This is potentially due to the high lipophilicity and slow uptake of atovaquone, which results in a relatively prolonged period of parasite exposure at ineffective concentrations. Specific mutations (Y268S, Y268C) have been shown to confer resistance in vivo, but the other mechanisms of resistance remain unknown. Adverse effects
Side effects are generally mild. While some people experience side effects, such as coughing, diarrhea, dizziness, headache, loss of appetite, mouth sores, nausea, stomach pain, vomiting, or weakness, the majority have none or few of these. Mechanism of action
Atovaquone selectively inhibits the malarial cytochrome bc1 complex in the parasitic electron transport chain, collapsing the mitochondrial membrane potential. The malarial electron transport chain does not contribute significantly to ATP synthesis; thus, it is believed that parasite death is due to the indirect inhibition of dihydroorotate dehydrogenase, which requires transport chain function and is essential to pyrimidine biosynthesis.Proguanil, via its metabolite cycloguanil, functions as a dihydrofolate reductase inhibitor, halting parasitic deoxythymidylate synthesis. Chemistry
A standard tablet of Malarone contains 100 mg of proguanil hydrochloride and 250 mg of atovaquone. A pediatric tablet contains 25 mg of proguanil hydrochloride and 62.5 mg of atovaquone. History
Glaxo Wellcome patented the combination of atovaquone and proguanil to treat malaria in 1999. Patent protection expired in 2013. The U.S. Food and Drug Administration (FDA) approved a generic formulation from Glenmark Generics in 2011. In February 2013, the United Kingdom High Court revoked Glaxos patent on grounds of obviousness, which clears the way for firms to sell generic versions there. References
External links
"Atovaquone mixture with proguanil hydrochloride".
The only anatomical landmark experiencing migration is the gingival margin in a coronal direction. In a gingival pocket, no destruction of the connective tissue fibers (gingival fibers) or alveolar bone occurs. This early sign of disease in the mouth is completely reversible when the etiology of the edematous reaction is eliminated and frequently occurs without dental surgical therapy. However, in certain situations, a gingivectomy is necessary to reduce the gingival pocket depths to a healthy 1–3 mm. Periodontal pocket
As the original sulcular depth increases and the apical migration of the junctional epithelium has simultaneously occurred, the pocket is now lined by pocket epithelium (PE) instead of junctional epithelium (JE). To have a true periodontal pocket, a probing measurement of 4 mm or more must be clinically evidenced. In this state, much of the gingival fibers that initially attached the gingival tissue to the tooth have been irreversibly destroyed. The depth of the periodontal pockets must be recorded in the patient record for proper monitoring of periodontal disease. Unlike in clinically healthy situations, parts of the sulcular epithelium can sometimes be seen in periodontally involved gingival tissue if air is blown into the periodontal pocket, exposing the newly denuded roots of the tooth. A periodontal pocket can become an infected space and may result in an abscess formation with a papule on the gingival surface. Incision and drainage of the abscess may be necessary, as well as systemic antibiotics; placement of local antimicrobial delivery systems within the periodontal pocket to reduce localized infections may also be considered.