Antiviral and Antifungal Agents Flashcards
Name 3 types of antifungal drugs
- Nystatin
- Amphotericin B
- Azole agents
Name 3 azole agents
- Fluconazole
- Miconazole
- Ketoconazole
What are 2 main features of antifungal agent treatments?
- Tend to use topically as most fungal infections tend to be superficial
- Only if infection resistant or patient is systemically unwell or immunocompromised is systemic drug used
What are 2 superficial fungal infections?
- Oral candida
2. Tinea
What are 2 fungal infections treated with systemic antifungal agents?
- Aspergillosis
2. Systemic candidiasis
Give an overview of amphotericin
- Polyene macrolide
- Poorly absorbed from GIT so given IV
- Amphiphile
- Nearly insoluble in water so given as colloid solution of liposomal delivery
What are the 3 steps of amphotericin’s mode of action?
- Binds to ergosterol in fungal cell membrane
- Forms a pore in the fungal cell wall
- Allows leakage of ions and macromolecules leading to cell death
Why does amphotericin avoid host cells?
Host cells have cholesterol in their membranes, as opposed to ergosterol, which amphotericin tends not to interact with
What are 4 immediate reactions to amphotericin?
- Fever
- Chills
- Headache
- Vomiting
Describe 3 ways in which immediate reactions to amphotericin can be reduced
- Give test dose to ensure patient can tolerate drug
- Anti-pyretics (reduce fever) and anti-histamines (reduce immune response)
- Slow infusion
What are 4 adverse effects of amphotericin due to gradual toxicity?
- Nephrotoxicity
- Hypokalaemia
- Abnormal LFTs
- Anaemia
What does LFT stand for?
Liver function test
Give an overview of nystatin
- Polyene macrolide
- Too toxic for systemic use
- No absorption from skin or mucous membranes
What is the dental use of nystatin?
Local treatment for mouth infections with candida albicans
Name 4 oral diseases with candida albicans
- Thrush
- Denture stomatitis
- Antibiotic induced stomatitis
- Some forms of mucocutaneous candidiasis
How do triazole agents tend to act as antifungal agents?
- Inhibit ergosterol synthesis by inhibiting fungal cytochrome P450 3A enzyme
- Depletion of ergosterol in membrane inhibits membrane-associated enzyme activity
- Prevents replication and hyphae transformation
Describe the ADME of fluconazole
- Absorbed well orally and available IV
- Good tissue and fluid penetration
- T½ = 25 hours
- 90% excreted through urine
What are 2 major considerations when using fluconazole?
- Caution with kidney function as mostly excreted through urine
- Careful if patient is taking drug processed by cytochrome P450 (warfarin) as drug levels will rise
Name 5 adverse effects of fluconazole
- Nausea
- Headache
- Abdominal pain
- Hepatitis *
- Stevens-Johnson syndrome *
(* rare symptoms)
What azole tends to be used as a first line treatment before fluconazole?
Miconazole
What are the 2 dental uses of triazole agents?
- Systemic fungal infections
2. Local candidiasis not resolved by nystatin
What are 4 types of herpesviruses?
- Herpes simplex
- Varicella zoster
- Epstein-Barr virus
- Cytomegalovirus
What drug is used to treat herpesviruses?
Aciclovir (famciclovir)
Give an overview how aciclovir inhibits herpesvirus infection
- Nucleoside analogue (guanosine)
- Inhibits viral DNA synthesis
- 2 point selective toxicity
What are the points of selective toxicity of aciclovir?
- Viral thymidine kinase
2. Viral DNA polymerase
How does aciclovir inhibit viral replication by viral thymidine kinase?
- Viral kinase tries to phosphorylate guanine for DNA replication
- Aciclovir is a guanine analogue
- Aciclovir occupies the receptors on guanine so prevent viral DNA replication
How does aciclovir inhibit viral replication by viral DNA polymerase?
- Aciclovir goes into cell and is monophosphorylated by viral kinase (does not happen if healthy cell as viral kinase not present)
- Host kinase adds 2 more phosphate molecules to form aciclovir triphosphate
- Aciclovir triphosphate adds 2 phosphate groups to viral DNA polymerase to inhibit the enzyme
Describe the 6 steps of the life cycle of an animal virus
- Viral entry and uncoating
- Reverse transcription
- Integrase
- Nucleic acid synthesis
- Post translational processing
- Budding and spread of new virions
How does resistance occur to aciclovir?
Deficient thymidine kinase activity
What are 4 adverse effects of aciclovir?
- Nausea
- Headache
- Nephrotoxicity
- Reduce doses in renal impairment
Describe famciclovir as an alternative to aciclovir
- Pro-drug of penciclovir
- Achieves higher cell concentration and prolonged effect
- Taken less times per day so better compliance
- More expensive
Describe remdesivir as an antiviral drug
- Pro-drug converted intracellularly to a nucleoside analogue
- Fake AMP converted to ADP and prevents RNA polymerase from reproducing
What are 2 ways to fight influenza viruses?
- Vaccination
2. Oseltamivir
Describe oseltamivir as an antiviral drug
- Inhibits neuraminidase glycoprotein used in viral budding
- Pro-drug activated by liver on 1st pass
Name 3 adverse effects of oseltamivir
- Nausea
- GI upset
- Headache
