Artemisinin is a Chinese herb (qinghaosu) that has been used in the treatment of fevers for
over 1,000 years, thus predating the use of Quinine in the western world. It is
derived from the plant Artemisia annua, with the first documentation as a
successful therapeutic agent in the treatment of malaria is in 340 AD by Ge Hong in his book Zhou Hou Bei Ji Fang (A
Handbook of Prescriptions for Emergencies). Ge Hong extracted the
artemesinin using a simple macerate, and this method is still
in use today.The active compound was isolated first in 1971 and named artemisinin.
It is a sesquiterpene lactone with a chemically rare
peroxide bridge linkage. It is this that is thought to be responsible for the
majority of its anti-malarial action, although the target within the parasite
remains controversial. At present it is strictly controlled under WHO
guidelines as it has proven to be effective against all forms of multi-drug
resistant P. falciparum, thus every care is taken to ensure compliance
and adherence together with other behaviors associated with the development of
resistance. It is also only given in combination with other anti-malarials.
Artemisinin has a very rapid action and the vast majority of acute patients treated show significant improvement within 1–3 days of receiving treatment.
It has demonstrated the fastest clearance of all anti-malarials currently used and acts primarily on the trophozite phase, thus preventing progression of the disease. Semi-synthetic artemisinin derivatives (e.g. artesunate, artemether) are easier to use than the parent compound and are converted rapidly once in the body to the active compound dihydroartemesinin. On the first day of treatment 20 mg/kg should be given, this dose is then reduced to 10 mg/kg per day for the 6 following days. Few side effects are associated with artemesinin use. However, headaches, nausea, vomiting, abnormal bleeding, dark urine, itching and some drug fever have been reported by a small number of patients. Some cardiac changes were reported during a clinical trial, notably non specific ST changes and a first degree atrioventricular block (these disappeared when the patients recovered from the malarial fever). Artemether is a methyl ether derivative of dihydroartemesinin. It is similar to artemesinin in mode of action but demonstrates a reduced ability as a hypnozoiticidal compound, instead acting more significantly to decrease gametocyte carriage. Similar restrictions are in place, as with artemesinin, to prevent the development of resistance, therefore it is only used in combination therapy for severe acute cases of drug-resistant P. falciparum. It should be administered in a 7-day course with 4 mg/kg given per day for 3 days, followed by 1.6 mg/kg for 3 days. Side effects of the drug are few but include potential neurotoxicity developing if high doses are given. Artesunate is a hemisuccinate derivative of the active metabolite dihydroartemisin. Currently it is the most frequently used of all the artemesinin-type drugs.
Its only effect is mediated through a reduction in the gametocyte transmission. It is used in combination therapy and is effective in cases of uncomplicated P. falciparum. The dosage recommended by the WHO is a 5 or 7 day course (depending on the predicted adherence level) of 4 mg/kg for 3 days (usually given in combination with mefloquine) followed by 2 mg/kg for the remaining 2 or 4 days. In large studies carried out on over 10,000 patients in Thailand no adverse effects have been shown.
Dihydroartemisinin is the active metabolite to which artemesinin is reduced. It is the most effective artemesinin compound and the least stable. It has a strong blood schizonticidal action and reduces gametocyte transmission. It is used for therapeutic treatment of cases of resistant and uncomplicated P. falciparum. 4 mg/kg doses are recommended on the first day of therapy followed by 2 mg/kg for 6 days. As with artesunate, no side effects to treatment have thus far been recorded.
Arteether is an ethyl ether derivative of dihydroartemisinin. It is used in combination therapy for cases of uncomplicated resistant P. falciparum. The recommended dosage is 150 mg/kg per day for 3 days given by IM injections. With the exception of a small number of cases demonstrating neurotoxicity following parenteral administration no side effects have been recorded.
Artemisinin has a very rapid action and the vast majority of acute patients treated show significant improvement within 1–3 days of receiving treatment.
It has demonstrated the fastest clearance of all anti-malarials currently used and acts primarily on the trophozite phase, thus preventing progression of the disease. Semi-synthetic artemisinin derivatives (e.g. artesunate, artemether) are easier to use than the parent compound and are converted rapidly once in the body to the active compound dihydroartemesinin. On the first day of treatment 20 mg/kg should be given, this dose is then reduced to 10 mg/kg per day for the 6 following days. Few side effects are associated with artemesinin use. However, headaches, nausea, vomiting, abnormal bleeding, dark urine, itching and some drug fever have been reported by a small number of patients. Some cardiac changes were reported during a clinical trial, notably non specific ST changes and a first degree atrioventricular block (these disappeared when the patients recovered from the malarial fever). Artemether is a methyl ether derivative of dihydroartemesinin. It is similar to artemesinin in mode of action but demonstrates a reduced ability as a hypnozoiticidal compound, instead acting more significantly to decrease gametocyte carriage. Similar restrictions are in place, as with artemesinin, to prevent the development of resistance, therefore it is only used in combination therapy for severe acute cases of drug-resistant P. falciparum. It should be administered in a 7-day course with 4 mg/kg given per day for 3 days, followed by 1.6 mg/kg for 3 days. Side effects of the drug are few but include potential neurotoxicity developing if high doses are given. Artesunate is a hemisuccinate derivative of the active metabolite dihydroartemisin. Currently it is the most frequently used of all the artemesinin-type drugs.
Its only effect is mediated through a reduction in the gametocyte transmission. It is used in combination therapy and is effective in cases of uncomplicated P. falciparum. The dosage recommended by the WHO is a 5 or 7 day course (depending on the predicted adherence level) of 4 mg/kg for 3 days (usually given in combination with mefloquine) followed by 2 mg/kg for the remaining 2 or 4 days. In large studies carried out on over 10,000 patients in Thailand no adverse effects have been shown.
Dihydroartemisinin is the active metabolite to which artemesinin is reduced. It is the most effective artemesinin compound and the least stable. It has a strong blood schizonticidal action and reduces gametocyte transmission. It is used for therapeutic treatment of cases of resistant and uncomplicated P. falciparum. 4 mg/kg doses are recommended on the first day of therapy followed by 2 mg/kg for 6 days. As with artesunate, no side effects to treatment have thus far been recorded.
Arteether is an ethyl ether derivative of dihydroartemisinin. It is used in combination therapy for cases of uncomplicated resistant P. falciparum. The recommended dosage is 150 mg/kg per day for 3 days given by IM injections. With the exception of a small number of cases demonstrating neurotoxicity following parenteral administration no side effects have been recorded.
About 
0 comments: