Carbamates Organophosphates and Riot Agents
Organophosphates
- Agents
- Dimethyl: azinphos-methyl, demeton-s-methyl, dichlorvos, dimethoate, fenitrothion, malathion, oxydemeton-methyl, parathion-methyl
- Diethy: Chlorpyrifos, diazinon, disulfoton, ethion, parathion, quinalphos
- diMethyl More important to give 2-paM
- Exposure
- Dermal exposure with the concentrated product or for prolonged periods of time.
- Volatility contributes to exposure: Dichlorvos > malathion
- Distributed in fat, liver, kidney, salivary gland => redistribute out, can have prolonged effects.
- Phosphorothioates (diethyl) may have delayed onset due to activation
- Clinical Manifestations
- PNS (muscarinic), CNS, Nicotinic. Onset within 5 minutes but always within 12 hours.
- Initial symptoms may be simply exhaustion and fatigue/weakness. Followed by n/v/d, sweating, hypersalivation. Miosis
- PNS (muscarinic), CNS, Nicotinic. Onset within 5 minutes but always within 12 hours.
- Clinical Toxicology
- Oxon phosphorylates the serine hydroxyl group at the active site of AChE
- Partial dealkylation of this serine hydroxyl group renders AChE renders the enzyme inactive and cannot be reactivated = AGING
- Rate of spontaneous reactivation faster with diETHYL. So aging a bigger risk with diMETHYL
- Must give 2pam within 2-4 hr of Dimethoxy; 48 hours after diethoxy
- Bronchorrhea: neuronal and nonneuronal cholinergic stimulation of the mucous glands, cilia, and cells producing ciliary fluid.
- Bronchconstriction-> M3 stimulation
- Atropine start with 2 mg
- 2-PAM 30mg/kg, repeat q6 or infusion of 8-10 mg/kg/hr. Continue for as long as atropine is required.
- Diazepam/Midazolam – can give phenytoin for seizures
- Notes
- Phosphates (P=0) are biologically active
- Phosphorothioates (P=S) must be bioactivated to the corresponding metabolite (“thion” to “oxon”)
- Activated by oxidative desulfuration by CYP450 (among other things)
- OP Delayed Neuropathy (1-4 weeks), phosphorylation and subsequent aging of > 70% of neuropathy target esterase (NTE) [distinct from AChE] – > linked to methamidophos
- Intermediate syndrome
- Recurrent cholinergic signs 24-96 hrs after exposure. Oximes can prevent IS
- Delayed neuropsychiatric effects – following long term, low-level exposures (occupational hazard)
- BuChE falls first, followed by RBC AChE
- RBC AChE: (1) more accurately reflects CNS AChE (2) Also more accurate at low hematocrits (3) takes weeks to recover
Carbamates
- Agents
- SALAD-> dithiocarbamates (fungicides= maneb, zineb, thiram) resemble disulfiram; metam sodium degrades to methyl-isothiocyanate
- Aldicarb, bendiocarb, benfuracarb, butoxycaroxim, carbosulfan, carbofuran, carbaryl, ethiofencarb, methomyl, theiocarb, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox
- Exposure
- Undergo 2 phase biotransformation:
- Phase 1 hydrolysis by nonspecific carboxylesterases or oxidation
- Phase 2 conjugative reactions
- Most carbamates DO NOT CROSS BBB
- Exposure via skin, inhalation, ingestion
- Clinical Manifestations/Toxicology
- Carbamates are hydrolyzed in alkali -> decon strategy
- Inhibit AChE by carbamylation of serine hydroxyl residue at the active site. Activity is restored after spontaneous hydrolysis of the carbamylated enzyme.
- Lab measurement is not helpful due to rapid course of toxicity. Blood samples must be kept frozen -> slows spontaneous decarbamylation of AChE
- Atropine, 2-PAM just like with OPs
- Notes
- Seizures are rare due to limited penetration into the CNS. So when they occur are usually due to hypoxia
- Not commonly associated with delayed neurological sequelae since they are short-acting.
- Gastric lavage NOT RECOMMENDED due to coformulation with hydrocarbons and risk of pneumonitits.
TOCP (tri-ortho cresyl phosphate)
- Ginger Jake Paralysis (contaminating bootlegged alcohol during prohibition)
Riot control/incapacitating agents
- Lacrimators (All have RAPID onset):
- CN (Chloroacetophenone)-Chemical Mace
- CS (Chlorobenzilidine malononitrile)-Capsaicin
- CR (Dibenzoxazepine)
- DM (Adamsite)
- Clinical Manifestations
- Vesication if severe/high dose
Incapacitating agent
- Agents
- 3-quinudclidinyl benzilatate (BZ)
- DELAYED onset (HOURS) – 25x more centrally potent than atropine (Central anticholinergic toxidrome)
- Super potent opioids
- PS- Chloropicrin (nitrochloroform)
- 10-chloro-5,10-dihydrodiphenarsazine (DM)
- Induces vomiting
- 3-quinudclidinyl benzilatate (BZ)
For more chapters, visit the ABAT Study Guide homepage
Carbamates Organophosphates and Riot Agents
Leave A Comment