Pharmacology of Antibiotics Flashcards
What is an infection? When does disease occur?
an infection results when a pathogen invades and begins growing within a host
disease results only if and when tissue function is impaired (cell damage)
- as a consequence of the invasion and growth of a pathogen
What are the different types of bacteria?
Gram +ve
- staph, strep, enterococcus, clostridium difficile
Gram –ve
- haemophilus influenzae, helicobacter pylori, escheria coli
Anaerobes
Atypical:
- not detected on Gram stain, and not cultivatable on standard bacteriologic media.
How can antibiotics be classed in terms of spectrum of activity?
broad spectrum
– antimicrobial drug is effective against large variety of microbes.
– disadvantage = high likelihood of destroying friendly bacteria of patient’s normal microbial flora
= e.g. Tetracyclines (treat Gram +/-)
narrow spectrum of activity
– antimicrobial drug that is effective against only a relatively small subset of bacteria
= e.g. Penicillin (treat only Gram +)
How can antibiotics be classed in terms of effect on micro-organism?
bactericidal
– interaction results in an irreversible disruption or binding leading to cell death
= e.g. Beta lactams (penicillins)
bacteriostatic
– interaction involves lower affinity binding and is reversible when antibacterial is removed from environment
= e.g. Tetracyclines
What can antibiotics target in bacteria?
cell wall synthesis
- beta lactams = penicillins, cephalosporins, carbapenams, monobactams
- vancomycin, daptomycin
cell membrane
- polymyxins
folate synthesis
- sulphonamides, trimethoprim
nucleic acid synthesis
- quinolones = ciprofloxacin, levofloxacin
- rifampin
protein synthesis
- macrolides = clarithromycin, erythromycin
- clindamycin, chloramphenicol
- tetracyclines = tetracycline, doxycycline
- aminoglycosides = gentimicin, neomycin
Why are most staphylococci resistant to benzylpenicillin? What can be used instead?
most staphlycocci resistant to BZP as they produce penicillinases
– flucloxacillin is not inactivated so is still effective against staphlycocci
= sole indication for its use.
Why does food reduce absorption of ampicillin?
mechanisms of action
mechanisms of action
- delaying gastric emptying time
- altering gastrointestinal pH
- stimulating bile flow
- increasing splanchnic blood flow
- physically interacting with drugs
Why are cefotaxime and ceftriaxone used to treat CNS infections? What is the risk associated?
they are able to cross the blood brain barrier but there is risk of C.difficile with their use
Why is ceftriaxone only given once daily?
has a half-life of 6-8 hours and extensive protein binding (85- 95%) which facilitates once or twice daily dosing
Why is imipenem combined with cilastatin?
imipenem is rapidly inactivated by renal dehydropeptidase I (DHP-1), it is given in combination with cilastatin, a DHP-I inhibitor
- this increases half-life and tissue penetration of imipenem.
What is the mechanism of action of daptomycin? Why does it have low toxicity for mammalian cells?
inserts into cytoplasmic membranes and form oligomeric pores that lead to loss of intracellular K+ and disruption of membrane potential
- binds to cytoplasmic membrane
bacterial cell membranes are rich in acidic lipids such as phosphatidyl glycerol which are rare in mammalian cells
- these acidic lipids allow a conformational change in daptomycin which enhances its poylmerisation and the formation of pores that permeabilise the cytoplasmic membrane
- are specific for bacterial cell membranes
What is the mechanism of action of tetracyclines?
block protein synthesis
- by inhibiting the binding of aminoacyl t-RNA to the mRNA- ribosome complex.
Why are tetracylines affected by food? Why should they not be given to children?
are strong chelating agents
– absorption is reduced in the presence of milk, antacids and iron preparations
tetracyclines cause permanent discoloration of teeth (affect calcification) and slow down the growth of bones
