Organophosphates and carbamates Flashcards
- What is the cause of intermediate syndrome? What species are typically affected?
- What is the pathogenesis of this syndrome?
- Seen in dogs/cats 24-96h after ingestion of highly lipophilic OPs, repetitive exposure to low doses of OPs, or prolonged dermal exposure. The OPs responsible include chlorpyrifos, diazinon, malathion, parathion, phosmet, bromophos, others. The CM carbofuran also causes IMS
- The pathogenesis is unclear but is thought to be due to decreased AChE activity and decreased nicotinic ACh receptor mRNA expression
- What are the clinical signs of intermediate syndrome?
- What is occurring physiologically?
- Where is there a defect?
- Anorexia, generalized muscular weakness, paralysis, tremors, seizures, depression, death
- There is severe AChE inhibition, but no muscarinic receptor associated hypersecretory activity
- Defect is at the neuromuscular and postsynaptic level
– Some OPs appear to be preferentially distributed to muscles and have higher affinity for nicotinic ACh receptor
- What is OP-induced Delayed Polyneuropathy (OPIDP)? What have some of these OP’s been used as?
- When does toxicity occur?
- Which species are the most sensitive to ingestion?
- What is this syndrome characterized by?
- What are the clinical signs?
- OPIDP, or Ginger Jake, is caused by ingesting OPs (e.g. TOCP = Tri-ortho cresyl phosphate, *EPN = *EPN = Ethyl p-nitrophenyl phenylphosphorothioate
, leptophos). Some of these compounds (known as triaryl phosphates eg, triorthocresyl
phosphate) have been used as flame retardants, plasticizers, lubricating oils, and hydraulic fluids - Toxicity occurs 1-4 weeks after exposure to the toxic agent.
- Chicken are the most sensitive animals
- OPIDP is characterized by distal degeneration of long and large diameter motor and sensory axons of both peripheral and spinal cord nerves. This is due to inhibition of neuropathy target esterase (NTE) and degeneration of axons and myelin sheaths.
- Signs: Weakness, ataxia and paralysis of limbs
They are weak cholinesterase inhibitors but do inhibit “neurotoxic esterase” (NTE) present in the brain and spinal cord.
- How do you Dx OP and Carbamate toxicosis?
When would you, the clinician, typically see clinical signs?
- History of access to or Tx with OP/CM
- Clinical signs
- Atropine test - no atropinization
- ChE activity in heparinized whole blood (Note: ChE activity is depressed in anemia). In dead animals: measure brain ChE activity
- Chemical residues in stomach contents, vomitus, hair, and bait by GC-MS
- Signs are seen when brain AChE activity is inhibited >70%
Define atropinization.
Atropinization: appearance of typical sign of atropine administration such as increased heart rate and mydriasis (dilation of pupils).
How do you perform the atropine test?
i). Obtain baseline heart rate from patient.
ii).Administer a preanesthetic dose of atropine to patient (0.02 - 0.04 mg/kg IV for dogs/cats).
How do you interpret atropine test results?
i). If there is atropinization (heart rate
increases and pupils dilate); Other signs of atropinization can be monitored but heart rate and dilation of the pupils are the signs typically monitored –> OP/ carbamate toxicity is not likely.
ii). If there is NO atropinization (heart rate does NOT increase and pupils do NOT dilate), OP/carbamate toxicity is likely.
The atropine test requires much _______ doses of atropine (as high as ___ times the pre-anesthetic dose) to resolve the muscarinic signs (DUMBELLS) of OP/ carbamate poisoning.
higher, 10
What would be your DDx in a case of OPIDP?
- Tremorgenic mycotoxicosis
- Amitraz toxicosis
- Pyrethrin/pyrethroid toxicosis
- Pancreatitis
- Garbage intoxication
- Blue-green algae toxicosis
- Muscarinic mushrooms
- Cationic surfactants
How do you treat acute syndrome?
- Initiate ASAP and stabilize patient first
- Decontaminate
– Emesis for recent oral exposure (<2h), then administer activated charcoal and a cathartic
– Gastric/enterogastric lavage for ingestion of large amounts of OP/CM before emesis has occurred or if emesis is contraindicated
– For dermal exposure wash animal with water and mild hand dishwashing detergent (e.g., Dawn). No scrubbing. - Give antidote
– Atropine: Blocks muscarinic ACh receptors and relieves muscarinic but NOT nicotinic signs - Primary goal is to control bradycardia and secretions
– Pralidoxime (2-PAM): Reactivates AChE (before aging). 2-PAM is ineffective for CMs - Symptomatic Tx and supportive
– Diazepam or short-acting barbiturate for convulsions
– Artificial respiration to mitigate effects of respiratory paralysis
Drug categories: Three categories of drugs are used to treat OP poisoning: 1) muscarinic
receptor–blocking agents, 2) cholinesterase reactivators, and 3) emetics,
cathartics, and adsorbents to decrease further absorption.
What is the treatment for intermediate syndrome?
- Atropine is not indicated (no muscarinic signs). Tx is mainly supportive
– Feed animal parenterally or by pharyngostomy tube
– Correct dehydration and electrolyte imbalance if present
– Bathe animal if exposure is dermal - Give 2-PAM: Surprisingly, many patients respond to 2-PAM
- Anatoxin-a(s) is produced by?
- What does the “S” stand for?
- Where can the causative agent typically be found?
- When are animals at risk of interacting with this causative agent?
- Which species are4 susceptible?
- Produced by blue-green algae (cyanobacteria). [Anabaena, Aphanizomenon & Oscillatoria spp.]
- Salivation
- Blooms generally occur in stagnant eutrophic (^ nutrients (NO3, SO4 & PO4))
water bodies (ponds, lakes, ditches) when temperatures are warm, and weather is calm - Animals are at risk when blooms are concentrated along the shoreline by wind
- Susceptible species: All: dogs, cattle, swine, waterfowl
What is an algal bloom?
- Rapid increase in algal growth due to high nutrients
- Wind concentrates algae along the shoreline of water body = ^risk
List the anatoxin-a(s)-producing Cyanobacteria.
Anabaena
Oscillatoria
Aphanizomenon
ADME
* Cyanobacteria are ingested with water –> ____ in acidic stomach & ______ of toxins
–> toxins absorbed in ____ intestine –> toxicosis
MOT: _______ inhibition of ____________ in PNS
Clinical signs: ____ onset. DUMBELS.
_______ signs occur in lethal cases
lysis, release, small
Irreversible, acetylcholinesterase, Acute, Nicotinic
What is pictured below?
Belladonna Plant (Atropa belladonna)
* a.k.a deadly nightshade, sleeping nightshade
* Coarse herb (1–2m)
* Native to Europe, a garden plant in the USA
* Contains hyoscyamine (atropine) and scopolamine
A significant hazard to children
What is pictured below?
Black Henbane (Hyoscyamus niger)
* a.k.a. poison tobacco, stinking nightshade, insane root, etc.
* Annual or biennial, coarse, hairy, erect herb (1–2m)
* Habitat: northern USA
* Contains hyoscyamine and scopolamine
What is pictured below?
Datura stramonium
* a.k.a Jamestown weed, devil’s trumpet, mad apple, stink weed etc
* Stout, coarse, annual herb (1–2m)
* Grows in Midwest US
* Contains atropine and scopolamine
