Disaster Medicine 9-27 PDF

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Disaster Medicine 9. Chemical disasters. Scope of the problem. Classification of the chemical. Chemical disaster procedures. o Chemical disasters result from the storage, processing and transportation of large amounts of highly flammable, explosive and toxic chemicals. o The released toxic substances or their by-products into the environment result in intoxication. o The most catastrophic chemical release or spills occur in the transportation phase of the industrial process. o The fires very often cause blast burn or inhalation injuries o Explosions result in mechanical traumatic lesions o The chemical contamination of the water, the soil and the food chain can cause delayed effects for years with impairment to neurological or immune system Scope of the problem The problems related to industrial safety in the developing countries include: o The inability to ensure the proper use of the new technology o The lack of effective urban zone that separate residential communities from the industrial sites o The lack of prehospital emergency medical services o Basic concepts  The term chemical disaster may be understood as a great calamity in which many people ( at least 50) perish and in which a chemical cause the death or injury of so many people that the normal health and emergency services are or threatened to become overburdened  A catastrophic situation maybe be considered a threat to 10 people. This is the number of the individuals which the crew of an emergency medical services (EMS) ambulance can effectively cope.  An event in which only one or a few persons are the victims may be considered as an accident.  A catastrophe can be considered to encompass any situation in which the need for aid surpasses the normal capacity to deliver medical and technical assistance.  A hazard exists where there is a situation that in particular circumstances could lead to harm Classification of the chemical disasters Disaster can be classified as follows: o According to the number of victims produced by the incident o The extent of the contaminated area o The population density in a contaminated area for volatile chemicals

o The amount of chemical involved o The toxicity of the chemicals o The magnitude of the measures that must be taken to counteract the accident and to limit its consequences. o Consequences on the environment Factors affecting the severity and occurrence of the industrial disasters is increased from some natural and human factors: o The location of industrial sites in regions subjected to natural disasters. Flood, earthquakes and hurricanes can destroy a community’s civil infrastructure and its industrial base, critical industrial safety systems etc. o Human factors as human errors from fatigue or inadequate training o Lack of strong occupational and industrial health expertise or functioning emergency medical systems. Chemical disaster procedures Chemical disasters pose some unique problems; o Substance identification is important prior to a massive rescue effort. o On-site decontamination procedures are essential for both victims and emergency medical services personnel. o On-scene separation of hot, warm and cold zones will facilitate safe initial responses to the injured. o Protective clothing may be essential for those involved in rescue and triage procedures. o Ambulances and other vehicles removing the injured require decontamination procedures o Hospitals require a triage area, a separate decontamination area and separate entrance o Transport vehicles may require placards to indicate the type of the chemical contamination involved o Mass evacuation of the population should be considered

10. Chemical disasters. Prevention and control measures. Prevention and control measures Hazard identification o This process called hazard identification requires identifying all chemical products that are stored manufactured or transported by local industry and that might affect the community in the event of an industrial disaster o It is necessary to detail:  The physical characteristics of the chemical agent  The expected health effect associated with human exposure  The information on chemical reactions and hazard-neutralization strategies Chemical Agent Detection o Some can be seen o Some can be smelled o Some can be tasted o Most can be felt (e.g. burning sensation, choking) o All can be detected by appropriate instruments Types of chemical Agents Some chemical agents are persistent many are not persistent o Persistent chemicals  Remain on surfaces without evaporating or breaking down for more than 24 hours  Can remain for days to weeks o Non-persistent chemicals  Quickly evaporate and break down  Carried in bulk on commercial carriers Types of chemical agents Chemical agents are commonly classified by the type of harm they cause. o Nerve Agents-disrupts nervous system, causes paralysis, fatal quickly o Blister Agents- destroy skin and tissues, cause blindness, may be fatal o Choking Agents- lung fills with fluid cause choking, quick or delayed fatality o Blood Agents- interferes with oxygen at the cellular level, fatal quickly o Riot-control Agents- skin and breathing irritations, rarely fatal Vulnerable populations may be: o People with disabilities o Children attending school o Patients with medical personnel working in nearby hospitals Emergency preparedness includes o Arranging medical care and proper referral destination for patients exposed to hazardous materials o Establishing warning systems to alert nearby communities of a chemical release o Determining minimal threshold concentrations of toxic chemicals that would require the community to evacuate in the event at a chemical release o An accurate and timely information is also necessary regarding to; o Physical properties of chemical agents and their clinical effects o Information on proper chemical neutralization and plume-dispersion estimation models o Appropriate antidotes for victims and their proper administration

11. General toxicology. Basic concepts. Routs of the entry of poisons. Toxicology is a scientific and medical discipline for the adverse effects of the poisons. The harmful toxic effects of certain substances- including plants, fruits, insect bites, animal venoms and minerals have been known since prehistoric times. Basic concepts o Poison is any solid liquid or gas that through either oral or topical routes can interfere with life processes in the organism o Poison could be defined any agent capable to produce a noxious response in a biologic system, seriously injuring function or producing death. o Every known chemical has the potential to produce injury or death if present in a sufficient amount Toxicology Terminology o Toxicants – substances that produce adverse biological effects of any nature  May be chemical or physical in nature  Effects may be of various types (acute, chronic etc) o Toxins-specific proteins produced by living organisms (mushroom toxin or tetanus toxin)  Most exhibit immediate effects o Poisons-toxicants that cause immediate death or illness when experienced in very small amounts o Organic toxins- substances that were originally derived from living organisms  Contain carbon and often are large molecules  Can be synthesized as well as obtained from natural sources o Inorganic toxins- specific chemicals that are not derived from living organisms (minerals)  Generally small molecules consisting of only a few atoms (NO2) o Toxicity is the potential for a compound to produce injury in biological system  Usually the word toxicity is used to describe the word of adverse effects  The toxicity of something is expressed as milligrams (mg) of the substance per kilograms (kg) of body weight that will produce defined biologic effects o The dose is the total amount of poison received per organism (person or animal) o The lethal dose (LD) the lowest dose that causes death in any animal during the period of observation which is 14 days . Various percentages can be associated to the LD value to indicate doses required to kill  1%(LD1)  50% (LD50)  100% (LD100) of test animals o Median lethal dose (LD50) is used to measure toxicity o The lethal concentration (LC) is the lowest concentration of compound in the air that causes death  It is expressed as milligrams of compound per meter cubic of the air Types of doses in toxicology o Exposure dose – the amount of a xenobiotic encountered in the environment o Absorbed dose- the actual amount of the exposed dose that enters the body o Administered dose- the quantity administered usually orally or by injection o Total dose- the sum of all individual doses Effective doses- are used to indicate the effectiveness of a substance.

o Usually effective dose refers to a beneficial effect (relief of pain) o It can also mean the harmful effect , therefore the specific endpoint must be indicated Therapeutic Index/Ratio (TI) o TI measures how safe a drug is o High TI indicates that the drug is safe o Low TI indicates that the drug is not safe o The larger the ratio of TI the safer the drug is Preliminary toxicity testing o NOAEL (no observed adverse effects level)- highest concentration that does have a toxic response o LOAEL (lowest observed adverse effects level)- lowest concentration that produces aa toxic response Acute poisoning is a term that describes the biologic effects of a single high dose of the poisons or multiple doses during 24-hour period. o Sub-acute poisoning- 1 month repeated doses o Fulminant poisoning o Sub-chronic poisoning-1-3 months repeated doses o Chronic poisoning (>3 months)- repeated (prolonged) exposure to relatively low doses of the poisons. The ratio of the acute to chronic LD50 doses is the chronicity factor.

Systemic and organ toxins o A systemic toxin is one that affects the entire body or many organs rather than a specific site o An organ toxin is one that affects only specific tissues or organs Adverse drug reactions (ADRs)- are noxious or unintended responses occurring at therapeutic doses (WHO definition)-5% of all acute admissions o Type A (augmented ADRs)- effects are  Related to known pharmacology, but undesirable  Common, dose related  Predictable o Type B (bizzare ADRs)- effects are  Unrelated to known pharmacology  Rare  Unpredictable Routes of the entry of poisons Factors determining adverse effects o Intrinsic toxicity  Chemical properties- molecular structure, solubility , volatility, stability , reactivity  Physical properties- gas , liquid and solid o Dose o Exposure conditions  Gastrointestinal tract (ingestion)  Lung (inhalation)  Skin (topical, percutaneous or dermal)  Injection (bite, puncture, cut) o Response of host  Prolonged exposure to a compound may allow people to develop tolerance to the poison.  In this case the size of the dose producing lethality upon repeated exposure increases Toxicokinetics- is the movement and disposition of poisons and in the organism (ADME)

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Absorption Distribution of chemical within the body Metabolism (biotransformation) Excretion A chemical absorbed into the bloodstream is distributed throughout the body, including the where it produces damage  This site is usually the target organ or target tissue  A chemical may have one or several target organs and in turn several chemicals may have the same target structure Toxicants do not affect all organs to the same extent A toxicant may have several sites of action and target organs Multi-toxicant exposure may target the same organ The target organ may not be the site for storage

12. General toxicology. Nature of the toxic effects. Classification of toxic Nature of toxic effects The major mechanisms of action of drugs and chemicals are; o Inflammation- frequently local response to irritant chemicals or components of systemic tissue injury  The inflammatory response may be acute or chronic o Necrosis- this is death of tissue or cells, resulting from a variety of pathological processes  Corrosion  Severe hypoxia  Membrane damage  Reactive metabolite binding  Inhibition of protein synthesis  Chromosome injury o Enzyme inhibition by chemical, which may inhibit biological vital pathway o Biochemical uncoupling of the synthesis of high-energy phosphate molecules  In this case the electron transport continues and results in excess liberation of energy as heat o Lethal synthesis occurs when foreign substances of close structural similarity to normal biological substances metabolize to a toxic product o Lipid peroxidation in biological membrane by free radicals starts a chain of events causing cellular dysfunction and death o Covalent binding of electrophilic reactive metabolite to nucleophylic macromolecules o Receptor interaction at a cellular or macromolecular level with specific chemical structures o Immune-mediated hypersensitivity reaction by antigenic materials, resulting respectively in allergic contact dermatitis and asthma type one to four hypersensitivity o Immunosuppresion by chemicals  The adverse effect is manifested as increased susceptibility to ineffective agents o Neoplasia resulting aberration of tissue growth and control mechanisms of cell division and leading to abnormal proliferation o Genotoxicity caused by chemicals which interact with DNA and possibly lead to heritable changes Teratogenesis- the creation of birth defects during fetal development o Teratogens: substances that induce birth defects o 1950’s thalidomide was synthesized by the Grunenthal, non-toxic at high doses in all animals species tested o 1957- marketed throughout Europe as a non-lethal hypnotic and sedative, recommended as an antiemetic to treat morning sickness in pregnant women o 1961-thalidomide was the best-selling sleeping pill in west Germany and the UK o Thalidomide produced teratogenic effects in 100% of fetuses exposed between 3-6 weeks gestation o An estimated 12,000 infants were born with deformities caused by thalidomide and only 5,000 of these survived beyond childhood o Now thalidomide is used to treat leprosy and multiple myeloma Classification of toxic agents The toxic agents are classified in a variety of ways, depending on their taget organ (liver, kidney etc) their use (pesticides, solvents etc) , their origin (animals and plant toxins) In our classification the poisons, which cause intoxications in disaster situations are divided into five groups, according to their mechanism of the toxic effect o Anticholinesterase compounds- organophosphorus ester, carbamate esters o Cellular asphyxia- inducing compounds: carbon monoxide, cyanide etc o Pulmonary edema- inducing compounds: phosgene, ammonia, chlorine, nitrogen oxides

o Sensory irritant compounds- mineral acids, modern riot control compounds o CNS depression (narcosis)- inducing compounds; aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, carbon disulfide 13. Biotransformation of the xenobiotics. Phase I and Phase II reactions. Biotransformation of xenobiotics Poisons are xenobiotics, but not all xenobiotics are poisonous o Xenobiotic- is a compound that is foreign to the body  Is a chemical which is found in an organism but which is not normally produced or expected to be present in body  Endogenous- pigments, hormones  Nonendogenous- such as drugs, food additives, pollutants, toxin Most of these compounds are subject to metabolism (biotransformation) in human body. Definition of biotransformation o Conversion of lipophilic xenobiotics to water-soluble chemicals by a process catalysed in the liver and other tissues o In most cases biotransformation lessens the toxicity of xenobiotics, but many must undergo the process to exert their toxic effects o This process leads to rapid excretion and therefore elimination of the compound from the organism o The biotransformation may also change the chemical and biological activity of the substances o The products of metabolism are usually more water-soluble than the original compound o Rarely metabolism may actually decrease water-solubility and so reduce excretion Metabolism – important points to remember o Most drugs entering the body are lipophilic o Drug molecules easily diffuse through the lipophilic membranes of the GIT o Some of the Xenobiotics are not completely excreted in the urine due to the reabsorption in the renal tubules Product of metabolism o The product of metabolism must become hydrophilic or converted to a water-soluble substance for elimination  Xerobiotics- must be converted to a water-soluble substances (hydrophilic)  Metabolites- are mostly lipophilic or lipid-soluble compounds  Metabolism- is also called detoxification or detoxication Purpose of Biotransformation o Facilitates excretion – converts lipophilic to hydrophilic compounds o Detoxification/inactivation- converts chemical to less toxic forms o Metabolic activation- converts chemicals to more toxic active forms The metabolism of the xenobiotics can be divided into two phases: phase 1 and phase 2 o Phase I reactions includes alteration of the original foreign molecule so as to add on a functional group which can be conjugated in phase o Phase II involves the addition of a readily available polar endogenous substances to the foreign molecule. o This polar moiety is conjugated either to an existing group or to one added in a phase I reaction o The polar moiety is conjugated either to an existing group or to one added in a phase I reaction o The polar moiety renders the foreign molecule more water-soluble and so more readily cleared from the body and less likely to exert a toxic effect o For many compounds there is an initial Phase I reaction to produce substances which are conjugated by phase II process. o In other chemicals only a phase II process may be utilized Introduction of Functional Polar Groups to Xenobiotics o Reduction of ketones and aldehydes to alcohol o Oxidation of Alcohol to acid

o Hydrolysis of Ester and Amide to Acid o Reduction of Nitro compounds to form NH2 moiety Sites of biotransformtion o Liver Primary site  Rich in enzymes  Acts on endogenous and exogenous compounds o Extrahepatic metabolism sites- Intestinal wall  Sulfate conjugation  Esterase and lipases- important in prodrug metabolism o Lungs o Kidney o Placenta o Brain o Skin o Adrenal glands o Gastrointestinal tract- absorb orally administered drugs o Liver (hepatic metabolism or first pass effect) – the most important organ in drug metabolism o Blood Circulation- absorb orally administered drugs First-pas metabolism- Xenobiotic metabolized before reaching general circulation

Phase I and Phase II reactions o Oxidation o Reduction o Hydrolytic reactions (enzymatic hydrolysis) o Dehalogenation Introduction of polar functional groups in a molecule o Increases a molecule’s polarity o Provide a functional group or handle on the molecule that can undergo Oxidation reaction- phase 1 o Do not produce sufficiently hydrophilic or inactive metabolites Conjugation reactions- Phase II reaction o Sulphation (sulphate conjugation) o Glucuronidation (Glucoronic acid conjugation) o Glutathione or mercapturic acid conjugation o Conjugation Glycine, Glutamine and other amino acids o Acetylation o Methylation

o Approximately 30 different enzymes catalyse reactions involved in xenobiotic metabolism. o Enzymes involved in biotransformation are called “drug metabolizing enzymes”

o RH: Xenobiotics o R-OH: metabolite o Enzymes; the oxidative system is often known as the ‘mixed function oxidase system’

o Anything that affects the activity of any oxidative enzyme can affect the way the body reacts to a given drug or other xenobiotic o

14.Principles of therapy of intoxication Factors affecting metabolism o Age- The metabolizing enzymes in neonates are not fully developed, therefore those cannot efficiently metabolize drugs. Also, in the elderly, enzymatic systems may not function well leading to same conclusion. o Sex (activity is generally higher in males than in females). Linked to hormonal differences. o Genetics - Genetic differences can influence amount and efficiency of metabolic enzymes o Organ (activity of many enzymes is highest in the liver) o General health status (e.g...