Oxidation, drug detoxification

Lacking GSH-dependent peroxidases, Plasmodium spp. rely on a Prx-linked detoxification for hydroperoxides and reduced GSH acts primarily as the principal redox buffer. It is also important in detoxification reactions as a co-factor for GST and glyoxalase and has been shown to be involved in the breakdown of free ferriprotoporphyrin IX. The lack of two major antioxidants present in other cells (catalase and GSH peroxidase) suggests that malaria parasites would be vulnerable to disturbances in their anti-oxidant systems. As a consequence, pro-oxidant drugs such as the artemisinins, which increase the oxidative stress, are efficient antimalarials. It has been proposed that a novel approach to malaria chemotherapy would be to develop drugs that disrupt the anti-oxidant and redox system of Plasmodium (Muller, 2004 Nickel et al., 2006 Rahlfs and Becker, 2005). 

Phase I metabolic reactions involve oxidation, reduction, or hydrolysis of the parent molecule, resulting in the formation of a more polar compound. Phase 1 reactions are mediated by the cytochrome P450 (GYP) family of enzymes. While metabolism used to be thought of as the body s detoxification process, phase I metabolites may be equally or even more pharmacologically active than the parent compound. Drug metabolism in general, and CYP-based mechanisms in particular, are discussed in detail in Chapter 5. 

Dmg rehabilitation programs may be either inpatient or outpatient. Inpatient, or residential, drug programs require a patient to live at the hospital or rehab facility for a period of several weeks to several months. Outpatient programs allow patients to spend part of their day at the treatment facility, and return home at night. Nitrous oxide is rapidly eliminated from the body, and abuse of NzO alone is not associated with withdrawal. This means that a lengthy detoxification period (removal of the drug from the body) is typically not required. 

While the term biotransformation generally implies inactivation and detoxification, there are exceptional cases where a metabolite is more chemically active or more toxic than the parent compound. In these situations, the processes of bioactivation and biotoxification are said to have occurred, respectively. An example of bioactivation is the formation of the commonly used drug acetaminophen from phenacetin in the liver (see Figure 3.2). The latter drug was once widely used as an analgesic agent but because of kidney toxicity has been replaced by other more potent, less toxic substitutes including, of course, acetaminophen itself. In this particular bioactivation pathway the process occurs via normal oxidative dealkylation. 

Nitric oxide formed from amyl nitrite inhibits cytochrome P450 (117) and ritonavir inhibits CYP2D6 (118), which has a major role in metamfetamine detoxification (119). This interaction could have led to fatal plasma concentrations of metamfetamine. It is therefore suggested that patients who take protease inhibitors are made aware of the potential risk of using any form of recreational drugs metabolized by CYP2D6, particularly metamfetamine. 

The enzymes are widely distributed in microorganisms, plants, and animals. " Three Mo-MPT enzymes have been found in mammals (1) xanthine dehydrogenase see Dehydrogenase) has many, varied roles in purine catabolism, drug metabolism, and oxidative stress response, (2) aldehyde oxidase is important in drug metabolism and the synthesis of retinoic acid from retinal, and (3) sulfite oxidase plays a cmcial role in the detoxification of sulfite produced in the degradation of cysteine and methionine. Genetic Mo-MPT deficiency in... 

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