10th symposium of ztm

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation

Kniga so prezentacii Book with presentations

EDUCATION CENTAR- DOJRAN: 01-03 APRIL 2016


X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

Organizing Committee of the Symposium  

Nestor Popovski Niko Bekjarovski

Symposium is accredited by the Medical Chamber of Macedonia (LKM) and Macedonian Medical Association (MLD)

GENERAL SPONSOR OF THE SYMPOSIUM AD Alkaloid Skopje

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

ORAL PRESENTATION

Tretament of opioid dependence during pregnancy-our first experiences University Clinic of Toxicology, Clinical Center “Mother Teresa”, Skopje Natasha Simonovska Pregnant women dependent on opioids should be encouraged to use opioid maintenance treatment whenever available rather than to attempt opioid detoxification. Biggest concern with opioid agonist medication during pregnancy is the potential for occurrence of neonatal abstinence syndrome. A NIDA-supported clinical trial has found buprenorphine to be a safe and effective alternative to methadone for treating opioid dependence during pregnancy. The infants born to women who received buprenorphine had milder symptoms of neonatal opioid withdrawal than those born to women who received methadone. Buprenorphine may be a good option for pregnant women, particularly those who are new to treatment or who become pregnant while on this medication. Key words: opioid dependence, pregnancy, neonatal abstinence syndrome

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

ORAL PRESENTATION

STUDY OF ACUTE POISONING WITH BETA BLOCKERS RAYNA STOYANOVA, JULIA RADENKOVA - SAEVA CLINIC OF TOXICOLOGY, UMHATEM "NI PIROGOV", SOFIA, BULGARIA Objective: To study the acute poisoning with beta blockers, in patients over 18 years old. Methods: Retrospective epidemiological study covers a period of two years. All cases of poisoning with beta blockers have been analyzed in terms to gender, age, clinical course, treatment and outcome. Results: For the study period - from 01.01. 2013 to 31.12.2014, in the Clinic of Toxicology, Department for adults, UMHATEM "NI Pirogov" 27 patients between 18 and 86 years with beta blockers intoxication were treated. Female were 20, male were 7. The severity of poisoning varies from mild to extremely severe. In three of the cases were observed signs of exotoxic shock. Conclusion: Acute poisoning with beta blockers are a serious challenge for the physician - toxicologist. Keywords: acute poisoning, beta blockers, exotoxic shock

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

ORAL PRESENTATION Identification of synthetic cannabinoids in herbal mixtures by GC-MS method Gordana Brajkovic, Snezana Djordjevic, Jasmina Jovic-Stosic, Vesna Kilibarda, Slavica Vucinic National Poison Control Centre, Military Medical Academy, Belgrade, Serbia

Introduction: New synthetic cannabinoids are pharmacologically active and toxic. They are appear in different herbal products. Illegal laboratoires continuosly change the chemical structure of these substances, design, modality of distributing in order to avoid law. Synthetic cannabinoids are CB1 receptor agonists. CB1 receptors in the brain mediate the psychoactive effects of THC but these compounds are several times more potent than tetrahydrocannabinol. Methodology: The methanol extract of synthetic cannabinoids was prepared for GC-MS analysis. Separation of compounds from methanol extract was performed on Thermo TP-5 capillary column. The injector was operated in split mode (10:1) at 200 °C. Helium gas was used as the carrier gas at flow rate of 0,3 ml/min. The oven temperature was held 100 °C for 1 min, ramped to 300 °C at a rate of 12° C/min and held for 9 min. The MS conditions were as follows: transfer line heater: 280 °C; ion source temperature: 220 °C. The injection volume was 1 µL. Results: We have identified AB-FUBINACA in herbal smoking mixture “Rainbow special”, 5F-AKB48 in herbal mixtures “Galaxy” and AB-PINACA in herbal mixtures “Badmad”. The analysis of packages with brand name “Sharp” and “Luminated” confirmed presence of MDMB CHMICA and AB-CHMINACA, and analysis of herbal products “Incense” presence of JWH-122 and JWH-210. Conclusions: These products are constantly change in terms of composition and their quantity. Developing and validating of analytical methods for their detection and continuous education about the toxic characteristic of these compounds will reduce their consumption. Key words: synthetic cannabinoids, gas chromatography-mass spectrometry, herbal mixtures

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

ORAL PRESENTATION

Acute bromazepam poisonings in Poisoning Control Centre in 2015. 1

1

Bojanic Milos, 1Branko Dujovic, 2Natasa Perkovic Vukcevic, 2Jasmina Jovic Stosic, 3 Zoran Segrt, 2Snezana Djordjevic

Student of Medical Faculty Military Medical Academy, Ministry of Defense, Belgrade, Serbia 2

National Poison Control Centre, Military Medical Academy, Belgrade, Serbia 3

Sector for treatment, Military Medical Academy, Belgrade, Serbia

According to the data of the National Poison Control Centre benzodiazepines are dominant cause of poisoning. They were detected in about 70% of acute poisonings. In the group of benzodiazepines, the most common cause of poisoning is bromazepam, then diazepam and lorazepam. During 2015, acute poisonings with bromazepam alone in toxic concentration higher than 0.2 mg/L were registered in 97 patients (70 female and 27 male), while 33 patients were hospitalized (24 female and 9 male). Average life expectancy of hospitalized patient was 48.5 (from 16 to 91 year). The most cases of poisonings were mild degree poisonings (PSS1) in 18 patients. With moderate (PSS2) and severe (PSS3) degrees of poisoning were 6 and 7 patients respectively. Two cases were with lethal outcome (PSS4). The main complications in patients after poisonings were bronchopneumonia (5 patients) and urinary (4 patients) infection. There was one patient with first grade AV block. Lethal outcome was registered in patients 77 and 88 years old. The mean concentration of bromazepam in the hospitalized patients was 1.22 mg/L (concentration range between 0.22 mg/L and 3.97 mg/L), which is several times higher than maximal therapeutic concentration. The concentration of the drug in the blood was not in correlation with clinical manifestation and state of consciousness. We can conclude that acute poisonings with bromazepam, as the most frequently cause of drug poisoning are mostly with mild degree. However, with elderly people, it could be complicated and could lead to fatal outcome. Key words: Bromazepam, poisoning, PCC

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

ORAL PRESENTATION Alternative biological samples: saliva and hair Snezana Djordjevic, Vesna Kilibarda, Slavica Vucinic National Poison Control Centre, Military Medical academy, Belgrade, Serbia Blood and urine are common biological matrices in toxicological analysis. They can be used for determination of drugs, drugs of abuse and their metabolites and monitoring of pharmacokinetics and toxicokinetics of these compounds. However, in past years alternative biological samples as saliva and hair are used for these purposes. Saliva is sample that can be used for both therapeutic drug monitoring and determination of illicit drugs, which has a big importance in forensic and toxicological cases. That sample is used in pediatric and old patients with problems in periphery circulation. Collection of saliva is non-invasive and simpler in comparison to collecting blood. However, saliva sampling has to be done under strictly defined and controlled condition. Saliva drug concentration is related to plasma free drug concentration, which is responsible for pharmacological effects of drugs. Relationships that exist between the saliva and blood concentrations of the most commonly used anticonvulsant drugs is useful for determining compliance with medication in pediatric patients, for analyzing the concentration of free drug and in situations where repeated sampling is necessary. Hair sample is used when history of ingesting drugs is unknown. Practical advantage of hair analysis, in relation to the blood or urine, is that the drugs can be detected for several months after use. Drugs incorporated into hair are very stable, so hair sample can be stored at room temperature for long period of time. But, hair analysis, in contrast of blood and urine analysis, is a very complex method. It involves: decontamination, segmentation, pulverization, incubation, sample preparation and analysis. In toxicological analysis different matrices could be used. Saliva is recommended as an alternative sample for therapeutic drug monitoring as well for identification of abusing drugs. Hair analysis may provide useful information about drug treatment, abusing drugs and the history of usage after their intake. Key words: alternative biological matrices, saliva, hair, toxicological analysis

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

ORAL PRESENTATION

DRUG INDUCED TOXIC EPIDERMAL NECROLYSIS - CASE REPORT JULIA RADENKOVA-SAEVA, HRISTO NAYDENOV Toxicology Clinic, Emergency University Hospital“N.I.Pirogov”, Sofia, Bulgaria Objective: Toxic epidermal necrolysis (TEN) or Lyell's syndrome is severe life-threatening adverse drug reactions, characterized by bullous and erosive lesions involve oral, ocular, and genital mucosa and vast areas of the skin with extensive dermoepidermal detachments. The drugs most commonly involved are: antibiotics; anticonvulsants; antiretroviral drugs; nonsteroidal anti-inflammatory drugs, allopurinol. An immunologic response to immunocomplexes formed by metabolites of the causal drug and the common tissue antigens is thought to be responsible for this disorder. We present a case of TEN, treated in the Toxicology clinic and Burn Centre, Emergency University Hospital “Pirogov”. Case report: A 68-year-old female, presented with complaints of fever and extensive rashes on the skin of the face, the neck and the trunk, severe itching of the skin, ulcerations and erythema of the conjunctiva and the oral cavity and difficulty in swallowing. She have a period of two or three days of general discomfort and fatigue, rash, fever up to 38°C, sore throat, arthralgia, myalgia, loss of appetite and have been treated with antipyretics, antibiotic - ampicillin, antihistamines, vitamins. Her state worsened during the next 3 days, so she was hospitalized in the Toxicology clinic. On general examination, she was well-oriented and conscious. Initial vital signs were: heart rate 88 beats per minute, blood pressure 145/89 mmHg, respiratory rate 26 breaths per minute Multiple maculopapular and bullous eruptions, plaques were present all over the body, blisters that cover a substantial portion of the body. The entire skin covering the body surface was denuded and peeled off with minor manipulation - Nikolsky's sign. Intraorally, multiple oral ulcers of the buccal mucosa, tongue, palate, labial mucosa, soft palate were seen. Hemorrhagic erosions were also seen on both the upper and lower lips. Conjunctivitis and ulceration of genitalia was also noted. Immunoassays revealed an expressed lymphopenia affecting all lymphocyte subpopulations, with the exception of NK cells, high levels of IgG. The patient was positioned in air-fluidised beds in burn unit and managed symptomatically by administering intravenous fluid and electrolyte replacement, systemic corticosteroids, antihistamines, antibiotic - klacid, fresh frozen plasma, vitamins, H2 blockers, topical wound care with chlorhexidine acetate (Bactigras), local treatment of mucosal changes - vaginal globules, ophthalmic preparations. Evolution was satisfactory with epidermization and she was discharged from the hospital after 1 months. Conclusion: Severe adverse drug reactions as toxic epidermal necrolysis are rare. Prompt recognition, withdrawal of suspected drug and hospitalization are crucial for favorable outcome. Key words: Toxic epidermal necrolysis, Lyell's syndrome

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

ORAL PRESENTATION

GREEN TEA HEPATOTOXICITY Afrodita Berat, Niko Bekjarovski University Clinic for Тoxicology, Clinical Campus “Mother Theresa, Skopje, Republic of Macedonia

Abstract: Aim of this case report is to show a unique case of transient hepatotoxicity developed after 51 days weight-diet protocol with 4 glasses of green tea. A young girl (22) was brought at the Clinic presented with fatigue, nausea, pain in the liver. The symptoms began 2 days prior the admission. We learned a fact, that she was finishing the III round of the 17 day green tea diet. During this health regime she didn’t have any health issues. Physical exam showed jaundice and a discreet pain under the right costal varnish. Initial labs included elevations in the serum aminotransferase levels (aspartate aminotransferase 344; alanine aminotransferase 288) serum bilirubin total 48; bilirubin direct 28; factor VII 66%. Because of the suspicion that the green tea is responsible for the hepatotoxicity, we stopped its intake immediately. The patient refused a liver biopsy. The controlled analysis that we performed 7 days on ongoing treatment showed a significant bilirubin decrees, a normalization of VII 7, and a discreet decrees of AST and ALT. .The control lab analysis we took after a month of initial treatment showed a complete normalization of the lab parameters . Three weeks after the normalization of the labs, the patient came to our clinic once again, with similar symptoms, but without the jaundicing. During the exam she admitted that she took green tea, the previous two days, in the morning prior breakfast. The lab showed a mild elevation in the AST 44 and ALT 48.

Key words: green tea, hepatotoxicity, diet

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

ORAL PRESENTATION

Representation of opiates in post mortem samples within the period from 2010. to 2014. Zorana Jovic1, Nada Bosnjakovic Pavlovic1, Nadica Marinkovic2, Gordana Brajkovic3, Vesna Kilibarda3, Snezana Djordjevic3 1 Faculty of physical chemistry, Belgrade, Serbia 2 Institute of Pathology and Forensic Medicine, Military Medical Academy, Belgrade, Serbia 3 National Poison Control Center, Military Medical Academy, Belgrade, Serbia Herion (diacetil morphine) is one of the most common substances of abuse. It has a short halflife, of approximately 2−6 min. In the liver, heroin undergoes deacetylation to 6monoacetylmorphine (6−MAM) and morphine. Detection of 6-acetylmorphine in the urine is indication of heroin use. In this study, the results of statistical analysis of death cases that occurred due to heroin abuse are represented. The results after analysis of the biological post mortem samples which were performed in the Department of toxicological chemistry, National Poison Control Center, Military Medical Academy, Belgrade, Serbia within the period from 2010. to 2014. were processed. Besides that, the potential contributions of the other psychoactive substances, drugs and alcohol, as their combined impact on lethal outcome are examined. The post mortem samples were prepared by liquid-liquid extraction with mixture chloroform-isopropanol (9:1). The analysis were performed by the use of HPLC/MS method, with the mixture of 5 mM ammonium acetate and acetonitrile (80:20, pH 3.5) as the mobile phase. The separation of opiates from the matrix components were performed on the ODS ® column. Mass detection was performed by electro spray ionization in positive mode. The retention times for morphine, codeine and 6-MAM were 6.66, 11.81 and 14.31, respectively, for their ion masses of 286, 300 i 328. The statistical analysis of the results was perfomed in Microsoft Office Excel 2007 program. Due to the period from 2010. to 2014. 107 from total of 1670 analyzed samples with the lethal outcome were positive for presence of the substances of abuse (6.41%). In 83.18% cases other substances (alcohol, benzodiazepines and other psychotropic drugs) which could contribute to the lethal outcome were used. The largest number of death cases (86.17%) was at the age between 20 and 40 (average number: 33 years). Statistical data shows that the consumers of the narcotics in 88% of cases were man of the different age. Shown results indicate that within the substances of abuse heroine is the most common agent that can cause the lethal outcome. Besides, obtained results show that the heroin abusers often and simultaneously abuse the other substances. Therefore, besides dealing with the problem of the heroine abuse, the more attention should be devoted to the control of the drug issuing and traffic, as to the problem of alcohol consuming. Key words: substances of abuse, liquid chromatograpy-mass spectrometry, post mortem samples

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

ORAL PRESENTATION

CLINICAL TOXICOLOGY TODAY K. Kanev Clinic of Emergency toxicology, Military Medical Academy – Sofia, Bulgaria.

The art of poisoning dates back to ancient times. However, today it is actual as in the past and nowadays it has a leading position in the rang-list for sudden death amongst the young people (up to 40 years old). In the present report the modern aspects of clinical toxicology are presented: to provide fast and accurate diagnostics of poisoning and modern concepts of poisoning treatment. The different therapeutic strategies for the most common cases of poisoning are presented and critical view is provided. The aim of the report is to summarize in a glance the clinical toxicology today and its reserved place in the emergency medicine and in the emergency hospital. Some organization concepts about its structure and its specifics are also discussed.

Keywords: clinical toxicology, emergency medicine

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

ORAL PRESENTATION

SUICIDE ATTEMPT WITH CLOZAPINE OVERDOSE: LIPID TREATMENT AND CARBOHEMOSORPTION L. Neykova-Vasileva, J. Angelov, S. Veli, V. Traykova, V. Atanasov, K. Kanev Clinic of Emergency toxicology, Military Medical Academy - Sofia

Clozapine (Leponex) is an atypical antipsychotic drug. Despite its limited clinical application, clozapine poisoning could be severe with fatal outcome. We present a case of severe intoxication with clozapine in 60-years-old woman with a primary diagnosis: paranoid schizophrenia. The patient was admitted in coma (GCS 4). The toxicological analysis found a lethal concentration of clozapine in blood. A complex depuration therapy was applied – simultaneous charcoal haemoperfusion and intravenous lipid therapy, repeated twice in 24 h. The vital signs and neurological status of the patient were improved significantly in first hours and remain stable. The clozapine was effectively removed from the body using the combination of intravenous lipid emulsion (ILE) infusion and carbohemosorption of the lipid-drug complex. The present protocol displays fast and effective results in case of severe intoxications with lipophilic drugs [1]. Simultaneous application of intravenous fat emulsion and charcoal hemoperfusion in quetiapine overdose case. CEJMed, 9(3), 2014, 505-507.

Keywords: clozapine, charcoal hemoperfusion, intravenous lipid therapy

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

ORAL PRESENTATION

SOME TOPICS OF ANALYTICAL TOXICOLOGY IN CLINICAL PRACTICE B. Mechkarska, S. Stoykova, V. Atanasov Analytical Toxicology Laboratory at Clinic of Emergency toxicology, Military Medical Academy - Sofia

The specific diagnostic of poisoning in the clinical practice is provided by the analytical (forensic) toxicology laboratory. Here we report some specific topics for the clinical practice: Metformin and metformin-associated lactate acidosis (MALA) is a life-threatening complication. In 2015 we had registered an increased number of MALA cases with a high mortality rate. The diagnostics of MALA needs measurement of arterial blood pH and serum lactate, but in all cases extreme concentration of serum metformin was also found. Formic acid as the main toxic metabolite of methanol is responsible for the clinical course of the poisoning. The measurement of formic acid in the blood allows estimating the severity of poisoning and prognosis as well as its forensic meaning. Red blood cells acetylcholinesterase (RBC-AChE) is a sensitive and specific marker which allows fast identifying poisoning with neurotoxic compounds (OPC, carbamates) without using special analytical equipment. Detection of some designer drugs (especially synthetic cannabinoid as JWH) is the main challenge nowadays in analytical toxicology practice. The analysis of the original source (“herbal incense”, “tea”, etc.) has more analytical significance than bio-samples from the victim. Finally, some problems about the most popular topics in forensic toxicology today – driving under influence – estimation of alcohol in blood and its effects (the scale of Dubowski), and smoking marijuana and legislation practice (zero tolerance, per se legislation or “under influence”).

Keywords: analytical (forensic) toxicology, metformin, formic acid, acetylcholinesterase, DUI

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

ORAL PRESENTATION Severe acetaminophen poisoning: Two cases in young women, demonstrating different extents of liver injury independent of the dose Margarita S Gesheva, Miroslava T Petkova, Maya A Tomova, Emilia V Kirova, Julia V Radenkova-Saeva Toxicology Clinic, Emergency University Hospital “N.I.Pirogov”, Sofia, Bulgaria Objective: Acetaminophen is one of the most frequently used analgesic and antipyretics worldwide. In Bulgaria these poisonings are typically a result of ingestion of a large quantity of acetaminophen with suicidal intent, while in American and European reports acetaminophen poisoning is most often reported to follow poorly controlled repeated doses in the treatment of febrile conditions and pain syndrome. The main mechanism of acetaminophen toxicity in overdose is depletion of glutathione resulting in the production of a toxic metabolite N -acetyl-p -benzoquinoneimine (NAPQI). When the concentration of glutathione is depleted to 30% of the normal concentration, injury to hepatocytes occurs. The serum acetaminophen concentration is the basis for diagnosis and treatment of poisoning, because of the delay in onset of clinical manifestations of toxicity. The aim of our study was to present a parallel between two cases of severe acetaminophen poisoning in young women, demonstrating different extents of liver injury independent of the dose ingested. Case series: We present two cases of acetaminophen poisoning respectively with 11 g and 40 g. Both cases were suicide attempts and presented within a two week period to the Clinic of Toxicology, Emergency University Hospital „N. I. Pirogov”. The chemico-toxicological analysis confirmed the presence of toxic concentrations of acetaminophen. In the first case the concentration was 74.7 mcg/mL 24 hours after ingestion and in the second case over 300 mcg/mL 4 hours after ingestion. We made a parallel between both of the patients, considering their clinical manifestations and the toxic injury of the liver. The first patient, hospitalized 8 hours after ingestion, was without clinical manifestations of toxicity and on the 3 rd day developed acute liver failure (ASAT 10 929 U/L, ALAT 6844 U/L, complete failure of coagulation). The second patient, hospitalized 4 hours after ingestion, was somnolent and repeatedly vomiting and on the 3rd day developed liver injury (ASAT 303 U/L, ALAT 1465 U/L, mild coagulation disturbances). General, enhanced elimination, hepatoprotective, replacement and antidote (N-acetylcysteine) therapy was administered. The patients were discharged on day 15 and 5 after admission in a good health. Conclusion: The parallel demonstrates discordance between ingested quantity, acetaminophen concentrations and liver laboratory findings of hepatic injury, when equal in volume and type therapy is administered. Probably the reason for this discordance can be found in the current state of the patient and differing glutathione stores in the liver, which determine the capacity to detoxify. Key words: Acetaminophen. Liver toxic injury.

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

ORAL PRESENTATION АМФЕТАМИН И ОСТРИ ИНТОКСИКАЦИИ Олимпиада А. Станчева, Евгения И. Бързашка1, Йордан Йорданов2 МУ- Плевен, Клиника по Клинична Токсикология “УМБАЛ - Д-Р Георги Странски” ЕАД 1

Клиника по Клинична Токсикология “УМБАЛ - Д-Р Георги Странски” ЕАД

РЕЗЮМЕ Амфетаминът (α-metilfeniletilamin.) - стимулант на централната нервна система, производно на фенилетиламин. Механизмът на действие се основава на увеличеното освобождаването на невротрансмитери, в частност допамин и норепинефрин, и в по-малка степен серотонин. Амфетамина е рекреационно психоактивно вещество, което може да доведе до зависимост. Оборотът на амфетамина е ограничен и се контролира от международното и националното законодателство. Амфетамин - безцветна, летлива, маслена течност с характерен "рибен" мирис, слабо разтворима във вода, разтворима в органични разтворители. Обикновено се среща под формата на соли, лесно разтворим във вода: сулфатна, фосфатна и хидрохлоридна. Найчесто срещана е сулфатната сол и е под формата на бял прах. Формиране на психическата зависимост към амфетамините е свързана с действието на допаминергичните невроне в вентралната областта на tegmentum area и nucleus accumbens. Въпросът за наличието на физическа зависимост към амфетамин е неодназначен. Внезапното спиране на препарата след продължителна употреба (в продължение на няколко дни във високи дози) причинява умора, сънливост, глад и депресия до такава степен изразена, че е налице реален риск от самоубийство. Представяме 3 клинични случая на ОЕИ с амфетамини при пациенти с хронична злоупотреба на психоактивни вещества, развили токсична кардиомиопатия, остър инфаркт на миокарда и шизофрения. Пациена, развил ОМИ завърши с летален изход. Key words: амфетамин, отравяне, зависимост.

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

ORAL PRESENTATION

ISONIAZID POISONING: A Case Report Ristic S1., Kovacevic B1, Brajkovic G.2

1

Institute for Mother and Child Health Care, Department of Pediatric Intensive Care, Belgrade, Serbia

2

Military Medical Academy, National Poisoning Centre, Department of Toxicological Chemistry, Belgrade

Isoniazid (INH) was first introduced as a chemotherapeutic agent for tuberculosis in 1952 respectively. Since then he is the mainstay of the antitiubercular treatment and are included in nearly all Anti Tubercular Treatment (ATT) regimes. Isoniazid, if acutely ingested, even 1.5 to 2 gram may cause toxicity in adults. Isoniazid intoxication produces a characteristic clinical syndrome including seizures, metabolic acidosis, and, in severe cases, respiratory depression and coma. Poisoning may occur with unintentional or accidental ingestion, suicidal intent, or in patients taking extra tablets to compensate for missed doses. Untreated or inadequately treated cases of gross isoniazid over dosage can be fatal, but good response has been reported in most patients treated within the first few hours after drug ingestion. Treatment of INH toxicity must address correction of Îł-aminobutyric acid deficiency with pyridoxine replacement and management of life-threatening events. We report a 14-year-old girl, who took massive overdose Isoniazid (>6 gr) and presented vomiting, recurent seizures, altered mental status, respiratory depression, metabolic acidosis and hyperglicemia. She was admitted to intensive care unit, treated successfully with pyridoxine, symptomatic

(midazolam,

phenobarbital, thiopental) and supportive care. She made a full recovery 36 hours after admission. Isoniazid was quantified with liquid chromatography-tandem mass spectrometry. Key words: isoniasid, poisoning, 14-years old girl

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

ORAL PRESENTATION

Cannabis intoxication - clinical, epidemiological and social aspects Stefanova K. B., Barzashka E. I. Department of Clinical Toxicology, UMHAT “Dr Georgi Stranski” – Pleven, Bulgaria

ABSTRACT: Cannabis is the most commonly substance which is abused with worldwide, because consumers consider it harmless and without adverse threatening health effects. In Bulgaria cannabis use, particularly among adolescents marks an increasingly larger size. Presented are the results of a study of patients with acute intoxication after cannabis use hospitalized in the Department of Clinical Toxicology UMHAT “Dr Georgi Stranski” – Pleven during the period 2011 – 2015. The distribution of the cases is analyzed by sex, age, social groups, motives and duration of use, clinical course and treatment. The patients are aged from 15 to 23 years, predominantly women, mainly students with prolonged use. The clinical symptomatology is mild to moderate, with mostly neurological, cardiorespiratory and upperdyspeptic symptoms and quickly influenced to the 24th hour. The diagnosis was confirmed with dry urine test for cannabinoids in the urine. The treatment is primarily symptomatic, and the outcome of the intoxication is favorable in all patients. Emphasis is placed on the adverse effects on individual and public health, and how they would multiply after the legalization of cannabis use for medical purposes. Keywords: cannabis, intoxication, cannabis use for medical purposes.

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

ORAL PRESENTATION

WATER FASTING DETOXIFICATION

Niko Bekjarovski University Clinic for Toxicology; University Medical Campus “Mother Theresa” Skopje

Historical records tell us that fasting has been used for health recovery for thousands of years. Hippocrates, Socrates, and Plato all recommended fasting for health recovery. Water fasting offers the quickest detoxification and strongest therapeutic effect. It is also the most challenging fast to perform in the first few days. Careful preparation in the days before a water fast can make all the difference in your level of comfort, but the emotional challenge will still be great. Getting professional supervision is an option and is recommended for water fast longer than 3 days. Fasting is powerful therapeutic processes that can help people recover from mild to severe health conditions. Some of the most common ones are high blood pressure, asthma, allergies, chronic headaches, inflammatory bowel disease (ulcerative colitis and Crohn’s disease), irritable bowel syndrome, adult onset diabetes, heart disease, degenerative arthritis, rheumatoid arthritis, psoriasis, eczema, acne, uterine fibroids, benign tumours, and systemic lupus erythematosus. We present several possible water fasting protocols, under full medical supervision with different time duration.

Key words: water fasting, detoxification, protocol

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

POSTER MODERN ASPECTS IN CLINICAL APPLICATION OF ANTIDOTES K. Paskalev2, L. Neykova - Vasileva1, V. Traykova1, Sh. Veli1, K. Kanev1 1

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Clinic of Emergency toxicology, Military Medical Academy - Sofia,Bulgaria. Military Medical Intelligence Unit, Military Medical Academy – Sofia, Bulgaria.

Intoxications are an important public health issue. The development of pharmacy, the chemistry, the industry and the agriculture alter the pattern of the intoxications in the modern world. The antidotes are lifesaving medical products (MP). The application of a specific antidote could determine the severity of the disease and reduce the medical resources for treatment. This requires the development of new antidotes and therapeutic regimens. The purpose of the material is to analyze the assessments of the availability and the effectiveness of the antidotes carried out by international and national institutions in order to optimize the antidote applied in our country. Here we analyze and review the national and the international assessments, and the shared in literature international experience. Results:The optimal treatment of intoxication depends on timely antidote administered in sufficient quantity, on the "benefit/risk" principle clinging to the good medical practice. Great Britain and the US introduced new policies to provide antidotes emergency wards (EW) in hospitals. Until 2006 the recommendations of IPCS were used according to which the timeframe required the antidotes to be available: within 30 min; within 2 hours and within 6 hours. The new levels of availability are: "immediately available" "available within 1 hour" and "rarely used and stored at a regional level." The latter are available if necessary after consulting the poison centers or the clinical toxicologist. The decision on what amount to be available is based on local epidemiological assessment of poisoning. Toxicological emergency aid increases its efficiency through the use of LP in modern formulations - for example the autoinjector. Conclusions: The use of a timeframe for the availability of antidotes and their application in modern LP ensures the efficiency of the emergency toxicological help. The analysis of the researches of IPCS are tools for building national strategies on the issue depending on development of the healthcare system and the financial means available. Their use helps to optimize the nomenclature of antidotes provided in Bulgaria, according to the акона за лекарствените средства и аптеките в хуманната медицина Law for Medical Products and Pharmacies for Human Medicine /LMPPHM/. The inclusion of these drugs in the medicinal resource in emergency words improves the quality of medical care. Keywords: antidotes, efficiency and availability

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

POSTER

FRAMEWORK FOR ANALYSING RISK IN CLINICAL TOXICOLOGY ANELIA LOUKOVA, JULIA RADENKOVA-SAEVA TOXICOLOGY CLINIC, EMERGENCY UNIVERSITY HOSPITAL “N.I.PIROGOV” SOFIA, BULGARIA

Objective: This study presents some aspects of risk management in toxicological practice as stages of risk management, and management strategies. An analysis of errors in medicine has been made by applying the personal and systemic approach. Methods: The possibilities of descriptive-evaluation method for analysis and summary of the risk in toxicological practice have been used. Results: The approaches to monitoring in toxicological practice should include active and passive mechanisms. Active surveillance initiates procedures to obtain reports of errors in medicine and suggests the need to develop valid definitions and standardized methods for measuring and recording errors. Emphasis should be placed on the assessment of the multifactorial nature of the errors that often result from interactions between the patient, the environment (health system) and medical staff. Patients have high expectations for the outcome of therapy and increasingly argued that there is an error in the treatment and turn to the judiciary for arbitration with the aim of compensation and benefits. The application of a modern system of risk management in the clinics became a challenge to the physicians. Medical errors represent an important public health problem and pose a serious threat to patient safety. The growing awareness of the frequency, causes and consequences of error in medicine reinforces an imperative to improve the understanding of the problem and to devise workable solutions and prevention strategies. Risk management is the responsibility of the managers of the clinic, which determine the levels of information, the algorithms for reporting the errors, the ways in which mistakes will further be processed, registration, analysis, discussion, training of staff. The change in attitude towards this issue is an important prerequisite for improving patient safety. Conclusion: With the change of the social culture and public expectations, the necessity for a strong focus on risk management in urgent medical practice became more and more evident. This is especially applicable to the field of clinical toxicology, which because of its nature is vulnerable to errors and frustration. Keywords: risk management, error in medicine, clinical toxicology.

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X Jubilee Symposium of Macedonian Association of Toxicologists with International Participation EDUCATION CENTER ALKALOID – DOJRAN 01-03.04.2016

POSTER

THERAPEUTIC APPROACH IN INTOXICATIONS WITH PSYCHOACTIVE DRUGS S.Veli, V. Traykova, L. Neykova-Vasileva, K. Kanev Clinic of Emergency toxicology, Military Medical Academy – Sofia, Bulgaria Psychoactive drugs are divided by their impact on Central Nervous System (CNS) in three groups: depressants (opioids); stimulants (cocaine, amphetamine, dexamphetamine, methamphetamine) and hallucinogens (LSD, ecstasy, psilocybine, phencyclidine, tetrahydrocannabinol, mescaline). The influence of different kinds of CNS receptors leads to the main clinical symptoms and syndromes. The aim of this subject is to present a therapeutic scheme used in Clinic of Emergency toxicology (Military Medical Academy, Sofia, Bulgaria) for the treatment of patients with psychoactive drugs’ intoxications. The diagnosis is based on history and clinical data of the usage of the current group of psychoactive drug and is confirmed by their qualitative and quantitative determination in biological samples. The therapeutic approach is correspondent to their toxicokinetics, toxicodynamics and pathogenesis. Antidotal treatment is a part of the regimen and there are two types of antidotes – specific for the group of opioids and nonspecific for the other groups. The complex therapeutic approach leads to very good results associated with quick overcome of clinical manifestations as well as in acute intoxications with psychoactive drugs and acute ones but evolved with chronic abuse. Keywords: psychoactive drugs, intoxication, treatment.

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