Anti virals, microbials and fungals Flashcards
Give 4 types of anti herpes drugs
aciclovir, gangciclovir, foscarnet, cidofovir
How do aciclovir, gangciclovir, foscarnet and cidofovir work?
All inhibit viral DNA polymerase, most by acting as guanosine analogue, except forscarnet which acts as a pyrophosphate analogue
Which virus is aciclovir used to treat?
HSV1 and 2 and VZV
How can you get resistance to aciclovir?
reduction/ removal of the TK enzyme which activates aciclovir
Give 3 ADRs of aciclovir and gangciclovir?
- nephrotoxic
- headache, confusion, behaviour change, psychosis, seizures, coma
Describe the order of drugs used to treat CMV
gangciclovir, then foscarnet, then cidofovir
Describe how resistance can arise to gangciclovir, foscarnet and cidofovir
foscarnet= resistance can arise from RT or polymerase mutations but are rare
Cidofovir and gangciclovir= DNA polymerase mutations (esp UL54)
What can cidofovir be used to treat?
CMV, adenovirus, EBV, polymavirus etc
Give 3 ADRs of cidofovir and foscarnet
- nephrotoxic
- myelosurpression
- CNS effects (headache, n+v, coma, seizures etc)
- diarrhoea
- fever
- anxiety
- fatigue
How is hepatitis B treated?
Lamivudine, adefovir, entacavir
How does lamivudine work?
Cystidine analogue- false substrate and chain terminator of reverse transcriptase enzyme.
Give an ADR of lamivudine
raised LFTs, otherwise well tolerated
Give one drug which may be used for treatment of hep C?
Ribavirin, also interferons. Sofosburvir is new drug with good data.
How does sofosbuvir work?
Inhibits HCV polymerase to inhibit replication of virus
How does ribavirin work?
Guanosine analongue, so inhibits RNA/mRNA synthesis and nucleoside stores
Name 2 antivirals to treat influenza
oseltamivir, zanamivir. Note: these can be used a prophylaxis, are not that effective and yearly vaccines are the preffered approach
How do oseltamivir (tamiflu) and zanamivir work?
inhibit neuraminidase, which prevents newly made virus leaving the host cell
How does resistance to anti- influenza drugs occur?
neuraminidase enzyme mutations,
Give 4 classes of drugs to treat HIV
- NRTIs (nucleoside RT inhibitors causing chain termination- lamivudine)
- NNRTIs (direct (non- nucleoside) RT inhibitors - neviapine)
- protease inhibitors (neviapine)
- fusion inhibitors (enfurvirtide)
- Integrase inhibitors
- CD4 receptor inhibitors
Give 2 ADRs of NRTIs such as zidovudine (AZT)
- hyperlactataemia
- lactic acidosis
- hepatomegaly
- steatosis
Why is anti- viral resistance monitoring important?
- optimises clinical outcomes and care of the pt
- reduce costs and ADRs of using ineffective therapy
- reducing spread of resistant viruses
When is viral resistance testing done?
when the treatment is not working, need to see if due to resistance, poor compliance or high baseline of viral load
how is viral resistance testing done?
By phenotype- intubate virus with varying concentrations of the drug and culture to see if virus can grow
By genotype- gene sequencing, PCR etc
What is an unfit virus? When do they often occur
A virus which has mutated to become resistant to an antiviral, but as a result has become less effective at replicating. The drug which the virus is resistant to is still given as it keeps replicating power of the virus low. This is common in lamivudine
When may anti- biotics be given for prophylaxis?
before surgery, meningitis contact, asplenia, immuno deficiency
What factors are taken into consideration when giving empirical antibiotics?
- likely organism (age, date, PMH, occupation, travel, duration and site of infection)
- likely susceptibility and consequences of wrong choice
- safety (age, allergies, interactions, toxcicity, cost, administration, pregnancy)
Give 3 general ADRs of anti- biotics?
- N+ V
- Most are neuro, nephro and hepatotoxic
- many may cause idiosyncratic reactions (dunno cause/ how it happens)
- ecological effects on microbiota (C. diff)
- drug interactions
How does vancomycin work? When is it used?
inhibits cell wall synthesis via phospholipids and peptidoglycan inhibition at a site earlier than penicillins . it is generally reserved for mutli drug resistant organisms (mainly gram+)
Which anti- microbials are most likely to cause C. diff?
- cephalosporins
- co- amoxiclav
- clindamycin
- fluoroquinolones
Give one ADR specific to tetracyline?
turns teeth yellow if given to children
Which drug would be given to treat cellulitis?
Flucoxacillin
What drug should be used to treat c. diff?
Metronidazole
What drug should be used to treat UTIs?
Trimethoprim or nitrofurantion
What drug should be used to treat neisseria meningitisis?
ceftriaxone
What drug should be used to treat gram + sepsis?
vancomycin
What drug should be used to treat uncomplicated community acquired pneumonia?
amoxicillin or doxycylin
What drug should be used to treat complicated community acquired pneumonia?
macrolides or tetracyline
What drug should be used to treat hospital acquired pneumonia?
co- amoxiclav
What drug should be used to treat severe, bacterial gastroenteritis (campylobacter, enterotoxic E. coli, shigella dysenteriae)
ciprofloxacin (if used in salmonella, may make you worse)
What drugs should be used severe giardia, entamoeba, cyclospora and cyptosporidium infections?
Giardia and entamoeba= metronidazole
Cyclospora= trimethoprim
cyptosporisium= nitazoxanide
How are trachomatis vaginalis, thrush and bacterial vaginosis treated?
TV and BV= metronidazole
thrush= fluconazole
How is syphilis treated?
IM benzathine penicillin G
How is gonorrhoea treated?
IM ceftriaxone and oral azithromycin
How is chlamydia trachomatis treated?
doxycycline
How is pyelonephritis treated?
trimethoprim, not nitrofurantoin as not systemic
What is the minimum inhibitory concentration?
The minimum concentration of antibiotics needed to inhibit growth of a bacteria in vitro to a specific single isolate and antibiotic
What is the difference between time and concentration dependant killing?
One theory is that successful treatment needs prolonged antibiotic prescence at a infection, but concentration doesnt matter as long as >MIC
Conc dependant killing is that time doesnt matter as much as concentration
How does carbapenem resistance occur?
- decreased permeability
- increased efflux
- carbepenemase production
State the 3 categories of antimicrobial stewardship and for each give an example
- persuasive: education, consensus, opinion leaders, reminders, audit, feedback
- restrictive: formulary restriction, automatic stop orders
- structural: computerised records, rapid lab tests, expert systems, quality monitoring
What 4 drugs are needed to treat TB?
- rifampicin (6 months)
- isoniazid (6 months)
- pyrazinamide (2 months)
- ethambutol (2 months)
Give 4 ADRs for drugs to treat TB?
- all hepatotoxic
- many nephrotoxic
- GI upset
- psychosis
- epilepsy
- anaphylaxis
- optic neuritis, colourblindness (ethambutol)
