32 - Anti-Viral Drugs Flashcards
Outline the structure of viruses
All viruses contain genetic material that can be DNA or RNA
Have a protein shell which encapsulates the genetic material
Some viruses have a lipid envelope which has envelope proteins
When do you treat Viral Hepatitis B and C?
Only chronic infection requires treatment
Some forms of Hepatitis (e.g. A) don’t need drugs and clear up on their own
Hep B doesn’t have a cure
Hep C can be cured
What is the tropism of viral hepatitis?
Liver hepatocytes
What is used to treat Viral Hepatitis B?
TENOFOVIR
- nucleotide analogue
- reverse transcriptase
- given sometimes with Peginterferon alfa
- don’t progress onto cirrhosis
- it is an anti-retroviral which is important because people often get co-infected with Hep and HIV
There is now a vaccine for Hepatitis B
Hep B is a DNA virus
What is used to treat Viral Hepatitis C?
RIBAVARIN & PEGINTERFERON ALFA
- Ribavarin is a nuceloside analogue
- prevents viral RNA synthesis
BOCEPREVIR
- protease inhibitor
- the protease normally cleaves part of the virus to allow it to infect but it is inhibited with this drug
- most effective against Hep C genotype 1
- completely cures Hep C within three months
Hep C is an RNA virus
Hep C can be cured
What is the goal of HCV treatment today?
Hepatitis C
The goal of HCV treatment today is to cure the virus
Combination of drugs
What do the specific drugs and duration of HCV treatment depend on?
VIRAL HEPATITIS C (HCV) TREATMENT DEPENDS ON:
- HCV genotype (genetic structure of the virus)
- viral load
- past treatment experience
- degree of liver damage
- ability to tolerate the prescribed treatment
- need for liver transplant
Outline the effect of direct acting antivirals (DAA) on the hepatitis C virus genome
Outline the HIV life cycle
HIV - chronic viral infection
1. ATTACHMENT AND ENTRY
- Viral membrane proteins interact with leukocyte membrane receptors
- Viral capsid endocytosis
2. REPLICATION AND INTEGRATION
- Within cytoplasm - reverse transcriptase enzyme converts viral RNA into DNA
- DNA transported into nucleus of human cell and integrated into host DNA (integrase)
3. ASSEMBLY AND RELEASE
- Host cell’s ‘machinery’ utilised to produce viral RNA and essential proteins
- Virus is assmebled within cell
- Mature virion is released
Describe the process of HIV entry as well as inhibitors of this process
1. ATTACHMENT AND ENTRY
- HIV Glycoprotein (GP)120 attaches to CD4 receptor
- GP120 also binds to either CCR5 or CXCR4
- GP41 penetrates host cell membrane
- Viral capsid enters
Enfuvirtide = attachment inhibitor
- Binds to HIV GP41 transmembrane glycoprotein
- HIV can’t attach to the receptor of the cell
- Administered subcutaneously twice a day
- Not used a lot in clinical practice due to its route of administration
Maraviroc
- Blocks CCR5 chemokine receptor
- CCR5 is the co-receptor for HIV
- HIV can’t bind to CCR5 with this drug
- About 5% of people don’t have CCR5
- Has a lot of side-effects so not used a lot in clinical practice
Outline the process of HIV replication as well as inhibitors of this process
2. REPLICATION
- Reverse transcription
- Viral single-stranded RNA
- Becomes double stranded DNA by reverse transcriptase
Mimic endogenous dexoynucleotide/side and block viral replication
If they are given alone, then the viruses quickly develop resistance. Therefore, HIV patients have 2-3 drugs prescribed
Nucleoside RT Inhibitors
- Activated by 3 step phosphorylation process
- e.g. Zidovudine
- First drug that was used to treat HIV
Nucleotide RT Inhibitors
- Fewer phosphorylation steps required
- e.g. Tenofovir
Non-Nucleoside RT Inhibitors
- No phosphorylation required
- Not incorporated into viral DNA
- e.g. Efavirenz
Outline the process of HIV Integration as well as inhibitors of this process
3. INTEGRATION
- DNA integration
- Viral integrase inserts viral DNA into host DNA
Integrase Inhibitors
- Raltegravir
- First of three licensed integrase inhibitors
- Well tolerated
Outline the process of HIV assembly and release as well as inhibitors of this process
4. ASSEMBLY AND RELEASE
- Gag prevursor - encodes all viral structural proteins
- HIV protease cleaves Gag precursor protein
Protease Inhibitors (PI)
- Saquinavir - 1st generation PI
- Low dose Ritonavir reduces PI metabolism - co-administered as ‘booster’
- Not pharmacologically great drugs because they are substrates of CYP450 at the level of first pass metabolism
- Must be administered with a booster as a result of this
- Victims of many drug-drug interactions (problem with patients on polypharmacy)
Describe the virology of the Herpes Simplex Virus (HSV)
Double-stranded DNA
Surrounded by tegument
Enclosed in a lipid bilayer
Outline the tropism of the Herpes Simplex Virus
HSV-1
- Cold-sores
HSV-2
- Genital herpes
Outline the virology of influenza
Multipartite single-stranded RNA virus
Envelope protein which has proteins on it
- one of these proteins is neuraminidase
- this protein allows the virus to be released by the cell and infect other cells
