Quinolones, Folic Acid Antagonists, Urinary Antiseptics, Metronidazole (ic9)

Question 1

Examples of Fluoroquinolones

Which is 1st gen, 3rd gen

Answer 1

LMC
3rd gen: Levofloxacin, Moxifloxacin

1st gen: Ciprofloxacin

Question 2

MOA of Fluoroquinolones (2 points)

Answer 2

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

Question 3

PK of Fluoroquinolones (Administration, absorption affected by, Clearance)

Answer 3

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

Question 4

Indication of Ciprofloxacin + dont use in?

Answer 4

Gram (-) resistant strains
Active against Pseudomonas (only oral agent)

DONT USE in simple UTI, MRSA (staph resistance)

Question 5

Indication of Moxifloxacin and Levofloxacin (3rd gen)
(3 points)

which one cannot cover pseudomonas

Answer 5

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

Question 6

Adverse events of Fluoroquinolones (7 points)

Answer 6

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

Question 7

Contraindications for Fluoroquinolones (3 points)

Answer 7

Not recommended for pregnancy

Pts with Myasthenia gravis
Like Aminoglycosides

G6PD deficiency

Question 8

MOA of Sulfamethoxazole

Answer 8

Competitive inhibitor of Dihydropteroate Synthase

Works on bacteria that synthesise their own folic acid

Question 9

PK of Sulfamethoxazole (Administration, Metabolism, Excretion)

Answer 9

Oral (well absorbed)

Metabolism
Acetylation, Conjugation in liver
Metabolite can precipitate in urine → cause crystalluria, damage kidney

Renal excretion

Question 10

Indication of Sulfamethoxazole

Answer 10

Used as combination with Trimethoprim

Many species become resistant eg. staph, strep

Question 11

Adverse effects of Sulfamothoxazole (4 points)

Answer 11

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

Question 12

MOA of Trimethoprim

Answer 12

Inhibit Dihydrofolate reductase

Reduced availability of Tetrahydrofolic acid req for DNA and amino acid synthesis

Question 13

Indication of Trimethoprim

Answer 13

Gram (-) eg. Enterobacter, E.coli, Klebs
Coverage similar to Sulfamethoxazole

Used for UTI

Question 14

PK of Trimethoprim (Administration, Excretion)

Answer 14

Rapidly absorbed after oral administration
Excreted renally, unchanged

Question 15

Adverse effects of Trimethoprim (2 points)

Answer 15

Effects of Folic acid deficiency
Eg. Megaloblastic anemia, leukopenia, granulocytopenia
Treatment: give folinic acid

Contraindicated in pregnancy
Folic acid important for development of baby

Question 16

What is the ratio composition of Cotrimoxazole

Answer 16

5S1T
5 sulfamethoxazole, 1 trimethoprim

Question 17

PK of Cotrimoxazole (administration, CSF penetration, clearance)

Answer 17

Oral, take with a cup of water
IV
Good CSF penetration, readily cross BBB
Renally cleared

Question 18

Indications of Cotrimoxazole (4 points)

Answer 18

Simple UTI
First line

Pneumocystis pneumonia (opportunistic infection in immunocompromised patients)

Respiratory Tract infections

MRSA

Question 19

Adverse events of Cotrimoxazole (5 points)

Answer 19

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

Question 20

Contraindication of Cotrimoxazole

Answer 20

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

Question 21

What is Nitrofurantoin used for

Answer 21

Prevention and treatment of lower UTI

Question 22

MOA of Nitrofurantoin

Answer 22

Inhibit enzymes and disrupt synthesis of proteins, DNA, RNA, metabolic processes

Produce reactive oxygen species
Hence CI in G6PD deficient patients

Question 23

Spectrum of activity of Nitrofurantoin + Resistant to what?

Answer 23

E.coli
Enterococci

Resistant to Pseudomonas, Enterobacter, Klebs

Question 24

PK of Nitrofurantoin (Administration, absorption, Distribution)

Answer 24

Oral
Rapid absorption in GI tract
Enter urine quickly → Ideal treatment for UTI

Question 25

Adverse effect of Nitrofurantoin (3 points)

Answer 25

GI nausea, vomiting, diarrhea

Colour urine brown

G6PD Deficiency
Cause Leukopenia, Hemolytic anaemia

Question 26

Contraindications of Nitrofurantoin (3 points)

Answer 26

Impaired renal function (CrCl<40ml/min)

Pregnancy
Dont know if child is G6PD deficient

Infants < 2 months

Question 27

What is Metronidazole for

Answer 27

target infection caused by amoebas

Question 28

MOA of Metronidazole

Answer 28

Nitro group in Metronidazole serves as electron acceptor → form cytotoxic free radicals, result in protein and DNA damage

Question 29

Indication for Metronidazole

Answer 29

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

Question 30

PK of Metronidazole (administration, CSF penetration, metabolism)

Answer 30

Good oral F
CSF penetration
Hepatic metabolism

Question 31

Adverse effects of metronidazole (3 points)

Answer 31

GI nausea, vomiting, epigastric distress
Metallic taste
Seizures, optic and peripheral neuropathy