Anti-viral drugs Flashcards
DNA viruses
- HSV, HBV
- genome replication takes place in the cell nucleus
- they are dependent on the host cell’s DNA and RNA synthesizing machinery
RNA viruses
- HCV, influenza virus
- replication usually takes place in the cytoplasm
- use their own enzymes to replicate RNA and create copies of their genomes
RNA retroviruses
- HIV
- integrate the DNA copy of viral RNA produced by reverse transcriptase into the host genome as a provirus
Which type of therapy has a greater clinical effectiveness?
Combination therapy
Viral replication
-steps
- Attachment of the virus to the receptors on the host cell surface
- Entry of the virus through the host cell membrane
- Uncoating of viral nucleic acid
- Synthesis of early regulatory proteins
- Synthesis of new viral RNA or DNA
- Integration into the nuclear genome
- Synthesis of late, structural proteins
- Assembly (maturation) of viral particles)
- Release from the cell
Drugs for herpes
- names
- mechanism of action
Acyclovir
Ganciclovir
Valaciclovir
-inhibits the synthesis of new viral DNA
Acyclovir
- mechanism of action
- pharmacokinetics
- indications
-acts as a competitive substrate for DNA polymerase (inhibits synthesis) and chain termination after its incorporation into viral DNA
- topica, oral, i/v, renal excretion
- herpes simplex virus and varicella zoster virus
- mucocutaneous and genital herpes lesions
- prophylaxis in AIDS and in other immunocompromised patients
- i/v: severe herpes disease
Acyclovir
- effect on which phase of viral replication?
- unwanted effects
- in comparison to Valacyclovir?
- Synthesis of new viral DNA
- nephrotoxicity
- Valacyclovir has a longer duration of action
Gancyclovir
- mechanism of action
- pharmacokinetics
- indications
-same as Acyclovir
- i/v, penetrates well into tissues, renal elimination, oral bio-availability less than 10%
- cytomegalovirus (HSV-5), HSV
-prophylaxis and treatment of cytomegalovirus infections in immunocompromised patients
Gancyclovir
- unwanted effects
- in comparison to Valganciclovir?
- bone marrow depression (neutropenia)
- high oral bio-availability and decrease use of i/v gancilovir in CMV
Drugs for influenza
-names
Amantadine
Rimantadine
Oseltamivir
Zanamivir
Amantadine and Rimantadine
- mechanism of action
- indications
- inhibit an early step in replication of the influenza A (but not influenza B) virus
- prevent uncoating by binding to proton channel
- used for prophylaxis, they have no effect if you are already sick
- can reduce the duration of symptoms if given within 48h after contact
Amantadine and Rimantadine
- effect on which phase of viral replication?
- unwanted effects
- Uncoating of viral nucleic acid
- GI irritation, dizziness, ataxia, slurred speech
Oseltamivir and Zanamivir
- mechanism of action
- pharmacokinetics
- indications
-inhibitors of neuraminidases produced by influenza A and B –> inhibit viral release from the cell
- Oseltamivir: oral, Zanamivir: inhalation
- should be used only if you already have symptoms
- decrease the time to alleviation of influenza symptoms; are more effective if used within 24h after onset of symptoms
- prophylatically decrease incident of influenza
Oseltamivir and Zanamivir
- effect on which phase of viral replication?
- unwanted effects
- release from the cell
- GI symptoms (Oseltamivir)m bronchospasms in asthmatic patients (zanamivir)
Drugs for HBV and HCV
-names
Interferon gama (PEGylated interferon) Ribavarin
Interferon gama (PEGylated interferon) -mechanism of action
- it is a cytokine –> increases formation of antiviral proteins (ribonuclease) –> degrades viral mRNA
- promotes formation of natural killer cells that destroy infected lived cells
Hepatitis C viral infection is treated with…
Protease + Polymerase inhibitors
Interferon gama (PEGylated interferon)
- pharmacokinetics
- indications
- intramuscular or subcutaneous infection, elimination via kidney
- given once weekly
-chronic HCB/HBV - monotherapy or in combinations with ribavarin
Interferon gama (PEGylated interferon)
- unwanted effects
- contraindications
- bone marrow depression
- pregnancy
Ribavirin
- mechanism of action
- effect on which phase of viral replication?
- inhibits virus replication of DNA and RNA viruses
- inhibits guanosine triphosphate formation –> prevents capping of viral mRNA and block RNA dependent RNA polymerases
- Synthesis of new viral RNA or DNA
Ribavirin
- pharmacokinetics
- indications
- oral (avoid antacids), i/v, aerosol, eliminated by the kidney
- used in combination with interferon gamma in chronic HCV infection
Ribavirin
- unwanted effects
- contraindications
- hemolytic anemia, conjunctival and bronchial irritation (aerosol)
- pregnancy
Drugs for HIV
-name
Zidovudine
Current approach to treatment of infection with HIV (4)
- initiation of treatment with 3 or more anti-retroviral drugs
- nucleoside reverse transcriptase inhibitors (NRTIs) together with inhibitors of HIV protease (PIs)
- combinations of at least 3 drugs (2 reverse transcriptase inhibitors + 1 protease inhibitor)
- change to new regimen if plasma viral concentration increases
Zidovudine
-mechanism of action
- Nucleoside Reverse Transcriptase inhibitor
- competitively inhibit binding of natural nucleotides to the binding site of reverse transcriptase
- act as chain terminators via their insertion into the growing DNA chain
- resistance emerges rapidly when are used as single agents
Zidovudine
- effect on which phase of viral replication?
- unwanted effects
- Synthesis of new viral RNA or DNA
- bone marrow suppression
