Microsoft powerpoint - chemter oview.ppt

• Describe the clinical presentation and Chemical Terrorism Overview management of patients poisoned with nerve agents • Describe the clinical presentation and management of cyanide poisoning Ziad Kazzi, MD, FAAEM • Discuss the various presentations and Assistant Professor of Emergency Medicine and Medical Toxicology management strategies of victims exposed Center for Emerging Infections and Emergency to sulfur mustard, Lewisite and pulmonary University of Alabama at Birmingham • "Nerve agents" are aptly named, since they affect the nervous system.
• Structural name for these agents is organic phosphorous compounds Nerve Agents: Part A Introduction (continued) • In fact, the OPCs also include several • Developed in pre-World War II Germany hundred "nonmilitary" compounds.
by Gerhardt Schrader, who discovered tabun in 1934. • Germany later developed sarin and soman. These are the G agents. • Never used by the Germans. The British • Used commonly as insecticides, where (R. Gosh) synthesized VX (the acronym military OPCs are used in warfare or allegedly stands for venomous) after Background (continued) Background (continued) • Sarin gas was released in the Tokyo subway • Iraq reportedly used tabun and system by the Aum Shinrikyo Cult, creating more maybe sarin in the Iran-Iraq war than 5,000 victims and causing 12 deaths.
• The same cult had released sarin in an apartment complex in Matsumoto in 1994, killing – Iranian soldiers had atropine auto- seven and injuring more than 600 people.
• In Tokyo, sarin was concealed in lunch boxes and bags. The terrorists punctured the bags with umbrellas and ran out of the subway tunnel.
Background (continued) Military Designations • The United States has around 30,000 tons of VX • The government is planning the destruction of this stock and has already destroyed small • There is an ongoing discussion about the best • Cyclosarin= GF way to dispose of the end products.
Physical Properties • Liquids with varying volatility and • Dermal toxicity: One drop of VX,1–10 ml of the G agents may be fatal.
• VX is the least volatile but the most • Onset of symptoms may be delayed persistent; "oily." Soman is odorless.
several hours from exposure to the liquid • Tabun, sarin, and soman have significant form, especially VX (up to 18 hours).
volatility. Sarin is the most volatile.
• Rapid development of symptoms after • Absorbed via skin, mucus membranes, exposure is more likely.
lungs, and gastrointestinal system.
Autonomic Nervous System
Mechanism of Action Nerve agents bind and inhibit acetylcholine esterases.
Acetylcholine esterase breaks down ACh mediates neurotransmission at ¾ Nicotinic receptors nicotinic muscular junctions, autonomic nicotinic synaptic junctions (sympathetic and parasympathetic), and ¾ Muscarinic receptors: ACh Epinephrine Norepinephrine end-organ synapses (GI tract, glands, bladder, pupils). Sweat Glands
Mechanism of Action (continued) Clinical Presentation Enzyme inhibition is reversible within a certain period of time that is agent dependent.
This time period in which structural changes to the enzyme occur is called "aging." Soman ages within minutes, whereas sarin After aging occurs, the enzyme is inactivated. GI distress (diarrhea, vomiting)
Enzyme regeneration usually takes several weeks.
Excess ACh at all these synapses accounts for the clinical presentation.
Clinical Presentation (continued) Clinical Presentation (continued) • Compared with adults, children exposed to • Nicotinic: MTWThF nerve agents are thought to be less likely to have miosis and more likely to have increased secretions.
• Children are also thought to have more seizures, – Weakness
hypotonia, and weakness than adults.
Detection at the scene Diagnostic Workup • Military test paper • No lab workup is useful for acute nerve • Other equipment agent poisoning.
• RBC and plasma cholinesterase (butylcholinesterase) levels may be
checked. These results are usually not
immediately available.
Prehospital Care and • First responders: Respirators, goggles, protective clothing • Self-contained breathing apparatus (SCBA) is recommended in response to any nerve agent vapor or liquid. • Butyl rubber gloves (most agents are lipophilic) Nerve Agents: Part B • 20% of healthcare workers in Tokyo had mild symptoms after taking care of patients. These symptoms included nausea, eye pain, and headache.
Different types of PPE Pick the appropriate PPE? Prehospital Care and Antidotes: Atropine • Muscarinic receptor antagonist.
• Inhalation exposure: removal from • Only treats muscarinic symptoms.
• Given IV, IM, or by ET tube.
• Dermal: wash with soap and water or mild • Dose is 2 mg every 5–10 minutes. End (0.5%) sodium hypochlorite (bleach) point is resolution of bronchorrhea. solution if availability of water is limited • For children, give 0.5–1.0 mg IM/IV every • Ingestion: no charcoal as these patients 5–20 minutes. For children < 6 months old, are at risk for vomiting and aspiration the dose is 0.05 mg/kg, with the minimum dose being 0.1 mg. Same end point.
Antidotes: Oximes Antidotes: Oximes (continued) • Reverses the binding of the nerve agent to • Side effect: elevated BP and occasional the enzyme, especially if given prior to EKG abnormalities • Other oximes (such as obidoxime and • Pralidoxime: Slow IV bolus. Dose is 25– P2S) are used in other countries and have 50 mg/kg in children or 2 g in adults. Is variable efficacy.
given IM via the MARK I kit.
• There is ongoing research to develop • May repeat dose in 1 h. Effect may decrease after 3 h of exposure to sarin better agents.
because of aging.
• Used to treat the seizures • Subjects pretreated with pyridostigmine will be less vulnerable to nerve agents. • Diazepam IM/IV appears to be better than • The U.S Army used pyridostigmine during the • Diazepam dose is 5 mg IV/IM. May be • Pyridostigmine is a carbamate that binds repeated every 5–15 minutes.
reversibly to AChE. It does not cross the CNS.
• Pretreated individuals will have a store of AChE that is bound to pyridostigmine and is protected from the nerve agent. • Bound pyridostigmine-AChE spontaneously breaks after several hours, releasing normal AChE. • Administration of 2-PAM stimulates release of AChE that was protected from the nerve agent by pyridostigmine. Antidotes: MARK I Kit Long-term effects • Contains pralidoxime • Organophosphate-induced delayed (600 mg) and atropine neuropathy (OPIDN) was described in one (2 mg) self injectors victim of the Matsumoto and one victim of the Tokyo attacks Sekijima, Y., Morita, H., Yanagisaw, N., 1997. Follow-up of sarin poisoning in Matsumoto. Ann. Intern. Med. 127, 1042 Himuro, K., Murayama, S., Nishiyama, K., et al., 1998. Distal sensory axonopathy after sarin intoxication. Neurology 51, 1195–1197 Long-term effects Okumura T, Hisaoka T. Environmental Toxicology and Pharmacology 19 (2005) 447–450 Sources and means of exposure Sources and means of exposure • Exposures are mostly intentional (suicidal • Via ingestion of cyanogens: lab technicians who have access to CN) • They may also be occupational, homicidal – Prunnus fuits (Cherry, apricot, peaches and (Chicago Tylenol tampering in 1982, Decongestant in 1991), Jonestown – Laetrile (contains amygdalin) massacre (900 people died) Sources and means of exposure • Acetonitrile (false-nail glue remover) or • Absorbed via GI, Skin or lung depending on its form.
• Iatrogenic with Nitroprusside • Very toxic: 200 mg for PO.
• Mostly excreted by the kidney as • Thiocyanate is formed by donation of a • The binding to Cytochrone a3 will interrupt sulfur group to the cyanide. The enzyme is the electron transport chain and therefore catalyzed by Rhodanese that relies on uncouple oxidative phosphorylation. ATP appropriate sulfur stores. When these are is no longer produced despite adequate depleted, the enzyme is slowed down.
supply of oxygen.
• Aneorobic metabolism prevails and Lactic Acute clinical findings • CNS: HA, anxiety, convulsions and coma • CV: end point is cardivascular shock • GI: ingestion of salts will cause N/V/D and • Bitter almond: only 60% of population can • Cherry red skin Chronic clinical findings • Survivors may develop parkinsonism over weeks to months.
• Whole blood Cyanide levels difficult to get.
• May be seen on CT or MRI as changes in the basal ganglia.
• O2 extraction will be impaired • Urinary thiocyanate levels Cyanide treatment • Supportive care including Oxygen • Administer the cyanide antidote kit (Lilly Kit) ¾ Amyl nitrite or sodium nitrite Converts hemoglobin to methemoglobin. Promotes dissociation of CN from the cytochrome. Forms non toxic cyanomethemoglobin. ¾ Sodium thiosulfate promotes the conversion of cyanohemoglobin to thiocyanate and hemoglobin through enzymes such as rhodanase • Hydroxycobalamin (Vitamin B12) Exchanges hydroxyl group with CN to form cyanocobalamin. Concentrated form of drug not available in the United States yet • Vesicant alkylating agent • Originally used in World War I • Other names: Yellow cross, Hun Stoff and • Used also by Japan and Italy (1930's), Egypt (1960's) and Iraq (1980's) Physical Properties Mechanism of Toxicity • Alkylating agent that • Persistent more than volatile yet deaths – Binds sulfhydryl and amino groups are usually secondary to vapor exposure – Cell necrosis occurs • Weak cholinergic properties Clinical Presentation – Latency of hours – Pain, miosis, photophobia, lacrimation, blurred vision, blepharospasm, and corneal damage An eye injury of lesser severity in an Iranian casualty – Permanent blindness is rare (shown 7 d after exposure) caused by exposure to mustard. The characteristic findings were edema of the lid and conjunctival injection Clinical Presentation • Dermal exposure – Latency of 4-12 hours – Burns with blisters of different sizes – Go through clothes – More damage over moist and warm areas such as the axillae – Possible long term effects: • Punctate hyperpigmentation Skin blisters secondary to dermalExposure to sulfur mustard The back of an Iranian casualty seen 16 hours after exposure to mustard Large and extensive bullae on the hands and the feet of Iranian casualties as they appeared 5 days after exposure to mustard Erythema of the chest of an Iranian casualty as it appeared 5 days after his exposure to mustard Clinical Presentation • Respiratory exposure – Chemical tracheobronchitis – Respiratory failure By 32 days after exposure, this Iranian casualty has punctate hyperpigmentationin a healing deep mustard burn Clinical Presentation • Highly incapacitating • Decontamination • Mortality rather low (<5%) several days • Supportive care later from bacterial pneumonia and • Blister unroofing respiratory failure as well as bone marrow • Topical antibiotics • Alternative to Mustard: – More volatile – Less persistent • Causes immediate pain upon contact • Similar clinical findings as mustard • BAL is the antidote (IM or topical) in addition to supportive therapy Phosgene and Chlorine • Cause pulmonary edema and respiratory • Chlorine causes a pungent odor • Phosgene produces a freshly mown hay • Toxicity may be delayed several hours Helpful Resources • http://www.bt.cdc.gov/agent• Your regional poison center• Medical Management of Chemical Casualties Chlorine exposure Phosgime exposure

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