Antivirals & Antibiotics Flashcards
How are the no. of influenza cases estimated? Why is this important to estimate?
Deaths —> mortality statistics (weekly)
Hospitalised cases
- –> lab reports (weekly)
- –> outbreak reports (ad hoc)
Community cases (seen by GP)
- –> spotter practice data (GPs sending records about incidence directly)
- –> virological surveillance (% of positive samples)
Community cases (not seen by GP):
- –> school data (weekly)
- –> sickness absence data (ad hoc)
- –> community studies (ad hoc)
- –> NHS Direct
Correlation between increased presentation and deaths from influenza, therefore indicates need to produce antiviral agents
Give some examples of complications of influenza. What are some high risk groups?
Complications:
- bronchitis
- pneumonia
- sinusitis
- exacerbation of underlying disease
High risk groups for infection/death:
- elderly & neonates
- diabetes and renal disease
- cardiac and resp. disease
Contrast the different types of influenza virus.
Influenza A:
- multiple host species
- antigenic drift & shift —> resistance develops rapidly
- seasonal epidemics
- pandemic potential
- need for vaccines to prevent infection
Influenza B:
- no animal reservoir
- lower mortality
- seasonal epidemics
Influenza C:
- like the common cold
Outline the sequence of events of viral replication. Where do different antiviral agents act?
- Absorption
- vaccines: haemagglutin antibodies prevent adherence to cell membrane - Endocytosis
- Uncoating
- M2 inhibitors: M2 ion channels pump protons into endosome to allow uncoating (fusion of virus with endosome and breakdown of nucleocapsid) - Synthesis of viral protein/RNA replication
- Assembly
- Budding
- neuraminidase inhibitors - Release
Outline the actions of M2 ion channel inhibitors. Give some examples. When are they indicated? What are some ADRs associated with these?
e.g. amantadine, rimantadine
Block M2 ion channel —> prevent proton pump action —> inhibits viral uncoating
Active against influenza A (inc. non-human subtypes)
ADRs:
- confusion
- insomnia
- hallucinations (esp. in elderly)
- dizziness
- GI disturbance
- hypotension
note: amantadine has greater risk of ADRs than rimantadine
Renal excretion
Rapid resistance to these drugs develops and is transmissable
Outline the actions of neuraminidase inhibitors. Give some examples. Describe the pharmacokinetics of these agents. What are some ADRs associated with these agents?
e.g. zanamavir, oseltamivir (Tamiflu)
Act as sialic acid analogues —> inhibit action of neuraminidase ——-> virion particles aggregate on cell membrane —> prevents release and multiplication of virion particles
Neuraminidase active site conserved across all subtypes
Zanamavir:
- low bioavailability (administer as dry powder aerosol)
- renal excretion
- used for treatment only
Oseltamivir:
- oral prodrug
- used for treatment and prophylaxis
- ADRs: vomiting, abdo pain, epistaxis
What types of viruses are vulnerable to or resistant to antiviral agents?
Highly variable rates of resistance to oseltamivir globally
Viruses generally remain sensitive to zanamivir
Swine flu (H1N1) remains oseltamivir sensitive (neuraminidase inhibitors deployed to treat severe cases to improve outcome and to treat early cases to buy time)
N2 structures less susceptible to resistance
Give some examples of clinical studies about the use of oseltamivir.
Placebo v.s. 75mg v.s. 150mg showed 40% decrease in symptoms with active treatment but no difference between doses
Earlier treatment is started, the shorter duration of symptoms (but no significant reduction after 48hrs)
One Canadian study showed ~70% reduction in mortality even wehn dose given 64hrs after onset of symptoms
6wks 75mg oseltamivir significantly reduced incidence of flu in health adults and frail elderly
Give some examples of antibiotics which target DNA synthesis.
Quinolones e.g. ciprofloxacin (affects DNA gyrase)
Folic acid antagonists (affect synthesis of nucleotides)
- trimethoprim
- sulfonamides
- co-trimoxazole (trimethoprim + sulfamethoxazole
Give some examples of antibiotics that target protein synthesis.
Aminoglycosides
- gentamicin (ADRs = nephrotoxicity, vestibulocochlear effect inc. deafness, irreversible impaired balance)
- streptomycin
Macrolides e.g. erythromycin
Tetracyclines e.g. doxycycline
Give some examples of antibiotics targeting cell wall synthesis.
Beta-lactams
- penicillins
- cephalosporins
- carbapenems
Glycopeptides (vancomycin)
How can the antibacterial activity of drugs be measured?
Disc testing (zone diameter)
Double dilution
E-test (gradient of antibiotic along strip allows estimation of MIC)
Define the minimum inhibitory concentration of antibiotics. What is the breakpoint minimum inhibitory concentration referring to?
Minimum inhibitory concentration (MIC) = minimum concentration of antibiotic required to inhibit the growth of a bacterium in vitro (mg/l)
note: specific to antibiotic and isolate
Breakpoint MIC = MIC at which an organism is considered to be susceptible, intermediate, or resistant based on clinical trial data averages (predicts likely response to antibiotic)
Contrast time-dependent and concentration-dependent killing antibiotics. Give some examples of antibiotics in each category.
Time-dependent killing = successful treatment requires prolonged antibiotic presence at site of infection (but not at a high concentration)
e. g. penicillins, cephalosporins, glycopeptides
e. g. inserting devices which elute antibiotic when treating infections surgically (e.g. osteomyelitis)
Concentration-dependent killing = successful treatment requires high antibiotic concentration at site of infection (but not for a prolonged period)
e. g. aminoglycosides, quinolones,
note: increased risk of ADRs, but dependent on the area under the curve (therefore can avoid if eliminated quickly)
Give some examples of the ADRs associated with antibiotics.
- hypersensitivity (esp. penicillins, cephalosporins, carbapenems, & glycopeptides)
- liver function (penicillins, cephalosporins, tetracyclines)
- renal function (esp. aminoglycosides, tetracyclines, glycopeptides)
- ototoxicity (esp. aminoglycosides, glycopeptides)
- bone marrow (esp. chloramphenicol, glycopeptides)
- CNS (penicillins, carbapenems)
- electrolytesm (penicillins)
- C. difficile (esp. cephalosporins, penicillins, carbapenems, tetracyclines)
- dental (tetracyclines)
- GI (tetracyclines, macrolides)
