Pharmacology S5 Flashcards
Infections treated with antiviral agents
DNA viruses
– Herpes simplex I
– Herpes simplex II
– Varicella-zoster
– Cytomegalovirus
– Epstein Barr Virus
– Human Herpes-virus 8
Hepatitis B
Infections treated with antiviral agents
RNA viruses
Influenza
– Human Immunodeficiency Virus
– Hepatitis C
Amantadanes: M2 ion channel inhibitors
Give E
Amantadine and Rimantadine
Amantadanes mechanism of action
M2 ion channel blocker
Tricyclic primary amines block M2 channel to inhibit viral uncoating Active against influenza A including non-human subtypes
M2 inhibitors reduce symptoms but have clinical limitations
Spectrum: influenza A only
Side effects: Central Nervous System Renal excretion (amantadine)
Single point mutation in M2 gene: S31N
– High-level, rapid emergence resistance
– Transmissible
– H5N1 isolates 2003-present: resistant
– H3N2 (>60% Asia 2003-4, >90% US 2005-6)
Novel antiviral target: neuraminidase
Features
Human and non-human influenza A
– Influenza B
– M2 resistant viruses
– Avian strains including H5N1
– Reconstructed 1918 pandemic H1N1
Time to treatment benefit of neuraminidase
Patients aged 12-70 yrs
– within 48 h of sudden onset of symptoms
Oseltamivir 75 mg bd for 5 days
neuraminidase drugs give E
Oseltamivir
Zanamavir
Pharmacokinetics of oseltamivir
Zanamivir
Zanamavir
Oseltamivir
– low bioavailability
– dry powder aerosol
– Remains detectable in sputum up to 24 hours post dosing
– Renally excreted
Oseltamivir
– Prodrug
– 80% bioavailability
Influenza virus life cycle
Absorption Endocytosis Endosomal vesicle Viral uncoating RNA replication New RNA Assembly Budding
Adverse events of neuramindase inhibitor
– Vomiting (15.0% vs 9.3%);
– abdominal pain (4.7% vs 3.9%)
– epistaxis (3.1% vs 2.5%)
Chloramphenicol inhibit protein synthesis by which mechanism
Binds to 50 S portion and inhibits formation of peptide bond
Erythromycin inhibit protein synthesis by which mechanism
Binds to 50S portion prevents translocation - movement of ribosome along mRNA
Tetracyclines inhibit protein synthesis by which mechanism
Interfere with attachment of tRNA to mRNA - ribosome complex
Streptomycin inhibit protein synthesis by which mechanism
Change shape of 30 S portion causes code on mRNA to read incorrectly
The two reasons for antibiotics
Prophylaxis of bacterial infections
Therapy of significant bacterial
infections
What is the likely cause of infection?
Duration of illness
Likely organism
Anatomical site
Personal background
Past medical history
Occupational history
Travel history
Age
Time of year
Which antibiotic is the best choice? (safety)
Age
Toxicity
Efficacy
Cost
Safety
Drug interactions
Administration route
Allergies
Organ function
Pregnancy, breast feeding
Antibiotic adverse events
Toxicities
• Allergic reactions
• Idiosyncratic reactions
Antibiotic associated diarrhea
Pharmacodynamics
- Time dependent killing
- Concentration dependent killing
Time dependent killing
• Concentration dependent killing
– Succesful treatment requires prolonged antibiotic presence at site of infection
– But not high concentration
– Succesful treatment requires high antibiotic concentration at site of infection
– But not for long
Chloramphenicol inhibit protein synthesis by which mechanism
Binds to 50 S portion and inhibits formation of peptide bond
Erythromycin inhibit protein synthesis by which mechanism
Binds to 50S portion prevents translocation - movement of ribosome along mRNA
Tetracyclines inhibit protein synthesis by which mechanism
Interfere with attachment of tRNA to mRNA - ribosome complex
Streptomycin inhibit protein synthesis by which mechanism
Change shape of 30 S portion causes code on mRNA to read incorrectly
