Antibiotics Flashcards
What are the 3 ways in which you would classify an antibiotic in terms of the site of action?
1) Inhibition of cell wall synthesis
2) Inhibition of protein synthesis
3) Inhibition of nucleic acid synthesis
Which antibiotics inhibit cell wall synthesis?
- Beta-lactams which are subdivided into penicillins, cephalosporins & cephamycins
- Lesser categories of beta-lactams which include carbapenams, monobactams and beta-lactamase inhibitors (clavulanic acid)
- vancomycin and teicoplanin
Which antibiotics inhibit protein synthesis?
- Aminoglycosides
- Tetracyclines
- Macrolides
- others including linezolid, chloramphenicol, sodium fusidate
Which antibiotics inhibit nucleic acid synthesis?
- Sulphanoamides
- Quinolones
- Azoles
What mechanisms have bacteria devised to combat beta-lactams?
- Beta-lactamase
- Modification of the penicillin binding proteins, so beta-lactam can’t bind the enzymes
- Reduced permeability of the cell membrane of gram negative bacteria
- Pumps that remove beta-lactam that enters the cell
Are penicillin time dependent or concentration dependent? and what does this mean?
Time dependent, so the dose increasing the dose doesn’t affect it’s efficacy, only keeping the concentration at a therapeutic dose for the right prolonged amount of time will have an effect. It is bacterocidal
Is it suitable for oral use?
Benzylpenecillin is not as it destroyed by gastric acid. Its only real use orally is for strep throat infections.
Others like phenoxymethyl penecillin resist gastric acid and are absorbed in the upper small bowel.
What is the plasma half life of penicillins?
Do penicillins enter the CSF?
Yes, they are distribute mainly in the body water.
How are penicillins excreted?
Urinary excretion, which is rapid. Dosage should be reduced in patients with severely impaired renal function.
What are the main adverse effects of penicillins?
Itching, rashes (eczematous or urticarial), fever and angioedema. Rarely (1 in 10,000) there is anaphylactic shock.
What % of patients with a supposed ‘penicillin allergy’ actually react to an intradermal test?
Only around 10%, suggesting huge over diagnosis.
What other non-allergic reactions can patients have to penicillins?
Diarrhoea (disturbance of normal gut flora), neutropenia for long doses (10+ days), and they are often combined with sodium or potassium so the clinician should take this extra source into account.
What is the half-life of benzylpenicllin and what does this mean for dosage?
t1/2 0.5hrs, so dosage has to be large and is normally well tolerated due to unusually large therapeutic ratio.
How is benzylpenicillin excreted?
Kidney, and it’s excretion can be blocked by probenecid if excretion needs to be slowed (e.g. to space out doses)
What is benzylpenicillin mainly used for?
- Streptococcus pneumonia
- Streptococcus pyogenes
- Streptococcus viridans (usually sensitive)
- Enterococcus is less sensitive (especially for endocarditis) and must be combined with an aminoglycaside, usually gentamicin
- Nisseria meningitidis (septicaemia, meningococcal meningitis)
- Bacillus anthacis (anthrax)
- Clostridium perfringens (gas gangrene)
- Tetani (tetanus)
- Corynebacterium diphtheriae (diphtheria)
- Treponema pallidum (syphilis)
- Leptospira spp. (leptospirosis)
- Actinomyces israelii (actinomyces)
- Borrelia burgdorferi (lyme disease) in children
- Nisseria gonorrhoeae has variable sensitivity
What is a particular complication of benzylpenicillin?
Patients with bacterial endocarditis, where the requirement of a high dose can co-exist with reduced clearance due to immune complex glomerulonephritis, does the risk of dose related toxicity arise (convulsions).
How is benzylpenicillin administered
I.V. - bolus 600mg 6 hourly is enough for sensitive infections, though in infective endocarditis, 7.2g are given daily in divided doses.
- Continuous I.V.
I.M. - procaine penicillin, largely fallen out of use due to slow onset of some hours after injection. 360mg 12-24 hourly
Orally - phenoxymethypenicillin 500mg 6 hourly, and generally used one infection has been controlled by initial i.v.
What are examples of beta-lactamase resistant agents?
1) Flucloxacillin - t1/2 1h, main adverse effect is thought to be cholestatic jaundice, particularly when used 10+ days or in patients >55yrs
2) Cloxacillin - t1/2 0.5hrs, gastric acid resistant, recently withdrawn form UK market
3) Methicillin + oxacillin - use now confined to lab due to MRSA
What do broad penicllins cover?
They extend beyond the gram-positive and negative cocci, covering gram-negatie bacilli.
Is there resistance to broad spectrum penicillins?
Yes, they do not resist beta-lactamase enzymes so their effectiveness is decreasing.
How does their activity compare to benzylpenicillin and the beta-lactamase resistant penicillins?
They are typically less active against the gram-positive cocci that benzylpenicillin, but more active than the beta-lactamase resistant agents.
Which organisms are the broad spectrum penicillins active against?
- Enterococcus faecalis
- Haemophilus influenzae (many strains)
- Enterobactae have varying sensitivity (requires lab testing)
NB. the differences between this group are largely pharmacological rather than bacteriological
Give 3 examples of broad spectrum penicillins.
1) Amoxicillin - t1/2 1h, 250mg 8-hourly P.O. For oral use amoxicillin has a greater bioavailability than ampicillin (it’s precursor)
2) Co-amoxiclav (Augmentin) - t1/2 1h, one tablet 8-hourly. This is a combination tablet containing the ‘suicide’ inhibitor clavulanic acid and Amoxicillin. The claculanic acid is in the form of a potassium salt and 125mg is combined with 250 or 500mg amoxicillin. Clavulanic acid conveys a beta-lactamase resistance to the amoxicillin. This makes it useful for beta-lactamase producing organisms, especially in the respiratory and urogenital tracts. This includes many strains of staphlococcus aureus, many strains of Escheria coli and an increasing number of strains of haemophilius influenzae.
3) Ampicillin - t1/2 1h - It is acid stable, moderately well absorbed, 250mg-1g 6-8hourly. I.M. and I.V. 500mg 4-6 hourly. Drug becomes concentrated in the bile.
