الفهرس 
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Abstract
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English Summary
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English Summary
As long as record history, most societies have used drugs that alter mood, though, and feeling. For example opioid have been used for thousands of years for treatment of pain. Ancient Egyptian papyrus records reported the use of opium for pain relief.
The liver and kidney are the two major organs responsible for eliminating drugs from the body; this predisposes them to toxic injury from conversion of the administered drug into an active or inactive metabolite which is eliminated from the body faster than the parent drug. These metabolites that are excreted from the kidney may also cause cellular damage leading to kidney dysfunction.
The use of illicit drugs has been associated with various forms of renal diseases which may be related to direct effect of the drugs themselves while others are caused by complications related to drug abuse.
Because traditional standard markers such as BUN, urea and creatinine have low sensitivity and specificity, the timing of diagnosis and treatment are often delayed because these measurements can be in the normal ranges despite of considerable impairment of renal function, and may not be measurably increased until renal function has deteriorated
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more than 50%. Therefore, development of new biomarkers is need for the specific diagnosis of nephrotoxicity at earlier stages. The acute or chronic nephrotoxicity can be detected by measuring a panel of a new specific urinary proteins or enzymes reflecting the integrity of glomerulus or of the proximal tubules.
The present work aims to investigate the effect of tramadol addiction among Egyptian tramadol addicts on urinary excretion of some metals e.g. Copper, Zinc, and Calcium in relation to structural integrity of proximal tubules which are evaluated by measuring the urinary excretion of proximal tubular specific enzymes e.g. Leucine aminopeptidase (LAP, membrane-bound enzyme) and N-acetyl-β-D-glucosaminidase (NAG, cytosolic enzyme). In addition, the study will be extended to evaluate the effect of cannabis addiction when it is coabused with tramadol.
Male drug addicted participated in the present study were recruited on voluntary bases from those attended the out-patient clinic, Institute of Psychiatry, Ain-Shams University, for treatment of drug addiction. All participates were subjected to interview using a questionnaire designed to obtain information on previous medical and occupational history, medication intake, actual health status, and subjective symptoms. The controls group was recruited from
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relatives of the addicted participants after applying the same exclusion criteria and clinical examination. The participated were excluded from the present study if they had:
1. A history of disease affecting the kidney or any disease likely to impair renal function or affect the urinary excretion of the investigated parameters e.g. (diabetes mellitus, hypertension, collagen diseases as systemic lupus erythromatosis, Urinary tract disease, Rheumatoid arthritis and gout.
2. A previous or present exposure to agents capable of damaging the kidney. Heavy metals such as Pb2+, Cd2+ and other nephrotoxins such as organic solvents.
3. Regular and prolonged treatment by drugs affecting the kidney e.g. aminoglycosides and antireheumatic drugs.
4. Dental mercury amalgam filling as it may affect the kidney.
5. Cigarette smoker’s individuals.
The study included Sixty-five males were included in the study and divided into three groups as following:
1. Control group was comprised of 19 males.
2. Tramadol addicts were comprised of 18 males.
3. Tramadol coabused with cannabis addicts was comprised of 28 males.
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Morning urine sample was suggested as the best sample for detecting early kidney abnormalities. Each urine sample was analyzed for the determination of:
1. Measurement of urinary creatinine concentration.
2. Measurement of urinary tramadol concentration in both tramadol addicted and tramadol coabused with cannabis addicted groups.
3. Measurement of urinary cannabinoid concentration in tramadol coabused with cannabis addicted group.
4. Tubular structural integrity:
i. Measurement of urinary N-acetyl-β-D-glucosaminidase concentration.
ii. Measurement of urinary leucine aminopeptidase concentration.
5. Tubular reabsorption integrity:
i. Measurement of urinary copper concentration.
ii. Measurement of urinary zinc concentration.
iii. Measurement of urinary calcium concentration.
Urinary concentrations of these substances were attributed to urinary creatinine.
The results demonstrated non-significant changes in urinary excretion of N-acetyl-β-D-glucosaminidase and each of leucine aminopeptidase, zinc and copper, while significant increase in urinary excretion of calcium when compared with control group in tramadol addicted group.
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In tramadol coabused with cannabis addicted group, the results showed non-significant changes in urinary excretion of N-acetyl-β-D-glucosaminidase and each of leucine aminopeptidase, zinc as well as copper while significant increase in urinary excretion of calcium when compared with each of control group and tramadol addicted group. Furthurmore, urinary cannabinoid was significantly correlated with leucine aminopeptidase and both of copper and zinc as well as calcium in tramadol coabused with cannabis addicted group, while urinary tramadol did not show correlation with any parameters in tramadol addicted group or tramadol coabused with cannabis group.
In conclusion among the investigated addicted individuals, addiction of tramadol alone or in combination with cannabis did not affect the structural integrity of proximal tubules. Moreover, reabsorption integrity of the nephron is affected only with respect to calcium reabsorption and not with respect to copper and zinc reabsorption. Also, to the best of our knowledge, this is the first study that investigates the effect of addiction of tramadol alone or coabused with other drugs on the reabsorption integrity of the nephron regarding urinary excretion of copper and zinc as well as calcium.