Antiamoebics - Anti-Infectives

Antiamoebics

Amoebiasis, like malaria, is a scourge of tropical countries such as India while it is relatively rare in the West. Infection is particularly common among lower socio-economic groups and institutionalised individuals.

Diloxanide Furoate

It is the furoate ester of a dichloroacetamide derivative which is given alone in asymptomatic cyst passers, and in combina-tion with metronidazole or tinidazole for patients with active amoebiasis. It is administered orally. Side effects are rare: flatulence, vomiting, urticarial

Quinidochlor and Clioquinol

These are halogenated 8-hydroxyquinolines which are used as luminal amoebicides to treat asymptomatic cyst passers. High doses can cause Subacute myelo-optic neuropathy (SMON).* A delayed onset retrograde amnesia is seen in some patients. More commonly they cause gastrointestinal upset, diarrhoea, allergic reactions, and thyroid enlargement. Optic neuropathies and optic atrophy have occurred in some patients who have taken large doses. These changes have resulted in visual impairment and in some cases, permanent blindness. An iron chelate of clioquinol may result in a green colour or green “fur” on the tongue in some patients. The urine may also be green coloured. The halogenated hydroxyquinolines have produced frequent allergic reactions in humans, and have included both sensitisation (1.4 to 1.9%) and cross-sensitisation to such agents as quinoline-based antima-larial drugs, and in a few cases, potassium iodide.

Because of the neurotoxicity seen between 1955 and 1970, clioquinol and similar halogenated hydroxyquinolines have been taken off the market in many countries.

Patients on these agents chronically, or who take large over-doses may require monitoring of visual fields, neurologic status, and folic acid and vitamin B₁₂ levels. No specific treatment has been effective, other than discontinuation of the drug. In some cases, there has been improvement of vision over the several months immediately following discontinuation of the clioquinol.

Emetine and Dehydroemetine

Emetine is an alkaloid obtained from Cephaelis ipecacuanha (Brazil root), the syrup prepared from which is a popular emetic today. Emetine and its derivative dehydroemetine were previously popular as systemic amoebicides. Both are rarely used today owing to cardiotoxicity as well as other adverse effects such as vomiting, hypotension, and myoneuralgia. The usual fatal dose of emetine is around 200 mg for an adult.

5-Nitroimidazoles

The 5-nitroimidazoles comprise metronidazole, nimorazole, ornidazole, secnidazole, and tinidazole. Much of the following discussion is centred around metronidazole which is the most important member of the group, and has an extremely broad spectrum of antiprotozoal and antimicrobial activity.

Uses

·      Drug of choice for the treatment of all symptomatic forms of amoebiasis.

·      Drug of choice for the treatment of giardiasis.

·      Treatment of genital infections with Trichomonas vaginalis.

·      Treatment of serious anaerobic infections.

·      Treatment of peptic ulcer due to Helicobacter pylori.

·      Treatment of pseudomembranous colitis.

·              Secnidazole is used in the treatment of giardiasis, intestinal amoebiasis, vaginal trichomoniasis, and bacterial vaginitis

·      Tinidazole is effective in the treatment of susceptible proto-zoal infections and prophylactic treatment of anaerobic bacterial infections. It is primarily used in the treatment of trichomoniasis, giardiasis, and amoebiasis or amoebic liver abscess.

Toxicokinetics

Metronidazole is completely absorbed on oral administration. Peak plasma level is generally achieved in 1 to 3 hours. It penetrates into all tissues and fluids. Metronidazole and related drugs are widely distributed in many body fluids including bile, breast milk, CSF, saliva; they can also cross the placenta readily, and be found in a variety of body tissues. Liver is the main site of metabolism, while excretion occurs mainly in the urine which may turn reddish brown. Most of these drugs are only minimally protein bound.

Adverse and Clinical (Toxic) Features

·      Adverse effects include headache, nausea, metallic taste, anorexia, and occasionally vomiting and diarrhoea. Glossitis and stomatitis may occur. Rare side effects include vertigo, insomnia, CNS depression, sensory neuropathies, encephalopathy, convulsions, and ataxia. Urticaria, dysuria, darkening of the urine, and cystitis have also been reported. Tinidazole is generally much better tolerated than metroni-dazole.

·      Dark urine (green/black) has been reported in some cases.

·      Concomitant intake of metronidazole with alcohol induces a disulfiram-like reaction. Psychotic responses have also been reported with concurrent ethanol and metronidazole therapy. Alcoholic beverages or products containing ethanol or propylene glycol should not be used during tinidazole therapy also (and for 3 days after the cessation of therapy), because nausea, vomiting, abdominal cramps, headaches and flushing may occur.

·      Animal experiments suggest that metronidazole is carcino-genic.

Treatment

Acute toxicity has rarely been reported with this drug. Single oral doses of metronidazole of 15 grams have been tolerated with only minimal clinical effects. However, standard treatment measures may be indicated in ingestions of greater than 1 to 2 grams. A baseline CBC and renal and hepatic function tests should be obtained. Treatment is symptomatic and supportive. Metronidazole is rapidly removed by haemodialysis.