Metronidazole

Question 1

What is the trade name for metronidazole?

Answer 1

Flagyl

Question 2

What is the formal drug classification of metronidazole?

Answer 2

-The injection is the parenteral dosage form of the synthetic antibacterial agent 1-(beta-hydroxyethyl)-2-methyl-5-nitroimadazole

Question 3

What are the clinical uses of metronidazole?

Answer 3

-it is active in vitro against most obligate anaerobes

Question 4

What does metronidazole NOT have any significant effects against?

Answer 4

facultative anaerobes or obligate aerobes

Question 5

Which organisms is metronidazole effective against?

Answer 5

• Anaerobic gram negative bacilli: Bacteroides species and the Fusobacterium species
• Anaerobic gram positive bacilli: Clostridium species and susceptible strains of Eubacterium
• Anaerobic gram positive cocci: Peptococcus species and Peptostreptococcus species

Question 6

What is the MOA of metronidazole?

Answer 6

• metronidazole is broken down and activated by anaerobic organisms to a compound that damages the parasite
• metronidazole is inactive until it is reduced within the host or microbial cell via an interaction with reduced ferredoxin or with specific nitroreductases
• the activated form of metronidazole forms reduced cytotoxic compounds that bind to proteins, membranes and leading to severe damage to the host organism

Question 7

What makes metronidazole sensitive for ameba and anaerobic organisms?

Answer 7

-due to the presence of PFOR activity that is lacking in most eukaryotes and eubacteria; however, poorly oxygenated tissues such as abscesses can activate metronidazole

Question 8

What is the elimination half life of metronidazole?

Answer 8

8 hrs in health adults; newborn infants have a diminished capacity to eliminate it

Question 9

How is metronidazole metabolized?

Answer 9

30-60% is metabolized by the liver

-metronidazole is the major component found in plasma with its 2-hydroxymethyl metabolite making up the lesser component

Question 10

How is metronidazole eliminated?

Answer 10

-major route of elimination (60-80%) is via urine with fecal elimination accounting for 6-15%

Question 11

What are the major metabolites that appear in the urine? what do they come from?

Answer 11

• they come from side chain oxidation
• 1-(beta-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole-1hy-acetic acid; holy cow this better now be something we need to know!
• glucuronide conjugation, with unchanged metronidazole accounting for 20% of the total

Question 12

Is metronidazole protein bound?

Answer 12

Less than 20% of the circulating metronidazole is bound to plasma protein

Question 13

What is the volume of distribution of metronidazole?

Answer 13

distributed rapidly throughout the tissues reaching high concentration in bodily fluids such as CSF, saliva and breast milk (concentrations in these bodily fluids are similar to that in plasma)

• also distributed to saliva, bile, seminal fluids, bone, liver and liver abscesses, lung and vaginal secretions
• also crosses the BBB and placenta

Question 14

With regards to a single dose of Metronidazole, how does decreased renal function alter it?

Answer 14

decreased renal function dose not alter the single dose pharmacokinetics of metronidazole; however, plasma clearance is decreased in patients with decreased liver function

Question 15

Can metronidazole be removed by dialysis?

Answer 15

YES

Question 16

What are the CNS side effects of metronidazole?

Answer 16

Convulsive seizures
encephalopathy
aseptic meningitis
optic and peripheral neuropathy
Ataxia
Confusion
Impaired Coordination
Dizziness
Headache
Insomnia
Irritibilit
Vertigo

Question 17

What are the endocrine/metabolic side effects of metronidazole?

Answer 17

Disulfiram-like reaction
Dysmenorrhea
Libido Decreased

Question 18

What are the respiratory side effects of metronidazole?

Answer 18

Nasal Congestion
Rhinitis
Sinusitis
Pharyngitis

Question 19

What are the cardiac side effects of metronidazole?

Answer 19

Flattening of the T wave and flushing

Question 20

What are the GI side effects of metronidazole?

Answer 20

N/V/D
Anorexia
Furry Tongue
Glossitis
Proctitis
Abdominal Discomfort
Stomatitis
Xerostomia
Constipation
Unpleasant metallic Taste

Question 21

What are the GU side effects of metronidazole?

Answer 21

Cystitis
Darkened Urine
Dysuria
Incontinence
Polyuria
Vaginitis

Question 22

What are the musculo-skeletal side effects of metronidazole?

Answer 22

Peripheral neuropathy and weakness

Question 23

What are the hematologic side effects of metronidazole?

Answer 23

Reversible neutropenia (leukopenia)
Reversible thrombocytopenia

Question 24

What can happen with IV administration?

Answer 24

Thrombophlebitis

Question 25

What can metronidazole cause dermatologically?

Answer 25

Erythematous rash, urticaria, and pruritis

Question 26

What are the symptoms of and OD of metronidazole?

Answer 26

N/V ataxia Seizures Peripheral neuropathy

Question 27

What are the contraindications of Metronidazole?

Answer 27

- History of hypersensitivity to metronidazole or other nitroimidazole derivatives - Careful administration of metronidazole injection should be done in patients with evidence of or history of blood dyscrasia because of mild leukopenias have been observed - Patients with a history of severe hepatic disease should be cautious due to decreased ability to metabolize metronidazole, which could result in accumulation of metronidazole and its metabolites in the plasma - careful with the elderly - Cautious to pts with history of: seizures, CHF, and sodium retention states - crosses the placenta and enters the fetal circulation rapidly

Question 28

What category is metronidazole for pregnancy?

Answer 28

Pregnancy category B

Question 29

Name the drugs that cause an interaction with metronidazole? (we will describe the interaction in a few :-)

Answer 29

``` Warfarin Phenytoin Phenobarbital Cimetidine Alcohol Corticosteroids Cisapride ```

Question 30

What happens when metronidazole and warfarin/coumadin are given together?

Answer 30

Increase the anticoagulant effect

Question 31

What happens if Phenytoin or Phenobarbital are taken with Metronidazole?

Answer 31

The simultaneous administration of drugs that increase microsomal liver enzymatic activity can accelerate the elimination of Metronidazole resulting in decreased plasma concentration. In addition it has been shown that when Metronidazole and phenytoin are used simultaneously patients have impaired clearance of phenytoin

Question 32

What interaction is caused between metronidazole and Cimetidine?

Answer 32

The simultaneous administration of drugs that decrease microsomal liver enzymatic activity can prolong the half-life and decrease plasma clearance of metronidazole

Question 33

What interaction occurs due to the use of metronidazole and alcohol?

Answer 33

Should not be consumed during metronidazole injection therapy because abdominal cramps, nausea, vomiting, headaches and flushing may occur. Should NOT be given to alcoholic patients that are on disulfiram therapy due to reported psychotic events occurring with combined therapy

Question 34

What is the drug interaction between metronidazole and corticosteroids?

Answer 34

Care should be given to patients prescribed Metronidazole injection who are simultaneously on corticosteroids or patients predisposed to edema b/c sodium retention may occur

Question 35

What is the drug interaction between metronidazole and Cisapride?

Answer 35

Metronidazole can inhibit the metabolism of Cisapride leading to arrhythmias

Question 36

How is metronidazole injection supplied?

Answer 36

is sterile and supplied in 100mL single dose plastic containers Each package contains 500mg/100mL of metronidazole injection

Question 37

What is the prophylaxis dosing of metronidazole?

Answer 37

- Usually preop 500mg over 10-20 minutes - 15mg/kg infused over 30-60 minutes approximately one hour before surgery followed by 7.5mg/kg infused over 30-60 minutes at 6 and 12 hours after the initial dose

Question 38

What is the usual adult oral dose of metronidazole?

Answer 38

Usual oral dose is 7.5mg/kg q6hrs

Question 39

What is the max dose of metronidazole?

Answer 39

4 grams; should not be exceeded during a 24hr period

Question 40

How should you dose for a patient in renal failure for metronidazole?

Answer 40

With renal impairment doses should be decreased by 50% or given every 12 hours rather than every 6hrs

Question 41

How should you dose for liver disease for metronidazole?

Answer 41

doses do not need to be altered in patients with mild liver disease but should be reduced in patients with severe liver disease

Question 42

What is the typical duration of therapy of metronidazole?

Answer 42

The typical duration of therapy is 7-10 days; however, infections of the bone and joint, lower respiratory tract and endocardium may require longer treatment

Question 43

What lab values may be altered with the use of metronidazole?

Answer 43

AST and ALT LDH Triglycerides Hexokinase Glucose

Question 44

What is important as to how metronidazole should be stored?

Answer 44

Should be protected from light because a darkening of the solution can result