Pharmacotherapy of drug Pharmacotherapy of drug poisoning and emergency poisoning and emergency

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Pharmacotherapy of drug Pharmacotherapy of drug poisoning and emergency poisoning and emergency

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UKRAINEUKRAINE

• In In 43 43 of of 190 190 most controlled large cities of most controlled large cities of our country concentration of substances our country concentration of substances dangerous for health isdangerous for health is overcomes critical overcomes critical allowed concentrations allowed concentrations 520 520 timestimes

• 34 % 34 % of population is under the negative of population is under the negative influence of atmospheric pollution influence of atmospheric pollution

Causes of acute poisoning

community-acquired Causes of acute poisoning

community-acquired

• Drugs• Chemical substances, also of plant origin • Alcohol and it’s surrogates• Pesticides

8 % of all poisonings - children(6 months of age)

Side effects Side effects ((SESE)) of of drugsdrugs

• Takes 5th place among causes of mortality on the Earth after heart-vascular diseases, malignant tumors, lungs diseases, traumas

• Among stationary patients frequency of SE after introduction of drugs makes 2 - 40 %

SE of drugsSE of drugs

• 150 000 – 200 000 people in U.S.A. 150 000 – 200 000 people in U.S.A. die from side effects of drugs die from side effects of drugs annuallyannually

• 76,6 76,6 billion $ are spared in U.S.A. billion $ are spared in U.S.A. annually to treat complications annually to treat complications attached to drugs usageattached to drugs usage

Medical mistakes in clinics

• Doctors: - overdosing - administration of drugs to patients with

allergy - mixing up names of the drugs• Medical nurses: - introduction of other drug by a mistake - violation of drug introduction regime - mistake in medical form - mixing up names of the drugs

Factors that influence on toxicity of the poison

• Physical and chemical properties• Dose• Concentration• Speed of introduction• Way of penetration into organism• Age• Condition of the organism• Accumulation of the poison• Tolerance to the poison

Comparing of dose-effect cures of the drugs with different limits of security

Therapeutic

diapason

Toxic diapason

Drugs А and B

Drug B

Drugs A

0

50

100

0,1 1 10 100 1000

Comparing of dose-effect curves of hypno-sedative drugs A and B

Drug A

Drug B

Breath stop

Narcosis

Sedative effect

0,1 1 10 100 1000

Stages of acute poisoningStages of acute poisoning

• TOXICOGENICTOXICOGENIC – the poison circulates in organism, there are obvious manifestations of its toxic action or its metabolites’ action on corresponding structures (receptors)

• SOMATOGENICSOMATOGENIC – the poison has been excreted from the organism but there are manifestations of damaging of organs and systems (kidney, liver insufficiency, lung edema, etc.)

Toxic damaging of nervous system

• Exotoxic comaExotoxic coma ( (barbituratesbarbiturates), ), complications complications – – toxic brain edema, toxic brain edema, syndrome of lifelong death of brainsyndrome of lifelong death of brain

• Acute intoxicative psychosisAcute intoxicative psychosis ( (atropine) atropine)

• Syndrome of toxic encephalopathySyndrome of toxic encephalopathy ( (salts salts ofof heavy metalsheavy metals, , carbon monoxidecarbon monoxide, , toxicomaniatoxicomania))

Toxic damaging of cardiac-Toxic damaging of cardiac-vascular systemvascular system

• Exotoxic shock• Hypertensive syndrome• Disorders of cardiac rhythm and

conductivity • Cardiac arrest• Acute cardiac-vascular insufficiency

(primary toxicogenic collapse, secondary somatogenic collapse, hematogenic lung edema)

PRINCIPLES OF ACUTE POISONINGSPRINCIPLES OF ACUTE POISONINGS’’ TREATMENTTREATMENT

• Clearing of gastro-intestinal tract, skin, Clearing of gastro-intestinal tract, skin, mucous membranes from the poisonmucous membranes from the poison

• Absorption, destroying or neutralization of Absorption, destroying or neutralization of the poison using specific antagoniststhe poison using specific antagonists

• Elimination of the desorbed poison from the Elimination of the desorbed poison from the blood and tissuesblood and tissues

• Pathogenetic, symptomatic treatment and Pathogenetic, symptomatic treatment and reanimationreanimation

Provoking vomitingProvoking vomiting

• mechanical method• hypertonic solution (10 %) of sodium chloride• Apomorphine hydrochloride (0,2-0,5 ml s.c.)

Contraindications:- coma- elderly patients- lung emphysema- pregnancy- poisoning with cauterizing substances- poisoning with volatile liquids- poisoning with antiemetic drugs- convulsive episode in anamnesis

STOMACH LAVAGESTOMACH LAVAGE

Fabre: stomach lavage performed in time even by an inexperienced person is much more effective than the most modern methods of treatment, if they are used late

- after 4-5 hours – in case of poisoning with spasmolytic drugs, soporific, salicylates

- after 12 hours and more – in case of poisoning with morphine derivates, noxirone

- after 15 min.-1 hour – in case of poisoning with cauterizing substances

- after 1-2 days – in case of poisoning with mushrooms

Gastric lavageGastric lavage

LAXATIVES

If the poison is unknown, only salt laxatives should be used (!!!) -

magnesiummagnesium ( (sodiumsodium) ) sulfatesulfate - 20-3 - 20-30 g0 g

Ricine oilRicine oil is contraindicated in case of is contraindicated in case of poisoning with fat-soluble substancespoisoning with fat-soluble substances

((phosphorusphosphorus, , POSPOS, , oil-productsoil-products, , benzole benzole derivatives etc.derivatives etc.))

Vaseline oilVaseline oil decreases resorbtive ability of decreases resorbtive ability of intestinesintestines

ANTIDOTES

GreekGreek antidoton – anti poisonantidoton – anti poison are used if poison is correctly specifically

identified- physical – absorb the poison (activated

charcoal, other enterosorbents,)- chemical – destroy the poison, transform it into

non toxic substance, form complex substances with it (acids – alkalis, ЕDТА, unithiol, protamine sulfate)

- physiological – act as antagonists relatively to the poison on the level of specific receptors (naloxon, atropine)

Activated charcoalActivated charcoaluniversal antagonist of physical action

1 g adsorbs 1800 mg of mercury dichloride, 950 mg of strychnine, 800 mg of morphine, 700 mg of atropine or nicotine, 550 mg of salicylic acid, it is highly effective in case of poisoning with alkaloidsalkaloids

Single dose - 20-100 g

not effectivenot effective – in case of poisonings with acids, alkalis, phenols, less effective – in case of poisoning with hydrocyanic acid

CHEMICAL ANTIDOTESTannin - 0,5 % solution for poisoning with heavy metals salts

and alkaloids (except morphine, physostygmine, nicotine, atropine and cocaine)

Potassium permanganate - 0,01-0,02 % - food poisonings, alkaloids (morphine, strychnine, nicotine, chinine, physostygmine)

Copper sulfate – poisoning with phosphorus

Sodium chloride – poisoning with silver salts (AgNO3)Iodine (15 drops per 100 ml of water) precipitates silver, lead,

mercury compounds, strychnine, chinineUnithiol (dimercaprol, BAL, i.m.) – poisoning with heavy metals

salts, cardiac glycosidesDeferoxamine – poisoning with iron preparationsEDTA (trilon B) – binding lead, copper, magnesium, radioactive

elements - plutonium, uranium, thorium, yttrium compounds

PHYSIOLOGICAL ANTAGONISTSdo not change physical-chemical condition of the poison

Naloxon – poisoning with opiates

Atropine – poisoning with M-cholinomimetics and POS

Physostygmine – poisoning with atropine, curare-like drugs

Analeptics – poisoning with soporific drugs, narcotics

Flumazenil (anexate) – poisoning with tranquilizers

Potassium chloride – poisoning with cardiac glycosides

Oxygen – poisoning with carbon monoxide

Ethanol – poisoning with methanol, ethylenglycol

MEASURES MEASURES TO ELIMINATE THE POISON TO ELIMINATE THE POISON out of THE ORGANISMout of THE ORGANISM

• substitutive blood infusion substitutive blood infusion (10-15 (10-15 l)l)• hemosorption hemosorption ((plasmaplasma-, -, lymph-sorptionlymph-sorption))• hemodialysishemodialysis ( (artificial kidneyartificial kidney))• peritoneal dialysisperitoneal dialysis• enterosorptionenterosorption• forced diuresisforced diuresis• lung hyperventilationlung hyperventilation• hyperbaric oxygenationhyperbaric oxygenation

Hemodialysis, hemosorption

• Effective, if the substance has a small if the substance has a small volume of distributionvolume of distribution– – theophylline, theophylline, carbamazepin,carbamazepin, lithium carbonate, salicylates, lithium carbonate, salicylates, valproic acid, barbituratesvalproic acid, barbiturates

• Not effective, if the substance has a big if the substance has a big volume of distribution volume of distribution – – rifampicin, lidocainrifampicin, lidocain, , sybazon, anaprilin, dyltiazem, digoxinsybazon, anaprilin, dyltiazem, digoxin

FORCED DIURESIS

In case of poisoning with substancesIn case of poisoning with substances – – weak weak acidsacids ((salicylatessalicylates, , barbiturates, nalidixic barbiturates, nalidixic

acid, antibacterial and antidiabetic acid, antibacterial and antidiabetic sulfonamidessulfonamides, , indometacin, indirect indometacin, indirect

anticoagulants, clofibrateanticoagulants, clofibrate) ) – alkalizing – alkalizing organism liquids withorganism liquids with NaHCONaHCO33

FORCED DIURESISFORCED DIURESIS

• In case of poisoning with substancesIn case of poisoning with substances – – weak alkalisweak alkalis

((chinin, amphetaminechinin, amphetamine, , amitryptilineamitryptiline, , caffeinecaffeine, , theophyllintheophyllin, , novocainnovocain) – ) –

changingchanging pH of mediumpH of medium to acid sideto acid side with with vitaminvitamin С, С, ammonium chlorideammonium chloride