Anaerobic antimicrobials - Metronidazole

Question 1

What is metronidazole used for?

Answer 1

1) Antibiotic associated colitis (C.diff which is gram positive anaerobe)
2) Oral infections or aspiration pneumonia caused by gram negative anaerobes from the mouth
3) Surgical and Gynaecological infections caused by gram negative anaerobes from colon

4) Protozoal infections
(trichomonal vaginal infection, amoebic dysentery, giardiasis)

Question 2

What type of bacteria if C.Diff?

Answer 2

• gram positive anaerobe

Question 3

Metronidazole is effective against some protozoal infections - give 3 examples?

Answer 3

1) Trichomonal vaginal infection
2) Amoebic dysentery
3) Giardiasis

Question 4

What is the mechanism of action of metronidazole?

Answer 4

• metronidazole enters bacterial cells by passive diffusion.
• In anaerobic bacteria reduction of metronidazole generates a free radical.
• this free radical binds to DNA - reducing DNA synthesis, DNA degradation and cell death.

Question 5

What are the side effects of metronidazole?

Answer 5

• Peripheral and Optic neuropathy
• seizures
• encephalopathy
• GI upset
• hypersensitivity

Question 6

Why should metronidazole be reduced in people with sever liver disease?

Answer 6

• Metronidazole is metabolised by cytochrome P450 enzymes. So reduce dose in liver disease to reduce risk of toxicity

Question 7

Why is metronidazole contraindicated with alcohol?

Answer 7

• alcohol + metronidazole —–> disulfiram like reaction = flushing, headache, nausea, vomiting

Question 8

Why is metronidazole contraindicated with warfarin?

Answer 8

Metronidazole (is metabolised by cytochrome P450 enzyme) BUT also has an inhibitory effect on cytochrome P450 enzymes therefor reduced metabolism of warfarin so increases risk of bleeding.

Question 9

Why is metronidazole contraindicated with phenytoin?

Answer 9

1) Metronidazole has some inhibitory effect on cytochrome P450 enzymes, this leads to reduced metabolism of phenytoin —-> increased risk of toxicity and impaired cerebellar function.
2) Phenytoin is a cytochrome P450 inducer so more metabolism of metronidazole —-> reduced plasma concentration and impaired antimicrobial efficacy.

Question 10

Why is metronidazole contraindicated with rifampicin?

Answer 10

Rifampicin is a cytochrome P450 inducer this increases metronidazole metabolism ——> so decreased plasma conc of metronidazole so impaired antimicrobial efficacy.

Question 11

What are the drug interactions of metronidazole?

Answer 11

1) drugs metabolised by P450
- warfarin
- phenytoin

2) Drugs that induce P450
- phenytoin
- rifampicin

3) Metronidazole increases risk of toxicity of lithium

Question 12

What is the typical starting dose of Metronidazole orall vs IV?

Answer 12

Oral:
400mg 8hrly oral

IV:
500 mg 8hrly IV (infused over 20 mins)

Question 13

What are the different routes of metronidazole?

Answer 13

• oral
• IV
• rectal
• topical gel