Renal failure, fetal

ACE inhibitors are contraindicated during the second and third trimesters of pregnancy because of the risk of fetal hypotension, anuria, and renal failure, sometimes associated with fetal malformations or death. Recent evidence also implicates first-trimester exposure to ACE inhibitors in increased teratogenic risk. Captopril, particularly when given in high doses to patients with renal insufficiency, may cause neutropenia or proteinuria. Minor toxic effects seen more typically include altered sense of taste, allergic skin rashes, and drug fever, which may occur in up to 10% of patients. 

Calcidiol la-hydroxylase is not restricted to the kidney, but is also found in placenta, bone cells (in culture), mammary glands, and keratinocytes. The placental enzyme makes a significant contribution to fetal calcitriol, but it is not clear whether the calcidiol 1-hydroxylase activity of other tissues is physiologically significant or not. Acutely nephrectomized animals given a single dose of calcidiol do not form any detectable calcitriol, but there is some formation of calcitriol in anephric patients, which increases on the administration of cholecalciferol or calcidiol. However, thus extrarenal synthesis is not adequate to meet requirements, so that osteomalacia develops in renal failure (Section 3.4.1). The enzyme is inhibited, or possibly repressed, by strontium ions this is the basis of strontium-induced vitamin D-resistant rickets, which responds to the administration of calcitriol or la-hydroxycalciol, but not calciferol or calcidiol (Omdahl and DeLuca, 1971). 

Skeletal muscle that is diseased or damaged (such as by extreme exercise) may contain significant proportions of CK-MB owing to the phenomenon of fetal reversion, in which fetal patterns of protein synthesis reappear. Thus serum CK-MB isoenzyme may increase in such circumstances. This explanation may also account for the elevated CK-MB values sometimes observed in chronic renal failure (uremic myopathy). 

Teratogenicity —> fetal hypotension, renal failure, skull and renal malformations. 

Cough hypotension, particularly with a diuretic or volume depletion loss of taste with anorexia skin rash bronchospasm acute renal failure with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney cholestatic jaundice angioedema hyperkalemia if also on potassium supplements or potassium-retaining diuretics blood dyscrasias and renal damage are rare except in patients with renal dysfunction, and particularly in patients with collagen-vascular disease may increase fetal mortahty and should not be used during pregnancy... 

In addition to congenital malformations, fetal and neonatal renal failure and oligohydramnios have been observed [21,22]. A change from ACE-I or AIIRB to other types of antihypertensive prior to... 

Renal failure Inflammation Neoplasm, especially those associated with B-lymphocytes Fetal/neonal period In urine tubular damage, kidney transplarrt rejection... 

Enalapril, captopril, and lisinopril (and presumably other ACE inhibitors) cross the placenta in pharmacologically significant amounts (17). There is clear evidence of fetotoxicity when ACE inhibitors are used beyond the first trimester of pregnancy. Since continuation of treatment beyond the first trimester carries an excess risk of low fetal birth weight and other more severe complications, it is important to withdraw the ACE inhibitor at this time. Intrauterine growth retardation, oligohydramnios, and neonatal renal impairment, often with a serious outcome, are characteristic (98) failure of ossification of the skuU or hypocalvaria also appear to be part of the pattern (17). There is also evidence that persistence of a patent ductus arteriosus is also more likely to occur. 

Adverse reactions Tachycardia, palpitations, flushing, anxiety, pulmonary edema Diplopia, fatigue, flushing, pulmonary edema. Toxic levels absent DTRs, respiratory depression and failure, cardiac arrest Headaches, tachycardia, flushing Bleeding fetal effects premature closure of ductus arteriosus, decreased renal function in preterm infants, increased IVH Minimal... 

The incidence of phenytoin toxicity may be increased in the eideriy, or in those patients with hepatic or renal impairment, because of alterations in its pharmacokinetics. Plasma level determinations may be indicated in these cases. Although a role for P-glycoprotein transporter alleles in the development of phenytoin toxicity remains controversial, phenytoin is a robust substrate for the non-ABC efflux transporter RLIP76. Because RLIP76 has been found to be overexpressed in excised human epileptic foci, its action may account for treatment failures conversely, inhibition of transport may cause toxicity (34). There is a 2 to 3% increase in the risk of fetal epilepsy syndrome if the mother is taking phenytoin. Phenytoin is contraindicated in cardiac patients with bradyarrhythmias. Induction of CYP2C19 by ginkgo biloba may increase phenytoin clearance and precipitate serious seizures (35). 

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