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Daraprim


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. more...

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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.

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).

Clinical use

Pyrimethamine is typically given with a sulfonamide and folinic acid:

  • 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.
  • Folinic acid (Leucovorin) is a compound that can be converted into folic acid by the human body without relying on dihydrofolate reductase. By doing so, folinic acid reduces side effects related to folate deficiency.

Side effects

Pyrimethamine may deplete folic acid in humans, resulting in hematologic side effects associated with folate deficiency.

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)

Contraindications

Pyrimethamine is contraindicated in patients with:

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

Read more at Wikipedia.org


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Clinical quiz - continuing medical education
From American Family Physician, 5/15/03

Clinical Quiz questions are based on selected articles in this issue. Answers appear in this issue.

American Family Physician has been approved by the American Academy of Family Physicians as having educational content acceptable for Prescribed credit hours. Term of approval covers issues published within one year from the beginning distribution date of January 2003. This issue has been reviewed and is acceptable for up to 3 Prescribed credit hours. Credit may be claimed for one year from the date of this issue. When reporting CME credit hours, AAFP members should report total Prescribed credit hours earned for this activity. It is not necessary for members to label credit hours as evidence-based or Prescribed for CME reporting purposes.

The American Academy of Family Physicians is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The AAFP designates this educational activity for a maximum of 3 hours in Category 1 credit toward the American Medical Association Physician's Recognition Award. Each physician should claim only those hours of credit that he or she actually spent in the educational activity.

AAFP Credit

Each copy of AFP contains a Clinical Quiz answer card. AAFP members may use this card to obtain the designated number of Prescribed credit hours for the year in which the card is postmarked.

AMA/PRA Category 1 Credit

AAFP members who satisfy the Academy's continuing medical education requirements are automatically eligible for the AMA/PRA.

Physicians who are not members of the AAFP are eligible to receive the designated number of credit hours in Category 1 of the AMA/PRA on completion and return of the Clinical Quiz answer card. AFP keeps a record of AMA/PRA Category 1 credit hours for nonmember physicians. This record will be provided on request; however, nonmembers are responsible for reporting their own Category 1 CME credits when applying for the AMA/PRA or other certificates or credentials.

For health care professionals who are not physicians and are AFP subscribers, a record of CME credit is kept by AAFP and will be provided to you on written request. You are responsible for reporting CME hours to your professional organization.

NOTE: The full text of AFP is available online (www.aafp.org/afp), including each issue's Clinical Quiz. The table of contents for each online issue will link you to the Clinical Quiz. Just follow the online directions to take the quiz and, if you're an AAFP member, you can submit your answers for CME credit.

Instructions

(1) Read each article, answer all questions on the quiz pages, and transfer your answers to the Clinical Quiz answer card (bound into your copy of AFP). This will help you avoid errors and permit you to check your answers against the correct answers.

(2) Mail the Clinical Quiz answer card within one year (by May 31, 2004). The bar code on the answer card contains your identification for CME credit hours.

Before beginning the test, please note:

Each Clinical Quiz includes two types of questions: Type A and Type X.

Type A questions have only one correct answer and may have four or five choices. Here is a typical Type A question:

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COPYRIGHT 2003 Gale Group

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