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Clinical Pharmacology, Therapeutics & Principles of Prescribing > Antivirals and Antimicrobials > Flashcards

Antivirals and Antimicrobials Flashcards

1
Q

Are antivirals virostatic or virucidal?

What does this mean?

A

Virostatic

They do not “kill” viruses, they stop the replication of new viruses

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2
Q

At which stages can viral replication be inhibited in order to elicit anti-viral effects?

A 
Attachment 
Uncoating 
RNA/DNA replication 
Protein synthesis 
Assembly 
Release
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3
Q

Give some examples of the down-sides of inhibiting viral replication in order to treat patients.

A

Interfere with host-cell metabolism
Ineffective against latent or non-replicating infections
Rebound effects when the drug is stopped
Drug resistance may develop

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4
Q

How can the hosts immune system be improved clinically to aid the outcome of their viral infection?

A

Replace host immunity that is compromised e.g. immunoglobulins

Enhance host immunity e.g. interferons

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5
Q

What is immunoglobulin therapy?

When might this be used clinically?

A

Pooled human sera from blood donors which contains preformed antibodies

Used post-exposure (ideally within 72 hours)

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6
Q

Give some examples of drugs used to treat HSV infections

A

Aciclovir (oral, IV)
Ganciclovir (IV, intravitreal)
Valganciclovir (oral, prodrug)
Penciclovir (topical, IV)

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7
Q

What is the mechanism of action of aciclovir?

A

Drug products acts on the viral DNA in the human nucleus.

It acts as a competitor for dGTP which is a substrate for viral DNA polymerase and a chain terminator

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8
Q

What is the mechanism of action of guanosine nucleoside analogues such as ganciclovir and valganciclovir?

A

They inhibit viral DNA polymerase

This slows down and terminates viral DNA elongation

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9
Q

Give an example of a drug used to treat Hepatitis B

What is it’s mechanism of action?

A

Lamivudine
Acts as a false substrate and chain terminator of reverse transcriptase

Adefovir
Competitive false substrate and terminator of reverse transcriptase

Emtrecitabine
Inhibits DNA polymerase

Entecavir
Inhibits DNA polymerase

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10
Q

Give an example of a drug used to treat Hepatitis C

What is it’s mechanism of action?

A

Ribavirin (oral, IV)

Inhibits RNA/DNA viruses by altering nucleotide stores

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11
Q

How can interferons be used to aid antiviral therapy?

How are they administered?

A

They are potent cytokines
Stimulate proteins to enhance the body’s defence against viral infection

IM injection

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12
Q

List some anti-influenza drugs are their mechanism of action

A

Oseltamivir (tamiflu)
Zanamivir
Both are reversible inhibitors of neuroaminidase

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13
Q

List some broad types of anti-retroviral (HIV) drugs

A 
Nucleoside RT inhibitors e.g. AZT 
Non-nucleoside RT inhibitors e.g. Nevirapine 
Protease inhibitors e.g. Saquinavir 
Fusion inhibitors e.g. Enfuvirtide 
Entry inhibitors e.g. Maraviroc
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14
Q

Antiviral drug resistance testing is available for which viruses?

A 
HIV 
Hep B 
CMV 
Influenze 
HSV
VZV
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15
Q

Why might we want to perform antiviral drug resistance testing?

A

To optimise clinical outcomes
To save costs and adverse effects
Reduce the resistant virus pool

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16
Q

When is antiviral drug resistance testing performed?

A

When there is evidence of therapeutic failure

  • poor adherence/compliance
  • resistant virus
  • patient unable to tolerate side effects
  • baseline check
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17
Q

How is antiviral drug resistance testing performed?

A

Incubate the specific virus in a culture system with varying concentrations of drug
Sequence and genotyping for the commonly seen resistant viruses

18
Q

What is the role of viral load testing in antiviral therapy?
How is it used to define treatment endpoints?

A

Used to monitor the response of the virus to the antiviral being used and see if the patient is taking the drug or not
Endpoint: when the virus is cleared/undetectable

19
Q

Describe the mechanism of antiviral drug resistance for 2 different viruses and the specific antivirals affected

A

HSV- change their active site structure so the drug cannot bind to active sites

Influenze- always changing its coat proteins so drug cannot bind

20
Q

What is meant by a low genetic barrier to resistance?

A

A high genetic barrier means that the virus has to acquire many mutations to avoid being suppressed
A low genetic barrier means that it only needs to acquire a few mutations to keep multiplying
i.e. viruses with a LOW genetic barrier to resistance require fewer critical mutations to render treatment ineffective

21
Q

What is meant by an “unfit” virus?

A

A virus that has mutated to become drug resistant but in doing so has become less virulent and therefore no longer really causes disease as it is replicating at such a low rate

22
Q

What is an antibacterial drug?

A

A chemical substance that inhibit the growth of bacteria at a discrete target site

23
Q

For what two reasons can we use antibiotics?

A

Prevention of infection- prophylaxis

Therapy of significant bacterial infection- treatment

24
Q

In what situations might we use antibiotics prophylactically?

A

Peri-operatively: prevent surgical site infections
Short-term: meningitis contact
Long-term: asplenia, transplant patients

25
Q

In what situations might we use antibiotics prophylactically?

A

Peri-operatively: prevent surgical site infections
Short-term: meningitis contact
Long-term: asplenia, transplant patients

26
Q

What does the term clinically significant mean in the following sentence?
“Antibiotics can be used in the therapy of a clinically significant bacterial infection”

A

It means an infection that, if left untreated, will cause death and permanent harm or medium to long term disability

27
Q

How can we improve on the empirical use of antibiotics in a way that doesn’t just involved following the local antibiotic formulary?

A

Use the thoughtful method:
What is the likely cause of the infection?
Which abc are likely to be effective?
Which one would be the best choice?

28
Q

What kind of features of a patients history might give some idea of the likely organism causing their infection?

A 
Site 
Duration 
PMH 
Occupational history 
Travel history 
Age 
Time of year 
Anatomical site
29
Q

What kind of things might give some idea of themes likely antibiotics to be effective against the patients infection?

A

Severity of the infection
Is it community or healthcare acquired?
Immune status of patient
Baseline rate of resistance

30
Q

What kind of things might give some idea of the best choice of antibiotic for a specific scenario?

A 
Safety: 
-organ function 
-allergy
-pregnancy
-age 
-DDRs 
Route of administration 
Cost 
Efficacy
31
Q

Like some adverse effects of antibiotics

A

Toxicities- pharmacological, immunological, idiosyncratic(rare and unpredictable)
Allergic reactions

32
Q

How can we measure susceptibility of bacteria to antivirals?

A

Disc sensitivity testing

E-test for minimal inhibitory concentration

33
Q

What is the minimum inhibitory concentration (MIC) of an antibiotic?

A

The minimum concentration of antibiotic required to inhibit growth of a bacterium in vitro

34
Q

Explain what is meant by time dependent killing?

A

When successful treatment of infection requires prolonged antibiotic presence at the site of infection, but NOT high concentrations

35
Q

Explain what is meant by concentration dependent killing?

A

When successful treatment requires high concentration of antibiotic at the site on infection, but NOT for long

36
Q

How can we measure time dependent killing?

A

% of time that free drug concentration is greater than MIC

37
Q

How can we measure concentration dependent killing?

A

A ratio of maximum drug concentration to MIC

38
Q

What are the two stages for the genetic basis of antibiotic resistance?

A

Chromosomal gene mutation

Horizontal gene transfer

39
Q

What is the definition of a MDR organism?

A

Multi-drug resistant

Non-susceptibilty to at least one agent in three or more antimicrobial categories

40
Q

What is the definition of a XDR organism?

A

Extensively drug resistant

Non-susceptibility to at least one agent in all but two or fewer antimicrobial categories

41
Q

What is the definition of a PDR organism?

A

Pan-drug resistant

Non-susceptibilty to all agents in all antimicrobial categories

42
Q

What are the three intervention types of antimicrobial stewardship?
Give some examples of each

A

Persuasive - education, audit, feedback
Restrictive - formulary restriction. automatic stop orders
Structural - computerised records, rapid lab tests

Clinical Pharmacology, Therapeutics & Principles of Prescribing (22 decks)

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