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MEDICOLEGAL ASPECTS OF DRUG-ABUSE

KRZYSZTOF S. BOROWIAK. MEDICOLEGAL ASPECTS OF DRUG-ABUSE. POMERANIAN ACADEMY OF MEDICINE FORENSIC MEDICINE DEPARTMENT. DRUG ABUSE HISTORY. POPE (OPIOIDS) known in Egypt since 1700 year b.Ch. – used with wine – both for therapeutic and addict useful. Nicotiana tabacum.

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MEDICOLEGAL ASPECTS OF DRUG-ABUSE

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  1. KRZYSZTOF S. BOROWIAK MEDICOLEGAL ASPECTS OF DRUG-ABUSE POMERANIAN ACADEMY OF MEDICINE FORENSIC MEDICINE DEPARTMENT

  2. DRUG ABUSE HISTORY POPE (OPIOIDS) known in Egypt since 1700 year b.Ch. – used with wine – both for therapeutic and addict useful Nicotiana tabacum Ramzes II was a havy tobaco smokers Ancient Egyptian mummies (XXI dynasty-1500 b.ch.) included low amounts of marihuana and Cocaine (S.Balabanowa -1992) In wine of Cleopatra queen have been Pope and Datura stramonium (Horacy) Ugarit and Mykeny since 1500 b.Ch. Were famous as market centers of wine , opium, Cannabis, Datura From ancient Greece - we know description of opium action on human from Homer It is known that most of Romanian Cezars were regulary drug abusers OPIUM

  3. The spread of global status of drug abuse since 1908 r. – illegal opium smokers in Chinatown (N.Y.) First International Low Regulation – 23th of January 1912 r. HAGA (with China ) Modern status of addiction problem result from Korean and Viet Nam wars nad cultural-habitual revolution in USA in 60. Of XX c. In Poland National Edict from 1997 April 27 (Dz.U.75 poz. 468) There are included 63 section in the 7 main Chapters and list of more than 450 substantions, chemical salts and chemicals need for synthesis of drugs profylactics and learning treatment and rehabilitation Supervision: agriculture, production, marketing

  4. All illicit dealings with drugs in Norway are covered by the Norwegian Penal Code § 162 Two Goverment-appointed committees • CUSTOMS SERVICE • STRATEGY OF PROFYLACTIC ACTIVITY • SUPERVISION FOR PRODUCTION, DISTRIBUTION AND STORAGE OF NARCOTICS • TREATMENT, REHABILITATION, READAPTATION OF ABUSERS • LAW AND LOGISTIC POSSIBILITIES OF CUT THE ILLEGAL MARKET • SUPERVISION FOR PLANT AGRICULTURE • The National Investigation Bureau (NBCI) –strategy, analysis of narcotics, economics aspects, logistic activity • Oslo Police Headquaters and local Police (Drug section) – operational assistance, technical, material and personal resources • Ministry of Justice – promotion of central and regional projects

  5. DETAIL LIST AS ADDICTION OF CODE • LIST No 1 (About 150 substances) • GROUP I-R (ephedrin, ergometrin, ergotamin, pseudoephedrin • GROUP IIA - R (Acetic acid, ethylic ether, piperidine, • Antranil acid, fenyloacetic acid,nitroetan) • GROUP IIB-R (aceton, aldehyd benzoesic, MEK, sulphuric acid, • HCl, toluen, butanon) • LIST No 2 – ABOUT 200 SUBSTANCES AND SALTS • GROUP I-N (opiats & opioids and their salts, Cocaine, • Cannabis indica vel sativa – near 130 compounds) • GROUP II- N (codein and derrivatives /narcocodein, / • etylmorfin –Dionine, propiam • GROUP III-N (mixed pharmaceutics included codein concentration more • than 50 mg or 1,5% ) • GROUP IV-N (acetorfin , Heroin , THC, • LIST No 3 – PSYCHOTROPIC SUBSTANCES – about 150 • GROUP I-P (LSD,psylocybin , amphetamine , metamphetamine, DOB, DET, DMA, • DMT, PCP, secobarbital, THC • GROUP II-P( psychedrine, barbiturans, pentazoocyn ) • GROUPS III-P i IV-P(barbituranes, benzodiazepines, TLPD, mazindol, pemolin)

  6. Governmental structures responsible for drugs • The Ministry of Health and Social Affairsis the responsible ministry for alcohol- and drug policy and the overall co-ordination of illicit drug abuse. • Norwegian Directorate for the Prevention of Alcohol and DrugProblems -MH give its full attention to all social conditions that are related to trends in consumption of legal and illicit drugs • The National Institute for Alcohol and Drug Research (SIFA)is an independent institute whose aim is to carry out scientific research on alcohol and drug issues with special attention to social science research. • A permanent co-ordinating body for law enforcement activities has been formed, comprising a representative for the Ministry of Justice and Police, the Director of Public Prosecutions, the Chief of the National Bureau of Crime Investigation and the Head of the Drug Section, Oslo Police force. • This committee keeps abreast of the development in drug use, continuously evaluates law enforcement efforts, ensures that resources are available and from an assessment of priorities, select specific issues to concentrate on.

  7. GENERAL SITUATION WITH THE FOCUS ON TRENDS/STATISTIC Fig. 1Number of seizures of drugs, opiates, cocaine, cannabis and amphetamines 1986-1996 The number of heroin seizures has steadily increased since the second half of the 1980s up to 1994. There was a large increase in the number of seizures in 1995 and 1996. At present the THC and Amphetamines (Ecstasy) are most popular drugs in Norway

  8. Heroin Cocaine Cannabis Amphetamines GENERAL SITUATION WITH THE FOCUS ON TRENDS/STATISTIC Fig. 2Number of seizures of drugs, other drugs, 1989-1996 Number of confiscations 1996 2340 75 4296 1775 • Ecstasy LSD Khat BDA/BARBIT • 192 36 102 2197/0

  9. GENERAL SITUATION WITH THE FOCUS ON TRENDS/STATISTIC Fig 3Percentage of young people in Oslo and Norway who say that they at some time have used different drugs in 1996 Fig. 4 Deaths caused by use of drugs, 1982-1996

  10. GENERAL SITUATION IN THE OTHER SCANDINAVIAN COUNTRIES • DENMARK – the most liberal low mostly similar to Duch solutions • „Om euforiserende stoffer” 1955 (1996) • National Penal Code § 191, § 88, § 191 • Penalty 2-10 years for possess 20-25 g of herroine, 100-125g morphine, 10-15 kg of Cannabis • discussed phenomenon of Free town Christiana (1971) (part of Copenhagen) – 1000 -1500 citizen, non-formal group out of national low • SWEDEN, FINLAND, ISLAND - law solutions strongly represive, restricted and trends of high criminalization for posses and dealing of narcotics is promoted • general polytic is based on rule of „ zero tolerancy”

  11. NEUROMOLECULAR MECHANISMS OF DRUG ABUSE IN THE BRAIN OF ABUSE HUMAN THE HIGHER PSYCHOLOGICAL ACTIVITY ARE DEEPLY CHANGED ABUSE STATUS IS CHRONIC AND BACKING DISEASE THE „PRICE, AWARD” BRAIN SYSTEM OF MOTIVATION • STIMULATION OF NEUROLOGICAL SYSTEMS • DOPAMINERGIC • GABA-ERGIC • STIMULANTS AMINOACIDS • NO SYNTHESY ACTIVITY DEPRESSION OF ADRENERGIC ANDSEROTONINERGIC NEURONS

  12. DOPAMINERGIC SYSTEM The main neurotransmission system due to abuse status. The mezzolimbic structure (  dopaminergic neurons -  release of dopamine ) Cocaine, Amphetamine, Opioids Ethanol (+ GABA) Nicotine, THC In the adrenergic neurons membrane - opioids receptors ( i ),  2adrenergic ADRENERGIC SYSTEM acsons cells located in the limbic structure and cortical cells also NEUROMOLECULAR MECHANISMS OF ABUSE

  13. SEROTONINERGIC SYSTEM The midbrain structures, spinal structure  the main role in the alcohol abuse syndrome  inhibition of activity of system BDA i ethanol abuse GABAERGIC SYSTEM The price agent is depression of panic and anxiety direct by GABA-ergic receptors, which modulate dopaminergic neurons activity NEUROMOLECULAR MECHANISMS OF ABUSE c.

  14. STIMULATING AMINACIDES • Important access of glutaminergic system in progress of addiction • Postsynaptic receptors connected with NMDA, kainic acid and AMPA  main in limbic area and cortex • Addiction  stimulation of receptors resulted in plastic and adaptaction changes of synapsas (memory, learning) • Ethanol  receptors NMDA • Opioids, cocain AMPA • OPIOID SYSTEM • Drug abuse substances rise of prodynorphine gen expresion in the CNS (stratium) and  of density of opioid  - receptors. • chronic use  activity of peptide synthesis neurons acting against to opioids: cholecystokinines and thyreoliberines NEUROMOLECULAR MECHANISMS OF ADDICTION c.d.

  15. NEUROMOLECULAR MECHANIZM OF ABUSE c. BY G-PROTEIN ACTING ACTIVITY DISTURBANCES CYKLIC NUCLEOTIDES ENZYMES ACTIVITY IN THE PHOSPHORILATION PROCESES The funcjonal changes of , ,  substructure G proteins due to genes expression changes which coded this structures ( tolerancy)

  16. NEUROMOLECULAR MECHANISMS OF ABUSE c. GENETIC CHANGES  DISTURBANCES PLASTIC ACTIVITY OF BRAIN LEARNING AND MOTIVATION MEMORY PROCESES NUCLEUS TRANSCRIPTION AGENTS that proteins connected with specyfic DNA seqency in the promotor’s part of genes. They are stimulated by cAMP mainly CREB (cAMP response element binding protein). Changes of that agents  release adaptation proceses in the neurons Plastic changes in memory processes of learning and motivation After break of using stimulation of aversion processes

  17. GENETIC MECHANISMS OF ABUSE c. FIRST PERIOD OF DEPENDANCE DEVELOPMENT Genes activity in the early cells answer induced by drugs abuse using in the short time Binding proteins cAMP (CREB) C-fos C-jun SECOND PERIOD After chronic using - started chronic genes - FRA (fos related antigen), which due to induction of chronic adaptation

  18. GENETIC MECHANISM OF DRUG ABUSE c.d. GENOTYP CHANGES IN THE PERSONS WITH ETHANOL ABUSE SYNDROME Allel A9 of dopamine gen frequent 2x more in the patients with tremors Polymorphism of DRD2 gene egzon 8 RFLP  higher frequency of drinking, depression, suicides motivation Depletion of serotonine gen SL C6A4  disturbances of asocciation personality Short DRD4 alleles of 3VNTR egzons  well treatment motivation Variants of egzons GABAB  personality disturbances

  19. IN THE 1974 r. WHO FOUNDED 8 BASIC DRUG ABUSE CLASSES HEROINA • TYPE I MORPHINICIncluded natural pope alkaloids derrivatives of Papaver somiferum:morphin, codein and tebain • (phenantren derrivatives) papaverine, narkotine, narceine (izochinoline derrivatives) and synthetic and halfsynthetic • Opioids:heroin (also oksykodon, fentanyl, pentazocyne) Way of introduce: vein injection (everywere vessels) Characteristic signs: strong and fast tolerancy nad psychological and somatic abuse, full syndrome withdrawal, high organs toxicity Symptoms after single dose: narcotic status, somnilence, piupils, locomotive coordination disturbances

  20. TYPE II barbituranes – alcohol Ethylic alkohol, volaitlable anesthetics and all psychotropic drugs Benzodiazepines (diazepam, oksazepam, nitrazepam, alprazolam) Barbituranes (phenobarbital, cyclobarbital...) Neuroleptics (chloropromazyna, promazyna, pernazyna ...) TLPD (doksepin, imipramin, amitryptylin ....) OTHERS– antihistaninic (cetrizin, astemizol), depressed foot neccessity (isolipan, mazindol), using in the locomotion disease (aviomarin) Strong psychological abuse, phisical different (ethanol), slight tolerancy,

  21. TYPE III COCAIN Leafs, cocain lavada, hydrochloride salt, cristalic (coca, freebase, crack, powder) Way of introduce: per os (leafs chewing), by membrane syrfaces: (by nose,by vagina) smoking, inhalation, intra venous Cocaine hydrochloride (Columbian, snow) Erythroxylon coca Sympatomimetic stimulant.  release i  back - keep of epinefryny i nor - E oraz AP in the presynaptic adrenergic neurons, and dopamine and serotonine in midbrain. Local anesthetic ( ester group) – blocked kanałnatrium channels . T ½ 0,5-1,5 hrs. Benzyloecognine 5-8 hrs. Strong abuse both psychical and physical , fast tolerancy, withdrawal syndrome, high organs toxicity, cardiotoxic action. Coctylen interferention with ethanol. Cocain pasta (lavada) Crystaliccocain (crack, dumex)

  22. Mechanismsof action and i biological effects of substances from tobaco and Cannabis Different action of main activ alkaloids Similar effects forgas (smoke) aromatic hydrocarbons, irritant and cancerogenic substances, CO, NO Nic THC Irritant, corrosive, proastmatic,cancerogenic i teratogenic action Nic THC THC  80% amount of ROS, and 81%  conc. of intracelular glutathion Nic THC Nic M.Roth - marihuana due to strong P4501A1 (CYP1A1) mRNA i aktywności tego układu nikotyna tetrahydrokanabinol 70 meroterpens (Mechoulam, 1973) THC (Δ-9–THC, Δ-8–THC), kanabidiol (CBD), kanabigerol (CBG), kanabinol (CBN), kanabichromen (CBC), olivetol

  23. Fast absorbed in the lungs and deposed in the fatty tissue Slight absorption in the mouth and pharyngx Fast absorbed in the lungs Slowly released in to blood biotransformationin the cyt. P-450 foractive 11-hydroksy-THC, andnon active11-nor-9-karboksy-delta-9-THC In serumconc.for 10 min.And fast(T1/2 - 10 min) After 1-2 h.-slowconc.(oxidation to kotynine -estimation of nicotinic abuse Slowly released from tissue for several days , Kinetic of Nicotin and THC 9-15 mg nikotyn -esrum concentration 130-200 nmol/l 150-500 mg marihuana, serum concentration 2- 8 ng, in urine > 50 ng/ml Fast dystributionto CNS

  24. CB 2 - regulation influence to CB 1 and distal: circulation, immunological cell activity ENDOTHELIC CELLS SPLEEN RECEPTOR ACTION OF THC •  activity of mezolimbic dopaminergic neurons •  adenyl cyklaze Ca (N i P/Q) channels •  K channels •  protein kinase activated of mitosis CB 1, (hipokamp, cerrebelum) Psychostymulation  panic, anxiety

  25.  sensitivity of sens neurons (pain relief)  release of lyphopolisacharides (LPS) and IL-6 by macrophags (anty-inflamatory action)  vomeeting  necrosis  peripheral neurons apoptosis and astrocites) BIOLOGICAL ACTIVITY THC • Hipothermic action on the way of cooperation with 5-HT i D2 receptors • Peripherial receptor CB2 – immunosupressive ( activity of lymphocites) • endocannabinols– are release in to bloodwhile rapidly blood preasure • Anandamidetogether with EDHF – regulation of homeostasy ofcardio-vascular system

  26. Short action katecholaminemia and sympatykotonia shorttachycardiaandRR Higher useof oxygenbyheart Corronary vessels spasm Psychical effects to 48 hrs action 3-6 hrs euphoric Change of time and perspectiveestimation well feeling RR, tachycardia hypotermia NIC THC Wypalenie 1 papierosa lub skręta to wprowadzenie do organizmu około 1,5-2,0 mg nikotyny lub THC Efekty i skutki ...

  27. Strong addiction (stimulation of mezzolimbic pathway -release of dopamin) Fast involved peripheral tolerancy small tolerancyfor CNSaction Abstynency sympotoms: irritation, agression,depletion of psychomotoric activityandsleepless psychical and phisical addiction tolerancy involved after 6 -12 months Periodic apathy,sleepness Depletion of memory, concentration, and orientation Muscle tens decreaseandlocomotive coordination acute psychose symptoms Sexual impotency and reproductive possibilities Immunosupresive action Adverts effectsof tobacoandmarijuana

  28. Shorten live Cancerogenesis risk Pulmonary system deseases Cardiovascular deseases Ulcerus risk Earlier menopause and osteoporosis (woman) Influence to pregnancy, higher death factor, worse psychofisical maturation of child to 7. year zaburzenia psychiczne (depresje, psychozy, napady lęku) zaburzenia osobowości zespół braku motywacji objawy ze strony układu sercowo-naczyniowego (hipotensja,tachykardia) podatność na infekcje ryzyko konwersji nowotworowej (faza gazowa)  procesów nekrozy i  apoptozy Dangerousof tobaco andmarijuana smoking (cont.)

  29. Nabilone (synteticanalog of THC) use in tratment of vomiting durring chemiotherapy Dronabinol – asan analgetyk for chronic cancer pain Dexanabinol– treatment of nusea, vomiting and for save the brain –blood border,when cranial and brain injuries clinical test for treatment Sclerosis multiplex (SM) Alzheimer disease depresion after injury asthmatic patients patients withAIDS POSSIBILITIES OF CLINICAL TREATMENT WITH THC DERRIVATIVES There are preclinical test to usean CB1 receptor antagonistsin treatment: • bullimia • schisophrenia ,

  30. TYPE V AMPHETAMINE (PSYCHEDRINE) Now on the market 30 derrivatives amphetamine and metamphetamine fluid  hydrochloride (ice, boon), sulphuric or phosphoric salts  powder and tablets as  ecstasy (MDMA) ECSTASY – postacie tabletkowane MDMA Siarczan amfetaminy i fosforan metamfetaminy (biały proszek, porcje użytkowe)

  31. TYP V AMFETAMINOWY c.d. Second after THC as popularity – psychical and physical stymulation, strong psychical abuse, fast increase tolerance. symptoms: deep psycho-locomotive stimulation, agresion, changes of mentality, high temperature and RR, tachycardia. Way of introduce: by nose membrane, smoking in the pipe, per os (peels, ice) Chronic effects: sleep disturbances, depression and psychoses agresion, , cardiac arrest

  32. TYPE V AMPHETAMINE MECHANISMS ACTION: by serotoninoergic receptors 5-HT2A i 5-HT2C/2B dopamine release in the straiatum ANSWER DEPRESION by NMDA:direct action on the na kompleks cholinergic channels complex (N) Depresion GABA – ergic synaptic neurotransmision by D2 receptors (amphetamine,cocain) Specyfic regulation by the same receptors (activation) DA receptors of midbrain neurons

  33. TYP V AMPHETAMINE First Single dose 100 - 200 mg. Drug abuser after 3- 6 months take 10-15 doses its mean 1-1,5 g of narcotic. Letal dose for adult not user that 200- 300 mg. After per os intake 10 mg max. Concentration in serum (after 1-2 hrs) that 20 - 50 ng/ml Most deal doses that only 30 - 50% of amphetamine – other that waste and dilute substances as meal, sugar, tablets powder... T ½ 4-12 hrs, metabolism  phenylaceton  benzoesic acid  hipuric acid (1%  norephedrine)

  34. TYP VI KHAT Khata edulis – bush growing in North-East of Afric Leafs contain alcaloid - katine (katin, [+] norpseudoephedrin) Kathin acting as psychostimulants closely simmilar as cocain and hallucinogenic as well as LSD Strong psychical addiction. There is no observed phisical addiction and tolerancy EXTREMELY RARE TYPE IN EUROPE

  35. TYPE VII HALLUCINOGENIC SUBSTANCES SEVERAL NATURAL and SYNTHETIC COMPOUNDS (psychodisleptic) INTAKE RESULTS IN : hallucination, religian vision , changes of mentality status- The rapid increase of popularity in the 90. - simple access, low price Psilocybe muschroom, Datura stramonium , Znaczki-kalkomanie z LSD-50 Characteristic flashback syndrome - even after several days

  36. INDOLOALKILOAMINES DERRIV. LSD-25dietylamid Lizergic acid Psilocin, psilocibin(mushroom Psylocibe) psylo, Harmina, harmalina, bufotenina( Amanita muscaria, skin of bananas) Lunch time, businessman lunch PHENYLETYLAMINE DERRIV. Meskaline(Lophophora wiliamsi, peyotl,) hoop, megi, meskal Miriscyne, elemicynamiristica, muscade Hioscyjamin, atropin, skopolamina (Datura stramonium, Hioscyamus niger, Atropa belladonna) S Y N TH E T I C PHENYLETYLAMINES MDMA , MDA (ecstasy)love, love pill, hormony miłości, adam, techno, disco biscuites MDEA, STIP – eva, dom PIPERIDINE DERRIV. PCP (fencyklidyne)angel dust DITRAN Ketamine - jet, kay, super acid NATURAL AND SYNTHETIC HALUCINOGENS

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