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Figure 5.17 Case example 15: Pregnancy and MDR TB EM is year-old patient who is first diagnosed with tuberculosis while in her first trimester. Given multiple sibling contacts with strains resistant to all first-line drugs, her sputum sample is sent for DST. Empiric treatment is deferred, with the plan to start therapy in her third trimester in order to achieve smear conversion prior to delivery. In the second trimester, the patient begins to experience hoarseness, worsened cough, and weight loss. DST reveals resistance to INH, RIF, EMB, and SM. After discussion with the patient about the risks of disease progression versus potential effects of MDR TB therapy on fetal development, she is started on a regimen of PZA 30mg kg ; , OFX 800mg ; , PAS 12g ; , THA 750mg ; , and AMX-CLV 1500mg ; . She smear and culture converts early in her third trimester and delivers a healthy boy without complications. CM 1g ; is added post-partum and etoposide.
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Adverse reactions: myambutol may produce decreases in visual acuity that appear to be due to optic neuritis.
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Intracellular pH and K concentrations must be tightly controlled because they affect many cellular activities, including cell growth and death. The mechanisms of homeostasis of H and K are only partially understood. In the yeast Saccharomyces cerevisiae, proton efflux is mediated by the Pma1 H -ATPase. As this pump is electrogenic, the activity of the Trk1 and -2 K uptake system is crucial for sustained Pma1p operation. The coordinated activities of these two systems determine cell volume, turgor, membrane potential, and pH. Genetic evidence indicates that Trk1p is activated by the Hal4 and -5 kinases and inhibited by the Ppz1 and -2 phosphatases, which, in turn, are inhibited by their regulatory subunit, Hal3p. We show that Trk1p, present in plasma membrane "rafts, " physically interacts with Ppz1p, that Trk1p is phosphorylated in vivo, and that its level of phosphorylation increases in ppz1 and -2 mutants. Interestingly, both the interaction with and inhibition of Ppz1p by Hal3p are pH dependent. These results are consistent with a model in which the Ppz1-Hal3 interaction is a sensor of intracellular pH that modulates H and K homeostasis through the regulation of Trk1p activity. Ion homeostasis is a fundamental property of living cells. The intracellular concentrations of the major monovalent cations H , K , and Na ; must be tightly regulated because they influence the activities of many cellular systems that require a narrow range of ion concentrations for operation 28, 51 ; . The homeostasis of monovalent cations is maintained primarily by systems that extrude H and Na and import K . Cellular volume, turgor, electrical membrane potential, and ionic strength depend mostly on intracellular K concentrations. In animal cells, Na extrusion is crucial for cell volume regulation 28 ; , but in fungi and plants, this cation is only toxic, probably by antagonizing Mg2 in the active sites of some key enzymes 51 ; . Intracellular pH, on the other hand, modulates the activities of many cellular systems, including those regulating cell growth 13, 22, 41 ; and death 23, 31 ; . The important roles of cellular H and K concentrations raise the unanswered question of whether these parameters are used as second messengers of external signals or are simply maintained within permissive ranges for the functionality of sensitive cellular systems 6, 21, 24, ; . In any case, the regulation of H , Na , and K transport is crucial for cellular physiology, and defects in these systems have a wide array of consequences in medicine and agriculture, which range from diseases related to the nervous system, muscle, kidney, and heart 42 ; to sensitivity to low-pH and high-Na environments of agriculturally important crop plants 51, 52 ; . The remarkable capability of living cells to adjust intracellular H is not completely understood. Known mechanisms include the pH dependence of H transporters, such as the bacterial 40 ; and animal 58 ; Na H exchangers, and the and tamsulosin.
After 60 days of myammbutol administration, decrease the dose to 15 mg per kilogram 7 mg per pound ; of body weight, and administer as a single oral dose once every 24 hours.
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