Artesunate + Sulphadoxine + Pyrimethamine Pharmacology

Artesunate + Sulphadoxine + Pyrimethamine

About Artesunate + Sulphadoxine + Pyrimethamine
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Mechanism of Action of Artesunate + Sulphadoxine + Pyrimethamine
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Pharmacokinets of Artesunate + Sulphadoxine + Pyrimethamine
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Onset of Action for Artesunate + Sulphadoxine + Pyrimethamine
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Duration of Action for Artesunate + Sulphadoxine + Pyrimethamine
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Half Life of Artesunate + Sulphadoxine + Pyrimethamine
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Side Effects of Artesunate + Sulphadoxine + Pyrimethamine
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Contra-indications of Artesunate + Sulphadoxine + Pyrimethamine
N/A
Special Precautions while taking Artesunate + Sulphadoxine + Pyrimethamine
N/A
Pregnancy Related Information
Contraindicated
Old Age Related Information
Use with caution
Breast Feeding Related Information
Contraindicated
Children Related Information
Use with caution
Indications for Artesunate + Sulphadoxine + Pyrimethamine
Treatment for all forms of malaria due to Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae.
Interactions for Artesunate + Sulphadoxine + Pyrimethamine
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Typical Dosage for Artesunate + Sulphadoxine + Pyrimethamine
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Schedule of Artesunate + Sulphadoxine + Pyrimethamine
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Storage Requirements for Artesunate + Sulphadoxine + Pyrimethamine
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Effects of Missed Dosage of Artesunate + Sulphadoxine + Pyrimethamine
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Effects of Overdose of Artesunate + Sulphadoxine + Pyrimethamine
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Artesunate

About Artesunate
A semi-synthetic derivative of artemisinin, a sesquiterpene lactone potent blood schizonticide, Anti malarial.
Mechanism of Action of Artesunate
This antimalarial drug binds tightly to parasitized erythrocyte membranes. Its endoperoxide bond is responsible for antimalarial activity. Release of an active oxygen species (free radicals) from this bond kills the parasite if accumulated in the erythrocytic cells. It also suppresses the production or activity of antioxidant enzymes in the erythrocytes, causing lysis of the parasitic cell due to the highly reactive free oxygen radicals.
Pharmacokinets of Artesunate
Absorption- Rapidly absorbed after administration
Distribution- Widely distributed in the body. High concentration is seen in liver, kidney and intestine
Metabolism- Metabolized in the liver to its metabolites
Excretion- Excreted through urine and feces
Onset of Action for Artesunate
N/A
Duration of Action for Artesunate
N/A
Half Life of Artesunate
N/A
Side Effects of Artesunate
1. Dizziness
2. Itching
3. Vomiting
4. Abdominal pain
5. Flatulence
6. Headache
7. Bodyache
8. Diarrhoea
9. Tinnitus
10. Alopecia
11. Macular rash
12. Neutropenia
13. Convulsions
14. Skin rash
15. Pruritis
Contra-indications of Artesunate
1. Hypersensitivity to the drug or any ingredients of it
2. G6PD deficiency
3. Immunocompromised patients.

Special Precautions while taking Artesunate
Parenteral artesunate should be used for the treatment of severe falciparum malaria only where there is evidence that the antimalarial efficacy of quinine is declining.
Pregnancy Related Information
Contraindicated (1st trimester)
Old Age Related Information
May be used.
Breast Feeding Related Information
Use with caution
Children Related Information
May be used
Indications for Artesunate
1.Uncomplicated falciparum malaria (in areas where there is evidence of chloroquine, pyrimethamine/sulfadoxine, mefloquine and quinine resistance).
2. Severe falciparum malaria (in areas where there is evidence of quinine resistance)

Interactions for Artesunate
NULL
Typical Dosage for Artesunate
Adults-
Oral-
Monotherapy:
4mg/Kg loading dose on the first day followed by 2mg/Kg once a day for 6 days
Combination therapy:
4mg/Kg once a day for 3 days plus mefloqine (15mg or 25mg of base per Kg) as a single dose or split dose on the second and/or third day.
Intramuscular-
2.4mg/Kg followed by 1.2mg/Kg at 12 and 24 hours then 1.2mg/Kg daily for 6 days.
Intravenous-
2.4mg/Kg on the first day followed by 1.2mg/Kg daily
Note: The speed for intravenous injection is 3-4 ml per minute
Schedule of Artesunate
H
Storage Requirements for Artesunate
Store in a cool dry dark place.
Effects of Missed Dosage of Artesunate
Take the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose. Continue the regular schedule. Do not double the dose.
Effects of Overdose of Artesunate
Give symptomatic and supportive treatment

Sulphadoxine

About Sulphadoxine
An ultra-long-lasting sulfonamide, Antimalarial with pyrimethamine.
Mechanism of Action of Sulphadoxine
Sulphadoxine is a structural analogs and competitive antagonists of para-aminobenzoic acid (PABA). They inhibit normal bacterial utilization of PABA for the synthesis of dihydrofolic acid, a compound that bacteria must be able to make in order to survive for the synthesis of folic acid, an important metabolite in DNA synthesis. It is usually given with Pyrimethamine in the treatment of Chloroquine resistant Plasmodium falciparum in a fixed dose formulation.
Pharmacokinets of Sulphadoxine
Absorption: Sulfadoxine is readily absorbed from the gastrointestinal tract. Distribution: It is distributed mainly in protein bound form. It is widely distributed to body tissues and fluids and it passes into the fetal circulation. Excretion: It is excreted very slowly in urine mainly in unchanged form.
Onset of Action for Sulphadoxine
N/A
Duration of Action for Sulphadoxine
N/A
Half Life of Sulphadoxine
4 to 9 days.
Side Effects of Sulphadoxine
1. Brownish coloration of urine
2. Skin rashes
3. Hives
4. Itching
5. Localized swelling
6. Reddened eyes
7. Headache
8. Dizziness
9. Ringing in ears
10. Loss of appetite
11. Irritation of mouth and tongue
12. Nausea
13. Abdominal pain
14. Diarrhea
Contra-indications of Sulphadoxine
1. Hypersensitivity to the drug or other ingredients it or other sulfonamides
2. Glucose-6-phosphate dehydrogenase (G6PD) deficiency
3. Kidney disease
4. Liver disease
5. Porphyria
6. Anemia or other blood problems
Special Precautions while taking Sulphadoxine
1.Renal impairment
2.Hepatic impairment
3.Blood disorders
4.Drink lots of high calorie fluids such as cranberry juice and nectars, up to 2 quarts daily, to make sure you have adequate volume of urine to prevent dehydration.
Pregnancy Related Information
Contraindicated
Old Age Related Information
Use with caution
Breast Feeding Related Information
Contraindicated
Children Related Information
Use with caution
Indications for Sulphadoxine
1. Malaria along with Pyrimethamine
Interactions for Sulphadoxine
N/A
Typical Dosage for Sulphadoxine
Adult: Initially 2 g, followed by 1 to 1.5 g weekly.
Children: 250 mg - 1 g dose is depend on body weight of children.
Schedule of Sulphadoxine
H
Storage Requirements for Sulphadoxine
Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Protect from light.
Effects of Missed Dosage of Sulphadoxine
Take the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose. Continue the regular schedule. Do not double the dose.
Effects of Overdose of Sulphadoxine
Give symptomatic and supportive treatment. Induce gastric lavage. Treat with blood products if needed.

Pyrimethamine

About Pyrimethamine
Folic acid antagonist, Pyrimidine derivative, Antiprotozoal, Antimalarial.
Mechanism of Action of Pyrimethamine
Pyrimethamine binds to dihydrofolate reductase enzyme and inhibits the reduction of Dihydrofolic acid (DHFA) to Tetra hydrofolic acid (THFA) .This will interfere the synthesis of folic acid in malarial parasite.
Pharmacokinets of Pyrimethamine
Absorption: It is well absorbed after oral administration.Distribution: It is widely distributed in the body in plasma protein bound form.Metabolism: It undergoes metabolism in the liver. Excretion: Excreted mainly through urine and also through breast milk.
Onset of Action for Pyrimethamine
30 - 60 minute
Duration of Action for Pyrimethamine
8 - 10 hours
Half Life of Pyrimethamine
2 - 6 days
Side Effects of Pyrimethamine
1.Nausea
2.Vomiting
3.Anorexia
4.Abdominal cramps
5.Thrombocytopenia
6.Megaloblastic anaemia
7.Glossitis
8.Pruritis
9.Rash


Contra-indications of Pyrimethamine
1.Hypersensitivity to Pyrimethamine
2.Megaloblastic anaemia caused by folic acid deficiency
Special Precautions while taking Pyrimethamine
1. Hepatic dysfunction
2. Renal impairment
3. Epilepsy
4. Patients with G -6-PD deficiency
5. Asthma
Pregnancy Related Information
Contraindicated.
Old Age Related Information
Use with caution
Breast Feeding Related Information
Contraindicated.
Children Related Information
Use with caution
Indications for Pyrimethamine
1. Malaria (treatment and chemoprophylaxis)
2. Toxoplasmosis
3. Isosporiasis
Interactions for Pyrimethamine
Antifolic drugs (e.g: Methotrexate, Sulphonamides TMP-SMZ): Do not use these agents while the patient is receiving sulfadoxine/pyrimethamine.

Typical Dosage for Pyrimethamine
Adult: Malaria: 50 mg once daily for 2 days followed by 25 mg once in 7 days for 2 - 3 months along with a Sulphonamide
Chemoprophylaxis: 25 mg once weekly for 2 - 3 months
Schedule of Pyrimethamine
H
Storage Requirements for Pyrimethamine
The drug should be stored in cool dark place. Protect away from sun light. Keep out of the reach of children
Effects of Missed Dosage of Pyrimethamine
Take the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose. Continue the regular schedule. Do not double the dose.
Effects of Overdose of Pyrimethamine
Give supportive measures and treatment. Gastric lavage has to be done followed by administration of cathartic. To control seizure Barbiturates can be given to the patient.Leucovorin is given to reduce the hematological side effect.

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