MicroB Antimicrobials 5. Nucleic Acid Synthesis Inhibitors

Question 1

Compared to ciprofloxacin which is active against gram negative strains and enteric coliform, third generation fluoroquinolones levofloxacin and moxifloxacin have better coverage against Gram […] organisms (especially S pneumoniae) and increased coverage against […] pathogens (such as Mycoplasma pneumoniae and Chlamydia pneumoniae)

Therefore Thus these 3rd gen FQs are useful against respiratory infections due to the above mentioned organisms and Mycobacterium tuberculosis, and are occasionally referred to as the […]

Answer 1

Compared to ciprofloxacin which is active against gram negative strains and enteric coliform, third generation fluoroquinolones levofloxacin and moxifloxacin have better coverage against Gram positive organisms (especially S pneumoniae) and increased coverage against atypical pathogens (such as Mycoplasma pneumoniae and Chlamydia pneumoniae)

Therefore Thus these 3rd gen FQs are useful against respiratory infections due to the above mentioned organisms and Mycobacterium tuberculosis, and are occasionally referred to as the respiratory quinolones

3rd gen levofloxaxin moxifloxacin useful for things that has “pneumoniae” inside lol (including MTB). Life hacks.

TLDR,

Vid on antibiotic ladder. Really good!
https://www.youtube.com/watch?v=rhFZ-yPfy2U

Question 2

Cotrimoxazole is the combination of […] and […] in 1:5 ratio.

Answer 2

Cotrimoxazole is the combination of Trimethoprim and Sulfamethoxazole in 1:5 ratio.
The synergistic antimicrobial activity of cotrimoxazole results from its inhibition of two sequential steps in the synthesis of tetrahydrofolic acid.
- Sulfamethoxazole inhibits dihydropteroate synthase (incorporation of PABA into dihydrofolic acid precursors)
- Trimethoprim inhibits dihydrofolate reductase (reduction of dihydrofolate to tetrahydrofolate)

Question 3

Folate Synthesis Inhibitors include Sulfonamides, Trimethoprim and Cotrimoxazole.

• Sulfonamides competitively inhibit […], which is the bacterial enzyme responsible for converting PABA into dihydropteroic acid
• Trimethoprim inhibits […], which converts dihydrofolic acid to tetrahydrofolic acid (required for purine, pyrimidine, and amino acid synthesis)

Answer 3

Folate Synthesis Inhibitors include Sulfonamides, Trimethoprim and Cotrimoxazole.

• Sulfonamides competitively inhibit dihydropteroate synthase (DHPS), which is the bacterial enzyme responsible for converting PABA into dihydropteroic acid
• Trimethoprim inhibits dihydrofolate reductase (DHFR), which converts dihydrofolic acid to tetrahydrofolic acid (required for purine, pyrimidine, and amino acid synthesis)

Mammalian cells require preformed folic acid, cannot synthesize it, and are thus insensitive to Sulfonamides (but not trimethoprim)

Trimethoprim and methotrexate both targets DHFR. Methotrexate used as an anti-cancer drug.

Question 4

Nitrofurantoin is a urinary antiseptic that is reduced by sensitive bacteria to a highly active intermediate that inhibits various enzymes and distrupt the synthesis of proteins, DNA, RNA, and metabolic processes.

Useful against* E. Coli* and Enterococci, but not against […], […], and […].

Administered […]

Distribution: It achieves very high urinary concentrations while limiting systemic exposure (due to rapid […]), making it an ideal targeted medication for the treatment of […]

THIS IS THE ANTIBIOTIC THAT COLOURS THE URINE […]

Answer 4

Nitrofurantoin is a urinary antiseptic that is reduced by sensitive bacteria to a highly active intermediate that inhibits various enzymes and distrupt the synthesis of proteins, DNA, RNA, and metabolic processes.

Useful against E. Coli and Enterococci, but not against pseudomonas, proteus, and klebsiella.

Administered orally

Distribution: It achieves very high urinary concentrations while limiting systemic exposure (due to rapid clearance), making it an ideal targeted medication for the treatment of UTI

THIS IS THE ANTIBIOTIC THAT COLOURS THE URINE BROWN

Question 5

Similar to tetracyclines, Fluoroquinolones should NOT be administered with dairy products (contains […]) or other substances that contain divalent and trivalent […] (magnesium and aluminium antacids or iron supplements) as it decreases […].

Also cannot be taken with dietary supplements containing […] or […]

Answer 5

Similar to tetracyclines, Fluoroquinolones should NOT be administered with dairy products (contains calcium) or other substances that contain divalent and trivalent cations (magnesium and aluminium antacids or iron supplements) as it decreases absorption.

Also cannot be taken with dietary supplements containing iron or zinc

So best to take on empty stomach

Just memorize: wheels and flowers dont go well with milk or antacids or iron supplements!!!

Question 6

Sulfonamide adverse events

• Solution: … and … of urine can prevent the problem by reducing the concentration of drug and promoting its ionization.

**DONT use **for … pts

DONT use for newborns, infants less than 2 months of age as well as pregnant women at term due to ….

Answer 6

Sulfonamide adverse events

Crystalluria: Sulfa drugs acetylated and conjugated in the liver, becomes devoid of antimicrobial activity but retains toxic potential to precipitate at neutral or acidic pH. This can potentially lead to nephrotoxicity.
- Solution: Hydration and akalinisation of urine can prevent the problem by reducing the concentration of drug and promoting its ionization.

DONT use for G6PD deficiency pts

DONT use for newborns, infants less than 2 months of age as well as pregnant women at term due to Kernicterus.

Sulfa allergy as well. Can have SJS.

FYI –> Kernicterus from sulfa drug use during pregnancy: because sulfa drugs displace bilirubin from binding sites on serum albumin. The bilirubin is then free to pass into the CNS, as the blood brain barrier is not fully developed.

Question 7

The fluoroquinolone antibiotics inhibits DNA replication in bacteria by targeting:

Answer 7

The fluoroquinolone antibiotics inhibits DNA replication in bacteria by targeting:

• DNA gyrase in mainly gram negs: Introduces negative supercoils into the DNA to prevent excessive positive supercoiling
• Topoisomerase IV in mainly gram pos: Promotes separation of chromosomal DNA into daughter cells

Eukaryotic cells do not contain DNA gyrase. They have a mechanistically similar DNA topoisomerase II, which are inhibited by quinolones at higher concentrations.

Question 8

Trimethoprim adverse effects

Trimethoprim can produce the effects of […]. These include megaloblastic anemia, leukopenia, granulocytopenia, especially in pregnant patients (Cat C) and those having very poor diets
- Effects can be reversed by the simultaneous administration of […] which does not enter bacteria.
- not dihydrofolic acid which requires reduction to the active form

Answer 8

Trimethoprim adverse effects

Trimethoprim can produce the effects of folic acid deficiency. These include megaloblastic anemia, leukopenia, granulocytopenia, especially in pregnant patients (Cat C) and those having very poor diets
- Effects can be reversed by the simultaneous administration of folinic acid which does not enter bacteria.
- not dihydrofolic acid which requires reduction to the active form

FYI –> Folinic acid is a 5 formyl derivative of tetrahydrofolic acid which is readily converted to tetrahydrofolic acid, which is then utilised for important cellular metabolic functions