Antimicrobial Chemotherapy 2 Flashcards
What can fungi be divided into
Yeasts Filamentous fungi (moulds)
What can be used to treat fungi
Anti-fungal drugs
What are the categories of anti-fungal drugs
Polyenes
Azoles
Allylamines
Echinocandins
What is the mechanism of action for polyenes
They bind to ergosterol that is present in the fungal cell wall but not in the bacterial cell wall
This results in an increase in the permeability of the cell wall
What are polyene drugs active against
Yeasts
Filamentous fungi
What is a disadvantage of polyene drugs
They bind to other sterols (e.g. cholesterol) in mammalian cell membranes and this is the reason for their toxicity
Which polyene can be used intravenously and what is it used for
Amphotericin B
Used for serious systemic fungal infection
Describe amphotericin B
It is exteremely toxic and has a wide range of side effects (e.g. renal, hepatic and cardiac toxicity)
The lipid complexed formulations of this drug offer a reduced incidence of such side effects
What is nystatin
A polyene drug available for topical use only
What do azoles do
Inhibit ergosterol synthesis
Name some azoles
Old: Miconazole Ketoconazole Newer: Fluconazole Voriconazole Itraconazole
Describe fluconazole
Used for oral and parenteral treatment of yeast infections
Has no serious toxicity problems
Resistance among some Candida species is emerging
Resistance can emerge during treatment
Describe itraconazole
Active against both yeasts and filamentous fungi, including Aspergillus spp. and dermatophytes.
What does voriconazole treat
Aspergillosis
Describe the mechanism of action for allylamines
They suppress ergosterol synthesis but act at a different stage of the synthetic pathway from azoles
Name an allylamine
Terbinafine (only one in common use)
What are allylamines active against
Dermatophyte infections of the skin
(e.g. ringworm, athlete’s foot) and nails (onychomycosis)
Mild infections will be treated topically and more serious infections
(including onychomycosis) orally
Describe the mechanism of action for echinocandins
They inhibit the synthesis of glucan polysaccharide in several types of fungi
They are fungicidal against the Candida species and inhibit the growth of several Aspergillus species
Name some echinocandins
Micafungin
Caspofungin
Anidulafungin
What does virustatic agents
Those that inhibit growth and/or replication
What are virucidal agents
Those that will kill the virus
Are anti-viral drugs virucidal or virustatic
Virustatic
How do anti-viral drugs tend to work
Many are nucleoside analogues which
interfere with nucleic acid synthesis
How can the treatment of herpes be effective
If started early
Will not erdicate any of the viruses
What do anti-herpes virus drugs treat
Herpes simplex virus
Cytomegalovirus
Varicella-zoster virus
Epstein-Barr virus
What is aciclovir
An anti-herpes virus drug
A nucleoside analogue
What is aciclovir active against
Herpes Simplex
Varicella Zoster
What must occur for aciclovir to become active
Be converted into its active form by an enzyme (thymidine kinase) coded for by the virus genome
What is an advantage of aciclovir
It’s specific for virus-infected cells and
has very low toxicity for uninfected host cells
When is the IV and oral forms of aciclovir used
IV: treats severe infections (e.g. herpes encephalitis and VZV pneumonitis)
Oral: cold sores (caused by HSV reactivation)
Name some anti-herpes virus drugs (at least 3)
Valaciclovir Famciclovir Valganciclovir Foscarnet Ganciclovir Cidofovir
Describe valaciclovir
and famciclovir
Oral agents related to aciclovir
They can treat HSV and shingles
What is foscarnet used for
HSV, VZV and CMV infections
Highly nephrotoxic
Only given through IV
Describe ganciclovir
Active against CMV
Toxic and given by IV infusion
Use is largely restricted to treating life or sight threatening infections in the immunocompromised
(e.g. AIDS, transplant recipients)
What is valganciclovir
Pro-drug of ganciclovir
Oral alternative for some CMV situations
Bone marrow toxicity so close blood count monitoring required
When is cidofovir used
For CMV retinitis
when other anti-viral drugs are inappropriate
What is zidovudine
First Treatment for HIV (1987)
A nucleoside analogue which interferes with the action of reverse transcriptase.
It is virustatic
What can zidovudine cause
Anaemia and neutropaenia
How is a HIV patients response to treatment monitored
Their viral load and CD4+ cell count
How is chronic hepatitis B and C treated
With pegylated interferon-a
Hep C also uses oral ribavirin
What has limited the use of pegylated interferon-a
Its low response rate, serious side effects and
the high cost of treatment
What can be used for the treatment of influenza A and B
Zanamivir and Oseltamivir
What can be used for the treatment of severe respiratory syncytial virus
Ribavirin is occasionally used
It must be inhaled as a fine spray to reach the site of infection in the lungs as administration is difficult
What is genotypic analysis
Helps in choosing rational treatment in selected patients
(e.g. in HIV infection, where the viral load is rising
despite adherence to treatment, or for HSV, VZV or CMV
not responding clinically to apparently adequate dosage).
When is drug monitoring used
To ensure therapeutic,
but not toxic, serum levels are achieved
For aciclovir, this is usually restricted to patients
with significant renal impairment
