Infection And Immunity Blagborough Flashcards
How can metal chelation alter the pharmacokinetics of drugs?
Absorption can be severely reduced
Due to complexes formed from chelation having reduced water solubility
This means they can’t cross lipid membranes
What is metal chelation?
Interaction of a metal ion with a chemical molecule to form a heteroatomic ring
When metals chelate with a drug what’s the most stable ring size that could form?
6 membered ring
Followed by 5 or 7 membered ring (not aromatic)
When metals chelate with drugs, what’s the least stable ring size that may form?
4 membered ring (strained)
Or 8 membered (bond overlap)
Adriamycin, actinomycin, synthetic acridine and quinolone antimalarials are all intercalating cytostatic agents. What do they interfere with?
Bacterial DNA replication
These drugs bind strongly to the DNA of chromatin in the bacterial cell nucleus by slipping between 2 base pairs
Form charge transfer complexes with the nucleotides
What are nitrogen mustard cytostatic agents?
Alkylating agents
They interfere with DNA replication
Which two antibiotics are both aminoglycosides in the group of anthracycline antibiotics produced by some streptomyces species?
Hint: they differ in structure by one hydroxyl group!
Adrimycin and duanomycin
Adriamycin and duanomycin are both anti cancer antibiotics. A big problem is their cardiotoxcity. What can reverse this toxicity?
Calcium
Quinine is a common antimalarial.
It’s more toxic than others.
What’s it mainly used in combo with?
Pyrimethamine
Some drugs may be DNA topoisomerase inhibitors. What is topoisomerase?
Topoisomerase I and II
Enzymes
Bacterial DNA must first unwind to be replicated. Unwinding introduces a supertwist. Top I removes this supertwist and produces more relaxed DNA.
Top II further promotes strand separation.
Topoisomerase inhibitors interfere with these enzymes so stop replication.
Used in cancer
Some agents like adriamycin and actinomycin D can stabilise the Topiosomerase enzyme and DNA complexes and therefore make the breaks in the DNA permanent
This way they have made the topoisomerase enzymes (DNA Gyrases) LETHAL enzymes
What other drugs can act by inhibiting DNA Gyrases (topoisomerases)?
Quinolone antibacterial agents but not that active
Ciprofloxacin is highly active
How do tetracyclines exhibit their antibacterial effects?
Interfere with protein synthesis
By inhibiting binding of tRNA to the 30S subunit if ribosomes in bacteria
What two (aminoglycoside antibiotics) antituberucloctics are very important?
Streptomycin
Kanamycin
Both have a fairly wide antibiotic spectrum
Antituberucloctics: anti TB bacteria
Why do we have to warn people on tetracyclines about dairy products?
Several chances for the antibiotics to chelAte with the calcium ions
6 places where tertacyclines can chelate
How do streptomycin and kanamycin work?
Decrease translation in the bacteria by binding to the 30S subunit of the bacterial ribosome. Therefore stops any more addition of amino acids to the growing peptides
Streptomycin is more ______ than kanamycin, what does this mean?
More ototoxic
Damaging to auditory nerve in the ear so patient goes deaf
(Same with gentamicin)
What is the drug of choice in tuberculosis and leprosy?
Rifampicin
Much safer than others as it inhibits only bacterial RNA polymerase, not mammalian.