Pyrimethamine (Daraprim®) is a medication used for protozoal infections. It is commonly used as an antimalarial drug (for both treatment and prevention), and is also used in the treatment of Toxoplasma gondii infections in immunocompromised patients, such as HIV-positive individuals. PubChem is a database of chemical molecules . ... DrugBank is a database available at the University of Alberta that provides information about thousands of products. ... A chemical formula (also called molecular formula) is a concise way of expressing information about the atoms that constitute a particular chemical compound. ... General Name, Symbol, Number carbon, C, 6 Chemical series nonmetals Group, Period, Block 14, 2, p Appearance black (graphite) colorless (diamond) Atomic mass 12. ... General Name, Symbol, Number hydrogen, H, 1 Chemical series nonmetals Group, Period, Block 1, 1, s Appearance colorless Atomic mass 1. ... General Name, Symbol, Number chlorine, Cl, 17 Chemical series halogens Group, Period, Block 17, 3, p Appearance yellowish green Atomic mass 35. ... This article does not cite its references or sources. ... The molecular mass of a substance (less accurately called molecular weight and abbreviated as MW) is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... The gram or gramme, symbol g, is a unit of mass. ... The mole (symbol: mol) is the SI term identifying the number of particles in a given amount of matter. ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of medication that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... Santorio Santorio (1561-1636) in his steelyard balance, from Ars de statica medecina, first published 1614 Metabolism (from μεταβολισμος (metabolismos), the Greek word for change, or overthrow (Etymonline)), is the biochemical modification of chemical compounds in living organisms and cells. ... The elimination half-life of a drug (or any xenobiotic agent) refers to the timecourse necessary for the quantity of the xenobiotic agent in the body (or plasma concentration) to be reduced to half of its original level through various elimination processes. ... The hour (symbol: h) is a unit of time. ... Excretion is the biological process by which an organism chemically separates waste products from its body. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother. ... ... The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ... A prescription drug is a medication that is regulated by legislation to require a prescription before it can be obtained. ... Sagittal section of nose mouth, pharynx, and larynx. ... A medication is a licenced drug taken to cure or reduce symptoms of an illness or medical condition. ... Protozoa (in Greek protos = first and zoon = animal) are single-celled eukaryotes (organisms with nuclei) that show some characteristics usually associated with animals, most notably mobility and heterotrophy. ... Antimalarial drugs are designed to prevent or treat malaria. ... Binomial name Toxoplasma gondii (Nicolle & Manceaux), 1908 Toxoplasma gondii is a species of parasitic protozoa, belonging to the Apicomplexa, that can cause the disease toxoplasmosis in humans. ... ... Human immunodeficiency virus, commonly called HIV, is a retrovirus that primarily infects vital components of the human immune system such as CD4+ T cells, macrophages and dendritic cells. ...

Mechanism of action

Pyrimethamine interferes with folic acid synthesis by inhibiting the enzyme dihydrofolate reductase. Folic acid is needed for DNA and RNA synthesis in many species, including protozoa. This article needs to be cleaned up to conform to a higher standard of quality. ... Categories: Biochemistry stubs | EC 1. ... Space-filling model of a section of DNA molecule Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions specifying the biological development of all cellular forms of life (and most viruses). ... Ribonucleic acid (RNA) is a nucleic acid polymer consisting of covalently bound nucleotides. ... In biology, a species is the basic unit of biodiversity. ...

Mechanism of resistance

Resistance to pyrimethamine is widespread. Mutations in the gene for dihydrofolate reductase may reduce the effectiveness of pyrimethamine (PMID 15155209). These mutations decrease the binding affinity between pyrimethamine and dihydrofolate reductase by steric interactions (PMID 14711307). Steric effects are the interaction of molecules dictated by their shape and/or spatial relationships. ...

Clinical use

Pyrimethamine is typically given with a sulfonamide and leucovorin:

• Sulfonamides inhibit dihydropteroate synthetase, an enzyme that participates in folic acid synthesis from para-aminobenzoic acid. Hence, sulfonamides work synergistically with pyrimethamine by blocking a different enzyme needed for folic acid synthesis.
• Leucovorin is a compound that can be converted into folic acid by the human body without relying on dihydrofolate reductase. By doing so, leucovorin reduces side effects related to folate deficiency.

Sulfonamides, also known as sulfa drugs, are synthetic antimicrobial agents derived from sulfonic acid. ... Para-Aminobenzoic acid (PABA) is a chemical used in sunscreen that is an essential nutrient for some bacteria. ... Folinic acid, generally administered as calcium folinate, is an adjuvant used in cancer chemotherapy involving the drug methotrexate. ...

Side effects

Pyrimethamine may deplete folic acid in humans, resulting in hematologic side effects associated with folate deficiency. Hematology is the branch of medicine that is concerned with blood and its disorders. ...

Side effects include:

• hypersensitivity reactions
• megaloblastic anemia
• leukopenia
• thrombocytopenia
• pancytopenia
• atrophic glossitis
• hematuria
• cardiac arrhythmias
• pulmonary eosinophilia (rare)
• hyperphenylalaninemia (particularly when used with a sulfonamide)

Hypersensitivity is the name given to a state in which an immune response damages the bodys own tissues. ... Megaloblastic anemia is anemia resulting from a deficiency of vitamin B12 and folic acid. ... Leukopenia, low white blood count is seen in: aplastic anemia pancytopenia Categories: Stub ... Thrombocytopenia (or -paenia, or thrombopenia in short) is the presence of relatively few platelets in blood. ... Pancytopenia is a condition in which there is a reduction in the number of Red and White blood cells, as well as platelets. ... In medicine, hematuria is the presence of blood in the urine. ... A cardiac arrhythmia, also called cardiac dysrhythmia, is a disturbance in the regular rhythm of the heartbeat. ... Eosinophilia is the state of having high eosinophil granulocytes in the blood. ...

Contraindications

Pyrimethamine is contraindicated in patients with:

• hypersensitivity to pyrimethamine
• megaloblastic anemia - depletion of folic acid may aggravate this condition

References

• Daraprim - Package insert (PDF file)