Antibiotics Flashcards

Revision

1
Q

What is the definition of an antibiotic?

A

A drug used to treat or prevent infection caused by microorganisms.

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2
Q

What is the definition of bacteriostatic?

A

Inhibit the growth of bacteria

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3
Q

What is the role of bacteriocidal?

A

Kill bacteria.

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4
Q

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?

A

Penicillin narrow spectrum active against Gram-positive bacteria.
Tetracycline active against many gram-positive and gram-negatives.

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5
Q

What are antibiotics not a substitute for?

A

Antibiotics are not a substitute for a functional immune system.
As antibiotics do not provide a cure in all circumstances.

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6
Q

The ideal antibiotic varies in different circumstances, therefore the pharmokinetics of each antibiotic varies. What properties need to be considered?

A

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.

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7
Q

How can antibiotics be administered and distributed, and how does this affect they way that they act?

A

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).

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8
Q

What are some common examples of Antibiotic Targets?

A
Cell wall - Peptidoglycan synthesis
Ribosomes - Protein synthesis
DNA replication - Nucleic Acid Synthesis
DNA gyrases
Metabolic pathways
Cell Membrane Function
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9
Q

What are some commonly prescribed cell wall antimicrobials?

A

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

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10
Q

What is the role of the cell wall?

A

Cell wall protects cell from internal osmotic pressur.

Consists of repeated sugar units cross-linked.

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11
Q

What are the main features of the penicillin?

A

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.

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12
Q

What are the limitations of the penicillins?

A

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.

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13
Q

What are the different types of Beta-Lactams?

A

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.

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14
Q

What are the properties of Amoxicillin (IV and Oral)?

A

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)

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15
Q

What are the properties of Co-amoxiclav (IV and Oral)?

A

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)

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16
Q

What is Flucloxacillin (IV and Oral) normally used for?

A

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).

17
Q

What are the structures of Piperacillin/ Tazobacttam (tazocin)?

A

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.

18
Q

What is Temocillin (IV) (Gram-negative spectrum) and how is it used?

A

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)

19
Q

What are the properties of Glycopeptides?

A

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.

20
Q

How do antibiotics target protein synthesis and what are some examples?

A

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)

21
Q

What are the properties of Tetracyclines (bacteriostatic)?

A

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.

22
Q

What are the properties of the Macrolides?

A

(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.

23
Q

What antibiotics affect Nucleic acids?

A
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
24
Q

What questions to ask when choosing an antibiotic?

A

(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?

25
Q

What are some general side effects of antibiotics and what are some side effects of specific antibiotics?

A

Nausea, vomiting, diarrhoea - common
- all antibiotics disrupt the gut bacterial flora
- may affect absorption of oral contraceptives
Gentamicin
- renal and VIII nerve damage
Ciprofloxacin
- tendonitis
Metronidazole
- interacts with alcohol
Broad spectrum antibiotics increase the risk the risk of C.difficile infection in the elderly.

26
Q

What are the 3 principle compounds of penicillin?

A

Three principle compounds
- Benzylpenicillin (penicillin G, Intravenous IV)
- Phenoxymethyl penicillin (penicillin V, oral)
- Benzathine penicillin (long-acting, intramuscular IM)
(Any organism that is sensitive to penicillin itself will be sensitive to most of the penicillin group of antibiotics).

27
Q

What are the properties in Cephalosporins?

A

Cephalosporins include cephamycins.
Cephalosporins inhibit cell wall synthesis and bactericidal
- Cephamycin more resistant to Beta-lactamases.
Longer half-life in plasma.
Excreted via kidneys and urine.
Have few side effects, reduced allergy.
Safe in pregnancy.
More resistant to Beta-lactamases
- Gram-negatives have still developed resistance.
Narrow Gram -ve to broad (3rd) and extended spectrum (4th).
These are broad-spectrum antibiotics, which significantly affect the normal bowel flora.
- They kill off the normal gut bacteria and allow the overgrowth of Clostridium difficile, which causes a nasty gastroenteritis. Their use in Tayside is now very restricted because of this.
Each successive generation increases spectrum over the previous, i.e. 4th>3rd>2nd>1st.
Many hospitals now try to avoid using these antibiotics.
Only very limited indications for their use now in Tayside.

28
Q

What are the properties of Gentamicin (a type of Aminoglycosides)?

A

Not absorbed from the gut - must be given intravenously IV (occasionally intramuscularly, IM).
Binds to ribosomes (30s) inhibiting protein synthesis, this is irreversible and so bactericidal (kills bacteria).
Active mainly against Gram negative aerobic organisms (e.g. coliforms and Pseudomonas aeruginosa) and effective in hospital for treating serious (life-threatening) Gram negative infection.
Excreted in the urine.
Toxicity - causes damage to kidneys and VIIIth cranial nerve (deafness and dizziness), so need to monitor blood levels of aminoglycosides.

29
Q

What are the properties of Metronidazole?

A

Metronidazole (oral & IV)
- activity against anaerobes
Drug activated by reduction process.
Intracellular low Eh leads to reduction (found in strict anaerobes).
Forms toxic intermediate that indices DNA strand breakage.

30
Q

How does Quinolones (bactericidal) carry out it’s role?

A

Mode of action - Bind to the A subunit of DNA gyrase (topoisomerase) and prevent supercoiling of DNA. Indirectly inhibit DNA synthesis.

31
Q

What are the properties of fluoroquinolones?

A

(Developed from Nalidixic acid)
Fluoroquinolones are bactericidal.
Developed with extended activity to cover not only Gram negatives but more Gram Positive pathogens.
Ciprofloxacin (IV and oral), levofloxacin (IV).
Can get as good blood levels when given orally as when given intravenously.
Excreted via the urine.
The use of these broad spectrum antibiotics is now severely restricted in Tayside in an attempt to reduce the risk of Clostridium difficile gut infection, especially in elderly patients.

32
Q

What is required for the inhibitors of folic acid synthesis?

A

Target Folic Acid Synthesis.

Folic acid vitamin required for synthesis of key components.

33
Q

What are the properties Trimethoprim?

A

Activity against some Gram negative and some Gram positive bacteria.
Excreted via the bacteria.
Common for acute urinary tract infections e.g. E.coli.
Can be given o its own (orally).
Combination therapy with sulphamethoxazole (a sulphonamide) (orally or IV)
- Co-trimoxazole

34
Q

Why are antibiotics sometimes given in combinations?

A

(especially with combination therapies).
Antibiotics are sometimes given in combinations for the following reasons:
- To cover a broad range of possible infecting organisms,
e.g. for the treatment of pneumonia
- To prevent the development of resistance, e.g. in the treatment of tuberculosis (TB).
- For the synergistic effect of combination (1+1 = 3) e.g. in the treatment of some cases of endocarditis
- Never combine bacteriostatic and bactericidal.

35
Q

What antibiotics do we try to avoid using?

A
The 4 "C" antibiotics.
These broad-spectrum antibiotics are particularly associated with an increased risk of Clostridium difficile ("C diff") infection
- Cephalosporins
- Co-amoxiclav
- Ciprofloxacin
- Clindamycin