Medicines used to treat amebiasis, trichomoniasis, leishmaniasis and other protozoal infections

Antiprotozoal drugs are a group of synthetic chemotherapy drugs that are used to treat infectious diseases caused by protozoa (protozoal infections).

Protozoa are a special class of microorganisms that differ from bacteria, fungi and viruses in their structure and function. Relatively speaking, protozoa occupy an intermediate position between bacteria and animals and combine the properties of both bacterial and animal cells.

Many protozoa have adapted to living in the human body, causing so-called protozoal infectious diseases.

The most common protozoa that cause protozoal infections in humans include:

• Plasmodium falciparum (causes malaria);
• dysenteric amoeba (causes amebic dysentery, liver amoebiasis);
• trichomonas (causes trichomoniasis, a sexually transmitted disease in men and women);
• Giardia (causes giardiasis of the intestines, gall bladder, giardia cholecystitis);
• leishmania (causes leishmaniasis of the skin and internal organs);
• toxoplasma (the causative agent of toxoplasmosis);
• trypanosoma (causes sleeping sickness - African trypanosomiasis or "sleeping sickness", as well as Chagas disease - American trypanosomiasis).

Some protozoa can be directly transmitted from person to person (for example, Trichomonas through sexual contact, amoeba and lamblia through dirty hands, drinking water or food contaminated with the feces of a sick person). Other protozoa require an intermediate host to enter the human body (mosquitoes and mosquitoes for Plasmodium falciparum and leishmania, cats for Toxoplasma, tsetse flies and bedbugs for trypanosomes).

The clinical manifestations and symptoms of protozoal infections are very diverse and depend primarily on the target organ, which is primarily affected by the protozoa. This may include severe diarrhea (diarrhea), fever, abdominal pain, genital discharge, skin ulcers, severe drowsiness, etc.

Taking into account the peculiarities of their effect on various protozoa, antiprotozoal drugs are divided into two broad groups:

1. Drugs for the treatment of malaria.
2. Preparations for the treatment of amebiasis, trichomoniasis, leishmaniasis and other protozoal infections.

Let us consider in detail the drugs for the treatment of amoebiasis, trichomoniasis, leishmaniasis and other protozoal infections.

Classification of antiprotozoal drugs

Antiprotozoal drugs are classified into:

• drugs for the treatment of amebiasis: nitroimidazole derivatives (metronidazole, tinidazole, ornidazole), hydroxychloroquine derivatives (chloroquine, tiliquinol + tiliquinol N-dodecyl sulfate + tilbroquinol);
• drugs for the treatment of trichomoniasis: nitroimidazole derivatives (metronidazole, tinidazole, ornidazole), nitrofuran derivatives (furazolidone);
• drugs for the treatment of toxoplasmosis: sulfonamide drugs and their combinations (pyrimethamine + sulfanidiazine, pyrimethamine + sulfadimidine, pyrimethamine + sulfadoxine, co-trimoxazole), antibiotics of the lincosamide class (clindamycin) and macrolides (spiramycin);
• drugs for the treatment of giardiasis: nitroimidazole derivatives (metronidazole, tinidazole, ornidazole), nitrofuran derivatives (furazolidone, nifuratel);
• drugs for the treatment of leishmaniasis: pentavalent antimony preparations (meglumine antimonate);
• drugs for the treatment of trypanosomiasis: African trypanosomiasis - suramin, eflornithine, melarsoprol; American trypanosomiasis – nifurtimox, benznidazole.

ANTIPARASITIC DRUGS

MODERN ANTIMICROBIAL CHEMOTHERAPY

MODERN ANTIMICROBIAL CHEMOTHERAPY

L.S. Strachunsky, S.N. Kozlov. Guide for doctors

Antiparasitic drugs include two main classes: antiprotozoal

, which are used in the treatment of infections caused by unicellular protozoa (malarial plasmodia, lamblia, amoebas, etc.), and
anthelmintics
.

For the convenience of clinical and pharmacological characteristics, antiprotozoal drugs can be divided into two groups: antimalarial and those used for other protozoal infections.

A number of drugs have activity against various types of malarial plasmodium, which, depending on the chemical structure, are divided into several groups (Table 15). Sulfonamides, tetracyclines and clindamycin, described above in their respective chapters, are not covered in this section.

Features of the clinical use of drugs are associated with their effect on various forms (stages of development) of plasmodium.

Schizontocidal

the drugs are effective against the erythrocyte forms directly responsible for the clinical symptoms of malaria.
Drugs that act on tissue forms
can prevent long-term relapses of infection.

Gametocytocidal

agents (that is, active against sexual forms of Plasmodium) prevent mosquitoes from infecting sick people and, therefore, prevent the spread of malaria.

Sporontocides

, without having a direct effect on gametocytes, lead to disruption of the development cycle of plasmodium in the mosquito’s body and thereby also help limit the spread of the disease.

Table 15. Classification of antimalarial drugs

(Martindale, The Extra Pharmacopoeia, 1996)

QUINOLINES

The quinolines, which are the oldest group of antimalarial drugs, include chloroquine, hydroxychloroquine, quinine, quinidine, mefloquine and primaquine.

CHLOROQUINE

Delagil, Hingamin

Synthetic 4-aminoquinoline. For many years it was most widely used for the treatment and prevention of malaria. Currently used more limited due to development of P. falciparum

(the causative agent of tropical malaria, characterized by the most severe malignant course) in most malaria-endemic regions of the globe: Africa, Southeast Asia, India and South America.

In addition to antimalarial activity, chloroquine also has antiamoebic effects. It exhibits slowly developing anti-inflammatory activity, therefore it is used as a basic antirheumatic agent, as well as for photodermatitis.

Activity spectrum

Pharmacokinetics

Bioavailability when taken orally is 85-90%, does not significantly depend on food. Well absorbed when administered intramuscularly and subcutaneously. Distributed in many organs and tissues, exhibits affinity for cells containing melanin (eye tissue, skin). It accumulates in erythrocytes, and the concentration of chloroquine in erythrocytes affected by Plasmodium is 100-300 times higher than in normal ones. Biotransforms to form an active metabolite. Excreted by the kidneys, 50% in the active state. T1/2 for short-term use - 4-9 days. With long-term use, the drug has a pronounced accumulation and can remain in the body for several months and even years after discontinuation.

Adverse reactions

In the treatment and prevention of malaria, they are rarely observed, more often with long-term use in patients with rheumatoid arthritis.

• Dyspeptic and dyspeptic disorders.
• Neurotoxicity - headache, dizziness, fatigue, lethargy, sleep disturbances, tinnitus, hearing impairment, psychosis (rare).
• Skin - rash, itching (more often in Africans), exacerbation of psoriasis and eczema.
• Hair depigmentation - the appearance of gray strands.
• Hematotoxicity - thrombocytopenia, neutropenia, aplastic anemia, agranulocytosis, hemolytic anemia due to deficiency of glucose-6-phosphate dehydrogenase in erythrocytes.
• Keratopathies and retinopathy are caused by deposition of the drug in the cornea and/or retina. Accompanied by diplopia and other visual impairments. Keratopathy is usually reversible. Retinopathy is one of the most severe adverse reactions caused by chloroquine (more often with long-term use as an antirheumatic drug). Retinal destruction is possible, especially under the influence of sunlight, with irreversible visual impairment. Preventive measures:
  avoid direct insolation, take breaks in treatment in the summer.
• Acute overdose (with simultaneous administration of a high dose, sometimes with intravenous administration) - headache, dizziness, abdominal pain, severe weakness, hypotension, even collapse, arrhythmia, cardiac arrest, sudden loss of vision, convulsions, respiratory disorders. A dose of 5.0 g is potentially lethal. Preventive measures:
  avoid intravenous administration if possible, administer slowly if necessary.
  Helpful measures:
  resuscitation measures, administration of adrenaline, gastric lavage using activated charcoal, symptomatic therapy (for convulsions - diazepam).

Indications

• Malaria - treatment and prevention (remember the widespread resistance of P. falciparum
  ).
  Since chloroquine does not act on tissue forms of Plasmodium, it does not lead to a complete cure of malaria caused by P.vivax
  and
  P.ovale
  .
• Extraintestinal (hepatic) amebiasis - in combination with dehydroemetine.
• Rheumatological diseases (rheumatoid arthritis, systemic lupus erythematosus) - as a basic drug.
• Photodermatitis.

Contraindications

• Retinal diseases.
• Psoriasis.
• Porphyria.

Dosage

Adults

For the treatment of malaria - orally (during or after meals): 1st dose 1.0 g, after 6-8 hours 0.5 g, then 0.5 g / day for 2 days; intravenously slowly (in severe cases and the impossibility of oral administration) - a total dose of 25 mg/kg in several administrations at intervals of 30-32 hours.

For the prevention of malaria - 0.5 g once a week, start 1-2 weeks before traveling to an endemic area and continue 4-6 weeks after returning, orally.

For amebiasis - 0.5 g every 12 hours for 2 days, then 0.5 g/day in one dose for 2-3 weeks, orally.

For rheumatological diseases - 0.25 g / day (course duration - from several months to several years, after achieving remission, the dose can be reduced), orally.

For photodermatitis - 0.25-0.5 g/day, orally.

Children

For malaria - 1st dose 10 mg/kg, after 6 hours 5 mg/kg, then 5 mg/kg/day for 2-3 days; for prevention - 5 mg/kg/day, orally.

For amebiasis - 16 mg/kg/day (no more than 0.5 g/day) in one dose for 2-3 weeks, orally.

For photodermatitis - 3 mg/kg/day, orally.

Release forms

Tablets 0.25 g; ampoules of 5 ml of 5% solution.

HYDROXYCHLOROQUINE

Plaquenil

In many properties it is close to chloroquine. Malarial plasmodia exhibit cross-resistance to both drugs.

Differences from chloroquine:

• slightly lower bioavailability (74%);
• According to some data, it is better tolerated.

Indications

• Malaria (however, experience with use compared to chloroquine is significantly less).
• Rheumatoid arthritis.
• Photodermatitis.

Dosage

Adults

Inside (during or after meals).

For malaria - 1st dose 0.8 g, after 6-8 hours 2nd dose 0.4 g, then 0.4 g / day for 2 days; for prevention - 0.4 g once a week.

For rheumatoid arthritis - initial dose 0.4 g/day, maintenance dose - 0.2 g/day.

For photodermatitis - 0.2-0.4 g/day.

Children

Orally - 6.5 mg/kg per day.

Release form

Tablets 0.2 g.

QUININE

Alkaloid of cinchona bark. The first effective antimalarial drug. Since its introduction into clinical practice, chloroquine has been used rarely, but in recent years due to the widespread prevalence of chloroquine-resistant strains of P. falciparum

the frequency of quinine use increased again. It has a weak analgesic and antipyretic effect.

Activity spectrum

Fast and powerful effect against erythrocyte forms of all types of malarial plasmodium. Moderately affects gametocytes P.vivax, P.ovale

and
P. malariae
.

Pharmacokinetics

Rapidly absorbed into the gastrointestinal tract. Bioavailability - 80%, independent of food. Distributed into many tissues and environments, the concentration in the cerebrospinal fluid in cerebral forms of malaria is 2-7% of the level in plasma. Metabolized in the liver, excreted by the kidneys (more intensely with acidic urine). T1/2 - 9-11 hours, with severe malaria it can increase to 18 hours. With renal failure does not change.

Adverse reactions

Quinine is a rather toxic drug; adverse reactions are observed in 25-30% of patients.

• “Cinchonism”* - ringing in the ears, visual and hearing impairment, headache, dizziness, nausea; in more severe cases - vomiting, abdominal pain, diarrhea.
• Cardiotoxicity - heart pain, arrhythmias, blockades, decreased myocardial contractility (may be accompanied by hypotension, especially with parenteral administration).
• Hepatotoxicity - hypoprothrombinemia, hepatitis.
• Curare-like effect - severe respiratory distress is possible in patients with myasthenia gravis.
• Uterus - increased myometrial contractility.
• Hematotoxicity - thrombocytopenia, agranulocytosis, hemolytic anemia. In severe tropical malaria, massive hemolysis with hemoglobinuria is possible - the so-called “black water fever ”
  .
• Hypoglycemia - caused by increased insulin production; most often in severe tropical malaria, when an additional factor is the active consumption of glucose by P. falciparum
  .
• Local reactions - very bitter taste when taken orally; with intramuscular injection, severe pain, possible development of abscesses and tissue necrosis.
• Acute overdose (see Chloroquine).

Indications

• Chloroquine-resistant falciparum - in combination with tetracycline, doxycycline, clindamycin or pyrimethamine/sulfadoxine.
• Night cramps of the calf muscles.

Warnings

It should be borne in mind that quinine does not lead to a complete cure of malaria, since it does not act on tissue forms of plasmodium. Not used for prophylaxis.

Dosage

Adults

For malaria

Orally (during or after meals) - 0.65 g every 8 hours for 3-7 days. Intravenously (in severe cases and the impossibility of oral administration) - a saturation dose of 20 mg/kg (no more than 1.4 g), then 10 mg/kg every 8-12 hours; administration is carried out slowly - over 4 hours.

For night cramps

Orally - 0.2-0.6 g at night.

Children

For malaria

Orally - 25 mg/kg/day in 3 divided doses for 3-7 days.

Release forms

Tablets and capsules of 0.2 g, 0.25 g, 0.3 g and 0.5 g; ampoules of 1 ml of 50% solution.

* Cinchona (lat.) - cinchona tree.

QUINIDINE

Dextrorotatory isomer of quinine. In many properties it is close to quinine. Like the latter, it is able to act on chloroquine-resistant strains of P. falciparum

.

Main differences from quinine:

• has more pronounced antimalarial activity;
• more toxic.

Indications

• Severe complicated forms of chloroquine-resistant tropical malaria requiring parenteral treatment (quinidine gluconate is used).
• Heart rhythm disturbances (more often with atrial fibrillation).

Dosage

Adults and children

For malaria

Intravenously - 10 mg/kg (no more than 0.6 g) over 1-2 hours, then infusion at a rate of 0.02 mg/kg/min for no more than 72 hours, followed by switching to oral quinine.

Quinidine dosage regimens for arrhythmias are described in special guidelines.

Release forms

10 ml bottles, 80 mg/1 ml quinidine gluconate.

MEFLOQUINE

Lariam

A synthetic drug similar in structure to quinine and quinidine.

Activity spectrum

Acts only on erythrocyte forms of all types of malarial plasmodium. The main clinical significance of mefloquine is its activity against P. falciparum

resistant to chloroquine and pyrimethamine/sulfadoxine.

Pharmacokinetics

Bioavailability when taken orally is 80-85%, with food improving absorption. It is well distributed and accumulates in high concentrations in red blood cells. Metabolized in the liver, excreted mainly in stool. Part of the drug undergoes enterohepatic circulation. T1/2 - 2-4 weeks, does not change with renal failure.

Adverse reactions

• Dyspeptic and dyspeptic disorders.
• Neuropsychiatric reactions (dose-dependent: more often when using therapeutic doses than prophylactic ones; mainly in women) - general weakness, dizziness, imbalance, paresthesia, polyneuropathy; in severe cases, convulsions, neuroses, feelings of fear, psychoses with hallucinations, disturbances in the cyclicity of sleep and wakefulness. Preventive measures:
  do not administer to patients with epilepsy and mental illness.
• Cardiotoxicity - arrhythmias, blockades. Preventive measures:
  do not administer to patients with conduction disorders.
• Hematotoxicity - thrombocytopenia, leukopenia or leukocytosis.
• Hepatotoxicity - increased transaminase activity.
• Others - arthralgia, myalgia, alopecia, in rare cases Stevens-Johnson syndrome.

Drug interactions

Mefloquine should not be combined with quinine or quinidine, nor should it be prescribed less than 12 hours after discontinuation of these drugs, in order to avoid additive toxic effects.

It is very dangerous to use mefloquine in patients prescribed drugs that slow conduction in the heart (beta blockers and others). Cases of sudden death of patients who took a single dose of mefloquine during treatment with propranolol have been described.

Indications

Malaria - treatment and prevention, especially in regions where multidrug-resistant strains of Plasmodium are common.

Dosage

Adults

Orally - 1st dose 0.75 g, then 0.5 g after 12 hours.

For prophylaxis - 0.25 g once a week, start 1 week before travel to an endemic area and continue for 4 weeks after return.

Children

Orally - 1st dose 15 mg/kg, then 10 mg/kg after 8-12 hours.

For prevention: with a weight up to 15 kg - 5 mg/kg, 15-19 kg - 1/4 tablet, 20-30 kg - 1/2 tablet, 31-45 kg - 3/4 tablet, over 45 kg - 1 tablet once a week according to the same scheme as for adults.

Release form

Tablets 0.25 g.

PRIMAKHIN

Synthetic 8-aminoquinoline.

Activity spectrum

Pharmacokinetics

Bioavailability when taken orally is 96%, independent of food. Distributed into many tissues and media. Metabolized in the liver. About 60% of the drug is converted into an active metabolite - carboxyprimaquine, the concentration of which in the body can be 50 times higher than the level of the original substance. It enhances and prolongs the effect of primaquine. Excretion is carried out by the kidneys. T1/2 of primaquine - 4-8 hours, active metabolite - up to 22-30 hours.

Adverse reactions

• Dyspeptic disorders (more often when taken on an empty stomach).
• Hematotoxicity - hemolytic anemia, methemoglobinemia, leukocytosis, less commonly leukopenia or agranulocytosis.

Indications

• Radical cure of malaria caused by P.vivax
  and
  P.ovale
  (in combination with chloroquine).
• Prevention of chloroquine-resistant malaria.
• Prevention of relapse of malaria caused by P.vivax
  and
  P.ovale
  in persons returning from endemic areas.
• Pneumocystis pneumonia (in combination with clindamycin).

Dosage

Adults

For malaria - three doses of 2.5 mg/kg every 48 hours; for the prevention of malaria - 30 mg/day according to the traditional regimen; to prevent relapses - 15 mg/day for 2-3 weeks or 30-45 mg once a week for 8 weeks, orally (during or after meals).

For Pneumocystis pneumonia - 30 mg/day for 3 weeks, orally.

Children

For the prevention of malaria - 0.5 mg/kg/day according to the traditional regimen; for the prevention of relapses - 0.3 mg/kg/day (no more than 15 mg) for 2-3 weeks.

Release forms

Tablets of 0.003 g, 0.009 g and 0.015 g.

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Last modified date: 05/24/2004 18:56

Indications for use

Antimalarial drugs are indicated for the treatment of malaria.

Also, certain antimalarial drugs are used to prevent malaria for those traveling to regions dangerous from the point of view of the spread of malaria, as well as for emergency self-help when malaria is suspected, when it is not possible to see a doctor.

In addition, aminoquinolines are prescribed for severe rheumatoid and autoimmune diseases - rheumatoid arthritis, chronic juvenile arthritis, systemic lupus erythematosus and discoid lupus.

Basics of Malaria Treatment

Antiprotozoal drugs are prescription drugs (prescribed only by a doctor), since they have a very wide range of adverse side effects, and can also enter into unwanted interactions with other medications, food, and alcohol.

When treating with antimalarial drugs, given their negative effect on hematopoiesis and the structure of blood cells, it is necessary to regularly do a general blood test.

When using chloroquine and hydroxychloroquine, which can provoke heart rhythm disturbances - arrhythmias, it is necessary to perform an electrocardiogram (ECG) on the patient 2-3 times a week.