinase mutation

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18
Q

Terbinafine

A

Inhibits ergosterol biosynthesis by blocking squalene epoxidase

Synthetic allylamine

Used systemically or topically

Accumulates in skin, nail, and fat

Targets tinea

Must be used continuously

Synergistic with triazoles

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19
Q

Peramivir

A

Anti-influenza drug

MOA=neuraminidase inhibitor

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20
Q

Famciclovir

A

Topical nucleoside analog for herpes, CMS

Guanosine derivative that does not cause chain termination

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21
Q

Miltefosine

A

Drug used for leishmaniasis

Inhibits cytochrome c oxidase activity needed for promastigotes and amastigotes, causing apoptosis

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22
Q

Ganciclovir

A

Topical nucleoside analog for herpes, CMS

Guanosine derivative that causes chain termination

Teratogenic

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23
Q

Amantadine

A

Viral entry inhibitor of influenza (adamantanes)

Binds M2 protein on virus to inhibit unsheathing

Resistance when M2 is mutated

Excreted unmetabolized

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24
Q

Rimantadine

A

Viral entry inhibitor of influenza (adamantanes)

Binds M2 protein on virus to inhibit unsheathing

Resistance when M2 is mutated

Excreted as metabolized form

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25
Q

Voriconazole

A

Newest triazole

Given for aspergillus fumigatus

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26
Q

Zanamivir

A

Neuramidase inhibitor for influenza

Sialic acid transition state analog; prevent viral exit

Inhaled

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27
Ribavirin
Nucleoside analog as first line treatment for HCV Guanosine analog that inhibits RNA synthesis, capping, and replication Side effects: psychiatric, teratogen
28
Ombitasivir
HCV NS5A inhibitor In Viekira Pak
29
Foscarnet
Aka foscavir Binds DNA pol, RNA pol, and HIV RT to inhibit cleavage Resistance in strands with mutations in DNA pol, but good for strains resistant to ganciclovir and cidofovir Administered via IV
30
Peramivir
Neuramidase inhibitor for influenza Sialic acid transition state analog; prevent viral exit Administered as a single IV dose
31
Interferons
Given for HCV and HBV as first line treatment Activate JAK-STAT pathway to initiate human antiviral response which inhibits viral transcription, translation, protein processing, and maturation MANY adverse side effects, so often have to stop taking Interferes with P450 metabolism of other drugs Administered via IV with polyethylene glycol (PEG) to increase half life
31
Entecavir
Nucleoside analog as first line treatment for HBV Guanosine analog that causes steric hindrance in helix, stopping replication 3' hydroxyl allows for additional bases to be added before termination Little resistance, little side effects
31
Tenofovir
Nucleotide analog used as first line treatment for HBV and HIV Inhibits reverse transcriptase Adenosine analog that already has first phosphate to overcome rate limiting step Chain terminator Little resistance Side effects: nephrotoxicity and decrease in bone mineral density
32
Truvada
Emtricitabine and tenofovir
35
Viral entry inhibitors for influenza
-adine Amantadine Rimantadine
36
Cidofovir
Nucleoside analog for herpes, CMV Phosphorylated twice, both times by host kinases Resistance due to mutations in viral DNA pol Cross resistance with ganciclovir Dose dependent nephrotoxicity made worse by probenecid (blocks tubular transport of cidovir so it is not cleared; given to treat gout)
37
Sofosbuvir
Nucleotide analog used as first line treatment for HCV Uridine chain terminator Prodrug-carries first phosphate to overcome RSL Daily pill Little resistance and little side effects
38
Oseltamivir
Neuramidase inhibitor for influenza Sialic acid transition state analog; prevent viral exit Aka tamiflu Oral administration
39
Ledipasvir
HCV NS5A inhibitor Binds NS5A tightly
40
Paritaprevir
HCV protease inhibitor In Viekira Pak
41
Simiprevir
HCV protease inhibitor
41
Grazoprevir
HCV protease inhibitor
42
Azoles
Fungistatic Inhibit ergosterol synthesis by blocking the third step, ERG11 gene Cause accumulation of toxic membrane methylsterols (more deleterious effect) Adverse effects: minor GI problems, some liver enzyme abnormality Resistance mechanisms: efflux pump, change in expression of enzyme to reduce affinity of azole or require more azole, and mutation in ERG3 so no longer make cytotoxic chemicals Interacts with P450 drugs
42
Elbasvir
HCV NS5A inhibitor
43
Viekira Pak
Combination for HCV Includes Two pills of paritaprevir (protease), ritonavir (booster for paritaprevir), and ombitasvir (NS5A) One pill of dasabuvir (RNA pol inhibitor)
44
Maraviroc
HIV fusion inhibitor Binds CCR5 to mask it from HIV Metabolized by p450s Resistance due to emergence of strains that use CXCR4 to get into CD4+ cells
45
Enfuvirtide
HIV fusion inhibitor Targets p41 on HIV virus
47
HIV integrase inhibitors
-gravir Raltegravir Elvitegravir Dolutegravir
48
Emtricitabine
HIV nucleoside analog with long half life Inhibits reverse transcriptase
49
Etravirine
Non-nucleotide reverse transcriptase inhibitor Strategic flexibility allows it to accommodate for mutations in the active site Reserved for resistant strands
50
Efavirenz
Non-nucleoside reverse transcriptase inhibitor Binds to site adjacent to active site on reverse transcriptase to cause conformational change
51
Raltegravir
HIV integrase inhibitor Binds Mg2+ in active site of Integrase-DNA complex to displace 3'OH First line therapy; very potent
51
Atazanavir
HIV protease inhibitor Once daily with fewer lipid distribution side effects
52
Elvitegravir
HIV integrase inhibitor Binds Mg2+ in active site of integrase-DNA complex to displace 3'OH Use cobicistat as a booster
53
Ritonavir
HIV protease inhibitor
54
Dolutegravir
HIV integrase inhibitor Part of Triumeq
54
HIV Protease Inhibitors
-avir Atazanavir Darunavir Ritonavir
57
HCV protease inhibitors
-previr Simiprevir Paritaprevir Grazoprevir
58
Darunavir
HIV protease inhibitor Take twice orally
58
HCV NS5a inhibitors
-asvirs Ledispasvir Daclatasvir Elbasvir Ombitasvir
59
Viral exit inhibitors of influenza
-amivir Zanamivir Oseltamivir Peramivir
60
Daclatasvir
HCV NS5A inhibitor Very potent

Microbiology (10 decks)

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