الفهرس 
Prevalence of substance abuseOnly 14 pages are availabe for public view
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Abstract
Substance and drug abuse is a problem that has been increasing immensely among our society today, it can lead to damage to the nervous system and the brain, sudden mood changes, deterioration of the immune system, nervous breakdowns, and many other side effects.
Nowadays tramadol is the most common drug of abuse; it has been associated with a wide range of drug abuse such as benzodiazepines. The combination of tramadol and BZDs drugs has serious detrimental effects.
The aim of this study was to study the magnitude of tramadol and benzodiazepine abuse in Menoufia Governorate, and to study the toxic effects of acute and repeated administration of tramadol, diazepam and their combination on the cellular (histological) picture of parenchymatous organs; brain and liver on experimental animals.
In order to achieve our aim, this study was carried out in two parts; a clinical part and an experimental part:
I. CLINICAL PART:
140 cases of substance dependence of different combinations admitted to Menoufia University Poison and Addiction Control Center throughout 2 years, one year retrospective and one year prospective from (July 2009 to June 2011) were included. The study was conducted after approval from ethical committee of faculty of medicine, Menoufia University.
(1) A valid written consent was taken from each patient or his parents before the study.
(2) A clinical examination sheet for every patient was fulfilled.
(3) Blood sample was taken from every patient for analytical and biochemical study.
II. EXPERIMENTAL PART:
The study was conducted on adult albino male rats weighting 180-200 gm which were divided into six groups:
Group 1 (control group):
This group consisted of 10 rats which were kept in the cages without handling to show the normal values of the tested parameters.
Group 2 (acute tramadol poisoning):
This group consisted of 10 rats which received tramadol orally as a single toxic overdose.
Group 3 (chronic tramadol poisoning):
This group consisted of 10 rats which received an increasing oral dose of tramadol daily for one month.
Group 4 (acute benzodiazepine (diazepam) poisoning):
This group consisted of 10 rats which received diazepam orally as a single toxic overdose.
Group 5 (chronic benzodiazepine (diazepam) poisoning):
This group consisted of 10 rats which received an increasing oral dose of diazepam for one month.
Group 6 (chronic tramadol and benzodiazepine (diazepam) poisoning):
This group received an increasing combined oral dose of tramadol and diazepam for one month.
At the end of experimental period blood samples were taken from all groups for evaluation of the biochemical tests then the rats were sacrificed, histopathological and immunohistochemical (IHC) examinations of the brain and liver tissues were carried out.
The main findings of the present study were as follow:
1- The clinical part:
Socio-demographic characteristics:
- As regards sex incidence, 98.6% of cases were males, Only 2 females (1.4 % of cases) were reported in this study, both of them were dependent on tramadol.
- The age group of 20-40 years comprised more than half of the total cases (71.4%) coming to the hospital seeking for treatment, followed by the age group <20 years by (18.6%). Adults aged above 40 years were the least by (10%) of the total cases.
- About half of the patient (46%) who were dependent on tramadol only drug were in the age group (20-30) years, while in the tramadol + others dependent group and others drugs dependent group, the largest number of patients were in the age group (30-40 years) by 40% and 25% respectively. It is noticed that the young dependent patients prefer tramadol, and by age increasing the patients abused other drugs besides tramadol.
- (45%) of patients included in this study started to abuse drugs at the age of adolescence (15-20 years age group).
- Concerning the residence the highest percent of cases (60%) were from urban areas, there was significant relation between the residence and the type of drug dependence as most of the tramadol only dependents cases came from rural localities (61.5%) opposite to (64.7%) of the tramadol+others dependence group belonged to urban areas.
- As regard the marital status 46.4% of cases in this study were married, 43.6% were unmarried and only 10% were divorced.
- As regards educational status (38.6%) of cases had a secondary technical certificate, (33.6 %) just read and write, (19.3 %) were illiterates and 8.6% received higher education. More than half of tramadol only group
(61.5%) were read and write only, while (41.2%) of cases in (tramadol + others) had a secondary technical certificate . Also half of the cases in the others drug dependent were read and write and the other half have secondary certificate.
- Drug dependence was prevalent among skilled laborers by (38.6%) of total cases, don’t work (25.7%), non-skilled laborers (17.9%), students (10.7%), while a very low incidence of employee (7.1%) was recorded. There was highly significant statistical difference between type of drug dependence regarding occupation, where the highest percent among tramadol only dependent group (38.5%) were student , while (43%) of tramadol + others dependent group and 50% of the others drug dependent were skilled laborer
- The majority of studied cases (85%) were smokers, and (52.1%) of them were heavy smoker. Significant relation between smoking and type of drug dependence, where (46.2%) of tramadol only dependent were light to moderate smoker , while more than half of the tramadol+others and others dependent group were heavy smoker.
- (42.9%) of cases their families had previous history of drug or substance abuse or dependence and (57.1%) had not. Also there was significant relation between previous family history of drug or substance abuse and type of drugs dependence where about (85%) of tramadol only drugs had negative family history while more than half of cases in tramadol + others had positive family history for drug abuse , so family history can be a risk factors for abusing drugs or substance other than tramadol alone.
- As regard the cause of first intake of drugs and drug dependence, peer influences play a crucial role in the involvement in dependence on various substances, as bad friends (35.7%) was the main cause of starting dependence in this study.
- Considering the source of drug, the highest percent of dependent cases (37.1%) in this study get their drugs through multiple sources as (peddlers, friends and pharmacies), followed by peddlers and friends by (27.1%) and (24.3%) respectively. Only (11.4%) of cases obtained their needs through pharmacies.
- As regard mode of drug intake there is significant relation between type of dependent drug and mode of intake where all cases of tramadol only dependent drug receive the drug through oral route, while the highest percent in tramadol +others and others group where through combined routes (oral, injection, smoking, snuffing) by (65%) and (58%) respectively. There was significant relation between type of dependent drug and frequency of its intake where half of tramadol only dependent cases use the drug more than once/ week, while more than half of tramadol+ others (71.5%) and others (66.7%) use the substances daily.
- Concerning the reasons of choosing a particular drug or another, availability (65%) and cheap price (22.9%) were the two main factors determining the choice.
- As regards sequel of dependence (40%) of cases experienced multiple sequels attributed to drug dependence i.e. weight loss and ill health, social and financial problems, (35%) of cases suffered from social and financial problems and (25 %) of dependents reported weight loss only.
Clinical examination:
Clinical examination of dependent patients was done, with the aim to assess the general health status, effects and complications of drug dependence.
laboratory investigation of the dependent cases:
Concerning the laboratory investigation of the dependent cases 21.4% had anemia, as regarded the liver and kidney function tests of the dependent cases17.1% and 5% respectively had elevated function testes.
About 10% of dependent cases in this study had viral infection HBV, HCV or HIV. All of them were in the tramadol+ others and others group. This can be explained by sharing injection equipment , so they can acquiring hepatitis virus (HCV or HBV)or HIV.
In light of the results obtained through the study, the tramadol was the frequent one used in dependent groups followed by cannabis. BZDs are rarely the preferred or sole drug of abuse they are often used with other types of medications, including other drugs with abuse potential, and these drugs can enhance the toxic effects of BZDs.
2- Experimental part:
Biochemical parameters:
- As regards liver biochemical parameters, AST, ALT were significantly increased in acute tramadol poisoning .
- In chronic tramadol poisoning AST, ALT were highly significantly increased, while serum albumin was significantly decreased.
- As regards liver biochemical parameters, AST, ALT, serum albumin, and total bilirubin were not significantly changed in acute diazepam poisoning.
- As regards AST, ALT they were significantly increased in chronic diazepam dependent group compared with that of control group, while serum albumin and total bilirubin were not significantly changed.
- AST and ALT of the liver function were highly significantly increased in group 6 the dependent group on both drugs (tramadol and diazepam).
- As regard brain ChE level in acute tramadol poisoning group was significantly decreased by 20% as compared to the control group while in tramadol dependent groups was not changed significantly compared to the control group.
- Brain ChE was not significantly changed neither in acute diazepam poisoning nor in diazepam dependent group as compared to the control group.
- Serum cortisol level was significantly increased in acute tramadol and in acute diazepam poisoning group as compared to the control group.
- Serum cortisol level was highly significantly decreased in chronic tramadol dependent group as compared to the control group
- Serum cortisol level was not significantly changed in chronic diazepam dependent group.
Histopathology result:
I-Hematoxylin and Eosin:
A-Brain:
Acute tramadol poisoning: Microscopic examination of the brain specimens of the rats showed marked brain congestion, edema, inflammatory cellular infiltrates multiple vacuolation in the neuropil, degeneration of some neuronal cells and red neuron which is marker of apoptosis.
Chronic tramadol poisoning: Microscopic examination of the brain specimens of the rats showed disarrangement of brain layers with neuronal cells degeneration which was detected in almost all of rats , disrupted ependyma of ventricle and hypertrophied choroid plexus with papillary projections, increased number of red neuron red neurons, which are the histopathologic markers of apoptosis.Acute diazepam poisoning: Microscopic examination of the brain specimens of the rats showed mild edema of and congestion of the blood vessels.
Chronic diazepam poisoning: Microscopic examination of the brain specimens of the rats showed increased the vaculation in neuropil, with inflammatory cellular infiltrate, pyknotic nuclei of pyramidal cells and degenerated cells.
Chronic tramadol and diazepam poisoning: Microscopic examination of the brain specimens of the rats showed dilated vascular space, hemorrhage, gliosis of the neuropil, degenerated pyramidal cells and marked increase in number of apoptotic neurocytes.
Liver:
Acute tramadol poisoning:
Microscopic examination of the liver specimens of the rats showed dilated congestion of hepatic artery, with sinusoidal dilatation, and perivascular inflammatory cellular infiltrations and degenerated cells with pyknotic nuclei and cell ghost.
Chronic tramadol poisoning:
Microscopic examination of the liver specimens of the rats showed an increase in the perivascular cellular infiltration, marked congestion, Kupffer cell hyperplasia were observed in almost all rats, steatosis and marked degeneration of hepatocytes and apoptotic cells .
Acute diazepam poisoning:
Microscopic examination of the liver specimens of the rats showed vascular dilatation and congestion.
Chronic diazepam poisoning:
Microscopic examination of the liver specimens of the rats showed congestion of central vein, marked steatosis and ballooning degeneration of hepatocytes in zone 1.
Chronic tramadol and diazepam poisoning:
Microscopic examination of the liver specimens of the rats showed vessels severe hemorrhage, sinusoidal dilatation and cells are highly degenerated of the liver with area of necroinflammation and kupffer hyperplasia in combined group.
II-Histochemical results
A-Brain:
Acute tramadol poisoning:
It showed normal PAS reaction (purplish-red) which is strong reaction in pyramidal cells and moderate one in granular cells.
Chronic tramadol poisoning:
It showed weak P. A. S. reaction especially in destructing neuron.
Acute diazepam poisoning:
It showed normal PAS reaction (purplish-red) which is strong reaction in pyramidal cells and moderate one in granular cells.
Chronic diazepam poisoning:
It showed weak PAS reaction in granular cells specially degenerated ones and moderate reaction in the pyramidal cells.
Chronic tramadol and diazepam poisoning:
It showed very weak (complete destruction) P. A. S. reaction in neuronal cells.
B-Liver
Acute tramadol poisoning:
Microscopic examination of the liver specimens of the rats showed normal strong P. A. S. reaction.
Chronic tramadol poisoning:
Microscopic examination of the liver specimens of the rats showed weak P. A. S. reaction in hepatocytes.
Acute diazepam poisoning:
Microscopic examination of the liver specimens of the rats showed normal strong P. A. S.
Chronic diazepam poisoning:
Microscopic examination of the liver specimens of the rats showed moderate P. A. S. reaction in hepatocytes.
Chronic tramadol and diazepam poisoning:
Microscopic examination of the liver specimens of the rats showed very weak P. A. S. reaction in hepatocytes.