What Is an Antiparasitic?

Parasitic diseases can be divided into protozoan and helminthiasis. Protozoan diseases include malaria, amoebiasis, leishmaniasis, etc., and helminthiasis include fluke disease, filariasis, and nematode disease. Can be divided into antiprotozoal drugs and antihelminthic drugs.

I. Antimalarials

(I. Overview

Antimalarial drugs are drugs used to prevent or treat malaria. Malaria is a parasitic infectious disease caused by Plasmodium. It is the parasitic disease that is most harmful to humans. The main pathogens include Plasmodium vivax, Plasmodium vivax, Plasmodium ovale, and Plasmodium falciparum, which cause Plasmodium vivax, Plasmodium vivax, Plasmodium ovale, and Plasmodium falciparum, respectively. The first three are also called benign malaria. The symptoms of malaria are mild and uncommon. Malignant malaria infection is the most widespread, with severe symptoms and the greatest harm to human health. None of the existing antimalarial drugs can kill all aspects of the life history of Plasmodium. Plasmodium at different growth stages have different sensitivities to different antimalarial drugs, which will better understand and use antimalarial drugs. Malaria medicine.

The life history of Plasmodium can be divided into the sexual reproduction stage in female Anopheles and the asexual reproduction stage in human. According to the development process of Plasmodium in the human body, malaria can be divided into primary extracellular phase, secondary extracellular phase, and intracellular phase.

1. Primary extracellular period of red blood cells. When an infected Anopheles mosquito bites a person, the sporozoites in its saliva are introduced into the human body, invading liver cells to transform, proliferate, and develop into tissue-type schizonts. Hepatocytes rupture within 5-15 days, releasing merozoites and entering red blood cells . Asymptomatic here, the incubation period for malaria. Pyrimethamine has a killing effect on this stage of Plasmodium and can be used as a causative agent.

2. Secondary extracellular period. Plasmodium vivax and Plasmodium ovale release a large number of merozoites into human red blood cells outside the primary red blood cells. Plasmodium is still present in the liver cells. These delayed sporozoites (called dormants) cause vivax The main cause of relapse. Drugs that can act on secondary extracorporeal red blood cells, such as primary aminoquine, have the effect of eradicating vivax. After the tissue-type schizonts of Plasmodium falciparum and Plasmodium falciparum rupture, there will no longer be any form of Plasmodium in the liver tissue. Therefore, there is no secondary extracorporeal period and no drug treatment is required.

3. Erythrocyte stage. The merozoites that are developed and released by the primary red blood cells enter the red blood cells, develop into trophozoites, merozoites, destroy red blood cells, and release merozoites and metabolites. Merozoites can invade red blood cells again, repeating the proliferation of the lysosomes during the red blood cells. Metabolites and red blood cell fragments produced during the proliferation of the schizont can stimulate the body to cause symptoms such as chills, high fever, and sweating. Drugs that kill Plasmodium during this period, such as chloroquine, quinine, and artemisinin, can control the onset of symptoms.

Some erythrocytes are endoplasmic and differentiate into male and female gametophytes. When Anopheles mosquitoes inhale the blood of malaria patients, the male and female gametophytes enter the body of Anopheles mosquitoes with the blood, combine to form zygotes, further develop into sporozoites, migrate into the salivary glands, and become a new source of infection for malaria transmission and spread. Both the gametophyte drug, primary aminoquine, and the drug, pyrimethamine, which inhibit the development of male and female gametophytes in Anopheles mosquitoes, can control the spread and spread of malaria. Therefore, according to the action link. Antimalarial drugs are mainly divided into the following categories: 1. Antimalarial drugs mainly used to control the symptoms of malaria. Chloroquine, artemisinin and its derivatives, quinine, mefloquine, pinaphthyridine, scopolamine. 2. Antimalarial drugs mainly used to control the recurrence and spread of malaria. Primary aminoquine. 3. Antimalarial drugs mainly used for malaria prevention. Pyrimethamine and sulfa.

(2) Antimalarial drugs mainly used to control the symptoms of malaria

Chloroquine

The drug is a synthetic 4-aminoquinoline derivative.

[Pharmacokinetics] Fast and complete absorption after oral administration, T _max is 1-2 hours, the concentration in red blood cells is 10-20 times higher than in plasma, and the drug concentration in red blood cells invaded by malaria parasites is 25 times higher than normal red blood cells. Conducive to killing erythroblastic schizonts. Chloroquine is mainly distributed in liver, spleen, lung, kidney and other tissues, and the drug concentration in these tissues is 200-700 times higher than plasma. It can enter the brain tissue through the blood-brain barrier, and the concentration in the brain tissue is 10-30 times the plasma concentration. Most of them are metabolized in the liver, and the metabolite desethylchloroquine still has antimalarial effects, and a small part is excreted in the form of the kidney. Because the drug is stored in tissues, its metabolism and excretion are slow, t _{1/2 is} about 50 hours, so the effect is long-lasting.

[Mechanism of action] The antimalarial mechanism of chloroquine is complicated, and it is related to the high concentration of chloroquine in the plasmin. Chloroquine can combine with guanine and cytosine base pairs in the double helix of the Plasmodium DNA to form a chloroquine-DNA complex, which inhibits DNA replication and transcription, breaks the DNA, and inhibits the reproduction of Plasmodium; Weak alkaline drugs easily enter the body of Plasmodium in large quantities, increase the pH in the body cells of the parasite, form an environment that is unfavorable to proteolytic enzymes, reduce the ability of Plasmodium to break down and use hemoglobin, and lead to a lack of amino acids to inhibit Plasmodium. Growth and reproduction; In the erythrocytes, the schizont produces malarial pigment after erythrocytes are destroyed. Its component, ferroprotoporphyrin, is considered to be a high affinity receptor for antimalarial drugs such as chloroquine. When combined with chloroquine, it can destroy the cell membrane of plasmodium. Dissolve Plasmodium.

[Function and clinical application]

(1) Antimalarial effect: Chloroquine can kill schizonts of P. vivax, P. vivax and sensitive Plasmodium falciparum, can quickly control the onset of malaria symptoms, have a curative effect on P. falciparum, and control malaria The drug of choice for symptoms. It is characterized by good curative effect. Generally, the temperature of the patient drops to normal within 24-48 hours after taking the medicine, and the symptoms quickly subside. Plasmodium in the blood disappears after 48-72 hours. Due to the slow metabolism and excretion of the drug in the body and its long-lasting effect, it can delay the recurrence of benign malaria symptoms. It is not effective for the extracellular period of red blood cells, and cannot be used for causative prevention and cure of benign malaria. Clinically, it is mainly used to control the acute onset of malaria and to eradicate malaria.

(2) Effect on other parasites: It has a good effect on parenteral amoebiasis. The concentration in the liver after oral administration is very high, and it can be used for metronidazole to treat ineffective or contraindicated amoeba hepatitis or liver abscess.

(3) Immunosuppressive effect: large doses can be used to treat rheumatoid arthritis and systemic lupus erythematosus.

[Adverse reactions] When used to treat malaria, it produces mild dizziness, headache, gastrointestinal discomfort, visual disturbance, urticaria, etc., and it can disappear quickly after stopping the drug. Long-term high-dose use can cause irreversible retinopathy, ototoxicity, cardiovascular reactions, leukopenia, and liver and kidney damage.

Artemisinin

The drug is a sesquiterpene lactone peroxide extracted from Artemisia annua and Acanthopanax grandiflorum. It is a new antimalarial drug screened by Chinese scientists based on the theory of traditional Chinese medicine.

[Pharmacokinetics] Oral absorption is rapid and complete, reaching C _max after 1 hour. Due to the first pass effect, the blood concentration is low, and it is widely distributed in various tissues. The concentration in bile is higher, followed by liver, kidney, and spleen. Easy to enter the brain tissue through the blood-brain barrier, so it is effective for cerebral malaria. Metabolism in the body is rapid, and metabolites can be quickly excreted from the kidney and intestine. Due to the rapid metabolism and excretion, the effective blood drug concentration is maintained for a short time, which is not conducive to the complete killing of Plasmodium, so the recurrence rate is high.

[Effects and clinical application] By generating free radicals, the drug can severely damage the biofilm of the inner stage of the red blood cells of P. falciparum, or combine with the protozoan protein to cause death, which has a killing effect on the trophozoites of the red blood cells. Erythrocytic malaria parasites are ineffective. Used to control the symptoms of vivax and falciparum and to treat chloroquine-resistant malaria. The drug can penetrate the blood-brain barrier and can also be used to treat dangerous malaria such as cerebral malaria and yellow gall malaria. Plasmodium is easily resistant to artemisinin, and combined with pyrimethamine can delay its resistance. The drug has a higher recurrence rate after application, and combined with primary aminoquine can reduce the malaria recurrence rate. Adverse reactions include gastrointestinal reactions, occasionally numbness in the extremities and tachycardia. Animal experiments have found that excessive doses can affect the hematopoietic system and cause liver damage, and produce embryotoxic effects.

Quinine

The drug is levidine of quinidine, which is an alkaloid native to the bark of Cinchona in South America. It was used clinically in 1820 and was the main drug for malaria. The drug of choice for malaria. The effect and mechanism of the drug are similar to those of chloroquine. It has a killing effect on various plasmodium erythrocyte trophozoites and can control clinical symptoms, but its effect is weak, and it has no obvious effect on the erythrocyte extraphase and gametophyte. The drug is oxidized and decomposed in the liver, quickly loses effect, has a short duration of action, but has high toxicity. It is mainly used clinically for chloroquine-resistant and multidrug-resistant malaria, especially cerebral malaria.

If the dosage is too large or the medication is taken for too long, the cinchona response often occurs, which is manifested as nausea, vomiting, headache, dizziness, tinnitus, and hearing loss. It can also cause blood pressure to drop, arrhythmias, and severe central nervous system disorders. It has an exciting effect on the pregnant uterus, so pregnant women are prohibited. A small number of patients have high sensitivity to quinine, and acute hemolysis can occur in small doses, causing high fever, chills and renal failure, which can be fatal.

(3) Antimalarial drugs mainly used to control relapse and transmission

Primaquine

The drug is a synthetic 8-aminoquinoline derivative.

[Pharmacokinetics] Oral absorption is fast and complete, reaching C _max within 1-2 hours, mainly distributed in the liver, followed by lung, brain, and heart tissues, most of which are metabolized into inactive products in the body, only 1% in the original form Renal excretion, because primary aminoquinol is metabolized and excreted quickly, the effective blood concentration concentration is maintained for a short time, requiring daily administration.

[Effects and clinical application] Primary aminoquine has a strong killing effect on the red blood cell period of benign malaria and the gametophytes of various types of Plasmodium. It can be used as the first choice for controlling relapse and preventing malaria transmission. The antimalarial mechanism of primary aminoquine is unclear, and it may be related to its induction of reactive oxygen species production by Plasmodium or its interference with mitochondrial electron transport. It has a weak effect on the inner stage of red blood cells and is not effective on the inner stage of malignant red blood cells. Therefore, it is not possible to control the onset of malaria symptoms. It is usually combined with chloroquine. Plasmodium is less resistant to the drug.

[Adverse reaction] This drug is more toxic than other antimalarials, and there is no suitable drug to replace it. The amount of treatment can cause fatigue, dizziness, nausea, vomiting, abdominal pain, cyanosis and other adverse reactions. A few people can have drug fever, agranulocytosis, etc., which can be recovered after stopping the drug. A few idiosyncratic patients can develop acute hemolytic anemia and methemoglobinemia.

(IV) Antimalarial drugs mainly used for prevention

Pyrimethamine

The drug is currently the drug of choice for causative malaria prevention.

[Pharmacokinetics] Oral absorption in the intestine is slow but complete, reaching C _{max in} 4-6 hours, mainly distributed in the kidney, lung, liver, spleen, red blood cells, and white blood cells. It is slowly excreted by the kidneys and can also be excreted by the breast. A small amount is excreted through the intestine, and t _1/2 is 80-95 hours.

[Mechanism] Plasmodium cannot directly use folic acid in the environment. It must synthesize folic acid and convert it into tetrahydrofolate. Pyrimethamine can inhibit the dihydrofolate reductase of Plasmodium and hinder its folate metabolism, thereby affecting the malaria parasite. Nucleic acid synthesis inhibits its growth and reproduction. When combined with sulfonamides or sulfones, it can enhance the efficacy and reduce the development of drug resistance.

[Effects and clinical application] Ethylpyrimidine has an inhibitory effect on the primary red blood cells of Plasmodium falciparum and Plasmodium vivax, which is a good pathogenic preventive drug due to slow excretion and long-lasting effects. It can be maintained for one week after taking it the above. The inhibitory effect on the erythrocytic stage of various Plasmodium is limited to the immature schizont stage, which can inhibit mitosis of trophozoites, but it is not effective for mature people, so the symptoms cannot be controlled quickly. Play a role. It has no direct killing effect on gametophyte, but after the blood containing the medicine is inhaled by Anopheles mosquito, it can prevent the normal spore proliferation of Plasmodium in the mosquito and play a role in preventing transmission.

[Adverse reaction] Oral antimalarial doses have low toxicity and are relatively safe. Taking long-term large doses can cause folic acid deficiency due to inhibition of dihydrofolate reductase, causing megaloblastic anemia or leukopenia. Occasionally a rash can occur. Overdose can cause acute poisoning. Because of its sweet taste, it is easy to be taken as a candy in large quantities by children. In the mild case, nausea, vomiting, burning in the stomach, palpitations, and irritability; in severe cases, cyanosis, dizziness, convulsions, convulsions, coma and even death. In case of poisoning, gastric lavage, infusion, intravenous barbiturates should be immediately used to fight convulsions.

Second, anti-amoebiasis drugs

Amoebiasis is caused by amolytic histoplasma. The protozoan is parasitic in the human intestine in two forms: trophozoites and cysts. Amoeba cysts are used as infectious bodies. With the contaminated diet, the cysts enter the lower part of the human small intestine, and the worms decapsulate in the intestinal cavity and quickly split into small trophozoites, parasitizing the intestine. At this time, the patient was asymptomatic, known as the cyst-elevator, and was the source of amebic disease. When the body's resistance is low, or when the intestinal wall is damaged, small trophozoites invade the intestinal wall tissues, develop into large trophozoites, destroy the intestinal mucosa and submucosal tissues, cause amoebic dysentery, and manifest as abdominal pain, diarrhea, Blood in the stool and dark red sauce-like stool. If incomplete treatment can be converted to chronic amoebic dysentery. At the same time, large trophozoites can invade human parenteral tissues such as liver, lung, brain and other tissues with blood flow, and reproduce in large numbers to produce amoeba inflammation or abscesses. They are called extraintestinal amoebiasis, such as amoebic liver, lung, or brain. Abscess.

Anti-amoebiasis drugs can be divided into several types that act inside the intestine, outside the intestine, or both. Most anti-amoebiasis drugs have a killing effect on trophozoites. A few drugs have a cysticidal effect. Certain antibacterial drugs, such as paromomycin and oxytetracycline, can directly kill trophozoites or inhibit symbiotic flora. And play an anti-amoebiasis effect.

Metronidazole

The medicine is also known as metronidazole.

[Pharmacokinetics] Oral absorption is rapid and complete. After taking a single dose of 500mg, the plasma drug concentration in one hour can reach 10µg / ml, which exceeds the average effective concentration of most sensitive protozoa and bacteria by 8µg / ml, and t _1/2 is 8 -10 hours. After absorption, the drug is widely distributed in various tissues and body fluids, including saliva, milk, semen and vaginal secretions, and can pass the blood-brain barrier. The drug is mainly excreted through the kidney through liver metabolism, metabolites and a small amount of the original drug, and the concentration in the colon is low.

[Function and clinical application]

(1) Anti-amoeba effect: It has a strong killing effect on amoeba trophozoites in tissues, and it is the drug of choice for the treatment of amoebiasis. The best treatment is for acute amoebic dysentery and parenteral amebiasis. Due to its complete absorption in the intestine and low intestinal concentration, it should be used alternately with anti-intestinal amoeba drugs in the treatment of amoebic dysentery to improve the efficacy and reduce the relapse rate.

(2) Anti-trichomonas effect: Metronidazole directly kills trichomoniasis. After oral administration, the drug can appear in vaginal secretions, semen and urine. Good curative effect, it is the drug of choice for the treatment of trichomoniasis, and has no effect on the normal vaginal flora when the amount of treatment is applied.

(3) Anti Giardiasis effect: Metronidazole is currently the most effective drug for treating Giardiasis.

(4) Anti-anaerobic effect: Metronidazole has a strong killing effect on all anaerobic cocci, gram-negative anaerobic bacteria and gram-positive anaerobic clostridium, and Gram-positive a Bacillus is resistant to it. Particularly effective against B. fragile infections.

[Adverse reaction] It is slight, and it is rare for people to be forced to stop the drug. Common headaches, nausea, dry mouth, metallic taste in the mouth, decreased appetite, diarrhea, abdominal pain, rash, and temporary decrease in white blood cells. Very few patients may experience neurological symptoms such as limb numbness, paresthesia, ataxia, and convulsions, and should be discontinued immediately if they occur. Because the adverse reactions of the nervous system are not easy to disappear, patients with organic central nervous system diseases and hematological diseases, women within three months of pregnancy and lactating women are prohibited. Metronidazole interferes with acetaldehyde metabolism, so alcohol should be abstained during the medication to avoid acute acetaldehyde poisoning, which may cause symptoms such as abdominal pain, nausea, vomiting, and headache.

Third, anti-trichomoniasis drugs

Trichomonas is mainly trichomonas vaginitis caused by Trichomonas vaginalis. Trichomonas vaginalis can also parasitize the male urinary tract, and most are transmitted through sexual contact. Metronidazole is currently the most effective drug for vaginal trichomoniasis. When it is resistant to metronidazole infection, acetamidine and the antibacterial agent trichomonin can also be used.

Fourth, anti schistosomiasis drugs

Schistosomiasis is a type of parasitic disease that seriously endangers human health. It is mainly caused by Schistosoma japonicum, Schistosoma mansoni, and Schistosoma japonicum. The prevalence of schistosomiasis in Japan is in China.

After human infection with schistosomiasis, acute schistosomiasis occurs. Fever, chills, night sweats, fatigue, liver and spleen canine, diarrhea or purulent bleeding, and sputum, hemoptysis and other symptoms can occur. Invasion of worm eggs into the brain can cause epileptic seizures. After repeated infections or incomplete treatment, it can be transformed into chronic schistosomiasis, which is manifested as obvious hepatosplenomegaly, and can cause severe anemia, portal hypertension, jaundice, cirrhosis, ascites, etc. in the later stages.

For a long time, potassium antimony tartrate is a very effective drug for the treatment of schistosomiasis, but its shortcomings such as high toxicity, long course of treatment, and the need for intravenous administration have limited its clinical application. At present, praziquantel is mainly used in clinical applications. The drug has the advantages of high efficiency, low toxicity, short treatment period, oral administration, etc., and has completely replaced the clinical application of antimony potassium tartrate. Artemisinin derivatives such as artesunate and artemether, which have been discovered in recent years, have the function of killing schistosomiasis, can prevent the infection of schistosomiasis, reduce the infection degree of infected people, and can be used as a preventive drug for schistosomiasis.

Praziquantel

The drug is a broad-spectrum anti-worm drug, and it has a strong killing effect on schistosomiasis.

[Pharmacokinetics] It is easily absorbed by the intestine quickly after oral administration, and reaches C _{max in} about 2 hours. Can be distributed in a variety of tissues such as liver, kidney, pancreas, adrenal gland, bone marrow, and pituitary and submandibular glands. It can be rapidly metabolized and inactivated in the liver. Most are excreted in the kidney and biliary tract within 24 hours. The liver of patients with schistosomiasis has different degrees of lesions, so its ability to degrade praziquantel is reduced, its peak plasma concentration will be increased, and its elimination half-life will be prolonged.

[Function and clinical application]

(1) Treatment of schistosomiasis: Praziquantel has a killing effect on a variety of schistosomiasis, has a strong effect on adults, and also has an effect on child worms. For the treatment of acute and chronic schistosomiasis.

It is generally believed that praziquantel can activate the slow calcium channels of somatic cells and increase the influx of calcium ions, leading to excitement, contraction and spasm of the somatic body, and finally cause spastic paralysis and fall off the blood vessel wall, and migrate to the liver to be mononuclear. -Macrophages inactivate phagocytosis. It is also believed that praziquantel agonists 5-HT receptors cause spastic paralysis.

(2) Anti-helminthic effects: Praziquantel has good curative effects on beef roundworm, pork roundworm, splithead roundworm, and short membrane shell roundworm disease. It can also be used for ginger pieceworm disease, clonorchiasis, pulmonary fluke disease and Treatment of liver fluke disease.

[Adverse reactions] The adverse reactions are mild, mainly found in the nervous system and digestive system, and are manifested as dizziness, headache, dreaminess, fatigue, muscle tremor, and anorexia, nausea, and abdominal distension.

Artemether

The drug is a derivative of artemisinin, which is now widely used in the prevention of schistosomiasis, in addition to being widely used in the treatment of malaria. The drug has a good killing effect on schistosomiasis larvae, especially the strongest killing effect on 7-21 days of juvenile worms. By killing juveniles, blocking female spawning and inhibiting a series of schistosomiasis eggs Immune response to prevent schistosomiasis infection. Artemether has a wide range of effects on the sugar metabolism of the insect body, including inhibiting the worm's uptake of glucose, promoting the decomposition of glycogen, inhibiting the alkaline phosphatase activity in the insect body, and significantly reducing the substantial glycogen content of the insect body. At the same time, it has a significant inhibitory effect on a variety of metabolic enzymes, destroying and dissolving the parenchyma tissue.

V. Intestinal worm medicine

There are many parasites in the human intestine, divided into worms and protozoa. Worms include roundworms, hookworms, roundworms, whipworms, and ginger leafworms. The main pathogens are amoeba. Anti-intestinal helminth drugs mainly drive parasites or spasms by interfering with worm activity, driving them out of the body.

Levamisole

The drug is a l-isomer of the imidazole derivative tetraimidazole, which has a significant deworming effect on roundworms, hookworms and roundworms. Its insect repellent mechanism may be to inhibit succinate dehydrogenase in the muscles of the insect body, block the reduction of fumaric acid to succinic acid, reduce ATP production, and block the energy supply of the insect body. When the insect body comes into contact with the drug, it can excite the ganglion, and then produce neuro-muscular depolarization. The muscles undergo continuous contraction, which causes paralysis, and the insect body is excreted from the body. It is mainly used for tsutsugamushi disease, hookworm disease, and mixed infections of hookworm. L-imidazole also has an immunomodulatory effect.

The side effects are mild and transient, including nausea, vomiting, abdominal pain, dizziness, fatigue, insomnia, and rash. Occasionally flu-like symptoms such as headache, arthralgia, myalgia, etc., and reversible leukocyte and thrombocytopenia, granulocyte deficiency, Photosensitivity. Liver and kidney dysfunction are disabled, pregnant women are disabled.

Pyrantel

The drug is a broad-spectrum insect repellent, which has the characteristics of high efficiency, broad spectrum, and small side effects. It has a good effect on roundworm, hookworm and roundworm infections. Thiamidine is a depolarizing neuromuscular blocker, and at the same time inhibits cholinesterase to accumulate acetylcholine, which can depolarize the neuromuscular of the worm body, cause worm body spasm, and then paralyze, and excreted through the feces. It is mainly used for roundworm, hookworm, and roundworm infection and mixed infection of roundworm and hookworm ^[1] .

What Is an Antiparasitic?

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