Quinolones, Folic Acid Antagonists, Urinary Antiseptics, Metronidazole (ic9) Flashcards
Examples of Fluoroquinolones
Which is 1st gen, 3rd gen
LMC
3rd gen: Levofloxacin, Moxifloxacin
1st gen: Ciprofloxacin
MOA of Fluoroquinolones (2 points)
Target DNA gyrase in Gram (-)
DNA gyrase causes negative supercoils to prevent excessive positive supercoils
Result: excessive (+) supercoiling
Topoisomerase 4 in Gram (+)
Topoisomerase 4 separates chromosomal DNA
PK of Fluoroquinolones (Administration, absorption affected by, Clearance)
Administration
Oral, IV, ophthalmic
Well absorbed orally
Divalent, Trivalent cations can reduce absorption (similar to Tetracyclines)
Take on empty stomach
Ciprofloxacin → Renal clearance
Moxifloxacin → Hepatic clearance
Indication of Ciprofloxacin + dont use in?
Gram (-) resistant strains
Active against Pseudomonas (only oral agent)
DONT USE in simple UTI, MRSA (staph resistance)
Indication of Moxifloxacin and Levofloxacin (3rd gen)
(3 points)
which one cannot cover pseudomonas
Better Gram (+) coverage
Atypicals (MCL)
Similar to Macrolides, Tetracyclines
Respiratory infections / Respiratory quinolones
Similar to Macrolides
Second line for TB but dont use when suspecting TB
Moxifloxacin cannot cover pseudomonas
Adverse events of Fluoroquinolones (7 points)
1) GI related nausea, vomiting
2) Aortic dissections (tear in aorta)
3) C. diff colitis
4) Phototoxicity
Like Tetracyclines
5) Tendonitis, Tendon rupture
6) Joint problems (Arthropathy)
Not recommended for children < 18 yo
7) Prolong QT interval
Like Macrolides
Contraindications for Fluoroquinolones (3 points)
Not recommended for pregnancy
Pts with Myasthenia gravis
Like Aminoglycosides
G6PD deficiency
MOA of Sulfamethoxazole
Competitive inhibitor of Dihydropteroate Synthase
Works on bacteria that synthesise their own folic acid
PK of Sulfamethoxazole (Administration, Metabolism, Excretion)
Oral (well absorbed)
Metabolism
Acetylation, Conjugation in liver
Metabolite can precipitate in urine → cause crystalluria, damage kidney
Renal excretion
Indication of Sulfamethoxazole
Used as combination with Trimethoprim
Many species become resistant eg. staph, strep
Adverse effects of Sulfamothoxazole (4 points)
Crystalluria
Lead to Nephrotoxicity
Treatment: Hydration and alkalinisation
Hypersensitivity
Sulfa allergies
Hemolytic Anaemia
In G6PD Deficiency patients
In G6PD Deficiency, patients have alot of reactive oxygen species, RBC vulnerable
Kernicterus
Sulfa drugs bind to albumin and displace bilirubin
Bilirubin pass BBB and cause defects in CNS
MOA of Trimethoprim
Inhibit Dihydrofolate reductase
Reduced availability of Tetrahydrofolic acid req for DNA and amino acid synthesis
Indication of Trimethoprim
Gram (-) eg. Enterobacter, E.coli, Klebs
Coverage similar to Sulfamethoxazole
Used for UTI
PK of Trimethoprim (Administration, Excretion)
Rapidly absorbed after oral administration
Excreted renally, unchanged
Adverse effects of Trimethoprim (2 points)
Effects of Folic acid deficiency
Eg. Megaloblastic anemia, leukopenia, granulocytopenia
Treatment: give folinic acid
Contraindicated in pregnancy
Folic acid important for development of baby
What is the ratio composition of Cotrimoxazole
5S1T
5 sulfamethoxazole, 1 trimethoprim
PK of Cotrimoxazole (administration, CSF penetration, clearance)
Oral, take with a cup of water
IV
Good CSF penetration, readily cross BBB
Renally cleared
Indications of Cotrimoxazole (4 points)
Simple UTI
First line
Pneumocystis pneumonia (opportunistic infection in immunocompromised patients)
Respiratory Tract infections
MRSA
Adverse events of Cotrimoxazole (5 points)
same as sulfamethoxazole and trimethoprim individually + hyperkalemia
1) Hypersensitivity
2) GI nausea, vomiting, CDAD
3) Haemolytic anaemia (from Sulfamethoxazole)
For pts with G6PD deficiency
4) Folic acid deficiency (from Trimethoprim)
5) Hyperkalemia
Contraindication of Cotrimoxazole
Hypersensitivity
G6PD deficiency
Folate deficiency
Pregnancy (avoid in 1st and 3rd trimester)
1st trimester: folic acid deficiency for development of fetus
3rd trimester: kernicterus (from Sulfamethoxazole)
Infants < 2 months
What is Nitrofurantoin used for
Prevention and treatment of lower UTI
MOA of Nitrofurantoin
Inhibit enzymes and disrupt synthesis of proteins, DNA, RNA, metabolic processes
Produce reactive oxygen species
Hence CI in G6PD deficient patients
Spectrum of activity of Nitrofurantoin + Resistant to what?
E.coli
Enterococci
Resistant to Pseudomonas, Enterobacter, Klebs
PK of Nitrofurantoin (Administration, absorption, Distribution)
Oral
Rapid absorption in GI tract
Enter urine quickly → Ideal treatment for UTI
Adverse effect of Nitrofurantoin (3 points)
GI nausea, vomiting, diarrhea
Colour urine brown
G6PD Deficiency
Cause Leukopenia, Hemolytic anaemia
Contraindications of Nitrofurantoin (3 points)
Impaired renal function (CrCl<40ml/min)
Pregnancy
Dont know if child is G6PD deficient
Infants < 2 months
What is Metronidazole for
target infection caused by amoebas
MOA of Metronidazole
Nitro group in Metronidazole serves as electron acceptor → form cytotoxic free radicals, result in protein and DNA damage
Indication for Metronidazole
Good Anaerobic coverage
Similar to Clindamycin
Added on to increase anaerobic coverage
Anaerobes eg. C.diff / CDAD, bacteroides
Amoebic infections caused by Protozoa eg. Entamoeba
PK of Metronidazole (administration, CSF penetration, metabolism)
Good oral F
CSF penetration
Hepatic metabolism
Adverse effects of metronidazole (3 points)
GI nausea, vomiting, epigastric distress
Metallic taste
Seizures, optic and peripheral neuropathy
