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SPR L5 Antimicrobials 1 Flashcards

1
Q

Aim

Describe the mode of action of common antibacterial, antiviral and antifungal drugs and apply this knowledge to treat common infections in theoretical clinical scenarios.

A

Key reading: Rang and Dale’s Chapter 45 (p647-659), Chapter 46 (p661-678), Chapter 47 (p679-690), Chapter 48 (p692-697), or Integrated Pharmacology Chapter 6 (p87-138)

Learning Outcomes

  • Describe the mode of action for commonly used antimicrobials (anti-biotics, anti-virals, anti-fungals and anti-protazoals)
  • Compare the different methods of drug antibacterial action
  • Discuss the development of antibiotic resistance
  • List the common treatments for common bacterial and viral infections
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2
Q

Anti-microbials 1-3

What will be covered (for general perusal)

A
  1. Common classes of antibiotic
  2. Other important antibiotic classes
  3. Other anti-microbials
  • Anti-virals
  • Anti-fungals
  • Anti-protazoals
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3
Q

Antimicrobial agents and chemotherapy 1+2
(Microbiology)

​Describe the bacterial cell wall

A

Cell membrane and peptidoglycan cell wall

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4
Q

Antibacterials

Name the cell wall active agents

A
  • Β-lactams
    • Penicillins
    • Cephalosporins
    • Monobactam
    • Carbapenems
  • Glycopeptides
    • Vancomycin
    • Teicoplanin
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5
Q

Antibacterials

Name those with Action on nucleoside precursors

A

Trimethoprim

Sulphonamides

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6
Q

Antibacterials

Name the Agents acting on nucleic acid synthesis

A
  • Metronidazole
  • Quinolones
  • Rifampicin
  • Nitrofurans
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7
Q

Antibacterials

Name the Protein synthesis inhibitors

A
  • Aminoglycosides
  • Tetracyclines
  • Macrolides
  • Oxazolidinones
  • Fusidic acid
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8
Q

B-lactams

Penicillin

  1. What do all b-lactam antibiotics interfere with?
  2. What do the penicillins attach to?
  3. What do they therefore inhibit
A
  1. the synthesis of the bacterial cell wall peptidoglycan
  2. Penicillin-binding proteins on bacteria
  3. inhibit the transpeptidase enzyme activity that catalyses the NAMA/NAG peptide chain cross-linking, and they inactivate the inhibitor of the autolytic enzymes in the cell wall (switch off the off switch) leading to cell lysis (bacteriocidal)
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9
Q

What is the structure of a penicillin?

A

see picture - be able to draw this

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10
Q

Types of penicillin

  1. Which shows poor GI absorption and is susceptible to b-lactamases?
  2. Name a broader spectrum penicillin
    1. What is it?
  3. Which is beta-lactamase resistant?
  4. Which has an extended spectrum?
A
  1. Benzylpenicillin
  2. Amoxicillin
    1. combined with β-Lactamase inhibitor clavulinic acid- Co-Amoxiclav) – rope-a-dope
  3. Flucloxacillin
  4. Extended spectrum – Piperacillin /Ticarcillin (combined with β-Lactamase inhibitors to make Tazocin / Timentin)
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11
Q

B-Lactams - Penicillin

Pharmacokinetics

  1. Describe oral absorption
  2. How is it distributed in body fluids?
  3. How is it mainly excreted?
  4. Describe the plasma half-life
A
  1. Oral absorption variable
  2. Widely distributed
  3. Mainly renal excretion (tubular secretion)
  4. Short plasma half-life
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12
Q

Beta-Lactams - Penicillin

What are the uses of the following penicillins?

  1. Benzylpenicillin
  2. Amoxicillin
  3. Flucloxacillin
  4. Piperacillin
A
  1. Bacterial meningitis
  2. Resp Infections, UTI, Otitis media
  3. Cellulitis
  4. Severe infection / pseudomonas
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13
Q

Beta-Lactams - Penicillins

What are the main adverse effects?

A
  • Hypersensitivity
    • Skin rash / fever
  • Anaphylaxis
  • Oral – antibiotic associated diarrhoea

(generally very few adverse effects)

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14
Q

Beta-Lactams - Cephalosporins

Give an example of the following

  1. 2nd Generation
  2. 3rd Generation

They are chemically related to penicillins, describe how this the case

A
  1. Cefuroxime (Zinacef)
  2. Cefotaxime

Ceftazidime

Ceftriaxone

  1. Have an R2
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15
Q

B-lactams - Cephalosporins

  1. Outline the mode of action of these
  2. What is an issue?
    1. Why?
A
  1. Mode of action similar to penicillins (interfere with the synthesis of the bacterial cell wall peptidoglycan, attach to Penicillin-binding proteins on bacteria and inhibit the transpeptidase enzyme activity that catalyses the NAMA/ NAG peptide chain cross-linking)
  2. Resistance to these drugs has increased especially gram negative bacteria
    1. Chromosomal gene coding for β-Lactamase that is more active in hydrolysing cephalosporins
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16
Q

B-lactams - Cephalosporins

Use had decreased in the last few years, but what are the following used for?

  1. Cefotaxime/Ceftriaxone
  2. Ceftazidime
A
  1. Meningitis
  2. Bronchiectasis infections (depending on organism)
17
Q

B-lactams - Cephalosporins

  1. How do most need to be given?
  2. What is excretion mostly by?
  3. What is the cross-sensitivity with penicillins?
  4. What can they sometimes give rise to?
A
  1. parenterally
  2. Excreted by the kidney (ceftriaxone 40% bile)
  3. 10%
  4. Occassional nephrotoxicity / alcohol intolerance
18
Q

Protein Syntesis Inhibitors - Macrolides

Give 3 examples of macrolides

A
  • Erythromycin
  • Clarithromycin
  • Azithromycin
19
Q

Protein Syntesis Inhibitors - Macrolides

What is the mechanism of action of macrolides?

A
  • Inhibit bacterial protein synthesis
  • Bind to the 50S subunit of the bacterial ribosome and prevent translocation of the growing peptide chain
  • Bacteriocidal or static depending on concentration and micro-organisim
20
Q

Protein Syntesis Inhibitors - Macrolides

  1. Macrolides have an antimicrobial spectrum similar to penicillin, what benefit does this incur?
  2. How is it usually administered?
  3. What does it show some activity against?
  4. Where does it have poor penetration?
  5. Where does it concentrate?
A
  1. alternative if allergic
  2. orally (can be given IV but may cause phlebitis)
  3. Atypical Pneumonia
  4. in the synovial fluid
  5. in phagocytes
21
Q

Protein Syntesis Inhibitors - Macrolides

​Adverse Effects

  1. What is the most common AE seen?
  2. What else can occur?
A
  1. GI upset common
  2. Hypersensitivity reactions (rash / fever) QT prolongation - proarrhythmic Interaction with other drugs due to their effects on cytochrome P450 system (liver) –Inhibit metabolism of ciclosporin / theophylline
22
Q

Agents Acting on Nucleic Acid Synthesis - Quinolones

Give 3 examples

A
  • Ciprofloxacin
  • Levofloxacin
  • Moxifloxacin
23
Q

Agents Acting on Nucleic Acid Synthesis - Quinolones

What is their mechanism of action?

A
  • They inhibit the bacterial DNA gyrase (Topoisomerase II)
  • This prevents the DNA double-helix from becoming supercoiled preventing transcription and replication
24
Q

Agents Acting on Nucleic Acid Synthesis - Quinolones

  1. Describe their absorption
  2. Against what do they have good activity?
  3. What do they have poor activity against?
  4. What are they used for?
A
  1. Well absorbed
  2. Good activity against Gm–ve enteric coliforms as well as H influ and pseudomonas
  3. Strep Pneum* and Staph
  4. Used for UTI / *Pneumonia-Levofloxacin
25
Q

Agents Acting on Nucleic Acid Synthesis - Quinolones

Outline the main adverse effects

A
  • GI upset – Caution re c. diff risk
  • Hypersensitivity
  • Rarely convulsions – caution in epilepsy (or if on theophylline / NSAIDs)
  • Inhibits CYP450 increasing theophylline toxicity
26
Q

Antibiotic Guidelines

  1. How do these vary?
  2. What should ideally be done?
  3. What is usually done?
A
  1. Vary geographically and chronologically
  2. Ideally match the anti-microbial to the micro-organism cultured along with the route of admin and pharmacokinetic properties
  3. Usually best guess (usual causative organism) – Guided by infection location
27
Q

Guidelines for management of community acquired pneumonia in adults

What do the guidelines state in terms of the following

  1. Low severity (CURB65=0-1)
  2. Moderate severity (CURB65=2)
  3. High severity (CURB65 = 3-5)
A
  1. Amoxicillin 500mg tds orally
  2. benzylpenicillin 1.2g qds IV plus clarithromycin 500mg BD IV
  3. Co-amoxiclav 1.2g tds IV plus clarithromycin 500mg BD IV

If legionella is strongly suspected, use levofloxacin

see picture!

29
Q

Outline the CREST Management of Cellulitis in Adults

  1. Class I
  2. Class II
  3. Class III
  4. Class IV
A
  1. Flucloxacillin 500mg qds po
  2. Ceftriaxone 1g od IV
  3. Flucloxacillin 2g qds IV
  4. Benzylpenicillin 2.4g 2-4 hourly IV

see picture

30
Q

Trust Guidelines - ICU

see picture of trust guidelines

31
Q

Bringing this together (summary)

A

Antibiotics have different:

  • Modes of action
  • Activity against micro-organisms
  • Susceptibility to bacterial defences e.g. β-Lactamases
  • Pharmacokinetic properties

If you know the common causative micro-organisms then you can base you choice of antibiotic on that

Consider the location of the infection and the drug delivery to that site

As the causative organisms and their susceptibilities change then need to follow up-to-date local guidelines

32
Q

Next lecture covers the following

Pharmacology (26 decks)

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