It’s about

• Epidemiology, ways of poisoning• Aspecific symptoms, aspecific therapy• Toxidromes• Specific therapy• Some more frequent poisonings:

– alcohol– street drugs, opiates– paracetamol– tricyclic antidepressants– benzodiazepins– ethylen-glycol and methanol– carbon monoxide

Poisons, decoctions and brews

Paracelsus: „Alle Ding' sind Gift, und nichts ohn' Gift; allein die Dosis macht, daß ein Ding kein

Gift ist.”

in other words:

Size do matter!

Epidemiology: “the numbers” Nearly 90% of medicinal exposures occur at home

During pre-adolescence: slight male predominance

This reverses in ages 13-19 with females accounting for 55 %

Children, especially under age 6, are more likely to have unintentional poisonings

About half of all poisonings among teens are classified as suicide

Approximately 1/3 of ingestions of toxic medications occur with meds intended for someone else

Contamination and poisoning

acute

chronic

unintentional intentional

LD50, LD95

Volume of distribution (Vd)

The nominal volume where the agent can be distributed

If Vd>5 L/kg low plasma cc. tissue binding ↑

Protein binding

If >90% low free fraction

Clearance (Cl)

The amount of plasma that can get rid of the agent during a given periodof time

e.g. renal clearance =

Half life

T(½) = 0.693 x Vd / Cl

urine conc. x urine volume.serum conc.

Some necessary basic pharmacology

Dose-response curve

NOAEL

LOAEL

NOAEL: No Observed Adverse Effect Level - safeLOAEL:Lowest Observed Adverse Effect Level – notrecommended

cum

ula

tive

resp

on

se(%

)

Dose (mg/kg)

Examples (LD50)

*

What happens inreality?

Primaryinsult

• recognition, unknown circumstances, associated injuries, mass intoxication

Secondarydamage

• circulatoiry, respiratory arrest, organdamage (direct and indirect), trauma during transport

Definitivecare

• aspecific therapy

• specific therapy

Scheme of care

SYMPTOMATIC, ASPECIFIC TREATMENT

DECONTAMINATION

ELIMINATION

ANTIDOTE

Aspecific symptoms

• (D)ABCDE

• Applies to ANY episode of poisoning

• WHAT

• HOW MUCH (Ideally mg/kg)

• WHEN

• WHAT ELSE (Including alcohol)

• WHY

• Use paramedics, friends, relatives, anyone!!

General Management -1

• A (Airway)

• B (Breathing)

• C (Circulation)

• D (Disability-AVPU/ Glasgow Coma Scale)

• DEFG ( Don’t Ever Forget the Glucose)

• G (Get a set of basic observations)

General Management -2

• Use all your senses, search for the clues• LOOK

– Track Marks– Pupil Size

• Hear– Type Breathing (Kussmaul, Hyperventilation)

• FEEL– Temperature, Sweating

• SMELL– Alcohol– Fruity– I would NOT taste

Airways in danger!

Aspecific therapy

• Ventilation

– As long as it’s required

– special cases:

• CO poisoning

• aspiration

• inhalation of direct irritants

Aspecific therapy

• Maintain circulation

– Ensure DO2, increase CaO2

– EGDT

– CPR

Toxidromes

ToxidromesSigns and symptoms

HR BP RR pupil size GIT sweating temp

ANTICHOLINERGIC ↑ ↑ ↓ ↓

CHOLINERGICSLUDGE (Salivation, Lacrimation, Urinary incontinence, Diarrhea/Diaphoresis, GI upset/hyperactive bowel, Emesis)

↓ ↑ ↑

OPIOID ↓ ↓ ↓ ↓ ↓ ↓ ↓

SYMPAThO-MIMETIC

↑ ↑ ↑ ↑ ↑ ↑ ↑

SEDATO-HIPNOTIC

↓ ↓ ↓ ↓ ↓ ↓

Toxidromes, cont’dToxidrome Most frequent poison

ANTICHOLINERGIC atropin, scopolamin

CHOLINERGIC carbamates, mushrooms, organophosphates

OPIOID opiates

Toxidrome Most frequent poison

SYMPATHOMIMETIC salbutamol, amphetamins, cocain, ephedrine (Ma Huang), metamphetamine, phenylpropanolamin(PPA), pseudoephedrin.

SEDATO-HYPNOTIC anticonvulsants, barbiturates (?), BDs, GHB, metaqualon, ethanol

Symptomorientated

differentiation

Main groups of symptoms

• Mental state

• CNS symptomes

• Muscles

• Circulation

• Respiration

• Kidney

• Liver

• Heat balance

• Carbohydratemetabolism

• Ion balance

MENTAL STATE

CONFUSION PREDOMINANT CONFUSIONDELIRIUM

PREDOMINANT AGITATIONPSYCHOSIS

AMANTADINANTICHOLINERG/HYCIMETIDINCOLITHIUM

AMPHETAMINCOCAINCOFFEINPCPMARIJUANATHEOPHYLLIN

MENTAL STATE

COMA CNS DEPRESSION

CELLULAR HYPOXIA

SYMPATHOLYTICS

OTHERS

BARBITURATEALCOHOLTCADSEDATO-HYPNOTICS

COCIANIDE

OPIATEMETHYLDOPA

BROMINEDIQUATLITHIUMSALICYLATE

CNS

SEIZURESADRENERGIC

ANTIDEPRESSANT

OTHER

AMPHETAMINCOFFEINTHEOPHYLLIN

TCADHALOPERIDOLPHENOTHIAZIN

ANTIHYSTAMINCARBAMAZEPINCHOLINERGICSORGANIC SOLVENTS

CNS

MUSCLE TONEDYSTONIA

RIGIDITY

DYSKYNESIS

HALOPERIDOLMETOCLOPRAMIDPHENOTHIAZIN

LITHIUMMAO-INHIBITORPCPNMS / MHSPIDER – TOXIN (BLACK W.)

AMPHETAMINCOCAINTCADPCP

CIRCULATION

ARRHYTHMIACONDUCTION DISTURBANCES

LONG QT

TORSADE DE POINTES

VT/VF

BETA-BLOCKERTCADDIGITALISQUINIDINE

ARSENICCITRATETCADORGANOPHOSPHAT

AMPHETAMINCOCAINDIGITALISFLUORIDETHEOPHYLLIN

RESPIRATION

ACUTE RESP. FAILURE

MUSCULAR

CENTRAL

PULMONARY

HYPOXIAINHALATIONCARDIOGENICCELLULARPULMONARY

BOTULINUMORGANOPHOSPHATCARBAMAT

BARBITURATOPIATEALCOHOL

ORGANOPHOSPHATEBETA-BLOCKERCHLORINE

METHANETCADCYANIDEOPIATE

LIVER

ACUTEHEPATICFAILURE

ACETAMINOPHENAMATOXINAROMATIC COMPOUNDSHALOGENIZED CARBOHYDRONSCOPPERETHANOLHALOTHANEIRONPHOSPHORUSVALPROATE

MUSCLE

RHABDOMYO-LYSIS

CELLULAR

MUSCULAR

OTHER

AMATOXINCOCOLCHICINGLYCOL

AMPHETAMINECOCAINTCADLITHIUMMAO-INHIBITORPCPSTRYCHNINETETANUS

BARBITURATEETHANOLSEDATO-HYPNOTICS

HEAT BALANCE

HYPERTHERMIA

MUSCULAR

METABOLIC

REGULATION

OTHER

AMPHETAMINECOCAINTCADLITHIUM LSDPCP

DINITROPHENOLSALICYLATE

ANTICHOLINERGICSANTIHYSTAMINTCADPHENOTHIAZIN

METALLIC VAPOURMNS / SS / MH

CARBOHYDRATE BALANCE

BLLOD SUGARHYPO

HYPER

BETA-BLOCKERSETHANOLINSULINOADSALICYL

BETA-ADRENERGICSCOFFEINCORTICOSTEROIDSDIAZOXIDEEPINEPHRINEGLUCAGONTHEOPHYLLINTHIAZIDE

ION BALANCE

POTASSIUM

HYPER

HYPO

ADRENERGIC AGENTSACEIDIGITALISFLUORIDELITHIUM

BARIUMCOFFEINDIURETICUSTHEOPHYLLINEPINEPHRINE

Specifictherapy

Specific care

• Starts with the aspecific therapy

• Sometimes they run parallel with frequentchecks

• „Semi-specific” therapy along with the toxi ABC– Oxygen!

– DEFG ( Don’t Ever Forget the Glucose)

– Thiamine (vitamin B1) 100 mg IV/IM

– Naloxone (Narcan) ADULT 0.2 mg IV/IM/ETT, CHILD: 0.01mg/kg IV/IO/ETT

Further steps

SYMPTOMATIC TREATMENT

DECONTAMINATION

ELIMINATION

ANTIDOTE

PLASMA COMPARTMENT

PROTEIN BOUNDFREE

LIVER

METABOLISM

KIDNEY

EXCRETION(MATERIAL / METABOL)

PHARMAC.ACTIVE

RECEPTOR

BOUNDFREE

TISSUE STOREBIO.INACTIVE

TISSUE

BOUNDFREEFREE FREE

FREE METAB/FREE

FREE

INGESTED AMOUNT

PATIENT COMPLIANCE

ABSORPTION

BIO. AVAILABILITY(NOT ABSORBED; FIRST PASS)

INDIVIDUALFACTORS

PLASMA COMPARTMENT

PROTEIN BOUNDFREE

LIVER

METABOLISM

KIDNEY

EXCRETION(MATERIAL / METABOL)

PHARMAC.ACTIVE

RECEPTOR

BOUNDFREE

TISSUE STOREBIO.INACTIVE

TISSUE

BOUNDFREEFREE FREE

FREE METAB/FREE

FREE

INGESTED AMOUNT

PATIENT COMPLIANCE

ABSORPTION

BIO. AVAILABILITY(NOT ABSORBED; FIRST PASS)

DECONTAMINATION

DecontaminationExternal

– clothes

– skin

– mucousmembranes

– oral cavity

Internal- induced emesis: NO!

- gastric lavage

Within 60 minutes, except drugs delaying gastricemptying: ANTICHOLINERGICS, TCA, BARBITURATES, OPIATES

- gut washoutPOLYETHYLENE GLYCOL 1500-2000 ml/h

- activated charcoal(1g = 1000-2000 m2 surface) 1 g / ttkg

Further steps

SYMPTOMATIC TREATMENT

DECONTAMINATION

ELIMINATION

ANTIDOTE

ELIMINATION – KIDNEYS

FORCED DIURESISNEUTRAL, ALKALINE, ACIDOTIC

Indication:

If the agent is filtrated by the kidneys(target: GFR ↑)

small molecular weight– small volume of distribution– low prot. binding

electrically charged molecules– ION TRAPPING

Method:

Monitor fluid balance, ion- and pH balance

Close observation

In: 300-500 mL/h Target urine output: 300 mL/h

(Furosemid, Etacrinic acid, Mannitol, Theophyllin /GFR↑/)

Alkalinization/acidification PRN

ELIMINATION - GIT

If the poison is excreted by bile:

20 g of activated charcoal/ 4 h

Observation!! (ileus, bleeding, check INR !)

ELIMINATION – EXTRACORPOREAL TECHNIQUES:

PERFUSION (HP),

ACT. CHARCOAL

ACETAMINOPHEN,AMMANITA TOX., AMOBARBITAL, ATENOLOL, CCl4, CHLORAMPHENICOL, CHOLHICIN, COFFEIN, DIGITOXIN, DYSOPYRAMID, DIPHEN.HYDANTOIN, GLUTETHIMID,INH,MEPBROMAT,NADOLOL, ORGANOPHOSPHAT,PARAQUAT, PHENYLBUTHAZON, PHENOBARBITAL, PHENYTOIN, QUININ, SALICYLAT , SOTALOL, THEOPHYLLIN, THYROXIN, CARBAMAZEPIN

If the agent binds to thematerial of the capsule(charcoal, resin)

HEMODIALYSIS

• SMALL MOLECULAR WEIGHT(< 500 D)

» WATER SOLUBLE

» SMALL Vd; LOW PROT. BIND.

» LOW CLEARANCE

ARSENIC, BORIC ACID, BROMINE, CHLORAT, DISOPYRAMID, ETHYLENGLYCOL, FLECAINID, INH, ISOPROPIL ALKOHOL, MAGNESIUM, OXALATE, SALICYLIC ACID, SOTALOL,

VALPROAT

APHERESIS / PLASMAPHERESIS

If the agent’s protein binding > 90 % AMMANITA TOXIN, SNAKE POISONS, METHAEMOGLOBIN, NEUROLEPTICS, NIFEDIPIN, PARAQUAT, PHENYTOIN, SEDATO-HYPNOTICS, THYROXIN, TCA,VERAPAMIL

Molecular Adsorbents Recirculation System (MARS)

• two separate dialysis circuits– first circuit consists of human serum albumin, is in

contact with the patient's blood through a semipermeable membrane and has two special filters to clean the albumin after it has absorbed toxins from the patient's blood

– second circuit consists of a hemodialysis machine -used to clean the albumin in the first circuit before it is recirculated to the semipermeable membrane in contact with the patient's blood

„ANTI-TOXINS”

SYMPTOMATIC TREATMENT

DECONTAMINATION

ELIMINATION

ANTIDOTE

ANTIDOTES

ACETAMINOPHEN NAC

ACEI ANGITENSINAMID

ANTICHOLINERG PHYSOSTIGMIN

NEOSTIGMIN

ARSEN BAL-MERCAPTOL

BENZODIAZEPIN FLUMANEZIL

ß-BLOCKER GLUCAGON

ISOPROTERENOL

BOTULINUS TOXIN ANTITOXIN

CARBAMATE ATROPIN

CA-CSATORNA BLOCK CALCIUM

ANTIDOTES

COUMARINS VITAMIN K

DIGITALIS Fab

CYANIDE 4-DMA

DICOBALT EDTA

HEPARIN PROTAMINE-SULPHATE

FORMALDEHYDE FOLATE

ETHYLEN GLYCOL ETHYLALCOHOL

FOMEPIZOL

MERCURY BAL-DIMERCAPTOL

HYDROGEN-FLUORIDE CALCIUM

INSULIN GLUCAGON

GLUCOSE

ANTIDOTES

OPIATES NALOXONE

METHGB METHYLENE BLUE

METHYL ALCOHOL ETHANOL

FOLIC ACID

PLUMB BAL-MERCAPTOL

ORGANOPHOSPHATE PAM

PARAQUAT FULLER EARTH

THEOPHYLLIN ADENOSIN

OXALATE CALCIUM

IRON DEFEROXAMIN

…

Special

poisonings

Alcohol

Level of alcohol (g/l) Level of alcohol (‰) Degree of drunkness

0,6-1,8 0,75-2,25 mild

1,8-3,0 2,25-3,75 medium

3,0-4,2 3,75-5,25 severe

>4,2 >5,25 life threatening

Therapy: supportive, frequent BM check, fluid administrationwith mechanical ventilation and circulatory support if requiredDisposition: depends merely on the initial state and theresponse to therapy but mainly home

Ethylene glycol and methanol

Ethylene glycol and methanol

• Treatment:– blocking alcohol dehydrogenase (with ethanol or fomepizol)

– PPI

– Bicarbonate (methanol)

– Hemodialysis, if• arterial pH < 7.10,

• pH decreases despite bicarb.infusion>

• pH < 7.3 despite bicarb.

• increase in serum creatinine

• if the initial plasma ethylenglycol/methanol level≥ 500 mg/l.

• Disposition: ITU

Ethylene glycol and methanol

fomepizol

Mg, B6

folate

thiamine

NaHCO3

Benzodiazepins

• The most frequent drug of choice in suicide• Symptoms: dizziness, confusion, somnolence, blurred

vision, loss of contact, anxiety, agitation• Treatment:

– Decontaminatiom: • gastric lavage within 60 seconds

– Aspec. and spec. therapy• single dose of 1 g/kg activated charcoal (aspiration!)• mechanival ventilation if required• flumazenil (0,3 + 0,1 mg), BUT REMEMBER: pts with BD abuse it might

trigger fits, in TCA overdose it may cause fits and arrhythmias!

– Differential diagnosis: other sedatives, controlled drugs

• Disposition: ED, ITU, psychiatry

Tricyclic antidepressants

Main pharmacodynamic effects:– Alfa1-blockade– Na-channel blockade– Inhibition of reuptake of biogen

amines (NADR, SER)– Muscarinic receptor blockade

(anticholinergic)– Histamin receptor blockade

(antihistamin)– Inhibition of K-efflux– Indirect GABAA -blockade

• Effects on peripheral nervoussystem– Anticholinergic effects

• tachycardia,hyperthermia,midriasis, anhydrosis, skin flush, ileus, urinaryretention

– Alfa1-blockade• reflex tachycardia,myosis

• CNS effects– Excitative

• agitation, delirium, myoclonus, hyperreflexia, generalized fits, hyperthermia

– Inhibitory• sedation, coma

Tricyclic antidepressantsPROBLEM/SYMPTOM TREATMENT

Hypertension Usually transient, no need to treat

Hypotension Crystalloid, NaHCO3, if QRS>100 ms, NADR, DA

Tachycardia Usually no need to treat

Monomorphic VT NaHCO3, syncDCCV, overdive pacing

Polymorphic VT (torsades) MgSO4

Bradydysrhythmia (late, usually notfrequent )

ACLS bradycardia protocol

QRS and QT prolongation If symptomatic: NaHCO3

Coma ETT, ventilatory support

Seizures diazepam, midazolam or propofol inf.

Hyperthermia GA, cooling

Disposition: depends on the initial state and the response to treatment

Paracetamol• Abssorption:

– Rapidly from GIT– Peak conc. between

60-120 min. • Half life:

– 0.9 -3.25 hours• Metabolism:

– Indepenedent of age– Not influenced by renal

disease– May be up to 17 hrs in liver

disease!

• Factors influencingtoxicity

– total quantity ingested– time from ingestion to

treatment– age of the patient– alcohol– enzyme inducing

medications

Paracetamol

Potential liver damage

– Adults: > 150 mg/kg in acute dose

– Adults: > 7.5 Grams in 24 hours (chronic)

– Children (<10 yrs): > 200 mg/k

4 Stages of Acetaminophen Poisoning

• Phase I (30 minutes to 4 hours)

– Within a few hours after ingestion, patients experience anorexia, nausea, pallor, vomiting, and diaphoresis. Malaise may be present.

Patient may appear normal

• Phase II (24 to 48 hours)

– Symptoms less severe. May seem like recovery. Right upper quadrant pain may be present due to hepatic damage.

– Liver enzymes become abnormal. Prothrombin time may be prolonged. Renal function may begin to deteriorate.

• Phase III (3 to 5 days)

– Characterized by symptoms of hepatic necrosis. Coagulation defects, jaundice, and renal failure have been noted. Hepatic encephalopathy has been noted. Centrilobular necrosis. Nausea and vomiting . Death due to hepatic failure.

• Phase IV (4 days to 2 weeks)

–Complete resolution or death

Rumack-Matthew nomogram

Based on this:N-acetil-cisztein (NAC)Tretment with NAC should be started ASAP withan initial dose of 150 mg/ttkg, followed by 50 mg/ttkg maintenace dosebased on the nomogramIf levesl can not be measured: 72 hDisposition: ITU

Treatment

– activated charcoal

– cathartics, bowel washout

– Haemodialysis

• Limited results due to rapid progression

– Haemoperfusion

• Ineffective

– Peritoneal dialyisis

• Ineffective

Amphetamin, metamphetamin, mefedron

• Symptoms:– CNS: headache, agitation, anxiety– dsykinesis– stroke-like symptoms– chest pain– palpitation– dry mouth– nausea/vomiting– diarrhoea– urinary retention– sweating– mydriasis

Treatment:• Gastric lavage: general indications• Bowel washout (body packers)• Supportive treatment:

– BZDs, circulatory support– beta-blockers are contrainidcated –

unopposed alpha effects!!– cooling– haloperidol?

Disposition: depends on symptomsand response to treatment

Opiates

• Versatile „usage”

• Quite severe dependency

• Conjugates in the liver–prolonged effects in liverdisease

• Quite often taken withsomething else

• Tipycal signs and symptoms:

– „skin popping, mainlining”

– nasal mucosa damage,

– poor general condition

– myosis (but mydrisasis insymp. tone!)

– RR: 4-6/min

– mild hypotension (if severelook for other causes!)

Opiates

• Treatment:

– supportive

– airway safety! mechanical ventilation if required–respiratory depression is the main cause of death

– naloxone: • 0,1-0,4 mg /1-2 min.

• rapid and specific antagonist

• Disposition: depends on the very complexbackground (dependency, amount, etc)

Carbon monoxide

• Might be a diagnosticchallenge

• Aspecific symptoms

• Quick poison

• Results from incompletecombustion

• Other sources

• Binds 230-270 timesbetter to Hb than oxygen

• 100 ppm causessymptoms

• Direct toxic effect on CIP-C and CIP 450

• Half-lives:– in room air: 3-4 h

– in 100 % oxygen: 30-90’

– in 100 % oxigénben AND at2,5 atm pressure:15-23’

Carbon monoxide• Symptoms

– fatigue– weakness– palpitation– chest pain– nausea– vomiting– visual disturbances– incontinence– tachypnoe

• Diagnosis:– think of the possibility!– co-oxymetry: 5-10 % CoHb

is significant (smokers!)

• Treatment:– immediate rescue– fresh air– O2!!– hiperbaric oxygen

chamber: 100% oxygen at2.4-3 atm pressure for 90-120 minutes

Disposition: ITU/ED

And at last:

Situation.

Background.

Assessment.

Recommendation.

S

B

A

R