Analgesic abuse nephropathy.

Analgesic abuse nephropathy is seldom considered as a cause in patients presenting with chronic renal disease. In a three-year period 450 patients were seen with chronic renal failure. Of these 103 had interstitial renal disease as the cause of their failure. Twenty of these 103 were due to chronic analgesic abuse, which indicates that need for a greater awareness of this problem. The spectrum of clinical and roentgenographic aspects of analgesic abuse nephropathy are discussed. What constitutes analgesic abuse, helpful clinical findings, frequency of other medical illnesses, and the low incidence of documented renal infection prior to onset of renal failure are discussed. Intravenous pyelographic findings related to visualization, renal size, corticomedullary margins and pelvicalyceal changes are also discussed and demonstrated.

Urinary enzymes and kidney damage by aspirin and phenacetin.

Two groups of rats were given aspirin and phenacetin in their food at daily doses similar to those taken by humans suffering from analgesic abuse. Both drugs damaged the kidney proximal tubules although phenacetin affected the kidney more severely than aspirin. At the start of the experiment aspirin increased the urinary excretion of lactate dehydrogenase (LDH) while phenacetin raised the excretion of all four enzymes studies (acid phosphatase, alkaline phosphatase, glutamate dehydrogenase (GDH), LDH indicating generalised cellular injury. Subsequent samples of urine collected from rats up to seven weeks showed normal urinary enzyme levels. The value of urinary enzyme measurements in detecting renal damage by drugs is discussed.

Capillary sclerosis of the urinary tract and analgesic nephropathy.

Morphology, frequency and significance of capillary sclerosis (CS) in the ureter and electron microscopic findings in early papillary necrosis are described. CS of the urinary tract is characterized by a thickening of the basement membrane of capillaries lying just underneath the urothelium. The basement membrane changes can be demonstrated by PAS, Sudan stain and autofluorescence with equal reliability. By electron microscopy the thickened basement membranes exhibit a tree ring like pattern permeated by lipid vacuoles. CS is most often present in the renal pelvis and the ureter and only in particularly severe cases also in the urinary bladder. The most severe CS is found in the proximal and middle third of the ureter. In a prospective autopsy study CS was found in 3.5% of autopsies of adults and in 83% of clinically recognized phenacetin abusers. Since there is no association with other renal or metabolic diseases, CS can be considered as specific for phenacetin abuse. This finding is further substantiated by a significant correlation between the degree of severity of capillary sclerosis and the daily dose of phenacetin in grams. In about half of the patients with known analgesic abuse but without CS, possible causes for the lack of CS can be identified, of which the most important is regression of CS after stopping the abuse. Electron microscopic studies of early papillary necrosis show the same BM changes as in the ureter in peritubular capillaries, loops of Henle and similar BM alterations in the collecting ducts. The morphologic findings in the ureter and in the renal papilla suggest that CS in papillary necrosis are the consequence of a toxic damage of endothelial and in the kidney of endothelial and epithelial cells.

Toxicological findings in a multi-drug death involving propoxyphene, caffeine, phenacetin, acetaminophen and salicylate.

The toxicological findings of a multi-drug related fatal poisoning are described here. A 35-year-old Caucasian male found dead on the kitchen floor was a known user of abused drugs and had been taking aspirin alone or in combination with phenacetin and caffeine for the relief of joint pains. The gross examination of the organs at autopsy revealed slight grooving of the uncus and various stages of necrosis in the renal papillae. Histological examination confirmed the gross appearance of pulmonary congestion and edema, cerebral edema and interstitial nephritis of the tubules. Toxicological evaluation of the blood and urine samples disclosed the presence of propoxyphene (51 and 250 mg/l), salicylate (185 and 2750 mg/l), caffeine (16 and 37 mg/l), and phenacetin (9.6 and 20 mg/l). Furthermore, acetaminophen also was present in the plasma (54 mg/l) and urine. A gas liquid chromatographic method for simultaneous analysis of phenacetin and caffeine utilizing a nitrogen phosphorus detector was proposed.

Phenacetin and cocaine in a body packer.

A case of acute intoxication of cocaine adulterated with phenacetin is reported. Twenty-four packages were found in the stomach and intestine of a 25-year-old male. The identification of phenacetin was performed by gas chromatography-mass spectrometry (GC/MS) analysis.

GC/MS confirmation of barbiturates in blood and urine.

A gas chromatography-mass spectrometric method is described for the quantitative measurement of 6 commonly used barbiturates in blood and urine specimens. The targeted barbiturates are butalbital, amobarbital, pentobarbital, secobarbital, mephobarbital and phenobarbital. They are recovered along with the internal standard, tolybarb, from blood and urine using liquid extraction then alkalated to form the N-ethyl derivatives. The ethylated barbiturates have symmetrical peaks which are well separated from each other on a non-polar methylsilicone capillary column. The derivatives on a non-polar methylsilicone capillary column. The derivatives facilitate quantitations between 50 and 10,000 ng/mL. The day-to-day CVs for all 6 barbiturates were between 4 and 9% at 200 and 5000 ng/mL. The method has been extended for identifying other acidic drugs and drug metabolites. They are mainly non-steroidal anti-inflammatory drugs, diuretics, and anticonvulsants. An additional 83 compounds can be qualitatively identified.

[Identification of organic substances by means of spectral methods in forensic toxicological analysis. II. Nuclear magnetic resonance]. / Identifikace organických látek spektrálními metodami v soudne toxikologické analýze. II. CAST. Nukleární magnetická rezonance

In opening the paper, the authors present a brief outline of the fundamentals of nuclear magnetic resonance. Using selected cases from practice, they demonstrate the use of nuclear magnetic resonance for the purpose of forensic toxicologic analysis. The method is particularly suitable for identifying unknown organic compounds and for analysing mixtures of substances.

[Severe Vicedrin poisoning in a 17-month-old girl]. / Tezká intoxikace Vicedrinem u 17 mesícního devcátka.

The child ingested 7 tabl. of VICEDRIN (a combination of phenacetin, ephedrin, chinin, acid. ascorbicum), the total dose of phenacetin was 140 mg/kg of b.w. Lethal doses of phenacetin vary between 100-200 mg/kg, the sensitivity to phenacetin being increased in infants. Toxicological examination in this case revealed a high concentration of phenacetin in urine. The clinical signs of intoxication were vomiting (hematemesis), methemoglobinemia and somnolence. 2 hemoperfusions were performed lasting 6 hrs and 5 hrs resp. (HEMASORB 400 A 4), the second one were combined with hemodialysis because after the first perfusion a high concentration of metabolic products of phenacetin was detected in urine. After the second perfusion the status of the child rapidly improved and we could discharge the patient of the 10th day after admission. Hemoperfusion is recommended in severe intoxication with phenacetin, the combination with, hemodialysis is possible to remove its metabolic product.

Optic atrophy after propoxyphene overdose: report of a case.

An 18-year-old woman suffered cardiac arrest and became comatose after ingesting a large amount of proxyphene and salicylates. Six days after admission, her pupils, initially miotic, became fixed and dilated. On the seventh day disc edema developed. This was due to optic neuritis from acute Darvon overdose. Within eight weeks the disc edema resolved into a pale white atrophy with severe loss of vision. This is the first reported case of optic atrophy after propoxyphene overdose.