Renal system susceptibility

People with Neurologic Dysfunction or Kidney Disease. This population is unusually susceptible to lead exposure. The neurologic and renal systems are the primary target organs of lead intoxication, which may become overburdened at much lower threshold concentrations to elicit manifestations of lead intoxication (Benetou-Marantidou et al. 1988 Chisolm 1962, 1968 Lilis et al. 1968 Pollock and Ibels 1986). 

Penem B-Lactamase Inhibitors. The synthesis and antibacterial properties of penems, the trivial name for the 4-thia-l-azabicyclo[3.2.0]hept-2-ene ring system (24), have been reviewed (107,108). Like the closely related carbapenems, many of the penems are potent antibacterials. Additionally, penems are also susceptible to degradation by renal dipeptidase, but to a lesser extent. The limited -lactamase inhibitory data available for penems are presented in Table 4. SCH-29,482 [77646-83-4] (24, R = H, R = CH(OH)CH2, R = SCH2H ), C2qH23NO S2, is reported to be an inhibitor of type I Cephases and the OXA-2 enzyme (109). Compounds [101803-54-7] and [101914-68-5] (24, R = H, R = CH2CH(OH),... 

NSAIDs can cause renal insufficiency when administered to patients whose renal function depends on prostaglandins. Patients with chronic renal insufficiency or left ventricular dysfunction, the elderly, and those receiving diuretics or drugs that interfere with the renin-angiotensin system are particularly susceptible. Decreased glomerular filtration also may cause hyperkalemia. NSAIDs rarely cause tubulointerstitial nephropathy and renal papillary necrosis. 

Comparative Toxicokinetics. The metabolism and excretion of orally administered phenol in 18 animal species have been compared to metabolism and excretion in humans (Capel et al. 1972). The rat was the most similar to the human with respect to the fraction of administered dose excreted in urine in 24 hours (95%) and the number and relative abundance of the 4 principal metabolites excreted in urine (sulfate and glucuronide conjugates of phenol and 1,4-dihydroxybenzene). The rat excreted a larger fraction of the orally administered dose than the guinea pig or the rabbit (Capel et al. 1972) and appears to be the least susceptible of the three species to respiratory, cardiovascular, hepatic, renal, and neurological effects of inhaled phenol (Deichmann et al. 1944). More rapid metabolism and excretion of absorbed phenol may account for the lower sensitivity of the rat to systemic effects of phenol. More information on the relative rates of metabolism of phenol in various species is needed to identify the most appropriate animal model for studying potential health effects in humans. 

The principal effects of carbon tetrachloride in humans are on the liver, the kidneys and the central nervous system. These effects are apparent following either oral or inhalation exposure, and limited data indicate they can occur after dermal exposure as well. All of the effects seen in humans except renal injury are demonstrable at roughly comparable exposure levels in animals, although there are some variations in susceptibility between species that are likely to be related to differences in metabolism. No studies were located regarding reproductive and developmental effects in humans after exposure to carbon tetrachloride. In rats, carbon tetrachloride was not shown to adversely affect reproduction or development. Studies with both mice and rats suggest that sufficiently high doses of carbon tetrachloride may increase the risk of liver tumors in exposed humans. 

Renal lithium excretion sensitive to changes in sodium balance. (Sodium depletion tends to cause lithium retention.) Susceptible to drugs enhancing central nervous system lithium toxicity. 

A potential drug interaction between simvastatin and danazol, causing rhabdomyolysis and acute renal insufficiency, has been reported (43). Rhabdomyolysis can occur with all statins when they are used alone and particularly when they are combined with other drugs that are themselves myotoxic or that increase the concentration of the statin. Statins are particularly susceptible to the latter effect because of their metabolism by the CYP450 system and their low oral systemic availability. 

Factors that may have contributed to this metabolic acidosis included low birth weight, renal tubular immaturity, and impaired renal function, which may have resulted in systemic accumulation with repetitive dosing. This case stresses the fact that topical medications can cause systemic effects if a sufficient amount of drug is absorbed in a susceptible subject. 

Lead. One of the most familiar of the particulates in air pollutants is lead, with young children and fetuses being the most susceptible. Lead can impair renal function, interfere with the development of red blood cells, and impair the nervous system, leading to mental retardation and even blindness. The two most common routes of exposure to lead are inhalation and ingestion. It is estimated that approximately 20% of the total body burden of lead comes from inhalation. 

Persons who suffer from hepatic or renal insufficiency can become susceptible to ammonia toxicity. Toxicity from ammonia in these cases, however, results from endogenously produced ammonia. The limited systemic absorption of ammonia following inhalation exposure would be insignificant when compared with concentrations produced within the body (WHO 1986). Persons with hyperactive airway disease or other conditions that alter airway function (colds, cough, nasal congestion) are expected to be more susceptible to irritant effects of ammonia. 

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