PS01 - Antiviral Agents Flashcards
What are the six stages of viral replication?
Attachment Entry Uncoating Macromolecular Synthesis Assembly Release
What is the MoA of Aciclovir?
Aciclovir is an analogue of Deoxyguanosine, but without a 3’ hydroxyl group
Both a 5’ and a 3’ hydroxyl group are required for the replication of DNA
Without the 3’ group DNA synthesis comes to a halt
How is Aciclovir selectively toxic?
Aciclovir has to be triphosphorylated to have its DNA chain termination effect
The initial phosphorylation is performed by HSV-TK (thymidine kinase)
HSV-TK is present in viral cells but not eukaryotic cells
What determines the cellular uptake of Aciclovir into specifically viral cells?
Diffusion down a concentration gradient
What three factors determine the selective toxicity of Aciclovir?
Only active in viral cells (HSV-TK)
Concentrated in viral cells
Higher affinity for viral DNA polymerase
Describe the spectrum of activity of Aciclovir
Narrow, only targets HSV1/2 and VZV
Only these families possess HSV-TK
How does resistance to Aciclovir arise?
Absence of Thymidine Kinase (TK-ve)
Alteration of Thymidine Kinase
Exist pretreatment, appear during therapy
Alteration of DNA polymerase
Why is Aciclovir resistance due to TK absence not a clinical issue?
Because the absence of HSV-TK renders the variants non-pathogenic
Alteration strains are also attenuated
What Aciclovir resistance mechanism is clinically important?
Alteration of DNA polymerase, strain is fully virulent
In what population is Aciclovir resistance a huge clinical problem?
AIDS patients suffering from repeated HZV infections
What is Valaciclovir?
A variant of aciclovir joined to a valine ester
What is the key property of Valaciclovir?
Valaciclovir has a much higher oral bioavailability than aciclovir
What is Penciclovir?
An antiviral agent which acts as a viral DNA polymerase inhibitor but is not a chain terminator
How does primary oral herpes present?
Painful, white lesions on the tongue and soft/hard palate
Where does herpes virus lie dormant?
Trigeminal ganglion
How does recurrent oral herpes present?
Cold sores
In what situation is treatment of oral herpes clinically justifiable?
Treatment of primary oral herpes ONLY
How does primary genital herpes present?
Painful, white lesions on the genitalia
How does recurrent genital herpes present?
Fewer, less painful lesions
In what situation is treatment of genital herpes clinically justifiable?
Treatment of primary genital herpes
Prophylaxis for frequent, severe, atypical genital HSV
How is treatment of atypical recurrent genital herpes managed?
Long term therapy
Titration of dose down to eventual cessation
What is herpes simplex encephalitis?
Inflammation of the cerebral hemispheres due to infection with HSV
How is herpes simplex encephalitis treated?
Immediate administration of i.v. aciclovir
What other forms of HSV can be treated with Aciclovir?
Ocular herpes simplex
Eczema herpeticum