Pharmacotherapy of drug poisoning and emergency states

1. Pharmacotherapy of drug poisoning and emergency states

2. UKRAINE • In 43 of 190 most controlled large cities of our country concentration of substances dangerous for health isovercomes critical allowed concentrations 520 times • 34 % of population is under the negative influence of atmospheric pollution

3. 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)

4. Side effects (SE)of drugs • 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 %

5. SE of drugs • 150 000 – 200 000 people in U.S.A. die from side effects of drugs annually • 76,6 billion $ are spared in U.S.A. annually to treat complications attached to drugs usage

6. 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

7. 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

8. Comparing of dose-effect cures of the drugs with different limits of security 100 Therapeutic diapason Drug B Drugs А and B Toxic diapason 50 Drugs A 0 0,1 1 100 10 1000

9. Comparing of dose-effect curves of hypno-sedative drugs A and B Breath stop Drug A Narcosis Drug B Sedative effect 0,1 1 100 10 1000

10. Stages of acute poisoning • TOXICOGENIC– the poison circulates in organism, there are obvious manifestations of its toxic action or its metabolites’ action on corresponding structures (receptors) • SOMATOGENIC– the poison has been excreted from the organism but there are manifestations of damaging of organs and systems (kidney, liver insufficiency, lung edema, etc.)

11. Toxic damaging of nervous system • Exotoxic coma (barbiturates), complications – toxic brain edema, syndrome of lifelong death of brain • Acute intoxicative psychosis (atropine) • Syndrome of toxic encephalopathy (salts ofheavy metals, carbon monoxide, toxicomania)

12. Toxic damaging of cardiac-vascular 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)

13. PRINCIPLES OF ACUTE POISONINGS’ TREATMENT • Clearing of gastro-intestinal tract, skin, mucous membranes from the poison • Absorption, destroying or neutralization of the poison using specific antagonists • Elimination of the desorbed poison from the blood and tissues • Pathogenetic, symptomatic treatment and reanimation

14. Provoking 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

15. STOMACH 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 hoursand 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

16. Gastric lavage

17. LAXATIVES If the poison is unknown, only salt laxatives should be used(!!!) - magnesium (sodium) sulfate - 20-30 g Ricine oilis contraindicated in case of poisoning with fat-soluble substances (phosphorus, POS, oil-products, benzole derivatives etc.) Vaseline oildecreases resorbtive ability of intestines

18. ANTIDOTES Greekantidoton – 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)

20. Activated 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 alkaloids Single dose - 20-100 g not effective – in case of poisonings with acids, alkalis, phenols, less effective – in case of poisoning with hydrocyanic acid

21. CHEMICAL ANTIDOTES Tannin- 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, chinine Unithiol (dimercaprol, BAL, i.m.) – poisoning with heavy metals salts, cardiac glycosides Deferoxamine – poisoning with iron preparations EDTA (trilon B) – binding lead, copper, magnesium, radioactive elements - plutonium, uranium, thorium, yttrium compounds

23. 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

24. MEASURES TO ELIMINATE THE POISON out of THE ORGANISM • substitutive blood infusion (10-15 l) • hemosorption (plasma-, lymph-sorption) • hemodialysis (artificial kidney) • peritoneal dialysis • enterosorption • forced diuresis • lung hyperventilation • hyperbaric oxygenation

25. Hemodialysis, hemosorption • Effective, if the substance has a small volume of distribution– theophylline, carbamazepin,lithium carbonate, salicylates, valproic acid, barbiturates • Not effective, if the substance has a big volume of distribution – rifampicin, lidocain, sybazon, anaprilin, dyltiazem, digoxin

26. FORCED DIURESIS In case of poisoning with substances –weak acids(salicylates, barbiturates, nalidixic acid, antibacterial and antidiabetic sulfonamides, indometacin, indirect anticoagulants, clofibrate) – alkalizing organism liquids withNaHCO3

27. FORCED DIURESIS • In case of poisoning with substances –weak alkalis (chinin, amphetamine, amitryptiline, caffeine, theophyllin, novocain) – changingpH of mediumto acid side with vitamin С, ammonium chloride