Folic Acid Antagonist ( All Drugs Related )

Question 1

Why is folic acid important ? And how ?

Answer 1

Folic acid is necessary for DNA replication and cellular growth , especially in Purine and pyramidine synthesis that require folate-derived cofactors

Question 2

Bacteria and folic acid :

Answer 2

Many bacteria are impermeable to folate , rely on de novo synthesis.

Question 3

De novo Sunthesis of folate in bacteria : (Steps)

Answer 3

1) P-Aminobenzoic acid ———> Dihydrofolic acid
“ Dihydropteroate synthatase “
“ Sulfonamides “
2) Dihydrofolic acid ———> tetrahydropholic acid
“ Dihydrofolate reductase “
“ Trimethoprim “
3) Tetrahydropholic acid —> Purines —> DNA

Question 4

Folic acid must be converted into :

Answer 4

Tetrahydrofolic acid.

Question 5

What are Sulfonamides derivatives?

Answer 5

1) Mafenide
2) Silver Sulfadiazine
3) Sulfasalazine

Question 6

MOA of sulfonamide :

Answer 6

Sulfonamides inhibit dihydropteroate synthetase by competition

Question 7

Antibacterial Spectrum of Sulfonamides :

Answer 7

Effective against H.infleunza, streptococcus spp. , staphylococcus spp. and enterobacteriaceae ( Causing UTIs )

Question 8

MOR of Sulfonamides :

Answer 8

1) Altered dihydropteroate synthetase
2) Decreased cellular permeability against Sulfonamides
3) Enhanced production of PABA

Question 9

Absorption of Sulfonamides

Answer 9

Sulfonamides are well-absorbed orally except sulfasalazine

Question 10

About Sulfasalazine :

Answer 10

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

Question 11

Distribution of Sulfonamides:

Answer 11

1) highly-bound to serum albumin
2) Distribute well through body fluids including CSF
3) Cross the placenta

Question 12

Metabolism of Sulfonamides:

Answer 12

They are metabolised in the liver by acetylation and conjugation

• acetylated metabolites can crystallise in urine causing renal stones

Question 13

Elemination of Sulfonamides:

Answer 13

• Eliminated by glomerular filtration and secretion
• eliminated in breast milk

Question 14

Adverse effects of Sulfonamides :

Answer 14

1) Crystalluria
2) Hypersensitivity
3) Hematopoitic disturbances
4) Kernicterus
5) Drug-drug interaction

Question 15

Crystelluria and Sulfonamides :

Answer 15

-Nephrotoxicity may develop as a result of crystalluria resulted in sulfa utilisation

• to prevent Nephrotoxicity requires adequate hydration and urine alkalinazation

Question 16

Hypersensitivity of Sulfonamides:

Answer 16

Sulfa allergies may develop , and patients suffering this allergy can not take sulfa

Question 17

Hematopoietic disturbances and Sulfonamides :

Answer 17

Haemolytic anemia in patients with G6PD deficiency

Question 18

Kernicterus and Sulfonamides :

Answer 18

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

Question 19

Drug-drug interaction and Sulfonamides :

Answer 19

Sulfonamides interact with warfarin causing increase in the anticoagulant effect of warfarin

Question 20

Sulfonamides Contraindications :

Answer 20

1) Forbidden in newborn, infants and breastfeeding women
2) with Methenamine ( Sulfonamides can crystallise in the presence of formaldehyde produced by methenamine )

Question 21

MOA of trimethoprims :

Answer 21

It inhibits dihydrofolate reductase , decreasing purine and pyramidine synthesis

Question 22

Antibacterial Spectrum of trimethoprim :

Answer 22

Against H.infleunza , streptococcus, staphylococcus spp. and enterobacteriaceae (causing UTIs )

Same as sulfa drugs

Question 23

Trimethoprim are ……………………. So it can be used ………….. in ………….&…………….

Answer 23

More potent as a single drug , alone , UTIs and bacterial prostatitis

Question 24

MOR of trimethoprim

Answer 24

1) Altered dyhydrofolate reductase
2) Efflux pumps

Question 25

Adverse effects of trimethoprim:

Answer 25

1) Effects of folic acid deficiency including megaloblastic anemia,leukopenia and granulocytopenia 2) Hyperkalemia

Question 26

How is folic acid deficiency reversed ?

Answer 26

By administration of folinic acid which does not enter bacteria

Question 27

About Cotrimoxazole :

Answer 27

- It is a combination of Sulfonamides and trimethoprim - it has a synergistic effect - it inhibits two sequential steps in the synthesis of tetrahyfropholic acid

Question 28

Antibacterial spectrum of Cotrimoxazol : (cases )

Answer 28

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.

Question 29

Pharmacokinetics of Cotrimoxazole :

Answer 29

- Administered orally and IV for severe cases of pneumocystis pneumonia - Cross BBB - Excreted in the urine

Question 30

Adverse effects of Cotrimoxazole

Answer 30

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

Question 31

About UTIs :

Answer 31

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

Question 32

Most frequently used agents :

Answer 32

1) flouroquinolones 2) Cotrimoxazole 3) Methenamine 4) Nitrofurantoin

Question 33

MOA Of Methenamine :

Answer 33

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

Question 34

Antibacterial Spectrum of Methenamine :

Answer 34

1) against Pseudomonas or Proteus spp 2) Chronic suppressive therapy in UTIs

Question 35

MOA of Nitrofurantoin :

Answer 35

Inhibit DNA and RNA Synthesis

Question 36

Antibacterial Spectrum of Nitrofurantoin :

Answer 36

Effective against E.coli

Question 37

Adverse effects of Nitrofurantoin:

Answer 37

Cause haemolytic anemia in patients with G6PD

Question 38

Nitrofurantoin Contraindications :

Answer 38

1) Patients with renal impairment 2) Pregnant women

Question 39

……………………… is now first-line for uncomplicated cystitis

Answer 39

Nitrofurantoin