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MD3001 Respiratory > Antiviral Drugs > Flashcards

Antiviral Drugs Flashcards

1
Q

Viruses are obligate, what does this mean?

A

They are reliant on the host cell for all aspects of their life cycle

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2
Q

What are the classifications of the viruses based on?

A
  • the type and structure of the nucleic acid (DNA/RNA and single/double stranded) virion and the strategy used in its replication
  • symmetry of the capsid
  • presence or absence of a lipid membrane (envelope)
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3
Q

What are the stages in a viral life cycle?

A
  1. attachment
  2. penetration
  3. disassembly
  4. transcription
  5. translation
  6. replication
  7. assembly
  8. release
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4
Q

What are the 3 mechanisms of action of antrivirals?

A
  • virucides
  • antivirals
  • immunomodulators
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5
Q

Describe the mechanism of action of virucides and examples

A
  • directly inactivate viruses
  • detergents, organic solvents, UV light
  • cryotherapy, laser, podophyllin (also damages normal tissues)
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6
Q

Describe the mechanism of action of antivirals and the disadvantage of them

A
  • inhibit replication at the cellular level

- ineffective in eliminating non-replicating/latent viruses

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7
Q

Describe what immunomodulators do and what they treat

A
  • replace deficient host response
  • enhance endogenous response
  • treat HCV and HBV
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8
Q

What are the targets for antivirals?

A
  • entry inhibition
  • block viral disassembly
  • block viral replication
  • viral release inhibitors
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9
Q

What are examples of antiviral drugs that block viral disassembly and what are they used to treat?

A
  • amantadine
  • rimantadine
  • influenza
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10
Q

What are the drugs that block viral replication?

A
  • viral polymerases
  • viral proteases
  • integrase blockers
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11
Q

Describe the mechanism of action of nucleos(t)ide analogues

A
  • competitively inhibits viral polymerase action

- mimics them and incorporates them to block replication of the new genetic material

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12
Q

What are retroviruses?

A
  • positive sense single stranded RNA virus

- contains reverse transcriptase

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13
Q

Explain how retroviruses replicate

A
  • use reverse transcriptase to make DNA copy of viral RNA
  • DNA integrated into genome of host cell (provirus)
  • DNA is transcribed into new RNA and mRNA for translation into viral proteins using host cell machinery
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14
Q

What are examples of retroviruses?

A
  • HIV

- human T cell leukaemia virus

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15
Q

Describe the structure of HIV

A
  • enveloped virus (gp120 protein)
  • single stranded RNA
  • contains lipid bilayer
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16
Q

What receptors does HIV bind to on the host cell?

A
  • CD4

- AND either CCR5 or CXCR4

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17
Q

What can be targeted in the HIV life-cycle?

A
  • CCR5 antagonists
  • fusion inhibitors
  • reverse transcriptase inhibitors
  • integrase strand transfer inhibitors
  • protease: post-translational processing
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18
Q

What are examples of fusion/entry inhibitors and what are they used to treat?

A
  • T20
  • fostemsavir
  • maraviroc (CCR5 blocker)
  • HIV
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19
Q

What are examples of reverse transcriptase inhibitors used in HIV?

A
  • competitive/non-competitive nucleoside reverse transcriptase translocation inhibitors
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20
Q

What are the 2 types of reverse transcriptase inhibitors and describe their mechanism of action

A
  • competitive: blocks RT through use of nucleos(t)ide analogue by binding to the chain, taking place of normal nucleosides to cause termination of chain
  • non-competitive (non-nucleoside): act by binding to enzyme itself causing conformational change to it cannot produce viral DNA
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21
Q

What are some examples of NRTIs and what can they be used to treat?

A
  • tenofovir (analogue of adenosine)
  • emtricitabine (analogue of deoxycytidine)
  • HIV/HBV
22
Q

NRTIs are prodrugs, what does this mean?

A

prodrugs require intracellular phosphorylation by viral and/or cellular kinases to convert them from the 5’-monophosphate form to the active 5’-triphosphates

23
Q

What are some examples of NNRTIs and what are they used to treat?

A
  • efavirenz
  • nevirapine
  • rilpivirine
  • HIV
24
Q

What are some disadvantages of NNRTIs?

A
  • EVP and NVP have a low barrier to resistance
  • drug interactions are common
  • EFV and RPV can result in neurologic and psychiatric AE
25
Why are pharmacokinetic enhancers used with HIV protease inhibitors?
- powerful inhibitors of cytochrome P450 | - means you can give lower dose of drug and it stays in the body for longer
26
What are some examples of protease inhibitors and the PK enhancers and what are they used to treat?
PI: - darunavir - atazanavir PK enhancers: - ritonavir - cobicistat - HIV - HCV
27
What are the key reactions of HIV integrase?
- 3' end processing of the double stranded viral DNA ends | - strand transfer which joins viral DNA to the host chromosomal DNA forming provirus
28
What are some examples of integrase inhibitors and what are they used to treat?
- raltegravir - dolutegravir - HIV
29
Describe HAART
- combination therapy | - 2NRTIs and additional drug from another class
30
What are the advantages of HAART?
- prevention of morbidity and mortality associated with chronic HIV - reduction in sexual/vertical transmission of HIV - restore and preserve immunological function
31
What are the different classes and genomes of RNA viruses?
- positive sense viral RNA: similar to mRNA and can be immediately translated by host cell - negative sense viral RNA: complementary to mRNA and must be converted to positive sense by RNA dependent RNA polymerase before translation genome: - dsRNA - +ssRNA - -ssRNA
32
Where does RNA virus replication take place?
host cell cytoplasm
33
What are some examples of RNA viruses?
- influenza | - hepatitis C virus
34
What type of virus is hepatitis C?
- flavivirus | - positive-sense single stranded RNA virus
35
What can hep C cause?
- acute and chronic hepatitis - cirrhosis - hepatocellular carcinoma
36
Examples of NS3 protease inhibitors used in HCV
- parita(pr)evir | - grazo(pr)evir
37
Examples of NS5A inhibitors used in HCV
- elb(a)svir | - pibrent(a)svir
38
Examples of nucleotide inhibitors and non-nucleoside inhibitors used in HCV
NI: - sofosbuvir - dasabuvir NNIs: -RNA-dependent RNA polymerase
39
What type of virus is influenza?
- orthomyxoviridae - types a, b and c - enveloped, negative sense, single-stranded RNA virus - viral neuraminidase
40
Describe the action of viral NA
- catalyses removal of terminal sialic acids from glycoprotein - allows mobility and extraction of viral progeny
41
Describe the action of neuraminidase inhibitors
NA inhibitors mimic sialic acid natural substrate by binding to NA active site preventing NA function and halting viral replication
42
Explain how amantadine/rimantadine works in influenza
- blocks H+ entering through M2 ion channel inhibiting disassembly of virus
43
Explain how baloxavir works in influenza
- inhibits viral mRNA replication | - virus release inhibitor
44
Explain how DNA viruses replicate
- entry of viral DNA into host cell nucleus - use cellular enzymes for transcription and replication of genomes - early (regulatory proteins and proteins for DNA replication) and late (structural proteins) mRNA transcripts are synthesised
45
What are examples of DNA viruses?
- herpes simplex virus - human papilloma virus - hepatitis B virus
46
What drug is used in herpes and how does it work?
- aciclovir - viral thymidine facilitates uptake and phosphorylation - competitively inhibits viral DNA polymerase - incorporated into viral DNA terminating chain and blocking DNA synthesis
47
What are the disadvantages of aciclovir?
- CNS toxicity | - renal impairment
48
What type of virus is hepatitis B?
- hepadnavirus - enveloped - partially dsDNA virus - genome in circular conformation - replication occurs by RNA intermediate
49
What can hep B cause?
- acute and chronic hepatitis - cirrhosis - hepatocellular carcinoma
50
What is the treatment of HBV?
- pegylated IFNa (flu-like, myalgia, depression, autoimmunity) - nucleos(t)ide therapies
51
What factors favour the development of antiviral resistance?
- high viral load - high intrinsic viral mutation rate - degree of selective drug pressure - antiviral target that can mutate without affecting fitness

MD3001 Respiratory (38 decks)

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