Folate Antagonist Flashcards
Lower urinary tract infection
Cystitis
Symptoms of Cystitis
Painful + frequent urination
Upper urinary tract infection
Pyelonephritis
What microorganism causes both lower+ upper UTI?
Escherchia coli
Why is UTI common in females?
Women’s urethra is shorter making them prone to infection
What does E coli cause?
UTI (entry from GIT to UT)
GASTROENTERITIS (eating infected food contaminated with pathogenic strains)
What is Escherchia coli?
Gram-negative, Coliform (any bacteria found in large intestines), rod-shaped, enteric bacteria
It forms natural flora of mammalian GI tract
What is the pathogenicity mediated by?
O-polysaccharide
Polysaccharide shell
Lipid A - causes Toxic shock
Virulence Factors
Outer membrane - protection from phagocytosis
Fimbriae/Adhesins - attach to epithelial cells
Exotoxins
Iron-binding proteins - acquire Fe needed for growth
Haemolysins - release Fe from blood cells
Type III secretion system builds an insertion (needle) to inject proteins into host cells
What is the first line treatment for simple UTI?
Trimethoprim
What is the second line for UTI?
Nitrofurantoin
What is the treatment for Urosepsis/Pyelonephritis?
IV Co-amoxiclav / Cefuroxime
Gentamicin
What to use for folate metabolism?
Sulphonamides, Trimethoprim, Pyrimethamine
What makes up folate?
Folic acid + Vit B9
Co-factor for all living cells
What is the use of folate?
In mammals, it is used during phases of rapid cell division e.g. pregnancy + infancy
Function of reduced form ‘Tetrahydrofolate’
A carrier of single fragments used to make adenine, guanine, thymine and methionine
How to make folate?
One molecule of pteridine + p-ABA (p-aminobenzoic acid) + glutamic acid = dihydropteric acid.
Dihydropteric acid reduce to tetrahydrofolate by dihydrofolate reductase
What are Sulphonamides + function?
Structural analogue p-ABA
Inhibit addition of pABA into the folate (dihydropteric acid)
Clinical use decreased due to bacterial resistance
Examples of drugs in Sulphonamides class
Sulfamethoxazole, Sulfadiazine
What drug can you have with sulfamethoxazole + why?
Trimethoprim because they exhibit synergistic activity
Sulfamethoxazole + Trimethoprim = Co-trimoxazole
Prescribed to treat urinary and respiratory infections
What is Trimethoprim?
Selective inhibitor of bacterial DHFR
Structural analogue of Dihydropteric acid + fits into DHFR active site normally by DHF forming hydrogen bonds with amino acid + water lining active site
How does trimethoprim resistance occur?
Occurs as a result of overproduction of DHFR by bacteria
Acquire dfr gene encodes resistant form of enzyme - commonly DHFR I, II, III amongst enterobacteria
Can mammals make DHF?
No so it needs to be supplied through diet and then reduced in liver
Symptoms of pyelonephritis
Fever
Lower back pain
Painful + frequent urination
