Antiamoebicides

Amoebicides

     Amoebiasis is an infection caused by Entamoeba histolytica, which causes dysentery and liver abscesses.
     The organism may be present in motile invasive form or as a cyst.

• Giardiasis is an infection of the small bowel by a single-celled organism called Giardia lamblia.
• People become infected with the Giardia parasite after swallowing Giardia cyst often found in water contaminated by raw sewage or animal waste.

• The cornerstone of therapy for amoebiasis and giardiasis is the Metronidazole or its analogue Tinidazole.
oThese are the drug of choice for the treatment of acute invasive amoebic dysentery since they are very effective against vegetative forms of Entamoeba histolytica, amoebic liver abscess, and any other extra intestinal form of amoebiasis.
oThese drugs are also used with other drugs in the eradication of helicobacter pylori and trichomonal vaginalis.
• Topical Metronidazole reduces the odour produced by anaerobic bacteria in fungating tumours, it is also used in the management of rosacea.

• Metronidazole is an alternative to penicillin for the treatment of many oral infections where the patient is allergic to penicillin or when the infection is due to beta-lactamase-producing anaerobes.
• For these purposes metronidazole in a dose of 200mg or 350 mg three times daily for five days is sufficient.
• Tinidazole is licensed for the treatment of acute ulcerative gingivitis.

Pharmacology of Metronidazole and Tinidazole

Metronidazole
• Available in different formulations such as tablets, syrups, gel for skin and infusion form.
• Pharmacokinetic aspects
o Metronidazole is usually given orally and is rapidly and completely absorbed,
achieving peak plasma concentration in 1-3 hours, with a half-life of about 7 hours
o Rectal and intravenous preparations are also available
o It is distributed rapidly throughout the tissues, reaching high concentrations in the body fluids, including the cerebrospinal fluid. Some is metabolised, but most is excreted in urine
• Dose
• Anaerobic infections is given in
o An adult dose of tablets 400 mg three times daily (usually treated for 7 days and for 10 days in antibiotic-associated colitis). Or stat dose of 800 mg followed by 400 mg every 8 hours.
o In children 7.5 mg/kg every 8 hours
• By rectum, for adult and children over 10 years: 1g (suppository) every 8 hours for3
days, then 1 g every 12 hours.
• For child: age up to 1 year 125 mg, 1–5 years 250 mg, 5–10 years 500 mg every 8 hours for 3 days, then every 12 hours.
• By intravenous infusion 7.5 mg/kg every 6 hours, up to a maximum of 4000 mg in any given 24 hours period.
• Caution
o Avoid use with alcohol, hepatic impairment, in pregnancy and breast-feeding
o Laboratory monitoring advised if treatment exceeds 10 days

• Unwanted effects
o The drug has a metallic, bitter taste in the mouth but causes few unwanted effects in therapeutic doses
o Minor gastrointestinal disturbances have been reported, as have central nervous system symptoms (dizziness, headache, sensory neuropathies)
o The drug interferes with alcohol metabolism, and concurrent use of the substance should be strictly avoided

Tinidazole
• Tinidazole is similar to metronidazole in its mechanism of action and unwanted effects, but has a longer duration of action. (is eliminated more slowly, having a half-life of 12-14 hours)
• Dose
o Anaerobic infections, 2 g initially, followed by 1 g daily or 500 mg twice daily, usually for 5–6 days
o Bacterial vaginosis and acute ulcerative gingivitis, a single 2-g dose
o Abdominal surgery prophylaxis, a single 2-g dose approximately 12 hours before
surgery

The Disulfiram like Reaction of Amoebicides
• This is the manifestation that occurs when a person consumes a drug called disulfirum concurrent with alcohol.
• This drug is used as an attempt to discourage alcohol drinking by inducing immediate unpleasant effects.
• Similar but fatal manifestations occur when a patient consumes amoebicides such as metronidazole or tinidazole concurrent with alcohol.

Mechanisms of Action of Disulfiram and Metronidazole to Bring About the Reaction
• The drugs inhibit the enzyme aldehyde dehydrogenase so that acetaldehyde (toxic metabolite of alcohol) accumulates.
• A typical reaction of medium severity comes on about five minutes after taking alcohol and consists of generalized vasodilatation and fall in blood pressure, sweating, dyspnoea, headache, chest pain, nausea and vomiting.
• Severe reactions include convulsions and circulatory collapse, they may last several hours.
o Ensure patients under anti-alcohol abuse therapy, undergo psychological/behavioural treatment before drug therapy, in order to have good outcome.
o Because of the severe reaction to alcohol associated with this treatment, the drug should be given to a person who really wants help and is willing to cooperate with health treatment counsellors
o But for disulfirum reaction induced by metronidazole, the patient may even not know what is happening and if no good history has been taken he or she may die.

Posted by
Welfate Jambo