Antibiotics and Anti-fungals Flashcards
Describe the distinctive features of:
a. Gram positive bacteria
b. Gram negative bacteria
c. Mycolic bacteria (mycobacterium)
a. Gram positive bacteria Thick peptidoglycan cell wall b. Gram negative bacteria Outer membrane that contains lipopolysaccharide (LPS) c. Mycolic bacteria Outer mycolic acid layer
All 3 contain an inner cell membrane
State the steps involved in the production of THF from PABA.
PABA –> DHOp (enzyme = DHOp synthase)
DHOp –> DHF
DHF –> THF (enzyme = DHF reductase)
What is DNA gyrase?
A type of topoisomerase (topoisomerase II)
It releases tension in DNA and is important in unwinding DNA to allow protein binding required for DNA replication
What does RNA polymerase do?
Produces RNA from a DNA template
What is the key difference between ribosomes in eukaryotes and prokaryotes?
Eukaryote = 40S + 60S Prokaryote = 30S + 50S
State two classes of drugs that interfere with nucleic acid synthesis and name the enzymes that they inhibit.
Sulphonamides – inhibits dihydropteroate synthase
Trimethoprim – inhibits DHF reductase
These two drugs are sometimes used together. What is this preparation called?
Co-trimoxazole
Name a group of drugs that interfere with DNA replication and state its targets.
Fluoroquinolones (e.g. ciprofloxacin) inhibits bacterial DNA gyrase and topoisomerase IV
Name a group of drugs that interfere with RNA synthesis and state its main target.
Rifamycins (e.g. rifampicin) – inhibits RNA polymerase
List 4 groups of drugs that interfere with ribosomes.
Macrolides
Chloramphenicol
Aminoglycosides
Tetracyclines
Describe how peptidoglycan is synthesized, transported to the cell wall and incorporated into the cell wall.
- A pentapeptide is created on N-acetyl muramic acid (NAM)
- N-acetyl glucosamine (NAG) associates with NAM forming PtG (PtG= NAG+ NAM + pentapeptide)
- PtG is transported across the membrane by bactoprenol into the periplasm
- PtG is incorporated into the cell wall when transpeptidase enzyme cross-links PtG pentapeptides
Main idea: bacterial cell wall is constantly produced at the cell membrane and transported to cell wall
Which groups of drugs interfere with peptidoglycan synthesis and how do they do this?
Glycopeptides (e.g. vancomycin) – they bind to the pentapeptides and inhibit peptidoglycan synthesis
This is used as a last resort for Gram-positive bacteria that are resistant to other antibiotics
Name a drug that interferes with peptidoglycan transport andstate its target.
Bacitracin – this inhibits bactoprenol, hence preventing peptidoglycan transport
NB this drug is no longer licensed
Name a class of drugs that inhibit peptidoglycan incorporation and explain how they do this.
Beta lactams – they bind covalently to transpeptidase, which inhibits peptidoglycan incorporation into the cell wall
What are the three subsets of beta lactams?
Carbapenems
Cephalosporins
Penicillins
Name two drugs that interfere with cell wall stability and explain how they do this.
Lipopeptides – disrupt Gram-positive cell walls
Polymyxins – bind to lipopolysaccharide and disrupt Gram-negative cell membranes
List five mechanisms of antibiotic resistance and give a brief description of each.
Additional target– the bacteria produce another target that is unaffected by the drug
Hyperproduction – the bacteria increase the production of the target so the antibiotics are less effective/overwhelmed (this is energy inefficient for the bacteria though)
Altered target site – there is an alteration in the drug target so that the drug is no longer effective
Alteration in drug permeation– down regulation of aquaporins (responsible for allowing drugs into cells) or the upregulation of efflux systems
Production of destruction enzymes– beta-lactamases hydrolyse the C-N bond in the beta-lactam ring rendering the beta-lactams inactive
What are penicillins G and V normally used to treat?
Gram-positive bacteria
Name two drugs that are relatively beta lactamase resistant.
Flucloxacillin and temocillin
Name a broad-spectrum antibiotic that must be administered with another drug to become resistant to beta lactamases. What is this other drug?
Amoxicillin Clavulanic acid (b lactamase inhibitor)
What are the four types of fungal infection, characterised based on the tissues/organs affected?
Superficial – outermost layers of skin
Dermatophyte – skin, hair or nails
Subcutaneous – innermost skin layers
Systemic – primarily respiratory tract
What are the two main groups of anti-fungals? Give an example ofeach.
Azoles (fluconazole)
Polyenes (amphotericin)
Describe the mechanism of action of azoles.
They inhibit CYP51p (enzyme of the CYP450 system), which is involved in ergosterol production
Describe the mechanism of action of polyenes.
These interact with membrane sterols and form channels (punching holes in the membrane)
