Drug exposure

The first issue lies in the whole realm of the human disease process itself. Many adverse drug events mimic diseases and vice versa. Is an adverse event really an adverse event, or is it merely a natural occurrence of a disease process that is entirely independent of drug exposure The science of drug safety is often complicated by the lack of objective markers of drug toxicity that can systematically separate a disease process from an adverse drug event process [2]. Clinical trials, often viewed as the gold standard to assess efficacy, are simply too limited in scope to answer safety questions in a systematic way. 

Opiate drug exposure has a significant impact on HIV infection as well as progression to HIV-associated dementia. On a cellular level it is comprehendible that drugs of abuse such as opioids would reduce the threshold for neurotoxicity such that a marginally toxic insult would now be exacerbated and lead to cell death or injury... 

Because AEDs are administered for long periods of time, adverse effects due to prolonged drug exposure are of concern. Some chronic adverse effects that have been associated with AEDs include peripheral neuropathy and cerebellar atrophy Other chronic adverse effects are extensions of acute adverse effects, for example weight gain. 

Discuss general methods by which teratogenic risk and drug exposure during pregnancy and lactation can be minimized. 

What resources can you use to help determine the risk of her drug exposures ... 

One of the major drawbacks of calcineurin inhibitors is their ability to cause acute and chronic nephrotoxicity. Acute nephrotoxicity has been correlated with high calcineurin inhibitor doses and usually is reversible. Chronic toxicity, however, typically is irreversible and is linked to chronic drug exposure. Table 52—4 expands on the more common calcineurin inhibitor-induced adverse events. 

W., Hilgendorf, C., Spahn-Langguth, H., Wunderli-Allenspach, H., Merkle, H. P., Langguth, P., P-glycoprotein (P-gp) mediated efflux in Caco-2 cell monolayers the influence of culturing conditions and drug exposure on P-gp expression levels, J. Pharm. Sci. 1998, 87, 757-762. 

Smit, J. W., Huisman, M. T., van Tellingen, O., Wiltshire, H. R., Schinkel, A. H., Absence or pharmacological blocking of placental P-glycoprotein profoundly increases fetal drug exposure, J. Clin. Invest. 1999, 104, 1441-1447. 

The BCS has been developed primarily for regulatory applications, although its use has been extended beyond this area (as discussed in more detail below). The aim of the BCS in a regulatory context is to provide a basis for replacing certain bioequivalence studies by equally or more accurate in vitro dissolution tests. This could reduce costs and time in the development process as well as reducing unnecessary drug exposure in healthy volunteers, which is normally the study population in bioequivalence studies. 

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