CPTP 3.10 Pharmacology of Antimicrobials 1 Flashcards
(49 cards)
What does antimicrobial chemotherapy include?
- Synthetic chemicals to destroy pathogens
* Naturally-occuring antibiotics
What is selective toxicity?
When one kind of cell is influenced strongly without any effect on other cells.
What two things must be considered when choosing an antimicrobial agent?
- The patient (pharmacokinetics, allergies, pregnancy, other medications)
- The pathogen (antimicrobial sensitivities)
What are broad spectrum and narrow spectrum antibiotics? What are the main differences between them and their use?
Broad spectrum:
• Target both gram positive and gram negative antibiotics
• More likely to cause resistance due to lack of specificity
• Prescribed if you don’t know the identity of the pathogen
Narrow spectrum:
• Targets either gram negative or gram positive bacteria
• Less likely to cause resistance due to increased specificity
• Prescribed if the causative agent is known
What is the main disadvantage of narrow spectrum antibiotics?
• If the causative agent is misidentified, the treatment may be completely ineffective
How are broad and narrow spectrum antibiotics used in practise?
Broad spectrum antibiotic is used until the causative agent is known, then the patient is switched to a narrow spectrum antibiotic
In what ways can antibiotics be classified?
Broad and narrow spectrum
Bacteriostatic & bacteriocidal:
• Bacteriostatic - Inhibits bacteria from reproducing but doesn’t kill them
• Bacteriocidal - Actively kills bacteria
How are antibiotics placed into bacteriostatic and bacteriocidal categories?
Categorisation is not distinct, it depends not only on the identity of the antibiotic, but also:
• Bacterial species targeted
• The concentration of the drug used
What are the ‘classes’ of targets for antimicrobial action in the bacterial cell?
Class I:
• Utilisation of carbon sources (e.g. glucose) to generate ATP
• Synthesis of carbon compounds used in Class II reactions
Class II:
• Utilisation of precursors to create:
> Amino acids
> Phospholipids
> Nucleotides
> Carbohydrates (from Class I precursors)
Class III:
• Assembly of small molecules into macromolecules:
> RNA
> DNA
> Proteins
> Polysaccharides
What are the limitations of using Class I targets?
- Bacteria often use similar mechanisms to humans to acquire and internalise sugars
- Bacteria are very good at switching to different substrates
Generally not effective
What is the best type of selective toxicity against bacteria?
Class III targeting - there are distinct differences between the pathogen and the host, therefore the toxicity is selective
What are the three major targets of antibiotics?
- Cell wall
- Nucleic acid synthesis
- Protein synthesis
What antibiotics does beta-lactam form the core structure of?
- Penicillins
* Cephalosporins
Name the penicillins in the formulary and their route of administration
Oral
• Amoxicillin
• Flucloxicillin
Parenteral
• Benzylpenicillin
What is the mechanism of action of the penicillins?
- Bacteriocidal
- Binds to penicillin binding proteins on susceptible microorganisms
- This inhibits peptide cross-linking within the cell wall
Describe the pharmacokinetics of penicillins, with regard to distribution and excretion.
Distribution
• Diffuse into all tissues but not CSF
• 60% is plasma protein bound
Excretion
• Excreted in the urine
In what case might a penicillin cross the blood brain barrier into the CSF?
If the meninges are inflamed
What can penicillins become metabolised into?
Penicilloic acid
In what population in clearance of penicillins reduced?
Neonates
Penicillin prevents peptide cross-linking between which proteins in the cell wall?
- N-acetyl glucosamine (NAG)
* N-acetyl muramic acid (NAM)
What are the penicillin binding proteins? What do they do?
Transpeptidase enzymes
These form the cross links between NAG and NAM using 4 amino acids
What are the components of penicillins? What does the active component do do?
(IMG 4)
• A carboxylic acid side chain
- An acylamino side chain
- Thiozidine ring
• Beta-lactam ring
>Forms a covalent bond with transpeptidase enzymes (penicillin binding protein)
>This blocks the active site and prevents the cross linking
What is the R (variable) group between the different penicillins?
The acylamino side chain
What are the adverse drug reactions of penicillins?
- GI disturbances
* Hypersensitivity and anaphylaxis
