Antibiotics Flashcards
Revision (35 cards)
What is the definition of an antibiotic?
A drug used to treat or prevent infection caused by microorganisms.
What is the definition of bacteriostatic?
Inhibit the growth of bacteria
What is the role of bacteriocidal?
Kill bacteria.
Antibiotics can have a narrow or broad spectrum. What is an example of an antibiotic with a narrow spectrum and what is an example of an antibiotic with a wide spectrum?
Penicillin narrow spectrum active against Gram-positive bacteria.
Tetracycline active against many gram-positive and gram-negatives.
What are antibiotics not a substitute for?
Antibiotics are not a substitute for a functional immune system.
As antibiotics do not provide a cure in all circumstances.
The ideal antibiotic varies in different circumstances, therefore the pharmokinetics of each antibiotic varies. What properties need to be considered?
Selective toxicity/ minimal toxicity to host.
Cidal - (i.e. kills bateria)
Long half life - (e.g. low binding to plasma proteins)
Appropriate tissue distribution.
No adverse drug interactions/side effects.
Oral and parental preparations.
How can antibiotics be administered and distributed, and how does this affect they way that they act?
Antibiotic that is absorbed is excreted either in the urine or via the liver, biliary tract and into the faeces.
Can be administered oral (usually) or intravenously (IV), but also (rarely) intramuscularly (IM).
When given orally will reach peak serum levels aprox 1 hour later (within 15 minutes if given IV)
When given rally, much of the antibiotics is not absorbed and is excreted unchanged in the faeces.
(These are important in understanding speed, distribution, dosing protocol and possible complications).
What are some common examples of Antibiotic Targets?
Cell wall - Peptidoglycan synthesis Ribosomes - Protein synthesis DNA replication - Nucleic Acid Synthesis DNA gyrases Metabolic pathways Cell Membrane Function
What are some commonly prescribed cell wall antimicrobials?
Penicillins
- Penicillin, flucoxaciliin, amoxicillin, temocillin, co-amoxiclav and piperacillin/ tazobactam
Celphalosporins
- Ceftriaxone
- Wider spectrum and more resistant to beta-lactamases
Glycopeptides (not a beta-lactam antibiotic)
- Vancomycin, teicoplanin
What is the role of the cell wall?
Cell wall protects cell from internal osmotic pressur.
Consists of repeated sugar units cross-linked.
What are the main features of the penicillin?
Safe, very few side effects.
Variety, very flexible molecule with side groups and chains able to alter multiple features.
Range from narrow spectrum to broad spectrum i.e. empeiric prescribing and can act on a wide range of bacteria, usually both gram negative and gram positive organisms, but also some can be quite specific.
Excreted (rapidly) via kidneys.
Safe in pregnancy.
What are the limitations of the penicillins?
Patients can be “hypersensitive” (“allergic”)
- allergy to one penicillin means allergy to all penicillins (and sometimes aso to the cephalosporins).
Rapid excretion via the kidneys
- results in frequent dosing (usually 3-6 times daily) is necessary.
Resistance;
- Long history of clinical use, many microbes exposed to these compounds and some resistant strains have been selected for.
What are the different types of Beta-Lactams?
Penicillins (narrow spectrum),
Amoxicillin (extended spectrum),
Flucloxacillin (methicillin or methicillin) (resistant to staph Beta-lactamases),
Co-amoxiclav (Clavulanic acid inhibits beta-lactamase).
Cephalopsorins
Cephoxtin (1st generation active against Staph & Streps)
Carbapenems
- Broad spectrum Gm+ve and Gm-ve
- Resistant to beta-lactamase
- Abiot of last resort for some Gm-ve e.g. Meropenem usually IV admin.
What are the properties of Amoxicillin (IV and Oral)?
Safe, well-tolerated antibiotic.
Well-absorbed when given orally.
Low binding to pasma proteins and good tissue distribution.
Effectiveness challenged by spread of beta-lactamases, (enzymes that destroy beta-lactam ring)
What are the properties of Co-amoxiclav (IV and Oral)?
Amoxicillin and Clavulanic acid
- Beta-lactam and beta-lactamase inhibitor
Clavulanic acid
- Inhibits the action of beta-lactamase
- Microbial enzyme
- Does not have antibiotic properties of its own
(combination extends the range f bacterial that can b treated and similar theme for iperacillin an tazobactam)
What is Flucloxacillin (IV and Oral) normally used for?
Flucloxaxillin is a very narrow spectrum antibiotic
- Useful for Staphylococci ad Streptococci ONLY
- Replaced methicillin or methicillin
- MRSA is resistant to Flucloxacillin
- Reporting labs use oxacillin to report resistance
Commonly prescribed antibiotic
- i.e. very common Staph and strep skin infections
- Skin and soft tissue infection
- Wound infection
- Cellulitis (infection of the soft tissues under the skin)
(Inability to be absorbed means this group can accumulate in GI tract and used for C.difficile treatments).
What are the structures of Piperacillin/ Tazobacttam (tazocin)?
Piperacillin has a polar side chain that enhances penetration into gram-negative bacteria (N.B. Pseudomonas)
Tazobatam, beta-lactamase inhibitor works well on SHV-1 and TEM groups of beta-lactamase.
What is Temocillin (IV) (Gram-negative spectrum) and how is it used?
Beta-lactamase resistant form of penicillin.
Activity largely restricted to coliforms
- e.g. Escherichia, Salmonella, Enterobacter
Active against ESBL-producing organisms
- Extended spectrum beta-lactamases
- Also resistant to ampC beta-lactamases
(an antibiotic that has been reintroduced because of increasing bacterial resistance)
What are the properties of Glycopeptides?
Vancomycin, Teicoplanin (both IV)
Cell-wall active antibiotics,
- Binds to end of peptide side chains (D-alanine D alanine) and prevent its incorporation into th cell wall.
- Blocks access to substrate by PBP (transpeptidase)
- (Also interferes with membranes and PG precursor carrier molecules (Lipid II))
- Inhibits peptidoglycan synthesis.
- Reduced cross-linking and activity of lytic enzymes weaken the bacteria cell wall.
Bactericidal.
Excreted via the kidneys and urine
- Toxic levels of vancomycin in the blood can build up in patients who have kidney failure, causing further kidney damage.
Restricted activity means limited to bacteria with a Gram-positive cell wall.
NO activity against any Gram negative organisms
- Excluded by outer membrane.
How do antibiotics target protein synthesis and what are some examples?
Protein synthesis involves ribosomes moving along mRNA molecules that have been transcribed from DNA.
Prokaryotic Ribosomes are structurally different from eukaryotic ribosomes.
Antibiotics that inhibit protein synthesis do so by attaching to bacterial ribosomes, which are structurally different from mammalian ribosomes.
usually protein synthesis can resume when the antibiotic is removed, so most of these antibiotics (macrolides, tetracyclines) are bacteriostatic.
The exception to this is the aminoglycosides, where the binding of these antibiotics to the ribosome is lethal (bactericidal).
- Aminoglycosides (Gentamicin)
- Tetracyclines (Deoxycycline/ minocycline)
- Macrolides (Erythromycin)
What are the properties of Tetracyclines (bacteriostatic)?
Mode of action
- Actively transported into cell binds to 30S subunit. (prevents attachment to tRNA to acceptor sites. Stops chain elongation).
Spectrum of activity - Broad spectrum; Useful against intracellular bacteria and atypical bacteria e.g. Chlamydia.
Resistance - increasing as more is used.
Adverse effects - Destruction of normal intestinal flora resulting in increased secondary infections; staining and impairment of the structure of bone and teeth, restricted use in infants, children and pregnancy.
What are the properties of the Macrolides?
(Commonly used for penicillin allergy and intracellular pathogens)
Erythromycin, clarithromycin and azithromycin.
This group of antibiotics is excreted via the liver, biliary tract and into the gut.
-i.e. not excreted in urine
Lipophilic antibiotics pass through cell membranes easily.
- They are useful for treating certain infections where intracellular bacteria “hide” from the host’s immune system.
- Erythromycin is safe in pregnancy.
What antibiotics affect Nucleic acids?
Metronidazole - Anaerobes and protozoa Trimethopim (+/- sulphonamide) - Primary use urinary tract infections Fluroquinolones - Gram negative and gram positive activity Rifampicin and Rifampin, - Targets DNA dependent RNA polymerase - Prevents transcription - Common use in combination therapy for Mycobacteria
What questions to ask when choosing an antibiotic?
(Antibiotic prescribing should be kept to a minimum).
What is the site of the patient’s infection and what are the likely infecting organisms?
Should it be given orally or through IV?
Does the patient have any antibiotic allergies?
- Age, immune status, previous eposures all examples of complicating factors.
Am I following local prescribing policies?
Is it cost effective?
