Folic Acid Antagonist ( All Drugs Related ) Flashcards
Why is folic acid important ? And how ?
Folic acid is necessary for DNA replication and cellular growth , especially in Purine and pyramidine synthesis that require folate-derived cofactors
Bacteria and folic acid :
Many bacteria are impermeable to folate , rely on de novo synthesis.
De novo Sunthesis of folate in bacteria : (Steps)
1) P-Aminobenzoic acid ———> Dihydrofolic acid
“ Dihydropteroate synthatase “
“ Sulfonamides “
2) Dihydrofolic acid ———> tetrahydropholic acid
“ Dihydrofolate reductase “
“ Trimethoprim “
3) Tetrahydropholic acid —> Purines —> DNA
Folic acid must be converted into :
Tetrahydrofolic acid.
What are Sulfonamides derivatives?
1) Mafenide
2) Silver Sulfadiazine
3) Sulfasalazine
MOA of sulfonamide :
Sulfonamides inhibit dihydropteroate synthetase by competition
Antibacterial Spectrum of Sulfonamides :
Effective against H.infleunza, streptococcus spp. , staphylococcus spp. and enterobacteriaceae ( Causing UTIs )
MOR of Sulfonamides :
1) Altered dihydropteroate synthetase
2) Decreased cellular permeability against Sulfonamides
3) Enhanced production of PABA
Absorption of Sulfonamides
Sulfonamides are well-absorbed orally except sulfasalazine
About Sulfasalazine :
1) Colon bacteria breakdown Sulfasalazine into 5-Aminosalicylic acid ( 5-ASA ) and Sulfapyridine
( 5-ASA has anti-inflammatory effect so it is used as an anti-inflammatory drug rather than anti-biotic
2) it is used to treatment of toxoplasmosis
3) it’s cream form used against bacterial contamination in burns
Distribution of Sulfonamides:
1) highly-bound to serum albumin
2) Distribute well through body fluids including CSF
3) Cross the placenta
Metabolism of Sulfonamides:
They are metabolised in the liver by acetylation and conjugation
- acetylated metabolites can crystallise in urine causing renal stones
Elemination of Sulfonamides:
- Eliminated by glomerular filtration and secretion
- eliminated in breast milk
Adverse effects of Sulfonamides :
1) Crystalluria
2) Hypersensitivity
3) Hematopoitic disturbances
4) Kernicterus
5) Drug-drug interaction
Crystelluria and Sulfonamides :
-Nephrotoxicity may develop as a result of crystalluria resulted in sulfa utilisation
- to prevent Nephrotoxicity requires adequate hydration and urine alkalinazation
Hypersensitivity of Sulfonamides:
Sulfa allergies may develop , and patients suffering this allergy can not take sulfa
Hematopoietic disturbances and Sulfonamides :
Haemolytic anemia in patients with G6PD deficiency
Kernicterus and Sulfonamides :
It occurs in newborn due to displacement of protein-bound bilirubin in plasma by Sulfonamides causing accumulation of free bilirubin in BBB that is not well-developed causing Kernicterus
Drug-drug interaction and Sulfonamides :
Sulfonamides interact with warfarin causing increase in the anticoagulant effect of warfarin
Sulfonamides Contraindications :
1) Forbidden in newborn, infants and breastfeeding women
2) with Methenamine ( Sulfonamides can crystallise in the presence of formaldehyde produced by methenamine )
MOA of trimethoprims :
It inhibits dihydrofolate reductase , decreasing purine and pyramidine synthesis
Antibacterial Spectrum of trimethoprim :
Against H.infleunza , streptococcus, staphylococcus spp. and enterobacteriaceae (causing UTIs )
Same as sulfa drugs
Trimethoprim are ……………………. So it can be used ………….. in ………….&…………….
More potent as a single drug , alone , UTIs and bacterial prostatitis
MOR of trimethoprim
1) Altered dyhydrofolate reductase
2) Efflux pumps
Adverse effects of trimethoprim:
1) Effects of folic acid deficiency including megaloblastic anemia,leukopenia and granulocytopenia
2) Hyperkalemia
How is folic acid deficiency reversed ?
By administration of folinic acid which does not enter bacteria
About Cotrimoxazole :
- It is a combination of Sulfonamides and trimethoprim
- it has a synergistic effect
- it inhibits two sequential steps in the synthesis of tetrahyfropholic acid
Antibacterial spectrum of Cotrimoxazol : (cases )
1) effective against UTIs , RTIs and GITIs
2) effective against pneumocystis jirovecll pneumonia
3) against skin and soft tissue MRSA
4) Listeriosis
5) Infections caused by Nocardia spp.
Pharmacokinetics of Cotrimoxazole :
- Administered orally and IV for severe cases of pneumocystis pneumonia
- Cross BBB
- Excreted in the urine
Adverse effects of Cotrimoxazole
1) N/V/D
2) Skin reactions
3) Glossitis / Stomatitis
4) Hyperkalemia
5)Megaloblastic anemia
6) haemolytic anemia in patients with G6PD deficiency
7) drug-drug interaction with warfarin
About UTIs :
1) More prevalent in Women and elderly
2) Most common cause is E.coli ( 80% of uncomplicated UTIs )
3) Second most common use is staphylococcus saprophyticus
Most frequently used agents :
1) flouroquinolones
2) Cotrimoxazole
3) Methenamine
4) Nitrofurantoin
MOA Of Methenamine :
1) Decomposes at an acidic pH of 5.5 or less in the urine
2) production of formaldehyde which is a toxic material for bacteria
Antibacterial Spectrum of Methenamine :
1) against Pseudomonas or Proteus spp
2) Chronic suppressive therapy in UTIs
MOA of Nitrofurantoin :
Inhibit DNA and RNA Synthesis
Antibacterial Spectrum of Nitrofurantoin :
Effective against E.coli
Adverse effects of Nitrofurantoin:
Cause haemolytic anemia in patients with G6PD
Nitrofurantoin Contraindications :
1) Patients with renal impairment
2) Pregnant women
……………………… is now first-line for uncomplicated cystitis
Nitrofurantoin
