stevan cordas do incapacitants1 incapacitants stevan cordas do mph

1Stevan Cordas DO Incapacitants

Incapacitants

Stevan Cordas DO MPH


Definition

Under the Department of Defense definition, an incapacitant is an agent that produces temporary physiological or mental effects, or both, which will render individuals incapable of concerted effort in the performance of their assigned duties.


History

600 BC – Solon used hellebore to cause diarrhea in enemy.

184 BC – Hannibal used belladonna to create disorientation.

1500 AD – Hashish used by Muslims.1672 AD - Bishop of Muenster proposed

belladonna grenades.1881 –1908 - Natives in Africa and

Vietnam used indigenous plant to cause disorientation in occupying troops.

Stevan Cordas DO Incapacitants 4

History

Following WWII the CIA and the DoD began to explore various substances to act as incapacitants.

1960- 1990 3-quinuclidinyl benzilate termed BZ (NATO) was the only one weaponized.

1997 - Department of Defense joint non-lethal weapons program (JNLWP).


Types of Psychoactive Incapacitants

Central nervous system stimulants – amphetamines, cocaine etc.

Central nervous depressants – antipsychotics, barbiturates, opioids, benzodiazepines.

Psychedelics –LSD –25, PCP, MDMA etc.

Delerients – scopolamine, BZ, atropine etc.


Epidemiology

Psychoactive drugs and plants readily available worldwide.

BZ is commercially available as QNB. Hard to make in a home lab.

Sudden delirium in a previously healthy person or group of persons should raise suspicion.


EpidemiologyAnticholinergics are readily found in plants

such as belladonna (Atropa belladonna), mandrake root, Black henbane (Hyoscyamus niger), the thornapple or Jimson weed (Datura stramonium) and woody nightshade (Solanum dulcamara) and Jerusalem cherry (Solanum pseudocapsicum), all members of the Solanaceae botanical family (along with tobacco coincidentally).

1998 British report that Iraq had stockpiled Agent 15, a glycolic acid ester, an agent similar to BZ.


Pathophysiology

BZ is an anticholinergic. This is a class of drugs that blocks, as a competitive inhibitor of acetylcholine, the post synaptic and postjunctional muscarinic receptor sites on the peripheral and/or the central nervous system. The nicotinic receptors in the skeletal muscle are not affected.


Pathophysiology

Anticholinergics, such as BZ and Agent 15, work the direct opposite of nerve gas agents and cause an understimulation of muscarinic exocrine gland, central and peripheral nervous system and smooth muscle receptors.


Differential Diagnosis

Lead, mercury.Solvents.Alcohol.Anxiety states.Recreational drug abuse.Medical disease –hepatic failure,

renal failure, hypothyroidism.


Toxicology of BZ

A stable crystalline solid. Not soluble in water but in DMSO and solvents. Can be aerosolized. Formula C21H23NO3.

MW is 337.41; melting 167° C; Boiling point 320° C.

Safety margin 30. ID50 is 6.2g/kg.Less than 1 mg will cause delirium

in a 70 kg man.


Clinical Manifestations of BZ

Ocular –Mydriasis, loss of near vision, dry eyes.

Oral – Xerostomia.Cardiac - unpredictable – usually

tachycardia lasting one to two days.

Skin – Dry, flushed, hyperthermic.GU – Bladder distended, decreased

force.



Dose dependent central effects.Level of consciousness –drowsy,

sedated, stupor to coma. Perceptual – mad as a hatter, hallucinations, illusions.

Attention and memory impairment.Disturbances in insight and

judgment – Vulgarity, confabulation.



Deficits in expression and comprehension. – Slurred speech, flat voice, preserveration, semiautomatic speech, handwriting deteriorates, cannot converse.

Disorientation – time and place, picking behaviors, mumbling, vulgarity.

Sharing of illusions and hallucinations.Paranoia – especially as other

symptoms resolve.


Laboratory Testing

There are no laboratory tests for BZ and no field detection equipment.


Treatment

Evacuate.Restrain if necessary.Treat hyperthermia if it is severe.Watch for cardiac arrhythmias,

destructive behavior and general status.

Give specific antidote IM or IV – Physostigmine. Not effective in the first four hours however.


Physostigmine

IM 2 to 4 mg every one to 4 hours for 4 or 5 doses.

IV, if restrained, 30 g/kg slowly.A fast bolus IV may cause a fatal

cardiac arrhythmia or convulsions.Available as Antilirium or Eserine.Other similar agents do not cross

the blood brain barrier.


Prophylaxis

If pre-warned, military protective gear will prevent the effects of anticholinergics.

No preventive therapy available for civilians.

Evacuate area as BZ persists especially in water, soil and moist surfaces.


Reporting

There are currently no formal reporting requirement for incapacitants. All unusual circumstances that are suspected of being related to terrorist actions must be reported to law enforcement officials.

It is also advisable to report such actions voluntarily to local health departments.


Ricin Toxin



Ricin

Ricin is a glycoprotein toxin derived from castor plant beans. It can be produced relatively easily and inexpensively in large quantities in a fairly low technology setting. Ricin can be prepared in liquid, crystalline or powder form.


Ricinus Communis (Castor Plant)


Ricin - A 66 Kilodalton Heterodimer With an A and B

Chains


History of Ricin

Since antiquity, it is known that the oil is helpful but the plant is poisonous.

Ricin, mainly in the seeds, first named 1888.

Ehrlich discovered the basic principle of antibody production using ricin – the beginning of immunology – 1896.

Named compound W after WWI – developed by both U.S. And Great Britain into weapons.


History of Ricin

Allies developed a W bomb in WWII but did not use it.

Increased production and weaponization by both allies and others starting in 1950.

United states ceased biological warfare production in 1969 and destroyed supplies.

Iraq and others produced ricin weaponry as part of their inventory.


History of Ricin

First shown to inhibit tumors in 1951.Modern use as research tool developed

in 1972 by Sharon and Lis.Chimeric toxins use is currently being

studied – native ricin is conjugated to tumor specific monoclonal antibody.

Used by Bulgarian secret police to assassinate a defector in 1978.


Epidemiology

World wide distribution of plant.Readily separated and concentrated.Widespread availability.Implicated with several domestic

terrorist incidents.A cluster of cases in the same locality

with severe pulmonary distress must include in differential diagnosis.


Pathophysiology

B chain has lectin properties - permit binding to galactosides on cell wall and permitting endocytic uptake of the protein.

• Once in cell, the A chain acts as an enzyme after a latent period of 8-24 hours in vivo, cell death occurs by cleaving the 28A subunit of RNA. Protein synthesis ceases.

• Multiple areas of multifocal ulcerations and hemorrhage. Nephritis, liver necrosis.


Toxicology

Ricin composes about 5% of the Castor plant. Especially in beans and seeds.

Both chains are glycoproteins 32 kd each.

It has been purified and crystallized.100 fold variation in toxicity for various

animals.Toxicity varies by route of

administration and is 100 times more lethal by injection than orally.


Toxicology

Low oral toxicity is due to poor absorption of toxin.

Target cell receptors are widespread over the body but macrophages and monocytes are the only white cells to contain galactose in cell membrane.

LD50 is 20 mg/kg(100 hours) orally. 4g/kg by inhalation and intravenously. (Mice).


Clinical Manifestations - Oral

Oral – Rauber et el – 751 cases. 14 fatalities.

Death rate in general said to be 6%.Often just nausea, vomiting, diarrhea

sometimes bloody and abdominal cramps with prostration. Also burning eyes noted.

More severe cases also had dilated pupils, shock, anuria, sore throat, fever, vascular collapse, shock and possibly death.


Clinical Manifestations - Injection

Low doses 18-20g/kg in cancer patients could be tolerated with fatigue and flu like symptoms. Vascular leak syndrome seen.

Lasted 1-2 days after a latent period of 4 to 6 hours.


Clinical Manifestations - Injection

Markov was assassinated in London by the Bulgarian KGB with 500g. Immediate local pain. 15-24 hours later high fever, nausea, vomiting.

36 hours later localized lymphadenopathy,then suddenly hypotensive, cardiac rate 160 then complete AV block, GI bleeding, anuria, shock and death.

Death 3-5 days.


Clinical Manifestations - Inhalation

Allergic reaction to castor beans in workers rhinitis, asthma and conjunctivitis seen.

Inhalation of ricin would produce same picture as by subcutaneous except that experimentally a diffuse necrotizing pneumonitis occurs with alveolar flooding. An 8 hour latent period is noted. Dose dependent. Tracheitis and mediastinal purulent lymphadenitis also seen.


Differential Diagnosis of Ricin Aerosol

Staphylococcus B enterotoxinOrganofluorine polymersPhosgeneOxides of nitrogenParaquat - Naphthylthiourea (ANTU)


Laboratory Diagnosis

ELISA analysis of swab of nasal mucosa if obtained within 24 hours of exposure.

Survivors after about 2 weeks develop antibodies. Identification in body fluids is difficult as it is bound rapidly and metabolized.

Immunohistochemical means on autopsy or tissue.


Field Testing

Field screening testing is now possible using tests such as the RAMP Ricin field test. This is a 15 minutes immunochromatographic test. See http://www.responsebio.com/productsbiodefense1c.htm for more details


Treatment

No vaccine or immunization is available for humans. Toxoid has been submitted to the FDA for an IND.

Experimentally inhalation of protective antibody (passive protection) is highly effective after exposure.

For oral – super activated charcoal and IV fluids.


Treatment

For aerosol – supportive measures -positive end expiratory ventilatory pressure, iv fluids, anti-inflammatory drugs and analgesics.

Research drugs to block enzymatic action of A protein.

Detoxify (decontaminate) using water or dilute bleach. Wear N95 mask if inhalation source.


Prophylaxis

No prophylaxis is currently possible though it is possible with animal experiments using a vaccination.


Reporting

Ricin is a putative bioterrorism weapon. Report to your local or state health department immediately.


Castor Beans


T2 and Other Mycotoxins


Consultant Texas Department of Health


FungiOver 100,000 species of fungi found in

four phyla.Consists of mushrooms, lichens, corals,

molds and others.Just as mushrooms can be used

beneficially but some can be fatal, molds also can be viewed in this manner.


Molds75% of fungi belong to the family

Ascomycota which produce the sexual spores internally in a structure called the ascus.

These fungi are molds that can produce products that are fatal to plants, animals and humans.

One product is called T2.


T2

(3",4$,8")-12,13,-Epoxytrichothec-9-ene-3,4,8,15-tetrol 4,15-diacetate 8-(3-methylbutanoate); 3" -hydroxy -4$, 15-diacetyloxy-8"-(3-methylbutyryloxy)-12,13-epoxy -)9 -

tricothecene


T2T2 is a mycotoxin.It was the only such toxin to be

weaponized until Sadam Hussein weaponized aflatoxin.

It is the only biologic agent that can kill by transdermal absorption.

Oral ingestion probably caused ATA (alimentary toxic aleukia).


History of T2 Evidence of T2 use as “yellow rain”

in Laos, Cambodia and Afghanistan by Soviets and their surrogates.

May have been used in the Iran- Iraq war.

No conclusive human case from a biological attack of T2 has been documented.


IraqUnited nations inspectors reported

in 1995 that Iraq weaponized a number of biologic agents including anthrax, clostridia botulinum and a mycotoxin, aflatoxin.

Aflatoxin is one of the most potent mutagens and carcinogens known.


Toxicology of T2Maintained as crystalline powders

or liquids. Non volatile.Can extract from fungal cultures

with organic acids.Cytotoxic to most eukaryotic cells

by inhibiting protein synthesis.LD 50 varies with species. In

monkey it is 0.8 mg/kg.


ToxicologyInhibits protein and DNA metabolism.Rapidly crosses pulmonary and

intestinal mucosa.Slowly absorbs across skin unless a

penetrant is added.Liver is main organ for metabolism of

T2.Metabolites can be detected up to 28

days.


Clinical EffectsAcute – gastric and intestinal

lesions. Hematopoetic and immunological effects are radiomimetic.

CNS –lassitude, anorexia, nausea.


Clinical EffectsVascular effects with shock and possibly

death.Reproduction organ function

suppressed.Weakness, cough, chest pain, diarrhea

often bloody.Dermal effects – if that route was used –

inflammation and necrosis, vesicles.Bloody ooze from nose and mouth.


Chronic Effects of T2ATA – immediate phase of GI

effects, weakness, and dizziness followed by leucopoenia primarily granulocytes. If exposure continues a dark red rash with ulcers and gangrenous areas – larynx gets involved with death by strangulation. If they survive it takes months to recover.


Chronic EffectsSince it is a potent inhibitor of

replication and is most toxic to rapidly proliferating cells. A phase I and II Cancer trial was done with a similar mycotoxin (anguidine or DAS) given IV 3 mg/m3 daily for 5 days.

Life threatening toxicity and severe hypotension occurred. Effects included confusion, ataxia, chills, vomiting diarrhea and burning erythema.


Differential DiagnosisA sudden attack on a otherwise

healthy cohort with irritant polysystemic symptoms including skin burning in the absence of miosis after being exposed to a vapor with yellow or reddish color.

Staph B does not affect the skin.Other vesicants have an odor this

does not.


Laboratory DiagnosisRequires a high index of suspicion.No detector to warn one ahead of time.Obtain samples for presumptive testing

by liquid - gas chromatography then mass spectroscopy for confirmatory testing.

Screening testing is becoming available.White count takes about 48 hours to

drop.


TreatmentIn the military a protective suit and

M40 or later mask is used. Or N95 mask.

Remove from area.Decontaminate after removing

clothing with soap and water.No specific therapy is known.Superactive charcoal may trap

some of the T2.


General Therapeutic Protocol in Animals

SupercharcoalMagnesium sulfateMetoclorpramideDexamethasoneSodium bicarbonateNormal saline


Prophylaxis

No vaccine is available though several are in research with some efficacy in animals.

If protective garment and mask is available use it.


Reporting

T2 is a putative bioterrorist agent and must be reported to the local or state health department and law enforcement immediately on suspicion.


Always Contact Local Public Health DepartmentTarrant County Public Health 1101 S.

Main Street Fort Worth, Texas 76104 817-321-4700

Dallas County Department of Health & Human Services2377 N. Stemmons Freeway Dallas, Texas 75207-2710 214-819-2004.

stevan cordas do incapacitants1 incapacitants stevan cordas do mph

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