Blood, levels

OSHA has set a standard to keep blood levels in the occupational work force below 40 //g/dL. ACGIH has set a goal relating to a biological exposure index of 50 //g/dL for lead in blood and 150 pjgjdL creatinine for lead in urine. 

The alimentary symptoms may be overshadowed by neuromuscular dysfunction, accompanied by signs of motor weakness that may progress to paralysis of the exterior muscles or the wrist (wrist drop), and less often, of the ankles (foot drop). Encephalopathy, the most serious result of lead poisoning, frequendy occurs in children as a result of pica, ie, ingestion of inorganic lead compounds in paint chips this rarely occurs in adults. Nephropathy has also been associated with chronic lead poisoning (147). The toxic effects of lead may be most pronounced on the developing fetus. Consequendy, women must be particulady cautious of lead exposure (148). The U.S. Center for Disease Control recommends a blood level of less than 10 p.m per 100 mL for children. 

Lead is known to cause reproductive and developmental toxicity. Decreased sperm counts and abnormal sperm development have been reported in male workers heavily exposed to lead. Increased incidences of spontaneous abortion have been reported in female lead workers as well as in the wives of male lead workers (13). Lead crosses the placenta and has been found to cause irreversible neurologic impairment to the fetus at maternal blood levels as... 

Metabolites of vitamin D, eg, cholecalciferol (CC), are essential in maintaining the appropriate blood level of Ca ". The active metabolite, 1,25-dihydroxycholecalciferol (1,25-DHCC), is synthesized in two steps. In the fiver, CC is hydroxylated to 25-hydroxycholecalciferol (25-HCC) which, in combination with a globulin carrier, is transported to the kidney where it is converted to 1,25-DHCC. This step, which requites 1-hydroxylase formation, induced by PTH, may be the controlling step in regulating Ca " concentration. The sites of action of 1,25-DHCC are the bones and the intestine. Formation of 1,25-DHCC is limited by an inactivation process, ie, conversion of 25-HCC to 24,25-DHCC, catalyzed by 24-hydroxylase. 

One method of treatment is to inject calcitonin, which decreases blood Ca " concentration and increases bone calcification (33). Another is to increase the release of calcitonin into the blood by increasing the blood level of Ca " ( 4). This latter treatment is accompHshed by increasing Ca " absorption from the intestine requiring dietary calcium supplements and avoidance of high phosphate diets. The latter decrease Ca " absorption by precipitation of the insoluble calcium phosphate. 

This technology is relatively expensive to produce. Special excipients and equipment, such as a laser unit to drill the necessary hole for dmg release, are required. However, the achievement of very steady blood levels of a dmg for sustained periods, ie, 2ero-order rate release, of therapy is advantageous. 

The development of easy-to-use assays for determining theophylline blood levels afforded a handle on maintenance of effective but nontoxic levels. The relatively good availabihty of such assays in the United States probably contributed to the historical preference for theophylline treatment by U.S. physicians. Careful titration of the dose must be done on a patient-by-patient basis because individual rates of metaboHsm vary widely. Most ( 85%) of an oral dose of theophylline is metabolized by Hver microsomal enzymes. As a result many dmgs, eg, cimetidine [51481-61-9], anticonvulsants, or conditions, eg, fever, cigarette smoking, Hver disease, which affect Hver function alter theophylline blood levels. 

Common side effects of theophylline therapy include headache, dyspepsia, and nausea. More serious side effects such as lethal seizures or cardiac arrythmias can occur if blood levels are too high. Many derivatives of theophylline have been prepared in an effort to discover an analogue without these limitations (60,61). However, the most universal solution has resulted from the development of reHable sustained release formulations. This technology limits the peaks and valleys in semm blood levels that occur with frequent dosing of immediate release formulations. ControUed release addresses the problems inherent in a dmg which is rapidly metabolized but which is toxic at levels ( >20 7g/mL) that are only slightly higher than the therapeutically efficacious ones (10—20 p.g/mL). Furthermore, such once-a-day formulations taken just before bedtime have proven especially beneficial in the control of nocturnal asthma (27,50,62). 

The main role of the human thyroid gland is production of thyroid hormones (iodinated amino acids), essential for adequate growth, development, and energy metaboHsm (1 6). Thyroid underfunction is an occurrence that can be treated successfully with thyroid preparations. In addition, the thyroid secretes calcitonin (also known as thyrocalcitonin), a polypeptide that lowers excessively high calcium blood levels. Thyroid hyperfunction, another important clinical entity, can be corrected by treatment with a variety of substances known as antithyroid dmgs. 

Pharmaceuticals. Examples of trace and ultratrace analyses of various dmgs and pharmaceuticals have been provided throughout. The purity of the active ingredient, its content and availabiUty in dosage form, therapeutic blood levels, deflvery to target areas, elimination (urine, feces, and metabohtes), and toxicity are always of importance. 

Up to 80% of oral doses of ascorbic acid are absorbed in humans with intakes of less than 0.2 g of vitamin C. Absorption of pharmacological doses ranging from 0.2 g to 12 g results in an inverse relationship, with less than 20% absorption at the higher doses. A single oral dose of 3 g has been reported to approach the absorptive capacity (tissue saturation) of the human intestine. Higher blood levels can be attained by providing multiple divided vitamin C doses per day. 

Although it is being found that vitamin D metaboUtes play a role ia many different biological functions, metaboHsm primarily occurs to maintain the calcium homeostasis of the body. When calcium semm levels fall below the normal range, 1 a,25-dihydroxy-vitainin is made when calcium levels are at or above this level, 24,25-dihydroxycholecalciferol is made, and 1 a-hydroxylase activity is discontiaued. The calcium homeostasis mechanism iavolves a hypocalcemic stimulus, which iaduces the secretion of parathyroid hormone. This causes phosphate diuresis ia the kidney, which stimulates the 1 a-hydroxylase activity and causes the hydroxylation of 25-hydroxy-vitamin D to 1 a,25-dihydroxycholecalciferol. Parathyroid hormone and 1,25-dihydroxycholecalciferol act at the bone site cooperatively to stimulate calcium mobilization from the bone (see Hormones). Calcium blood levels are also iafluenced by the effects of the metaboUte on intestinal absorption and renal resorption. 

Vitamin D intoxication causes 25-hydroxy vitamin blood levels to go from a normal of 30—50 ng/mL to 200—400 ng/mL. At this high level, the metabohte can compete with 1 a-25-dihydroxy vitamin for receptors in the intestine and bone and induce effects usually attributed to the dihydroxy vitamin D. Thus, 25-hydroxy vitamin is beUeved to be the critical factor in vitamin D intoxication. Vitamin D2 is metabolized slower than vitamin and thus appears to be less toxic (218). 

The pharmacology of penicillins differs markedly from compound to compound but has been well reviewed (57). The majority of derivatives, including penicillin G and the antipseudomonal penicillins, ate unstable in gastric acid and ate not available orally. The isoxazolyl penicillins ate relatively acid stable but not consistendy well absorbed by the oral route. Nafcillin and oxacillin ate poody absorbed orally cloxacillin, dicloxacillin, and ducloxacillin ate more teUable. Penicillin V, ampicillin, and patticulady amoxicillin ate relatively well absorbed orally. Esters of ampicillin such as bacampicillin, pivampicillin, and talampicillin improve the level of oral absorption of ampicillin to that achieved by amoxicillin. Absorption can be diminished by food after oral adruinistration, however, and peak blood levels, usually achieved after 1 to 2 h, ate somewhat delayed after ingestion of food. 

Therapeutic blood levels range from 0.3—0.9 lg/mL. Mean elimination halflife is 9 h (32). 

Environmental exposures to PCBs are significantly lower than those reported in the workplace and are therefore unlikely to cause adverse human health effects in adults. However, it is apparent from the results of several recent studies on children that there was a correlation between in utero exposure to PCBs, eg, cord blood levels, and developmental deficits (65—68) including reduced bkth weight, neonatal behavior anomaUes, and poorer recognition memories. At four years of age, there was stiU a correlation between prenatal PCB exposure levels and short-term memory function (verbal and quantitative). In these studies the children were all exposed to relatively low environmental levels of PCBs. Although these effects may be related to other contaminants, it is clear that this is an area of concern regarding the potential adverse human health impacts of PCBs. 

Medical researchers studying high blood pressure have consistently found that people with hypertension have high blood levels of some sort of Na, K -... 

Oil-soluble derivatives of testosterone itself predate those of its 19-nor congener these agents too are used to administer depot injections so as to provide in effect long-term blood levels of drug. Thus, acylation of testosterone with propionyl chloride in the presence of pyridine yields testosterone propionate (76a)acylation by means of decanoic anhydride yields testosterone decanoate (76b).Finally, reaction of 75 with 3-cyclopentylpropionyl chloride affords testosterone cypionate (76c)This last undergoes hydrolysis unusually slowly because of the presence of two substituents at the 5 position (see Newman s Rule of 6). ... 

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