Q31

Name some macrolide antibiotics?

Erythromycin, roxithromycin, azithromycin, clarithromycin.

Pass: 2

Describe the mechanism of action of macrolides?

Inhibits bacterial protein synthesis by binding to 50S ribosomal RNA, which blocks the aminoacyl translocation reaction and formation of initiation complexes (transpeptidation). May be inhibitory or bactericidal, particularly at higher concentrations.

Pass: Bold

What organisms are macrolides effective against?

Gram + orgs: pneumococci, streptococci, staphylococci, corynebacteria|
Mycoplasma, Legionella, Chlamydia sp, listeria, some mycobacteria
Gram — orgs: Neisseria sp, Bordatella pertussis, Treponema pallidum, Campylobacter sp, bartonella
(Haemophillus less susceptible)

Pass: 3


Q32

By what mechanisms can bacteria be resistant to beta lactam antibiotics?

1.           Inactivation by beta lactamase (commonest mechanism)

2.           Modification of target proteins (PBPs- Penicillin-binding proteins) (MRSA, pneumococci, enterococci)

3.           Impaired penetration through cell wall to PBPs (gram negatives only- outer cell wall membrane)-which enhances efficacy or beta lactamase enzymes within the cell.

4.           Efflux pump (gram negatives only)

Pass: No 1 and one other

What circumstances encourage the development of bacterial resistance to antimicrobial agents?


Resistance is an example of natural selection, and arises through spontaneous mutations or DNA exchange between different species of bacteria (either directly by plasmids or via bacteriophages).

Therefore resistance is promoted by:

  1. Dirty hospital environments with multiple species of bacteria co-existing and “exchanging” between environment, patients and staff
  2. A course of antibiotics that only partially treats a target population (inadequate potency, dose or duration)

(Thus, paradoxically, both under-use and overuse of antibiotics plays a role in the development of resistance!)

Overall, however, total consumption of antibiotics within a human population is the critical factor in development of resistant strains

Pass: Understands at least one mechanism well


Q33

In treatment of a new case of Tuberculosis, what are the important principles of drug use?
Prompt: How might the problem of drug resistance influence your therapy?

1.            Multiple drugs used initially (usually 4) ensures efficacy

2.            Prolonged course, usually 6 months

3.            Close supervision to ensure compliance and detect adverse effects

Pass: Bold

Describe the pharmacology of Rifampicin.

  1. Well absorbed orally
  2. Highly lipid soluble – widely distributed in tissues
  3. Metabolism in liver, excreted in faeces
  4. Induces P450 enzymes – many drug interactions
  5. Discolouration (orange) of body fluids
  6. Can be used prophylaxis

2/6 bold to pass


Q34

What are the indications for acyclovir in the ED?

HSV – encephalitis; VZV, patients with HIV

Pass: Bold

To which class of antiviral drugs does acyclovir belong?

Prompt: Describe the mechanism of action of acyclovir.

DNA polymerase inhibitors
(Specificity for virus-infected cell (virus-specific thymidine synthase). Inhibition of viral DNA synthesis (irreversible binding to viral DNA polymerase)

Pass: Bold

Describe the pharmacokinetics of acyclovir?

Short half life 2.5 hrs ( 5times daily dosing oral); low oral bioavailability; mostly excreted unchanged in urine; CSF 50% of plasma; wide distribution

Pass: Bold


Q35

What class of drug is Ciprofloxacin?

  • Fluoroquinolone

Pass Criteria:

  • Bold to pass

What is the mechanism of action of Ciprofloxacin?

  • Blocks DNA synthesis by inhibiting bacterial topoisomerase II and IV

Pass Criteria:

  • Bold to pass

What is its antimicrobial spectrum?

  • Excellent gram negative activity and moderate gram positive activity
  • Methicillin susceptible strains of Staphylococcus aureus are susceptible, but methicillin resistant Staphylococci are resistant
  • Also active against agents of atypical pneumonia – Mycoplasma and Chlamydiae
  • Intracellular pathogens such as Legionella and Mycobacterium
  • Ciprofloxacin the drug of choice for anthrax.

Pass Criteria:

  • Bold + 1 to pass
  • Note – MIC for Gram neg are 1-2 mcg/mL

What are the potential adverse effects of Fluoroquinolones?

  • Prolonged QT (with some)
  • Nausea, vomiting, diarrhoea (including Clostridium difficile)
  • Rash
  • Abnormal LFTs
  • Photosensitivity
  • Hyperglycaemia in diabetics
  • Growing cartilage damage (not routinely recommended for <18yo or pregnancies)
  • Tendinitis
  • Allergy

Pass Criteria:

  • Bold + 2 dot points

Q36

What are the indications for acyclovir in the Emergency Department?

  • HSV – encephalitis
  • VZV, patients with HIV, Genital herpes

Pass Criteria:

  • Bold to pass

Describe the mechanism of action of acyclovir.

  • Inhibition of viral DNA synthesis
    • Irreversible binding to viral DNA polymerase
    • Incorporation into viral DNA with termination
  • Specificity for virus-infected cell (virus-specific thymidine kinase).

Pass Criteria:

  • Bold to pass

Describe the pharmacokinetics of acyclovir.

  • Short half life 2.5 hours (5x daily dosing oral)
  • Low oral bioavailability
  • Mostly excreted unchanged in urine
  • CSF 20-50% of plasma
  • Wide distribution

Pass Criteria:

  • Bold + 1 other

Name some side effects of acyclovir.

  • Nausea
  • Vomiting
  • Diarrhoea
  • Headache
  • Reversible renal toxicity
  • Neuro
    • Tremor
    • Delirium
    • Seizures

Pass Criteria:

  • 2 to pass

Q37

What type of antibiotic is ceftriaxone?

  • Third generation cephalosporin
  • Beta lactam

Pass Criteria:

  • 1/2 bold 

Describe the pharmacodynamics of ceftriaxone.

  • Inhibits transpeptidation reaction of bacterial cell wall synthesis. Halts peptidoglycan synthesis, leading to inhibition of growth and ultimately cell death (bacteriocidal)

Pass Criteria:

  • Bold to pass

Explain the microbiological spectrum of activity of ceftriaxone.

  • Stable to bacterial beta-lactamases, therefore broader spectrum of activity.
  • Expanded gram-negative cover and crosses the blood brain barrier.
  • Effective against beta-lactamase producing Haemophilus and Neisseria

Pass Criteria:

  • Bold to pass

What is the clinical relevance of ceftriaxone's half-life?

  • Half life of 7 to 8 hours, meaning it may be administered once daily at 15 to 50mg/kg

Pass Criteria:

  • Bold to pass

Q38

Describe the mechanism of action of gentamicin.

  • Irreversible inhibitor of protein synthesis
  • Binds 30s ribosome & inhibits protein synthesis by:
    1. Interfering with initiation complex of peptide formation
    2. Inducing misreading of mRNA thus producing non functional protein
    3. Causing break up of polysomes into non-functional monosomes

Additional Information:

  • Enters cell by passive diffusion via porin channels across outer membrane, then enters cytoplasm by O2 dependant active transport process (transport coupled to a proton pump the transmembrane electrochem gradient supplies the energy)
  • Low ecf pH & anaerobic conditions inhibit transport as reduces gradent
  • Transport enhanced by cell wall active drugs ie: penicillin, vancomycin

Pass Criteria:

  • Bold to pass

What are the benefits of once daily dosing of gentamicin?
Prompt: How does this improve clinical effectiveness?

  • Concentration dependant killing
    • At increased concentration, kill increased number of bacteria at a more rapid rate
  • Post antibiotic effect
    • Effect lasts longer than detectable serum levels
  • Reduced toxicity
    • Toxicity is time and concentration dependant
    • Time above critical level will be longer with multi dose than single dose schedule
  • Less nursing time
  • OPD therapy possible
  • Convenience

Pass Criteria:

  • Bold to pass

What micro-organisms is it effective against?
Prompt: What group of organisms?

  • Gram -ve bacteria
    • E. coli
    • Pseudomonas
    • Proteus
    • Klebsiella
    • Serratia
  • Gram +ve
    • Staph
    • Strep with beta lactams, vancomycin
  • No anaerobic activity

Pass Criteria:

  • Bold + 3 organisms

Q39

What micro-organisms are susceptible to flucloxacillin?
Prompt: Is flucoxacillin active against all Staph?

  • Staphylococci – including 8 lactamase producing
  • Streptococci
  • Not active against:
    • Enterococci
    • Anaerobes
    • Gram negatives
    • MRSA

Pass Criteria:

  • Bold to pass

What is the mechanism of action of flucoxacillin?
Prompt: How does penicillin work?

  • Inhibits bacterial growth by binding to active site of PBPs
  • Interferes with transpeptidation of bacterial cell wall synthesis –> cell death (bactericidal)

Pass Criteria:

  • Bold to pass

Why is oral flucloxacillin given before meals?

  • It is acid labile (inactivated by gastric acid)
  • Binds to food proteins – decreasing absorption

Pass Criteria:

  • 1 of 2

What are the important side effects of flucloxacillin?

  • Liver (cholestasis)
  • GI upset – nausea, vomiting, etc
  • Renal interstitial nephritis
  • Neutropenia/thrombocytopenia
  • Allergy/Anaphylaxis
  • Serum sickness

Pass Criteria:

  • Bold to pass.

Extra question: What is the frequency of cross allergenicity between flucloxacillin and cephalosporins?

  • Around 5-10%

Pass Criteria:

  • Any % in range

Q40

What class of antibiotic is azithromycin?

Macrolide

Pass Criteria:

  • Bold to pass.

Describe the mechanism of action of azithromycin.

Inhibition of bacterial protein synthesis by binding to the 50S ribosomal RNA, blocking aminoacyl translocation and formation of initial peptide complexes. May be bacteriostatic or bacteriocidal (especially at higher concentrations).

Pass Criteria:

  • Bold to pass.

Against which micro-organisms is azithromycin effective?

  • Gram positive:
    • Pneumococci
    • Streptococci
    • Stapylococci
    • Corynebacterium
    • Mycoplasma
    • Legionella
    • Chlamydia sp
    • Listeria
    • Some mycobacteria
  • Gram negative
    • Neisseria sp
    • Bordatella pertussis
    • Treponema pallidum
    • Campylobacter sp
    • Bartonella

Pass Criteria:

  • 3 to pass but must include one atypical.

How does azithromycin differ from other macrolides?
Prompt: Compared to erythromycin and clarithromycin.

  • Higher tissue penetration (tissue concentration is much higher than serum concentration)
  • Long elimination half-life (2 – 4 days) versus 2 – 5 hours
  • Single daily dosing
  • More effective against Haemophillus, M. catarrhalis and Neisseria sp
  • Highly effective against Chlamydia sp
  • Less active against staphylococci and streptococci
  • Excreted unchanged in the urine
  • Absorption impeded by food
  • Does not inhibit the hepatic cytochrome P450 system so drug interactions are uncommon

Pass Criteria:

  • Bold plus one other to pass.


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