ANTIMALARIAL MEANS — the chemotherapeutic means having specific activity concerning causative agents of malaria.
- 1 Features of action and classification of antimalarial means
- 2 Mechanisms of action of antimalarial means
- 3 Use of antimalarial means
- 4 Side effect of antimalarial means
Features of action and classification of antimalarial means
P. page have unequal activity concerning different life-forms of plasmodiums and can have the shizotropny (shizontotsidny) effect directed to sexless forms of these activators, and the homotropic (gamontotsidny) action directed to sexual forms during their development in a human body. In this regard emit shizotropny and homotropic drugs.
Shizotropny antimalarial means
Shizotropnye P. differ with page on activity concerning sexless erythrocyte and ectoglobular forms of causative agents of malaria therefore drugs of this subgroup divide on gistoshizotropny (fabric shizontotsida) and gematoshizotropny (blood shizontotsida). Gistoshizotropnye P. pages cause death of ectoglobular forms: the early preeritrotsitarny forms developing in a liver and forms which remain in an organism out of erythrocytes in an abeyance throughout the period preceding the remote displays of the malaria caused by Plasmodium vivax and Plasmodium ovale. Gematoshizotropnye P. pages are active concerning sexless erythrocyte forms and stop their development in erythrocytes or interfere with it.
Homotropic antimalarial means
Gamotropnye P. of page, influencing sexual forms of plasmodiums in blood of the persons infected with them, cause death of these forms (gamontotsidny action) or damage them (gamostatichesky action). Gamostatichesky action of P. of page on character can be disflagelliruyushchy, i.e. interfering formation of men's gametes as a result of an eksflagellyation of men's sexual forms in a stomach of a mosquito and breaking at the expense of it the subsequent fertilization of female sexual forms, or to the late gamostatichesky (sporontotsidny), i.e. interfering ends of a sporogony and formation of sporozoit (see Malaria).
On a chemical structure among P. the page is distinguished: derivative 4 aminoquinolines — Chingaminum, (see), Nivachinum (chloroquine sulfate), amodiaquine, hydroxychloroquine (plaquenil); derivatives of a diaminopyrimidine — Chloridinum (see), Trimethoprimum; derivatives of guanyl guanidine — Bigumalum (see), chlorproguanil; derivatives 9 aminoacridines — quinacrine (see); derivatives 8 aminoquinolines — Primachinum (see), Chinocidum (see); streptocides — Sulfazinum (see), sulfadimethoxine (see), Sulfapyridazinum (see), sulfalene, sulphadoxine; sulphones — diafenilsulfon (see). As P. villages use also drugs of quinine (see) — quinine sulfate and quinine dihydrochloride. As action derivative 4 aminoquinolines, 9 aminoacridines, streptocides, sulphones and drugs of quinine are gematoshizotropny. Derivatives of a diaminopyrimidine (Chloridinum, Trimethoprimum) and guanyl guanidine (Bigumalum, chlorproguanil) are gistoshizotropny, are active concerning the early preeritrotsitarny fabric forms developing in a liver. These derivatives possess also gematoshizotropny action. Derivatives 8 aminoquinolines (Primachinum, Chinocidum) are gistoshizotropny P. of page, active in the relation is long the tare forms existing vneeritrots. Derivatives of a diaminopyrimidine, guanyl guanidine and 8 aminoquinolines have homotropic P.' properties of page.
Mechanisms of action of antimalarial means
Mechanisms of action on causative agents of malaria of P. of page of a different chemical structure are not identical. E.g., derivative 4 aminoquinolines break processes of intracellular exchange at erythrocyte forms of plasmodiums, causing deficit of amino acids and formation of cytolysosomes. Quinine interacts with DNA of plasmodiums. Derivatives 8 aminoquinolines oppress functions of mitochondrions of ectoglobular forms of plasmodiums. Chloridinum and streptocides break biosynthesis folic to - you. At the same time streptocides interfere with education dihydrofolic to - you at the expense of competitive antagonism with n-aminobenzoic to - that, and Chloridinum is inhibitor of a digidrofolatreduktaza and breaks recovery dihydrofolic to - you in tetrahydrofolic.
Items of page apply to treatment and chemoprophylaxis of malaria.
Use of antimalarial means
According to WHO recommendations P. distinguish page for stopping a wedge, symptoms of malaria, for radical and preliminary treatment of a disease.
For stopping wedge. symptoms of a disease by the termination of reproduction of the activator in erythrocytes at acute displays of malaria and a parasitosis apply gematoshizotropny P. of page — Chingaminum, Nivachinum, amodiaquine, quinine, etc. At the same time drugs or their combinations choose taking into account medicinal sensitivity of the activator, and the scheme of appointment — taking into account weight of disease and immunol. conditions of an organism of the patient.
In zones where there are no drug resistant activators, for treatment appoint usually one of drugs: derivatives of 4-amino-quinoline (Chingaminum, amodiaquine, etc.), quinine. Persons with partial immunity to causative agents of malaria (e.g., to adult aboriginals of endemic zones) can appoint these drugs in the reduced course doses. At the heavy course of tropical malaria instead of derivatives 4 aminoquinolines sometimes appoint quinine. In endemic zones of spread of drug resistant tropical malaria the wedge, treatment carry out, appointing gematoshizotropny P.' combinations of page, napr, quinine in combination with Chloridinum and streptocides of long action.
For radical treatment (full suppression of the activator in an organism of the patient) at a tetrian fever and an oval of malaria, except gematoshizotropny P. page (Chingaminum, etc.), it is necessary to appoint in addition gistoshizotropny drugs (Primachinum or Chinocidum), active in the relation it is long the ectoglobular forms of the activator remaining in an organism. At tropical malaria radical treatment is reached by correctly carried out therapy of acute displays of a disease or a parasitosis.
Preliminary treatment (P.'s use by the village at suspicion of malaria) carry out to establishment of the diagnosis for easing a wedge, displays of a disease and the prevention of possible infection of mosquitoes. For this purpose once appoint any gematoshizotropny drug, napr, Chingaminum or quinine (taking into account sensitivity of local strains of the activator) right after capture of blood for a research to malaria. At danger of infection of mosquitoes and a possibility of end of a sporogony in addition to the specified drugs appoint gemotropny antimalarial means (e.g., Chloridinum, Primachinum). At confirmation of the diagnosis conduct a full course of radical treatment.
Tactics of use of the transferred funds in the USSR — see. Malaria .
Use of antimalarial means for chemoprophylaxis of malaria
is Distinguished by three types of chemoprophylaxis of malaria — personal, public and interseasonal; the choice depends on a goal, the protected contingents, epidemiol. conditions, type of the activator. Different types of chemoprophylaxis of malaria shall be dated for the certain terms caused by phenology of an infection.
The contingents of the persons which are subject to chemoprophylaxis are defined with their vulnerability in the relation of infection with malaria or degree of danger as source of an infection. P.'s choice by the village depends on type of the carried-out chemoprophylaxis, sensitivity of local strains to P. of page and individual portability of drugs. Doses and schemes of appointment of P. of page establish depending on features of pharmacokinetics of drugs, the type of plasmodiums dominating in this area and degree of endemicity of a zone, in a cut P. of page for chemoprophylaxis are appointed.
Personal chemoprophylaxis is directed to the full prevention of development of the activator or prevention of attacks of disease at the persons which are endangered infection. Distinguish two forms of this type of chemoprophylaxis — radical (causal) and clinical (palliative).
For the purpose of radical chemoprophylaxis of tropical malaria it is possible to apply P. the pages operating on preeritrotsitarny forms of plasmodiums, napr, Chloridinum, Bigumalum. However these drugs differ by efficiency concerning different strains of the activator. At the malaria caused by Plasmodium vivax and Plasmodium ovale, these drugs prevent only early displays of a disease.
Wedge. chemoprophylaxis is carried out by means of P. of the pages operating on erythrocyte forms of plasmodiums. In zones where drug resistant forms of activators are not registered, at the same time use hl. about river Chingaminum and Chloridinum. Drugs are appointed during the entire period of possible infection, and in high-endemic tropical zones where transfer of malaria can continuously happen — during the whole year. In zones where there are seasonal breaks in transfer of malaria or at temporary stay in an endemic zone, drugs are appointed some days before approach of possible infection and continue 6 — 8 weeks after the termination of danger of infection.
Personal chemoprophylaxis allows to prevent completely development of the tropical malaria caused by Plasmodium falciparum. At caught P. vivax and P. ovale after the termination of personal chemoprophylaxis attacks of a disease can arise in the terms characteristic of the remote Manifestations (within 2 years, and sometimes later). In this regard the persons leaving districts with high risk of infection with these types of plasmodiums should appoint Primachinum or Chinocidum.
Chemoprophylaxis of malaria at hemotransfusion, i.e. the prevention of infection of recipients as a result of a hemotransfusion or a hematotherapy blood of donors who are possible carriers of a malarial infection (e.g., aboriginals of endemic zones) is considered as a version by a wedge, chemoprophylaxis. For this purpose to the recipient directly after administration of donor blood appoint any gematoshizotropny P. of page (Chingaminum, amodiaquine or other) according to the scheme of treatment of acute displays of malaria.
Public chemoprophylaxis to malaria it is directed to prevention or restriction of possible transfer of a disease through mosquitoes by destruction or damage of sexual forms of activators to blood of the infected persons. This type of chemoprophylaxis is carried out by appointment gamontotsidny (Primachinum, Chinocidum) or gamostatichesky P. by page (Chloridinum, Bigumalum, chlorproguanil). The choice of drug is defined by sensitivity to it local strains of the activator. As public chemoprophylaxis of P. of page appoint to patients with malaria, parazitonositel and persons who on epidemic, to conditions could be infected, and also persons at whom the disease of malaria is suspected.
Interseasonal chemoprophylaxis aims to prevent the remote manifestations of a tetrian fever with a short incubation and primary manifestations of a tetrian fever with a long incubation at the persons which caught in the previous malarial season who by the beginning of the next malarial season can be sources of an infection. For this type of chemoprophylaxis use gistoshizotropny P. the page (Primachinum or Chinocidum) operating on is long the existing ectoglobular forms of the activator. At intolerance of these drugs (e.g., at persons with genetically caused deficit glyukozo-6-fosfatdegidrogenazy in erythrocytes) instead of interseasonal chemoprophylaxis during possible manifestations appoint gematoshizotropny drugs according to the scheme of personal chemoprophylaxis.
Side effect of antimalarial means
P.'s Most page differs in good tolerance and at short reception in therapeutic doses usually does not cause serious side effects. The last arise at prolonged use of P. of page more often.
The nature of side effect of P. of the page belonging to the different classes of chemical connections is various. So, Chingaminum and other derivative 4 aminoquinolines can make sick and vomiting. At prolonged continuous use (within many months) drugs of this group can cause vision disorders and vestibular frustration, a depigmentation of hair, damages of a liver and dystrophic changes in a myocardium. At bystry intravenous administration of Chingaminum development of kollaptoidny reactions is possible.
Derivatives of a diaminopyrimidine (Chloridinum, etc.) at short-term use sometimes cause a headache, dizziness and dispeptic frustration. Megaloblastichesky anemia, a leukopenia and teratogenic effect which are caused by anti-folic properties P. of page of this group can be the heaviest manifestations of side effect of these drugs at prolonged use.
Bigumalum and other guanyl guanidines cause in some patients passing increase in number of neutrophils in blood and leukemoid tests. Long reception bigumalya on an empty stomach is followed by loss of appetite, perhaps, owing to oppression of gastric secretion.
The item of page from among derivatives 8 aminoquinolines (Primachinum, Chinocidum) more often than other P. pages, cause side effects (dispeptic frustration, stethalgias, cyanosis, etc.). It must be kept in mind that side effect of Chinocidum develops more often and proceeds heavier at co-administration of this drug with other P. of page. The heaviest manifestation of side effect of derivatives 8 aminoquinolines can be an intravascular hemolysis which develops at persons with inborn insufficiency of enzyme glyukozo-6-fosfatdegidrogena-zy in erythrocytes.
Drugs of quinine differ in more high toxicity in comparison with other P. of page. Side effect of quinine — a sonitus, dizziness, nausea, vomiting, sleeplessness, uterine bleedings. At overdose quinine can cause decrease in sight and hearing, a sharp headache and other disturbances from c. N of page, and also kollaptoidny reactions. In case of an idiosyncrasy to quinine there are an erythema, urticaria, exfoliative dermatitis, scarlatiniform rash. At persons with insufficiency glyukozo-6-fosfatdegidroge-nazy under the influence of quinine hemoglobinuric fever develops.
See also Malaria (treatment and chemoprophylaxis).
Bibliography: Clinical pharmacology, under the editorship of V. V. Zakusov, page 550, M., 1978; The Medicines used at parasitic diseases under the editorship of A. I. Krotov, page 5, M., 1979; M about rn-k with to and y III. D. Chemoprophylaxis of malaria, Medical parazitol., t. 4, century 3, page 161, 1935; Instructions on treatment and chemoprophylaxis of malaria, under the editorship of Sh. D. Moszkowski, M., 1972; Chemotherapy of malaria and antimalarial drugs resistance, It is gray. tekhn. dokl. No. 529, Geneva, WHO, 1975; Chemotherapy of malaria, Wld Hlth Org. Monogr. Ser. No. 27, Geneva, 1981, bibliogr.; The pharmacological basis of therapeutics, ed. by A. G. Gilman a. o., N. Y., 1980.
S. A. Rabinovich.