Presentation at hospital

1. METRONIDAZOLE
Jawad Ahmad
FY2

2. Outline
•Anaerobic Infections
•Introduction
•Dosage forms and Trade names
•Pharmacokinetics
•Mechanism of action
•Indications
•Side effects
•Drug Interactions
•Important things to remember
•References

3. ANAEROBIC BACTERIA OF MEDICAL
INTEREST
MORPHOLOGY GRAM STAIN GENUS
Spore forming (+) Clostridium
Non-Spore Forming Bacilli
(+)
(-)
Actinomycetes,
Bifidobacterium,Eubacte-
rium,Propionibacerium,
Mobilncus,Lactobacillus
Bacteroides,Fusobacterium
Prevotella,Porphyromonas
Non-Spore Forming Cocci
(+)
(-)
Peptococcus,
Pepto-streptococcus
Streptococcus
Veilonella

5. SITES AND INFECTION
PRODUCED BY ANAEROBES

6. CLASSIFICATION OF
AMEBICIDAL DRUGS
According to the site where the drug is effective, the amebicidal
drugs are classified as:
• Luminal amebicides (Act on the organisms in the lumen of bowel)
• Systemic amebicides (Against amebas in intestinal wall & liver)
• Mixed amebicides ( Against both the luminal
and systemic form of diseases).

7. Introduction
•Metronidazole (Flagyl) is a synthetic antiprotozoal and antibacterial
agent,( l-β-hydroxyethyl)-2-methyl-5-nitroimidazole, which has the
following structural formula:
•It belongs to the group of Nitro Imidazoles.
•It is a Mixed Amebicidal which means it has both Luminal and Extra-
Luminal effect.
•Other members related to metronidazole are
Tinidazole and others.

8. Dosage forms and Trade
names
•Trade names: Flagyl, Flagyl ER.
Dosage Forms: Tablet, Gel, Cream, Capsule, Tablet, Suspension
•Flagyl tablets contain 200 mg or 500 mg of metronidazole.
• Inactive ingredients include cellulose, hydroxypropyl cellulose.

9. BRANDS

10. PHARMACOKINETICS
•Absorption
• Bioavailability: 80% absorption from GI tract (PO)
• Protein binding (<20%)
• Peak serum time: 1-2 hr
•Distribution
• Widely distributed; similar pattern for PO and IV
•Metabolism
• Liver
• Enzymes inhibited: Hepatic CYP2C9
•Elimination
• Half-life: 25-75 hr (neonates); 8 hr (others); prolonged in patients with hepatic
impairment
• Excretion: Urine (77%); feces (14%)

11. Mechanism of Action
• Metronidazole acts by inhibiting nucleic acid synthesis by disrupting the DNA
of microbial cells.
• This function only occurs when metronidazole is partially reduced, and
because this reduction usually happens only in anaerobic cells, it has relatively
little effect upon human cells or aerobic cells.
•Metronidazole is activated (reduced) by the microbial proteins flavodoxins and
ferredoxins found in anaerobic bacteria and certain protozoans Mammalian
cells are unharmed because they lack flavodoxins and ferredoxins that reduce
the nitro group of metronidazole
•Flavodoxins and Ferredoxins are electron-transfer proteins that serve as
electron donors in the reductive activation of anaerobic ribonucleotide
reductase, biotin synthase,…etc
•Once activated, the drug (a short-lived reduction product, most probably the
protonated one electron nitro radical anion) oxidizes DNA causing strand
breaks and subsequent cell death.

12. Mechanism of Action

13. Indications
Anaerobe infections
C. difficile
H. pylori(triple regime)
Bacterial vaginosis
Trichomonas vaginitis
Amebiasis
Giardiasis
Dental Abscesses
Prophylactic after
surgery

14. 1.AMEBIASIS
 Metronidazole is the drug of choice for the treatment of all tissue
infections with Entamoeba histolytica
 It is not reliably effective against luminal parasites and so must be
used with a luminal amebicide to ensure eradication of the infection
 Tinidazole, a related nitroimidazole, appears to have similar activity
and a better toxicity profile than metronidazole

15. 2.GIARDIASIS
 Metronidazole is the treatment of choice for Giardiasis
 The dosage for Giardiasis is much lower— and the drug thus better
tolerated—than that for Amoebiasis
 Efficacy after a single treatment is about 90%
 Tinidazole is equally effective

16. 3.TRICHOMONIASIS
Metronidazole is the treatment of choice. A single dose of 2grams is
effective or 200mg TDS for 7days.
Metronidazole-resistant organisms may lead to treatment failures
Tinidazole may be effective against some of these infections
T. vaginalis infection is a venereal disease. Therefore, asymptomatic
sexual partners of treated patients should be treated simultaneously if
the organism has been found to be present, in order to prevent re-
infection of the partner

17. 4.BACTERIAL INFECTIONS
 Metronidazole has potent antibacterial activity against anaerobes,
including bacteroides and clostridium species
 Metronidazole is indicated for treatment of anaerobic or mixed intra-
abdominal infections, vaginitis (bacterial vaginosis), antibiotic-
associated enterocolitis, acute gingivitis and other dental infections
 Metronidazole is indicated for treatment of vaginitis due to bacterial
Gardnerella or Mycoplasma hominis infection in symptomatic patients
 Helicobacter pylori eradication therapy, as part of a multi-drug regimen
in peptic ulcer disease

18. SIDE EFFECTS OF
METRONIDAZOLE
Nausea, vomiting, diarrhea, epigastric distress, abdominal cramping and
constipation. Taking the drug with meals lessens gastrointestinal irritation
A sharp, unpleasant Metallic taste, furry tongue, glossitis, dry mouth and stomatitis.
These may be associated with a sudden overgrowth of Candida which may occur
during therapy
Proliferation of Candida in the vagina, dysuria, polyuria, Dark urine, cystitis,
incontinence and proctitis
Reversible neutropenia (leukopenia) and reversible thrombocytopenia
Although teratogenic in some animals, metronidazole has not been associated with
this effect in humans
Metronidazole and its metabolites are mutagenic in bacteria. Chronic administration
of large doses led to Tumorigenicity in mice and rats
Convulsive seizures and peripheral neuropathy (with prolonged use) are serious
adverse effects, however they are rare

19. SIDE EFFECTS OF
METRONIDAZOLE
Epigastric distress
Metallic taste in mouth
Darkening of urine
Pancreatitis
Hepatitis
Fever
Peripheral neuropathy
Seizures
Reversible neutropenia

20. SIDE EFFECTS OF
METRONIDAZOLE
Gastrointestinal Haematological
Genitourinary: Neurolological

21. DRUG INTERACTIONS
DRUG INTERACTION
ALCOHOL Mild disulfiram like reaction (Nausea,
headache, vomiting, abdominal cramps)
ANTICOAGULANTS (WARFARIN) Prolonged PT(Prothrombin time)
CIMETIDINE Prolong half life & decrease clearance of
Metronidazole
PHENYTOIN & PHENOBARBITONE Decrease serum concentration and increase
metabolism of Metronidazole

22. PREGNANCY AND LACTATION
•Pregnancy category: B
•Lactation
•Excreted in human milk; not recommended
•Following PO administration, concentrations in human milk are similar to
concentrations in plasma, therefore advice patient to stop breast feeding
whilst taking metronidazole and for 12-24 hours after.

23. PREGNANCY CATEGORY-B
Category A: Means that controlled studies have found no risk to the
fetus when the mother takes the medication during any trimester
of pregnancy.
Category B: Means that controlled studies in pregnant women have not
shown an increased risk of fetal abnormalities, although some adverse
findings have occurred in animals

24. IMPORTANT THINGS TO
REMEMBER BEFORE
DISPENSING
METRONIDAZOLE•Patient should be asked about other medications he/she is taking as well as
other important questions like allergies and intolerances.
•Any woman in child bearing age should be asked if she is pregnant.
•Any old man should be asked about history of chronic illness, especially
hepatic and renal diseases.
•Social history must inquire alcohol consumption of the patient. Patient
advised not to take alcohol whilst taking this medicine and for48 hours after
finishing the course.

25. REFERENCES
•Katzung & Trevor's Pharmacology Examination and Board Review,13th
Edition (Katzung & Trevor's Pharmacology Examination & Board Review),
ISBN-13: 978-0071789233
•Lippincott Illustrated Reviews: Pharmacology 6th edition (Lippincott
Illustrated Reviews Series), ISBN-13: 978-1451191776
•www.reference.medscape.com
•www.webmd.com
•www.medicinenet.com
•BNF Online
•www.nice.org.uk

27. THE DUTY OF A DOCTOR
TO CURE SOMETIMES
TO RELIEVE OFTEN
TO CARE ALWAYS
ABOVE ALL, DO NO HARM