Other Antimalarial Drugs

In summary, allergic reactions are not a problem in treatment of protozoal infections. The aetiology of quinine-induced thrombocytopenia remains a fascinating immunological problem for future study. 

Adner MM, Altstatt LB, Conrad ME (1967) The possible role of quinine in the hemolysis of malaria. Clin Res 15 302 

Albertini F, Nizet F, Vergoz A (1972) Epistaxis grave par allergie a la quinine. Ann Otolaryngol Chir Cervicofac 89 63-68 

Baer RL, Harber LC (1961) Photosensitivity to drugs. Arch Dermatol 83 7-14 Baines EJ (1978) Metronidazole its past, present and future. J Antimicrob Chemother [Suppl C] 4 97-111 

Bandmann H-J (1966) Die Kontaktallergie durch Arzneimittel. Pharm Zeitung 40 1470 Bandmann H-J, Huber-Riffeser G, Woyton A (1966) Kontaktallergie gegen Triamcinolona-cetonid. Hautarzt 17 183-185 

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Proguanil appears to have a dual activity. Part of it is metabolized to cycloguanil, which subsequently inhibits the protozaon dihydrofolate reduc-tase/thymidylate synthase (DHFR/TS) (Fig. 4). In addition, the native form, proguanil itself, exerts a potent antimalarial activity, especially in combination with other antimalarial drugs. The target of proguanil is unknown. 

Abdel-Salam et al. [21] described a sensitive and simple spectrophotometric method for the determination of primaquine and other antimalarial drugs. The method is based on the formation of complexes between iodine (as an acceptor) and the basic drug in chloroform solution. Optimum conditions were established for the determination of primaquine, in pure form or in pharmaceutical preparation. Results were accurate and precise. 

Bergqvist and Churchill [146] reviewed the methods used for the detection and determination of primaquine and other antimalarial drugs and their metabolites in body fluids. 

Thus the main quality of chloroquine that exceeds all other antimalarial drug is its effect on erythrocytic schizonts (hematoschizotropic action). However, chloroquine also possesses amebicidal action. It has also been observed to have immunodepressive and antiarrhythmic properties. 

Other antimalarial drugs The malaria parasite is sensitive to many different gronps of drugs, and different combinations of drugs are used depending on each specific case. 

It is concentrated in parasitized erythrocytes, where it is activated by parasite haem, generating free radicals. Hence it causes increase in oxidant stress on the infected red cells promoting cytotoxicity and death of parasites. It rapidly clears parasitaemia, faster than any other antimalarial drug. 

A postal survey of the incidence of psychiatric disturbances in 2500 returning Israeli travellers (505) showed that travellers with this class of adverse effects were more likely to have taken mefloquine than other antimalarial drugs. Of 117 travellers with psychiatric adverse effects, 115 had taken mefloquine compared with 948/1340 for the entire cohort. This was a retrospective postal study with a response rate of 54% (1340 out of 2500), and of those who responded 71% had taken mefloquine, 5% had taken chloroquine, and 24% had taken no prophylaxis. In this study 11% (117) of the respondents reported psychiatric disturbances, mainly sleep disturbance, fatigue, vivid dreams, or lack of mood. Only 16 of the respondents had symptoms lasting 2 months or more. Those who had had a psychiatric disturbance were also more likely to have been female and to have taken recreational drug use. 

In another major review the risk of depression, psychosis, a panic attack, or a suicide attempt during current or previous use of mefloquine was compared with the risk during the use of proguanil and/or chloroquine or doxy-cycline (513). The study population (n = 35 370) was aged 17-79 years (45% men). There was no evidence that the risk of depression was increased during or after the use of mefloquine, but psychoses and panic attacks were more frequent in current users of mefloquine than in those using other antimalarial drugs. 

All three Artemisia derivatives are quickly hydrolysed to the active substance dihydroartemisinin. They produce a more rapid clinical and parasitological response than other antimalarial drugs. There are no reports of significant toxicity, and as late as 1994 there was no convincing evidence of specific resistance, but chloroquine-resistant Plasmodium berghei is resistant to artemisinin as well. The recrudescence rate is fairly high (1). 

Gastrointestinal adverse effects are more common with halofantrine than with other antimalarial drugs (11). 

The adverse effects of mefloquine have been extensively reviewed both for prophylaxis (when rare neuropsychiatric adverse effects make its use controversial) and in treatment doses, when it has been linked to an increased incidence of the postmalaria neurological syndrome. A retrospective review of 5120 Itahan soldiers showed an overall chemoprophylaxis curtailment rate of less than 1%, which was not significantly different from the combination of chloroquine and proguanil (11). A semi-systematic review also suggested no significant difference in tolerabihty compared with other antimalarial drugs (12). 

It has tentatively been suggested that mefloquine can exacerbate psoriasis (as can other antimalarial drugs, such as quinidine, chloroquine, and proguanil) (38). 

A review of the use of mefloquine in pregnancy (47) did not suggest that mefloquine has a worse effect in pregnancy than other antimalarial drugs, such as chloroquine and pyrimethamine + sulfadoxine. 

However, a further study of 208 pregnant women on the Thai-Burmese border showed a significantly increased incidence of still-births compared with 1565 women treated with other antimalarial drugs (51). Other adverse effects were no more common than with other antimalarial drugs. The study was performed during a period of emerging mefloquine-resistant malaria, and the findings may also reflect the effect of suboptimal malaria treatment. 

Quinine was originally extracted from the bark of the Cinchona tree (Peruvian bark or Jesuits bark) and was used to treat ague, that is fever, usually due to malaria. It fell out of fashion with the advent of other antimalarial drugs, but has once again become the drug of first choice for malaria originating in areas with multiresistant Plasmodium falciparum. To be effective, quinine plasma concentrations greater than the minimal inhibitory concentration must be achieved and maintained. 

Halofantrine. Structurally, halofantrine (Halfan) differs from all other antimalarial drugs. It is a good example of drag de.sign that incorporates bioisosteric principle , as evidenced by the trifluoroethyl moiety. Halofantrine is schiz-... 

Looareesuwan, S., Viravan, C., Webster, H. K., Kyle, D. E., Hutchinson, D. B., and Canfield, C. J. (1996). Clinical studies of atovaquone, alone or in combination with other antimalarial drugs, for treatment of acute uncomplicated malaria in Thailand. Am. J. Trop. Med. Hyg. 54, 62-66. 

Cinchona alkaloids have been used since the sixteenth century to treat malaria. It is well established that quinine, quinidine, cinchonidine, cinchonine, and their dihydro derivatives exhibit similar antimalarial activity (50, 51). Quinine owes its favored position in malaria therapy to its earlier isolation. Its use is becoming increasingly important in treating infections caused by strains of Plasmodium falciparum which are resistant to all other antimalarial drugs (52). However, some of the... 

Quinine sulfate is the standard drug for oral treatment of acute attacks of malaria due to chloroquine-resistant P falciparum. It should be used in combination with one or more other antimalarial drugs such as doxycycUne, clindamycin, or pyrimethamine plus sulfadiazine. The answer is (E). 

P. falciparum. Quinine is therefore an effective suppressive agent but has no prophylactic or radically curative properties. It is, however, becoming increasingly important as a last resort for treating infections with strains of P. falciparum resistant to all other antimalarial drugs [10]. Nevertheless, quinine-resistant strains of P. falciparwn have now been reported in the field, from Vietnam [92]. 

Lancaster DL, Adio RA, Tai KK, Simooya 00, Broadhead GD, Tucker GT, Lennard MS. Inhibition of metoprolol metabolism by chloroquine and other antimalarial drugs. JPharm Pharmacol (1990) 42, 267-71. 

It is worth noting that the two optical isomers of ferroquine exist due to the planar chirality of the unsymmetrically 1,2-substituted ferrocene moiety. Both enantiomers were prepared by enzymatic resolution of an ester intermediate in >98% optical purity. Both isomers display similar activity in vitro " Although both enantiomers are less active than the racemate in vivo the (+)-enantiomer displays better curative effects than the optical antipode. This different behavior indicates different pharmacokinetics of the two enantiomers. Ferrocene derivatives of other antimalarial drugs like artemisinine, quinine, and mefloquine have also been tested, as well as various other chloroquine-derived organometallics. Moss and coworkers synthesized and tested chloroquine and ferroquine derivatives with other organometallic groups. 

Quinine was quantitated from serum, plasma, and red blood cell samples [794]. A silica column (A = 254 nm) and a 100/9/0.4 DCM/methanol/water (1 M perchloric acid) mobile phase were used. Elution was complete in < 1S min and detection limits of <250 ng/mL were reported. The,linear concentration range was 0.25-20 pg/mL. The k values for potential interferents were tabulated (e.g., quinidine, dihydroqui-nine, chloroquine, primaquine, dapsone, pyrimethamine). Further discrimination between other antimalarial drugs and quinine was achieved through the use of fluorescence detection (A = 350 nm, ex 418 nm, em). The authors noted that an increase in either the DCM or the perchloric acid concentration led to an increase in the k for quinine. 

After war broke out in the Pacific at the end of 1941, the Dutch quinine plantations in the East Indies became inaccessible, and synthetic alternatives like chloroquine (see p433) came into use. These drugs were successful for some years, but after a while the Plasmodium falciparum and Plasmodium vivax parasites developed resistance to chloroquine and other antimalarial drugs, meaning that new treatments were needed. 

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