Antimalarial medication
Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young children and pregnant women. As of 2018, modern treatments, including for severe malaria, continued to depend on therapies deriving historically from quinine and artesunate, both parenteral drugs, expanding from there into the many classes of available modern drugs. Incidence and distribution of the disease is expected to remain high, globally, for many years to come; moreover, known antimalarial drugs have repeatedly been observed to elicit resistance in the malaria parasite—including for combination therapies featuring artemisinin, a drug of last resort, where resistance has now been observed in Southeast Asia. As such, the needs for new antimalarial agents and new strategies of treatment remain important priorities in tropical medicine. As well, despite very positive outcomes from many modern treatments, serious side effects can affect some individuals taking standard doses.
Specifically, antimalarial drugs may be used to treat malaria in three categories of individuals, those with suspected or confirmed infection, those visiting a malaria-endemic regions who have no immunity, to prevent infection via malaria prophylaxis, and or in broader groups of individuals, in routine but intermittent preventative treatment in regions where malaria is endemic via intermittent preventive therapy. Practice in treating cases of malaria is most often based on the concept of combination therapy, since this offers advantages including reduced risk of treatment failure, reduced risk of developed resistance, as well as the possibility of reduced side-effects. Prompt parasitological confirmation by microscopy, or alternatively by rapid diagnostic tests, is recommended in all patients suspected of malaria before treatment is started. Treatment solely on the basis of clinical suspicion is considered when a parasitological diagnosis is not possible.
Anti-malaria aid campaigns have a globally positive effect for health outcomes and beyond.
Medications
It is practical to consider antimalarials by chemical structure since this is associated with important properties of each drug, such as mechanism of action.Quinine and related agents
has a long history stretching from Peru, and the discovery of the cinchona tree, and the potential uses of its bark, to the current day and a collection of derivatives that are still frequently used in the prevention and treatment of malaria. Quinine is an alkaloid that acts as a blood schizonticidal and weak gametocide against Plasmodium vivax and Plasmodium malariae. As an alkaloid, it is accumulated in the food vacuoles of Plasmodium species, especially Plasmodium falciparum. It acts by inhibiting the hemozoin biocrystallization, thus facilitating an aggregation of cytotoxic heme. Quinine is less effective and more toxic as a blood schizonticidal agent than chloroquine; however, it is still very effective and widely used in the treatment of acute cases of severe P. falciparum. It is especially useful in areas where there is known to be a high level of resistance to chloroquine, mefloquine, and sulfa drug combinations with pyrimethamine. Quinine is also used in post-exposure treatment of individuals returning from an area where malaria is endemic.The treatment regimen of quinine is complex and is determined largely by the parasite's level of resistance and the reason for drug therapy. The World Health Organization recommendation for quinine is 20 mg/kg the first dose and 10 mg/kg every eight hours for five days where parasites are sensitive to quinine, combined with doxycycline, tetracycline or clindamycin. Doses can be given by oral, intravenous or intramuscular routes. The suggested course of action is determined by the need for therapy and the available resources.
Use of quinine is characterised by a frequently experienced syndrome called cinchonism. Tinnitus, rashes, vertigo, nausea, vomiting and abdominal pain are the most common symptoms. Neurological effects are experienced in some cases due to the drug's neurotoxic properties. These actions are mediated through the interactions of quinine causing a decrease in the excitability of the motor neuron end plates. This often results in functional impairment of the eighth cranial nerve, resulting in confusion, delirium and coma. Quinine can cause hypoglycaemia through its action of stimulating insulin secretion; this occurs in therapeutic doses and therefore it is advised that glucose levels are monitored in all patients every 4–6 hours. This effect can be exaggerated in pregnancy and therefore additional care in administering and monitoring the dosage is essential. Repeated or over-dosage can result in kidney failure and death through depression of the respiratory system.
Quinimax and quinidine are the two most commonly used alkaloids related to quinine in the treatment or prevention of malaria. Quinimax is a combination of four alkaloids. This combination has been shown in several studies to be more effective than quinine, supposedly due to a synergistic action among the four cinchona derivatives. Quinidine is a direct derivative of quinine. It is a distereoisomer, thus having similar anti-malarial properties to the parent compound. Quinidine is recommended only for the treatment of severe cases of malaria.
Warburg's tincture was a febrifuge developed by Carl Warburg in 1834, which included quinine as a key ingredient. In the 19th-century it was a well-known anti-malarial drug. Although originally sold as a secret medicine, Warburg's tincture was highly regarded by many eminent medical professionals who considered it as being superior to quinine. Warburg's tincture appeared in Martindale: The complete drug reference from 1883 until about 1920. The formula was published in The Lancet 1875.
Chloroquine
was, until recently, the most widely used anti-malarial. It was the original prototype from which most methods of treatment are derived. It is also the least expensive, best tested and safest of all available drugs. The emergence of drug-resistant parasitic strains is rapidly decreasing its effectiveness; however, it is still the first-line drug of choice in most sub-Saharan African countries. It is now suggested that it is used in combination with other antimalarial drugs to extend its effective usage. Popular drugs based on chloroquine phosphate are Chloroquine FNA, Resochin and Dawaquin.Chloroquine is a 4-aminoquinolone compound with a complicated and still unclear mechanism of action. It is believed to reach high concentrations in the vacuoles of the parasite, which, due to its alkaline nature, raises the internal pH. It controls the conversion of toxic heme to hemozoin by inhibiting the biocrystallization of hemozoin, thus poisoning the parasite through excess levels of toxicity. Other potential mechanisms through which it may act include interfering with the biosynthesis of parasitic nucleic acids and the formation of a chloroquine-haem or chloroquine-DNA complex. The most significant level of activity found is against all forms of the schizonts and the gametocytes of P. vivax, P. malariae, P. ovale as well as the immature gametocytes of P. falciparum. Chloroquine also has a significant anti-pyretic and anti-inflammatory effect when used to treat P. vivax infections, and thus it may still remain useful even when resistance is more widespread. According to a report on the Science and Development Network website's sub-Saharan Africa section, there is very little drug resistance among children infected with malaria on the island of Madagascar, but what drug resistance there is exists against chloroquinine.
Children and adults should receive 25 mg of chloroquine per kg given over three days. A pharmacokinetically superior regime, recommended by the WHO, involves giving an initial dose of 10 mg/kg followed 6–8 hours later by 5 mg/kg, then 5 mg/kg on the following two days. For chemoprophylaxis: 5 mg/kg/week or 10 mg/kg/week divided into six daily doses is advised. Chloroquine is only recommended as a prophylactic drug in regions only affected by P. vivax and sensitive P. falciparum strains. Chloroquine has been used in the treatment of malaria for many years and no abortifacient or teratogenic effects have been reported during this time; therefore, it is considered very safe to use during pregnancy. However, itching can occur at intolerable level and chloroquinine can be a provocation factor of psoriasis.
Hydroxychloroquine
was derived in the 1950s by adding a hydroxy group to existing chloroquine, making it more tolerable than chloroquine by itself.Amodiaquine
is a 4-aminoquinolone anti-malarial drug similar in structure and mechanism of action to chloroquine. Amodiaquine has tended to be administered in areas of chloroquine resistance while some patients prefer its tendency to cause less itching than chloroquine. Amodiaquine is now available in a combined formulation with artesunate and is among the artemisinin-combination therapies recommended by the World Health Organization. Combination with sulfadoxine=pyrimethamine is not recommended.The drug should be given in doses between 25 mg/kg and 35 mg/kg over three days in a similar method to that used in chloroquine administration. Adverse reactions are generally similar in severity and type to that seen in chloroquine treatment. In addition, bradycardia, itching, nausea, vomiting and some abdominal pain have been recorded. Some blood and hepatic disorders have also been seen in a small number of patients.