Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology > Chemotherapy (Antiviral Drugs) > Flashcards

Chemotherapy (Antiviral Drugs) Flashcards

1
Q

List the steps in viral replication

A
  1. Adsorption and penetration into cell
  2. Uncoating of viral nucleus acid
  3. Synthesis of regulatory proteins
  4. Synthesis of RNA/DNA
  5. Synthesis of structural proteins
  6. Assembly of viral particles
  7. Release from host cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

State the major sites of antiviral drug action and the drugs that act on them

A
  1. Viral attachment + entry : enfurvitide; maraviroc; docosanol; palivizumab
  2. Penetration : interferon-alfa
  3. Uncoating : amantadine; rimantadine
  4. Nuclei acid synthesis : NRTIs; NNRTIs; acyclovir; foscarnet; entecavir
  5. Late protein synthesis : protease inhibitors
  6. Packaging + assembly for viral release : neuraminidase inhibitors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

State the classification of antiviral drugs according to MoA

A

NRTIs
NNRTIs
Protease inhibitors
DNA polymerase inhibitors
Neuraminidase inhibitors
Inhibitors of viral coat assembly
Integrate inhibitors
Entry inhibitors
Biological agents + immunomodulators

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

List the NRTIs used to treat HIV

A

abacavir
emtricitabine
lamuvidine
stavudine
tenofovir
zidovudine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

List the NRTIs used to treat hepatitis B

A

lamuvidine
tenofovir
adefovir dipivoxil
entecavir
telbivudine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the mechanism of action of NRTIs

A

Competitive inhibitors of reverse transcriptase
Phosporylated by host cell enzymes to give 5’-triphosphates which compete with equivalent host cellular triphosphates for incorporation into viral DNA which causes premature termination of viral DNA synthesis
Inhibit viral replication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What mechanisms are involved in the resistance to NRTIs

A
  1. Impairment of the incorporation of the analogue into DNA
  2. Removal of the analogue from the prematurely terminated DNA chain

(occur as a result of mutations leading to a change in the structure of reverse transcriptase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the general adverse effects of NRTIs?

A

GI disturbances
CNS and related effects
Musculoskeletal
Dermatological effects
Blood disorders
Liver damage
Pancreatitis
Metabolic effects including lactic acidosis and lipodystrophy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

List the NRTIs used in HIV treatment and state their specific adverse effects

A
  1. Zidovudine: Bone marrow depression, GI intolerance, cardiomyopathy, myopathy
  2. Stavudine: Peripheral neuropathy, lipodystrophy, hepatotoxicity
  3. Abacavir: Hypersensitivity reactions (predisposing factor: presence of HLA-B5701 gene), increase in myocardial infarction
  4. Tenofovir: Nephrotoxicity, osteoporosis, exacerbation of hepatitis B with discontinuation
  5. Lamivudine: Pancreatitis
  6. Emtricitabine: Hyperpigmentation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How are NNRTIs classified?

A
  1. First generation: Efavirenz (EFV) and nevirapine (NVP)
  2. Second generation: Etravirine and rilpivirine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe the MoA of NNRTIs

A

Bind to reverse transcriptase near the catalytic site and denature it.
They are non-competitive inhibitors of HIV-1 RT i.e. do not compete with nucleoside triphosphates and do not require phosphorylation
They do not inhibit HIV-2 reverse transcriptase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Differentiate the action of NNRTIs in drug sensitive vs drug resistant viruses

A

In drug-sensitive viruses, NNRTIs bind to a pocket next to the active site and block the polymerization of DNA by reverse transcriptase
In drug-resistant viruses, mutations prevent the binding of NNRTIs to their binding site, allowing DNA polymerization to proceed normally

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the side effects and contraindications of efavirine?

A

Neuropsychiatric effects (insomnia, somnolence, dizziness, amnesia, nightmares, neuropathy, anxiety, psychosis, seizures etc.), hepatotoxicity, skin reactions and gynaecomastia. Contra-indicated in patients with seizure disorders, neurological disorders and psychiatric disorders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the side effects and contraindications of nevirapine?

A

Hepatotoxicity and skin reactions (including Steven-Johnson syndrome and toxic epidermal necrolysis); more frequent and more severe than with EFV. Contraindicated in patients with hepatic impairment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

State the general contraindications of first gen NNRTIs

A

Hypersensitivity
Concurrent administration of drugs that depend on cytochrome P450 for metabolism, and those that induce or inhibit cytochrome P450
Concomitant use of NNRTIs is not recommended

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the first gen NNRTIs drug-drug interactions

A
  1. NVP induces CYP3A: increases metabolism of protease inhibitors (PIs), oestrogens, ketoconazole, rifampicin (reduced efficacy)
  2. EFV induces CYP3A4: increases metabolism of drugs metabolised by these enzymes e.g. some PIs (reduced efficacy)
  3. Cytochrome P450 inducers (e.g. rifampicin) increase metabolism of NNRTIs (reduced efficacy)
  4. Cytochrome P450 inhibitors (e.g. ketoconazole, cimetidine) reduce metabolism of NVP (increased toxicity)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the side effects of second gen NNRTIs?

A

Etravirine adverse effects: Hypersensitivity reactions that include skin reactions and hepatitis
Rilpivirine adverse effects: Rash, depression, headache, insomnia, increased serum aminotransferases and QTc prolongation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the mechanism of action of protease inhibitors in HIV?

A

Protease inhibitors prevent viral replication by selectively binding to viral proteases and blocking proteolytic cleavage of the polyproteins into functional and structural proteins that are necessary for the production of infectious viral particles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Describe protease inhibitor drug resistence

A

Resistance to PIs is the consequence of amino acid substitutions on proteases. These amino acid changes modify the number and the nature of the points of contact between the PIs and the proteases, thereby reducing their affinity for the enzymes.

20
Q

List the protease inhibitors used in HIV treatment

A

amprenavir
atazanavir
darunavir
lopinavir
ritonavir

21
Q

What are the adverse effects of protease inhibitors?

A

fatigue
GI disturbances
CNS and related effects, musculoskeletal and dermatological effects, blood disorders, and metabolic effects including pancreatitis, liver damage and lipodystrophy
These agents cause a syndrome of altered body fat distribution, insulin resistance and hyperlipidemia (metabolic syndrome)

22
Q

What is the function of NS3/4A serine protease?

A

involved in post-translational processing in hepatitis C (HCV)

23
Q

List the NS3/4A protease inhibitors and state their mechanism of action

A

grazoprevir,
paritaprevir and
simeprevir
are inhibitors of the NS3/4A serine protease, an enzyme involved in post-translational processing in hepatitis C (HCV)

24
Q

List the entry inhibitors used to treat HIV

A

enfuvirtide and maraviroc

25
Q

What is the general mechanism of action of entry inhibitors?

A

Entry inhibitors prevent HIV from entering human cells by inhibiting key proteins involved in the entry process

26
Q

Describe how enfuvirtide works

A

Inhibits gp41, an HIV glycoprotein, resulting in prevention of fusion of the viral and cellular membranes, and thereby inhibits entry of HIV into the human cell

27
Q

What are the adverse effects of enfuvirtide?

A

Local injection site reactions,
hypersensitivity reactions,
headache,
insomnia,
anorexia,
asthenia,
peripheral neuropathy,
depression,
pancreatitis

28
Q

Describe how maraviroc works

A

binds to the CCR5 receptor on the membrane of human cells such as CD4 cells. This binding prevents the interaction of the HIV glycoprotein, gp120, and human CCR5 which is necessary for HIV entry into the cell.

29
Q

What are the limitations of maraviroc?

A

HIV can also use another co-receptor on human cells, CXCR4, which maraviroc does not affect. Maraviroc does not prevent HIV entry into CXCR4-tropic or dual-tropic cells.
A tropism test must therefore be performed to determine if the drug will be effective

30
Q

What are the adverse effects of maraviroc?

A

Hepatotoxicity (may be preceded by a systemic allergic reaction, pruritic rash and eosinophilia),
dizziness,
postural hypotension,
increased risk of cardiac ischaemic events (e.g. myocardial infarction)

31
Q

List the integrase strand transfer inhibitors

A

raltegravir,
dolutegravir and
elvitegravir

32
Q

What is the mechanism of action of integrase strand transfer inhibitors?

A

Bind they viral enzyme integrase, thereby inhibiting strand transfer, the final step of provirus integration, thus interfering with the integration of HIV DNA into the DNA of host cells

33
Q

State the adverse effects for each of the specific ISTIs

A

Raltegravir
Rash, hypersensitivity reactions, myopathy and rhabdomyolysis
Dolutegravir
Headache, insomnia, anxiety, depression, increased serum aminotransferase levels, and hypersensitivity reactions
Elvitegravir
Diarrhea, rash, and elevation in serum aminotransferases

34
Q

List the DNA polymerase inhibitors used to treat cytomegalovirus (CMV) infections

A

Cidofovir,
foscarnet,
ganciclovir,
valganciclovir

35
Q

List the DNA polymerase inhibitors used to treat of herpes infections

A

Aciclovir,
famciclovir,
penciclovir,
valaciclovir,
idoxuridine,
trifluridine and
vidarabine

36
Q

What is the MoA of aciclovir, valaciclovir, famciclovir and penciclovir ?

A

Phosphorylated by viral thymidine kinase then metabolised by host cell kinases to a nucleotide analogue. The nucleotide analogue then inhibits viral DNA synthesis by inhibiting DNA polymerase.

37
Q

What could cause viral resistance to aciclovir?

A

(a) Decreased production of thymidine kinase
(b) Altered thymidine kinase substrate specificity
(c) Altered viral DNA polymerase
Cross-resistance occurs with valaciclovir, famciclovir and ganciclovir

38
Q

What are the adverse effects of aciclovir?

A

Nausea,
diarrhea,
headache,
tremors and
delirium

39
Q

What are the adverse effects of Valaciclovir, famciclovir and penciclovir?

A

Nausea, diarrhea and headache

40
Q

State the MoA of Idoxuridine and trifluridine

A

converted by cellular enzymes to their triphosphate analogs which inhibit viral DNA polymerase

41
Q

What are the adverse effects of idoxuridine and trifluridine?

A

Pain,
pruritus,
edema involving the eye or lids and
allergic reactions (rare)

42
Q

State the MoA of vidarabine

A

Converted by cellular enzymes to its triphosphate analog which inhibits viral DNA polymerase

43
Q

What are the adverse effects of vidarabine?

A

Neurotoxicity, GI intolerance and myelosuppression, syndrome of inappropriate secretion of ADH

44
Q

What is the mechanism of action of ganciclovir?

A

Requires triphosphorylation for activation monophosphorylation is catalyzed by a phosphotransferase in CMV and by thymidine kinase in HSV cells
Phosphorylated ganciclovir inhibits DNA polymerase

45
Q

How does ganciclovir resistance occur?

A

Results from impaired phosphorylation due to a point mutation or a deletion in the viral phosphotransferase

46
Q

What are the contraindications of etravirine and rilprivirine?

A

Etravirine is a very potent inducer of CYP3A4 thus it should not be given with other NNRTIs, unboosted protease inhibitors and atazanavir/ritonavir
Rilpivirine is primarily metabolized by CYP3A4, and drugs that induce or inhibit CYP3A4 may thus affect the clearance of rilpivirine

Pharmacology (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions