Antivirals and Antimicrobials Flashcards
Are antivirals virostatic or virucidal?
What does this mean?
Virostatic
They do not “kill” viruses, they stop the replication of new viruses
At which stages can viral replication be inhibited in order to elicit anti-viral effects?
Attachment Uncoating RNA/DNA replication Protein synthesis Assembly Release
Give some examples of the down-sides of inhibiting viral replication in order to treat patients.
Interfere with host-cell metabolism
Ineffective against latent or non-replicating infections
Rebound effects when the drug is stopped
Drug resistance may develop
How can the hosts immune system be improved clinically to aid the outcome of their viral infection?
Replace host immunity that is compromised e.g. immunoglobulins
Enhance host immunity e.g. interferons
What is immunoglobulin therapy?
When might this be used clinically?
Pooled human sera from blood donors which contains preformed antibodies
Used post-exposure (ideally within 72 hours)
Give some examples of drugs used to treat HSV infections
Aciclovir (oral, IV)
Ganciclovir (IV, intravitreal)
Valganciclovir (oral, prodrug)
Penciclovir (topical, IV)
What is the mechanism of action of aciclovir?
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
What is the mechanism of action of guanosine nucleoside analogues such as ganciclovir and valganciclovir?
They inhibit viral DNA polymerase
This slows down and terminates viral DNA elongation
Give an example of a drug used to treat Hepatitis B
What is it’s mechanism of action?
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
Give an example of a drug used to treat Hepatitis C
What is it’s mechanism of action?
Ribavirin (oral, IV)
Inhibits RNA/DNA viruses by altering nucleotide stores
How can interferons be used to aid antiviral therapy?
How are they administered?
They are potent cytokines
Stimulate proteins to enhance the body’s defence against viral infection
IM injection
List some anti-influenza drugs are their mechanism of action
Oseltamivir (tamiflu)
Zanamivir
Both are reversible inhibitors of neuroaminidase
List some broad types of anti-retroviral (HIV) drugs
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
Antiviral drug resistance testing is available for which viruses?
HIV Hep B CMV Influenze HSV VZV
Why might we want to perform antiviral drug resistance testing?
To optimise clinical outcomes
To save costs and adverse effects
Reduce the resistant virus pool
When is antiviral drug resistance testing performed?
When there is evidence of therapeutic failure
- poor adherence/compliance
- resistant virus
- patient unable to tolerate side effects
- baseline check
How is antiviral drug resistance testing performed?
Incubate the specific virus in a culture system with varying concentrations of drug
Sequence and genotyping for the commonly seen resistant viruses
What is the role of viral load testing in antiviral therapy?
How is it used to define treatment endpoints?
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
Describe the mechanism of antiviral drug resistance for 2 different viruses and the specific antivirals affected
HSV- change their active site structure so the drug cannot bind to active sites
Influenze- always changing its coat proteins so drug cannot bind
What is meant by a low genetic barrier to resistance?
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
What is meant by an “unfit” virus?
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
What is an antibacterial drug?
A chemical substance that inhibit the growth of bacteria at a discrete target site
For what two reasons can we use antibiotics?
Prevention of infection- prophylaxis
Therapy of significant bacterial infection- treatment
In what situations might we use antibiotics prophylactically?
Peri-operatively: prevent surgical site infections
Short-term: meningitis contact
Long-term: asplenia, transplant patients
In what situations might we use antibiotics prophylactically?
Peri-operatively: prevent surgical site infections
Short-term: meningitis contact
Long-term: asplenia, transplant patients
What does the term clinically significant mean in the following sentence?
“Antibiotics can be used in the therapy of a clinically significant bacterial infection”
It means an infection that, if left untreated, will cause death and permanent harm or medium to long term disability
How can we improve on the empirical use of antibiotics in a way that doesn’t just involved following the local antibiotic formulary?
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?
What kind of features of a patients history might give some idea of the likely organism causing their infection?
Site Duration PMH Occupational history Travel history Age Time of year Anatomical site
What kind of things might give some idea of themes likely antibiotics to be effective against the patients infection?
Severity of the infection
Is it community or healthcare acquired?
Immune status of patient
Baseline rate of resistance
What kind of things might give some idea of the best choice of antibiotic for a specific scenario?
Safety: -organ function -allergy -pregnancy -age -DDRs Route of administration Cost Efficacy
Like some adverse effects of antibiotics
Toxicities- pharmacological, immunological, idiosyncratic(rare and unpredictable)
Allergic reactions
How can we measure susceptibility of bacteria to antivirals?
Disc sensitivity testing
E-test for minimal inhibitory concentration
What is the minimum inhibitory concentration (MIC) of an antibiotic?
The minimum concentration of antibiotic required to inhibit growth of a bacterium in vitro
Explain what is meant by time dependent killing?
When successful treatment of infection requires prolonged antibiotic presence at the site of infection, but NOT high concentrations
Explain what is meant by concentration dependent killing?
When successful treatment requires high concentration of antibiotic at the site on infection, but NOT for long
How can we measure time dependent killing?
% of time that free drug concentration is greater than MIC
How can we measure concentration dependent killing?
A ratio of maximum drug concentration to MIC
What are the two stages for the genetic basis of antibiotic resistance?
Chromosomal gene mutation
Horizontal gene transfer
What is the definition of a MDR organism?
Multi-drug resistant
Non-susceptibilty to at least one agent in three or more antimicrobial categories
What is the definition of a XDR organism?
Extensively drug resistant
Non-susceptibility to at least one agent in all but two or fewer antimicrobial categories
What is the definition of a PDR organism?
Pan-drug resistant
Non-susceptibilty to all agents in all antimicrobial categories
What are the three intervention types of antimicrobial stewardship?
Give some examples of each
Persuasive - education, audit, feedback
Restrictive - formulary restriction. automatic stop orders
Structural - computerised records, rapid lab tests
