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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
Q

Why are pharmacokinetic enhancers used with HIV protease inhibitors?

A
  • powerful inhibitors of cytochrome P450

- means you can give lower dose of drug and it stays in the body for longer

26
Q

What are some examples of protease inhibitors and the PK enhancers and what are they used to treat?

A

PI:

  • darunavir
  • atazanavir

PK enhancers:

  • ritonavir
  • cobicistat
  • HIV
  • HCV
27
Q

What are the key reactions of HIV integrase?

A
  • 3’ end processing of the double stranded viral DNA ends

- strand transfer which joins viral DNA to the host chromosomal DNA forming provirus

28
Q

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

A
  • raltegravir
  • dolutegravir
  • HIV
29
Q

Describe HAART

A
  • combination therapy

- 2NRTIs and additional drug from another class

30
Q

What are the advantages of HAART?

A
  • prevention of morbidity and mortality associated with chronic HIV
  • reduction in sexual/vertical transmission of HIV
  • restore and preserve immunological function
31
Q

What are the different classes and genomes of RNA viruses?

A
  • 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
Q

Where does RNA virus replication take place?

A

host cell cytoplasm

33
Q

What are some examples of RNA viruses?

A
  • influenza

- hepatitis C virus

34
Q

What type of virus is hepatitis C?

A
  • flavivirus

- positive-sense single stranded RNA virus

35
Q

What can hep C cause?

A
  • acute and chronic hepatitis
  • cirrhosis
  • hepatocellular carcinoma
36
Q

Examples of NS3 protease inhibitors used in HCV

A
  • parita(pr)evir

- grazo(pr)evir

37
Q

Examples of NS5A inhibitors used in HCV

A
  • elb(a)svir

- pibrent(a)svir

38
Q

Examples of nucleotide inhibitors and non-nucleoside inhibitors used in HCV

A

NI:

  • sofosbuvir
  • dasabuvir

NNIs:
-RNA-dependent RNA polymerase

39
Q

What type of virus is influenza?

A
  • orthomyxoviridae
  • types a, b and c
  • enveloped, negative sense, single-stranded RNA virus
  • viral neuraminidase
40
Q

Describe the action of viral NA

A
  • catalyses removal of terminal sialic acids from glycoprotein
  • allows mobility and extraction of viral progeny
41
Q

Describe the action of neuraminidase inhibitors

A

NA inhibitors mimic sialic acid natural substrate by binding to NA active site preventing NA function and halting viral replication

42
Q

Explain how amantadine/rimantadine works in influenza

A
  • blocks H+ entering through M2 ion channel inhibiting disassembly of virus
43
Q

Explain how baloxavir works in influenza

A
  • inhibits viral mRNA replication

- virus release inhibitor

44
Q

Explain how DNA viruses replicate

A
  • 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
Q

What are examples of DNA viruses?

A
  • herpes simplex virus
  • human papilloma virus
  • hepatitis B virus
46
Q

What drug is used in herpes and how does it work?

A
  • aciclovir
  • viral thymidine facilitates uptake and phosphorylation
  • competitively inhibits viral DNA polymerase
  • incorporated into viral DNA terminating chain and blocking DNA synthesis
47
Q

What are the disadvantages of aciclovir?

A
  • CNS toxicity

- renal impairment

48
Q

What type of virus is hepatitis B?

A
  • hepadnavirus
  • enveloped
  • partially dsDNA virus
  • genome in circular conformation
  • replication occurs by RNA intermediate
49
Q

What can hep B cause?

A
  • acute and chronic hepatitis
  • cirrhosis
  • hepatocellular carcinoma
50
Q

What is the treatment of HBV?

A
  • pegylated IFNa
    (flu-like, myalgia, depression, autoimmunity)
  • nucleos(t)ide therapies
51
Q

What factors favour the development of antiviral resistance?

A
  • 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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