toxicology ii. toxic compounds in cases of intoxication at present m. balíková

TOXICOLOGYTOXICOLOGY

II. Toxic compounds in cases of II. Toxic compounds in cases of

intoxication at presentintoxication at present

M. BalíkováM. Balíková

M. Balíková: Toxic compounds 2

Toxicological cases in Toxicological cases in laboratorylaboratory

a)a) Clinical – examination from reasonsClinical – examination from reasons:: DiagnosticsDiagnostics Therapy controlsTherapy controls PreventionPrevention

b)b) Clinical – forensic developmentClinical – forensic developmentc) Forensicc) Forensic

Autopsies (suicides, homicides…)Autopsies (suicides, homicides…) Traffic accidentsTraffic accidents Occupational injuriesOccupational injuries Violence associated with roberies, rapes, Violence associated with roberies, rapes,

injuries…injuries… OthersOthers


CLINICAL TOXICOLOGY - SYMPTOMSCLINICAL TOXICOLOGY - SYMPTOMS

Importance of anamnestic data, Importance of anamnestic data, symptomssymptoms

Differential diagnosis – Differential diagnosis – Is it Is it poisoning?poisoning?

Preliminary results – therapeutic Preliminary results – therapeutic actionaction

BUTBUTnonspecific symptoms of intoxicationnonspecific symptoms of intoxication

Gastrointestinal problemsGastrointestinal problems

Cramps (strychnin, cyanides, antidepressants, Cramps (strychnin, cyanides, antidepressants, cocaine…cocaine…

Hallucinations (LSD, psilocybine, MDMA, Hallucinations (LSD, psilocybine, MDMA, cannabis….)cannabis….)

Mydriasis / MiosisMydriasis / Miosis


Acute intoxicationsAcute intoxications

Intentional (suicides, homicides, Intentional (suicides, homicides, associated with violence to associated with violence to others)others)

Drug abuseDrug abuseNonintentional (small children, Nonintentional (small children,

accidental ingestion, expositions)accidental ingestion, expositions)


FORENSIC TOXICOLOGYFORENSIC TOXICOLOGY

Careful individual attitude Careful individual attitude

Examination in series not Examination in series not commoncommon

Individual optimalization of Individual optimalization of examinationexamination

Principle in toxicologyPrinciple in toxicology::

results results confirmationconfirmation by another by another independent and specific method independent and specific method – if available– if available

The final toxicological evidence – The final toxicological evidence – defensible scientifically and defensible scientifically and legallylegally


Frequent toxic Frequent toxic compoundscompounds

in acute intoxicationsin acute intoxicationsEthanolEthanolPharmaceuticalsPharmaceuticalsDrugs of abuseDrugs of abuseCarbon oxideCarbon oxideVolatiles Volatiles GlycolsGlycolsMushrooms, herbal toxinsMushrooms, herbal toxins


EthylalcoholEthylalcohol Hydrophilic compound, rapid resorption, in Hydrophilic compound, rapid resorption, in blood blood distributed in favour of plasmadistributed in favour of plasma Pharmacokinetics:Pharmacokinetics:

rate of resorption rate of resorption > > rate of eliminationrate of elimination

elimination with zero order rate elimination with zero order rate (0.12-0.2 g/kg/h)(0.12-0.2 g/kg/h)

Metabolism: 70% alcoholdehydrogenase, 25% Metabolism: 70% alcoholdehydrogenase, 25% MEOS, 5% excreted in parent formMEOS, 5% excreted in parent form

Effects: Narcotic – fat solubility – CNS Effects: Narcotic – fat solubility – CNS depressantdepressant

Endogenous bacterial production (0,001 –Endogenous bacterial production (0,001 –0,002 g/kg)0,002 g/kg) Postmortem production (ethanol and other Postmortem production (ethanol and other alcohols)alcohols)


Ethanol blood level and Ethanol blood level and methodsmethods

Breathanalysers – indirect testBreathanalysers – indirect test Gas chromatography – direct Gas chromatography – direct

alcohol measurement in venous alcohol measurement in venous blood, specific forensic methodblood, specific forensic method

Enzymatic method – clinical cases Enzymatic method – clinical cases O. K., but potentional interferences O. K., but potentional interferences (lactate)(lactate)

Widmark method – nonspecific Widmark method – nonspecific (based on reduction of bichromate)(based on reduction of bichromate)


Ethanol and drivingEthanol and driving Two general types of legislation in the Two general types of legislation in the

worldworld: : 1) Impairment1) Impairment2) Per2) Per sese

In Czech RepIn Czech Rep. – Impairment type. – Impairment typeJurisdiction: Jurisdiction: 0.2 g/kg cut off value0.2 g/kg cut off value 0.5 g/kg – impairment very probable, 0.5 g/kg – impairment very probable,

administrative sanctionsadministrative sanctions 1.0 g/kg – unfit for driving, dangerous, 1.0 g/kg – unfit for driving, dangerous,

penal proceedings at courtpenal proceedings at court


MethanolMethanol

Lethal doses 5 –100 mlLethal doses 5 –100 mlMetabolites: formaldehyde, formic Metabolites: formaldehyde, formic

acidacidVery slow oxidation, max level of Very slow oxidation, max level of

formic acid – 2 days after ingestionformic acid – 2 days after ingestionDangerous delayed effects:Dangerous delayed effects:

at first – narcoticat first – narcoticlater – metabolic acidosis , later – metabolic acidosis ,

retina damage, blindness, deathretina damage, blindness, death


Methanol poisoningMethanol poisoning

Antidotum ethanol Antidotum ethanol Competitive alcohols oxidation Competitive alcohols oxidation

(long term ETOH infusion – blood (long term ETOH infusion – blood level maintenance 1.5 g/kg) level maintenance 1.5 g/kg) protection from methanol protection from methanol oxidationoxidation

HaemodialysisHaemodialysisNaHCO3 infusion – correction of pHNaHCO3 infusion – correction of pH


Glycols - DiolsGlycols - Diols Intoxications – intentional ,accidentalIntoxications – intentional ,accidental Antifreezers – FRIDEXAntifreezers – FRIDEX Solvents, also vehiculum in some Solvents, also vehiculum in some

pharmaceutical products (injections)pharmaceutical products (injections)Ethanediol and dimers, trimers, Ethanediol and dimers, trimers,

polymerspolymersPropanediol 1,2 and 1,3 isomersPropanediol 1,2 and 1,3 isomersButanediol- precursor of GHBButanediol- precursor of GHBGlycol monoalkyl ethers – brake liquids Glycol monoalkyl ethers – brake liquids

(celosolve, carbitols)(celosolve, carbitols)


Ethylene-glycolEthylene-glycolToxic oxidative metabolitesToxic oxidative metabolites::glycolaldehyde, glycolic acid, glyoxylic glycolaldehyde, glycolic acid, glyoxylic

acid, oxalic acidacid, oxalic acidToxic effectsToxic effects:: narcotic (alcohol)narcotic (alcohol) gradual development of acidosisgradual development of acidosis renal failure, anuriarenal failure, anuriaTherapyTherapy as soon as possible – as in as soon as possible – as in

methanol poisoning- ethanol as methanol poisoning- ethanol as antidotum, haemodialysis, natrium antidotum, haemodialysis, natrium bicarbonatebicarbonate


Volatiles – CNS Volatiles – CNS depressantsdepressants

HydrocarbonsHydrocarbonsa) gaseous (propane, butane…)a) gaseous (propane, butane…)b) liquid (toluene, chloroform…)b) liquid (toluene, chloroform…)

FuelsFuelsVarious solventsVarious solventsAenesthetics (ether, halothane…)Aenesthetics (ether, halothane…)Intentional or accidental intoxicationsIntentional or accidental intoxicationsDrug abuse by inhalation, euphoria, Drug abuse by inhalation, euphoria,

hallucinationshallucinationsDangerous overdoses, fatal intoxicationsDangerous overdoses, fatal intoxications


Volatiles abuseVolatiles abuseChronic abuseChronic abuse:: psychical addictionpsychical addiction hepatorenal toxicityhepatorenal toxicity neurotoxicityneurotoxicity cardiotoxicitycardiotoxicity

Overdose:Overdose:

agitation, cramps, coma, cardiac agitation, cramps, coma, cardiac failure, deathfailure, death


Volatiles metabolismVolatiles metabolism Partly expired in parent formPartly expired in parent form Only some produce known metabolites Only some produce known metabolites

into urine (toluene 80-90% hippuric acid, into urine (toluene 80-90% hippuric acid, butane only 1% as 2-butanol)butane only 1% as 2-butanol)

Only some can appear in urine in parent Only some can appear in urine in parent form (aromates)form (aromates)

Some metabolites expired into air Some metabolites expired into air (dichloromethane – 50% CO metabolite)(dichloromethane – 50% CO metabolite)

Useful sample for toxicology – bloodUseful sample for toxicology – blood Method : gas chromatographyMethod : gas chromatography


Carbon oxideCarbon oxideBurning of organic compounds Burning of organic compounds

at insuffient access of airat insuffient access of airStrong affinity to haemoglobin Strong affinity to haemoglobin

- in the same molar ratio as - in the same molar ratio as oxygen but 220 times stronger, oxygen but 220 times stronger, competition for binding – even competition for binding – even low traces in air can be low traces in air can be gradually boundgradually bound

Degree of poisoning correlates Degree of poisoning correlates with time of exposition, with time of exposition, physical activitiesphysical activities


Carbon oxide cont.Carbon oxide cont.

Toxic effects:Toxic effects: reduction of oxygen transport in blood, reduction of oxygen transport in blood,

neurotoxicity, potentional neurotoxicity, potentional development of Parkinsonism in development of Parkinsonism in chronic expositionchronic exposition

Endogenous levels COHb Endogenous levels COHb < 0.5 < 0.5 %%Smokers up to 10 %Smokers up to 10 %Light intoxication 10-20 % COHbLight intoxication 10-20 % COHbSevere intoxication – 30-40% COHbSevere intoxication – 30-40% COHbComa, respiratory failure 40 –50% COHbComa, respiratory failure 40 –50% COHbFatal 50 –70% COHbFatal 50 –70% COHb


CyanidesCyanidesHydrogen cyanide, HCN, boiling point 26° Hydrogen cyanide, HCN, boiling point 26°

C, bitter almond like odor, colorless, very C, bitter almond like odor, colorless, very toxic gas or liquid (hydrocyanic acid)toxic gas or liquid (hydrocyanic acid)

NaCN, KCN unstable in acidic media, NaCN, KCN unstable in acidic media, hydrolysis to toxic HCN, unstable in air – hydrolysis to toxic HCN, unstable in air – carbonatescarbonates

HCN present in exhaust gases, in tobacco HCN present in exhaust gases, in tobacco and wood smoke, in smoke from burning and wood smoke, in smoke from burning nitrogen containing plasticsnitrogen containing plastics

HCN in air300 p.p.b. will kill a human in a HCN in air300 p.p.b. will kill a human in a few minfew min

LD50 in humans very individual (0.005 – 1 LD50 in humans very individual (0.005 – 1 g)g)


Cyanides cont.Cyanides cont.BiotransformationBiotransformation in the liver : thiocyanates in the liver : thiocyanates Toxic mechanismToxic mechanism: Inhibition of : Inhibition of

cytochromoxidase, cells can not accept cytochromoxidase, cells can not accept oxygen, tissues hypoxiaoxygen, tissues hypoxia

Therapy:Therapy: administration of compounds with Co or administration of compounds with Co or

Fe(III)Fe(III) Amylnitrite, natrium nitrite as antidotum –Amylnitrite, natrium nitrite as antidotum –

cyanomethaemoglobine production, enzyme cyanomethaemoglobine production, enzyme block releasingblock releasing

Thiosulphate infusion – metabolites SCNThiosulphate infusion – metabolites SCN Oxygen ventilationOxygen ventilation


MercuryMercury Metallic form – water insolubleMetallic form – water insoluble Salts – water soluble, partial resorption p. Salts – water soluble, partial resorption p.

o.o. Fine particles in air – dangerous entrance Fine particles in air – dangerous entrance

via lungs into blood, subsequent via lungs into blood, subsequent oxidation, cumulation in the brain, kidney oxidation, cumulation in the brain, kidney – potentional neurotoxicity, nefrotoxicity– potentional neurotoxicity, nefrotoxicity

Elimination into urine – very slowElimination into urine – very slow Organic mercury –lipophilic, molecular Organic mercury –lipophilic, molecular

effects, accumulation in CNS, embryotoxiceffects, accumulation in CNS, embryotoxic Mercury in water sediments – bacteria Mercury in water sediments – bacteria

transformation into organic mercury- transformation into organic mercury- contamination of fish meat - dangerouscontamination of fish meat - dangerous


Pesticides-1Pesticides-1

InsecticidesInsecticides HerbicidesHerbicides FungicidesFungicides RhodenticidesRhodenticides

Organic compounds of Organic compounds of various structures, various various structures, various toxic mechanisms, various toxic mechanisms, various symptoms of intoxication, symptoms of intoxication, various effectsvarious effects

Human acute intoxications in EUROPE at present not Human acute intoxications in EUROPE at present not frequentfrequent ORGANOPHOSPHATES (sarin, parathion, ORGANOPHOSPHATES (sarin, parathion, malathion...)malathion...)

CARBAMATES (aldicarb, carbofuran...)CARBAMATES (aldicarb, carbofuran...)

CHLORINATED HYDROCARBONS CHLORINATED HYDROCARBONS (chlophenothane=DDT, (chlophenothane=DDT, lindan, aldrin...)lindan, aldrin...)

BIPYRIDINE DERIVATIVES (paraquat, diquat...)BIPYRIDINE DERIVATIVES (paraquat, diquat...)

ANTICOAGULANS (warfarin, diolan...)ANTICOAGULANS (warfarin, diolan...)


Pesticides - 2Pesticides - 2Organophosphates:Organophosphates:

irreversible potent acetylcholinesterase inhibition, irreversible potent acetylcholinesterase inhibition, respiratory difficulties, salivation, miosis, nausea, respiratory difficulties, salivation, miosis, nausea, paralysis...paralysis...antidotum atropineantidotum atropinep-nitrophenol in urine – marker of exposure to parathionp-nitrophenol in urine – marker of exposure to parathion

Carbamates:Carbamates:derivatives of methylcarbamic acidderivatives of methylcarbamic acidreversible inhibition of acetylcholinesterasereversible inhibition of acetylcholinesteraseantidotum atropineantidotum atropine

Polychlorinated hydrocarbons:Polychlorinated hydrocarbons: free radicals by biotransformationfree radicals by biotransformation

convulsions, nausea; chronic neurotoxicity, hepato and convulsions, nausea; chronic neurotoxicity, hepato and nefrotoxicitynefrotoxicity

Bipyridine derivatives: Bipyridine derivatives: paraquat, diquat (GRAMOXONE, ATRAZINE)paraquat, diquat (GRAMOXONE, ATRAZINE)

contact toxicity, inflamation, bleeding, local necrosis, contact toxicity, inflamation, bleeding, local necrosis, muscle stiffness, blurred vision, pulmonary fibrosismuscle stiffness, blurred vision, pulmonary fibrosis

Anticoagulants:Anticoagulants:warfarin, diolan (KUMATOX, TALON-G)warfarin, diolan (KUMATOX, TALON-G)


PharmaceuticalsPharmaceuticalsAccidental and intentional overdoses, suicides Accidental and intentional overdoses, suicides Combination with alcohol, mixtures of drugsCombination with alcohol, mixtures of drugsDrug abuse – narcotic and psychotropic substancesDrug abuse – narcotic and psychotropic substances

Mostly organic substances with low molecular mass up to 400 Mostly organic substances with low molecular mass up to 400 DaltonsDaltons

ClassificationClassification::1) 1) StructureStructure – important for analytical toxicology, laboratory – important for analytical toxicology, laboratory attitudeattitude2) 2) ATC system (WHO) – Anatomical-Therapeutical-Chemical ATC system (WHO) – Anatomical-Therapeutical-Chemical ::

A – Gastrointestinal tract (spasmolytics, anticholinergics….)B – Blood systemC – Cardiovascular system (cardiotonica, , antihypertensiva……)D, G, H – Dermatologica, urologica, gynekologica, hormonesJ, L – Antibacterials, antivirotics, antimycotica, cytostaticaM – Muscle-sceletal system (antirevmatica, antiphlogistica,

myorelaxancia)N – Neurological system

(anestetica,analgesica,antiepileptica,psycholeptica)P – AntiparasiticaR – Respiratory system (antiasthmatica, antitusica,

antihistaminica…..)S, V – Varia

A C M N R – significant participation in drug overdose cases


BarbituratesBarbiturates

BarbiturátyBarbiturátyPsychotropic substances – CNS suppressionThe first derivative at the market – barbitalCommon structure of various derivatives - barbiruric acidAcidic character – after p. o. resorption mainly in small intestine

Variable effect duration, therapeutic indicationVariable effect duration, therapeutic indication:

Short time effect – pentobarbital halflife 20-30 h)Long time effect – phenobarbital halflife 2-6 days)

Thiobarbital (thiopental) – i. v. anestheticumThiobarbital, pentobarbital – intracranial pressure reduction Phenobarbital – sedative, antiepilepticsVarious barbiturates in pharmaceutical composites, analgesics, antiphlogistics (Spasmoveralgin, Alnagon,Bellaspon, Dinyl, Eunalgit……)

At present – less prescription due to significant mortality at overdose, replacement by more safe substances


BenzodiazepinesBenzodiazepinesPsychotropic substances with CNS sedationPsychotropic substances with CNS sedation

Frequent therapeutical indication Frequent abuse (sometimes with alcohol or illegal drugs) Potential criminal misuse

More than 30 various structures with variable therapeutic More than 30 various structures with variable therapeutic indication:indication:

sedatives (diazepam, alprazolam)sedatives (diazepam, alprazolam)hypnotics (nitrazepam, flunitrazepam), hypnotics (nitrazepam, flunitrazepam), antiepileptics (clonazepam)antiepileptics (clonazepam)

Shortly active – midazolam – introduction into anesthesia (halflife Shortly active – midazolam – introduction into anesthesia (halflife 1-4 h)1-4 h)

Long term active – diazepam – sedative (halflife 21-37 h)Long term active – diazepam – sedative (halflife 21-37 h)At overdose – accummulation in tissues, prolonged elimination At overdose – accummulation in tissues, prolonged elimination Extensive biotransformation – metabolites of phase I and IIExtensive biotransformation – metabolites of phase I and IIIdentification of toxic substance – important for differential Identification of toxic substance – important for differential

diagnosisdiagnosisPlasma level monitoring no correlation to effectPlasma level monitoring no correlation to effectAddictive substances at chronic use, development of toleranceAddictive substances at chronic use, development of toleranceLow mortality when related to barbituratesLow mortality when related to barbituratesAdditive sedation at combination with alcohol and sedative drugsAdditive sedation at combination with alcohol and sedative drugsComa state - Coma state - antidote flumazenil (ANEXAT)antidote flumazenil (ANEXAT), short halflife 40-60 , short halflife 40-60

minminGeneral danger at coma – vomit aspirationGeneral danger at coma – vomit aspiration


AntidepressantsAntidepressantsTCA – tricyclic antidepressantsTCA – tricyclic antidepressants(amitriptyline, imipramine, trimipramine, clomipramine, dibenzepine…)Tetracyclic antidepressants Tetracyclic antidepressants – maprotiline, mianserineFrequent drugs at suicidal attemptsPacients with psychiatric treatment, endogenous depressions Lipophilic substances with protein bounds, large Vd At overdose – drug accumulation – prolonged effectNormetabolites more potent related to parent drug form

Therapeutic effect: CNS sedation, inhibition of neurotransmiters resorption Overdose:Overdose: cardiotoxicity, neurotoxicity

Symptoms of overdose:Cardivascular disturbances (hypotension)Coma, cramps, hyperthermiaRespiratory collaps, death

Therapy of overdoseSymptomatic proceduresHemoelimination, hemoperfusion

New types with lower toxicityNew types with lower toxicitySelective serotonin reuptake inhibitors fluoxetine, citalopram, sertraline, venlafaxine, paroxetine……….


PhenothiazinesPhenothiazinesAntihistaminics – Antihistaminics – promethazine, dithiadeneNeuroleptics – Neuroleptics – chlorpromazine, levopromazine, chlorprothixene, thioridazine…………

Treatment of psychosesFrequent substances in overdose cases, suicidal attemptsLipophilic substances bounded to proteinsExtensive biotransformationAt overdose – accumulation in tissues, prolonged effect Antipsychotic effect, CNS sedation, affinity to neurotransmittersSymptoms of overdose:Delirium and comaTachycardia, bradycardia, arythmia, hypotoniaBreath center suppressionLife endargement: circulation and respiratory failureTherapy: symptomatic, sometimes physostigmine recommended


MAO InhibitorsMAO InhibitorsMAO inhibitors – the first ones among antidepressivesStructurally hydrazines, hydrazides, amides, amines

MoclobemideMoclobemide (AURORIX)Extenzive oxidation, hydrolysisEffect mechanism:Interaction with catabolism of dopamine, noradrenaline, adrenaline, serotonine – with impact of neurotransmitters accumulation - serotonine syndromserotonine syndrom – endargement of hyperpyrexia and shockPotential interaction with other MAO inhibitors – amphetamines,TCASymptoms of overdose:similar to overdose by amphetamines, cocaine, caffeine ...

agitation, confusion, hallucination, convulsions, coma, cardiovascular disturbances – tachycardia, hypertension,

renal failure

Phentermin (ADIPEX)Treatment of obesiteMethamphetamine isomerAddictive potential


Opiates and opioidesOpiates and opioidesOpiatesOpiates – alkaloides of natural origine and their structural synthetic analogs: morphine, codeine, dihydrocodeine, hydrocodone, oxycodone, pholcodine, ethylmorphine) – phenanthrene structure

OpioidesOpioides – – synthetic origine, another structure but similar effect, interaction with opioide CNS receptors: methadone, buprenorphine, tramadol, pethidine, fentanyl....NarcoticsNarcotics – in therapy part of analgetics, antitussives Abuse Abuse – illegal heroin – risk of fatal overdoseChronic abuse: somatic addiction, tolerance

Effects:Effects: Euphoria and sedation of CNS, miosis, suppressed intestine motility, constipation, respiration center suppression, coma, hypothermia, hypotonia, bradycardia, respiration and circulation collaps, deathSymptoms of fatal overdose: lung and brain edemaTherapyTherapy:Respiratory support, antidote naloxone, short halftime, repeated administration Naloxone – antagonist of opiate receptors – careful dosing – risk of abstinence syndrom


Acetaminophen - ParacetamolAcetaminophen - ParacetamolPart of pharmaceutical products (COLDREX, KORYLAN, PANADOL…)Overdose– hepatotoxicityAssessment of hepatotoxic risk:

temporal profile of serum level after resorption (4 h after dose)

hepatoprotective antidotum – substance with SH groups(N-acetylcysteine)


SalicylatesSalicylatesSalicineSalicine – – glycoside in willow-tree rind laic treatment of rheumatismAspirine, AcylpyrineAspirine, Acylpyrine – acetylsalicylic acidacetylsalicylic acidAntipyretics, analgetics, antiphlogistics, anticoagulantsMetabolism: hydrolysis, conjugation)Effect mechanism:Irreversibile inactivation of cyclooxygenase, local and systemic effectsToxic effects:Mucosal irritation, bleeding in GI, vomittingStimulation of respiratory center, disturbances in electrolytic and acidobasic balance, metabolic acidosis Rey syndrom in children with virosis: risk of encephalitis and hepatodamage, risk at susceptive asthmatics – abstinence from salicylates application


TheophyllineTheophylline

Methylxantines: Methylxantines: Theophylline, caffeine – in coffee, teaTheobromine - cacao

Pharmaceutical products:Pharmaceutical products:Theophylline Theophylline (1,3-dimethylxanthine)(1,3-dimethylxanthine) – antiasthmaticum, bronchodilatator AminophyllineAminophylline – theophylline-ethylenediamineTheophylline- narrow terapeutic window

potential of overdoseSignificant plasma level monitoring (TDM)

Adverse effects, overdose, intoxication:CNS stimulationcardiovascular disturbances, arythmia (even fatal), convulsions, GI problems, vomiting , nausea


CardiotonicsCardiotonicsGlycosides of digitalis Glycosides of digitalis DigoxineDigoxine (C (C4141HH6464OO1313), ), DigitoxineDigitoxine (C(C4141HH6464OO1414))

Cardiotonics – lipophilic substances, localized in myocardium, bonded to cardiac receptors, slow excretion. Digoxine excreted rather faster when related to digitoxine In cases of overdose – digoxine level in myocardium much higher than in plasma (100x). No correlation between effect to plasma levelTDM: control of therapeutic plasma level

Laboratory methods with respect to higher Mr (765, 781) – ICH, HPLC, not GCToxicita:Vomiting, nausea, confusion, visual disturbancesIon balance disturbance, hypokalemiaCardiac arythmia – life endargement, cardiac failureDigoxine fatal intoxication – death within 24 hoursDigitoxine fatal intoxication - dysrythmia prolonged to 5 days, prolonged toxic effects related to digoxine


Pharmaceticals with cardiovascular effectsPharmaceticals with cardiovascular effectsDrugs affecting heart function directlyDrugs affecting heart function directly Heart glycosidesHeart glycosidesAntidysrythmics – Antidysrythmics – amiodarone, propafenol, verapamil, chinidine….amiodarone, propafenol, verapamil, chinidine….

Drugs affecting circulation systemDrugs affecting circulation systemAntihypertensivaAntihypertensivaCardioselective beta-blocking agents – Cardioselective beta-blocking agents – atenolol, metoprolol, labetalol, pindolol, sotalol, propafenone….atenolol, metoprolol, labetalol, pindolol, sotalol, propafenone….Diuretics – Diuretics – enhanced salts and water excretion– enhanced salts and water excretion– chlorothiazide, furosemide….chlorothiazide, furosemide….

Therapeutic indicationTherapeutic indication:: heart ischemia, arythmia,heart ischemia, arythmia, heart failure, cardiomyopatia,heart failure, cardiomyopatia, hypertensionhypertensionToxic effectsToxic effects:: dizziness, nausea, vasoconstriction, bradycardiadizziness, nausea, vasoconstriction, bradycardia bronchoconstriction, coronar spasms, hypotension, bronchoconstriction, coronar spasms, hypotension, cardiac and circulatory failure – life endargement, deathcardiac and circulatory failure – life endargement, death


Abuse of addictive substancesAbuse of addictive substancesPharmaceuticals, illegal drugsPharmaceuticals, illegal drugs

CNS sedative substances, narcotics CNS sedative substances, narcotics opiates/opioids, benzodiazepinesopiates/opioids, benzodiazepines........

CNS stimulating substances:CNS stimulating substances:

amphetamines and derivatives, ephedrine, cocaine....amphetamines and derivatives, ephedrine, cocaine.... Substances affecting perception, psychedelics, hallucinogens:Substances affecting perception, psychedelics, hallucinogens:

PEA derivatives (MDMA, PMA, DOB, mescaline.....),PEA derivatives (MDMA, PMA, DOB, mescaline.....),tryptamine derivatives (harmine, dimethyltryptamine....) tryptamine derivatives (harmine, dimethyltryptamine....) ketamine, 9-THC, LSD, psilocybine, muscarine, atropine, ketamine, 9-THC, LSD, psilocybine, muscarine, atropine, scopolamine....... scopolamine.......

Tribe rituals - shaman leadership– application of natural Tribe rituals - shaman leadership– application of natural productsproducts

New trends – new synthetic drugs (NSD), dancing drugs New trends – new synthetic drugs (NSD), dancing drugs stimulating and psychedelic effects stimulating and psychedelic effects

PEA, tryptamine, piperazine structure analogues, PEA, tryptamine, piperazine structure analogues, synthetic cannabinoidssynthetic cannabinoids

NSD available via internet, frequent origine – Asia, ChinaNSD available via internet, frequent origine – Asia, China

Health risk of application of an illegal product – Health risk of application of an illegal product – no guarancy of its composition or content no guarancy of its composition or content


Correlation of anamnesis and toxicology findingsCorrelation of anamnesis and toxicology findingsPacient Anamnestic

data Laboratory findings

M- 26 years

Deep coma, serious hypotensia, cardiac dysrythmia, anuria.

Assumpted: drug addict or epileptic

G: prothiaden (dothiepine) S: prothiaden 10590 ng/ml !!! S: northiaden 455 ng/ml (therapy 50- 150 ng/ml)

F- 20 years

Somnolent

Assumpted: Alcohol, I buprofen

B: ethanol 2,7 g/kg S: alprazolam 59 mg/ml (therapy 5- 50 ng/ml) G: ibuprofen+codeine+fluoxetine U: ibuprofen+metab.+ codeine+ fluoxetine+ salicylates+ caff eine

M- 21 years

Coma, convulsions U: methamphetamine+amphetamine+ephedrine+ bromazepam metabolites

F- 21 years

Coma, circulation failure, death - suicide Sectral 20 tbl.x 400mg = 8 g

G: acebutolol U: acebutolol + metabolites

M- 53 years

2 incidental gulps (cca 60 ml) of FRI DEX - 45 min before visiting a doctor and sampling for toxicology

S: EG 337 ng/ml U: EG 9640 ng/ml

G: gastric content; B: blood; S: serum; U: urine

toxicology ii. toxic compounds in cases of intoxication at present m. balíková

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