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RUSVM Toxicology > Organophosphates > Flashcards

Organophosphates Flashcards

1
Q

What are the uses?

A

Animal and plant insecticides, insecticides synergistic, anthelmintics, antiglaucoma, soil nematocides, fungicides, herbicides, rodenticides, and insect repellents

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2
Q

What do organophosphate contain in their names?

A

“Phosphate”
“Phos”
“Photo”
“Phosphor”

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3
Q

What is the source of organophosphate toxicosis?

A

Contaminated feed or drinking water
Empty pesticide containers used for feeding or watering animals
Dusting or spraying animals or animal premises
Overdosing
Widely used

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4
Q

What are the properties?

A

Not very persistent in the environment (2-4 wks)
Some may persist longer (36 wks)
Poorly soluble in H2O, but soluble in organic solvents and in fats and oils
Penetrate intact skin and waxy coatings of leaves and fruits

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5
Q

What are the factors influencing toxicity?

A

Toxicant factors

Animal factors

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6
Q

What are some of the toxicant factors?

A

Toxicity decreases by degradation of the compound in the environment
Storage activation of certain compounds
Technical grades are more toxic than pure compounds bc of heat isomerization and impurities
Some vehicles increase toxicity such as organic solvents

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7
Q

What are organophosphates?

A

Naturally occurring associated with DNA, RNA, and many cofactors that are essential for life

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8
Q

What is their MOA?

A

Irreversibly inactivate acetylcholinesterase causing persistent acetylcholine activity

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9
Q

What is the most common organophosphate?

A

Malathion

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10
Q

True or False. Organophosphates are lipid soluble but not water soluble.

A

False, have some degree of both

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11
Q

What are some chemically properties of organophosphates?

A

Various degrees of solubility in water and fat

Most are NOT very persistent in the environment (2-4 weeks)
Some may persist longer (up to 36 weeks)
Can penetrate intact skin and waxy coating of leaves and fruits

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12
Q

Tissue accumulation varies on type of OP, but generally ________________ are more lipophilic than phosphates

A

Thiophosphates

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13
Q

Where are these drugs generalized metabolized?

A

The liver

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14
Q

What lethal synthesis?

A

-is de-sulfuration by the liver enzymes

“Lethal synthesis?- liver enzymes CYP450 metabolize or bioactivate thiophophate OPs (ex. Malathion)

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15
Q

What require hepatic bioactivation (lethal synthesis)?

A

Thiophosphates (P=S)

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16
Q

What are thiophosphates?

A

Biologically inactive until transformed (desulfurated) by the liver to oxon metabolites

17
Q

What is the major round of elimination?

A

Paraoxonase- a serum bound enzyme

18
Q

What is the mechanism of action?

A

Irreversible inhibition of cholinesterases

-Ach accumulates through the CNS resulting in over stimulation of muscarinic and nicotinic receptors

19
Q

What are the muscarinic effects?

A

-overstimulation of the parasympathetic NS- use DUMBELLS

Diarrhea
Urination
Miosis
Bronchospasm
Emesis
Lacrimation
Salivation
20
Q

What are some nicotinic effects?

A

Paralysis

Stimulation of sympathetic NS could produce sweating, hypertension, and tachycardia

21
Q

What are some CNS effects?

A
  • Increased pulmonary secretions coupled with respiratory failure then death
  • recovery depends ultimately on generation of new enzyme or Ach-esterase in critical tissues
22
Q

What are two delayed effects (thiophosphates) and when do they develop?

A

Organophosphate-induced delayed polyneuropathy; develops 10-14 days after exposure

Organophosphate-induced intermediate syndrome; occurs 2-4 days after acute cholinergic effect and signs of the acute effects are no longer obvious

23
Q

What are the clinical signs of organophosphate-inducted polyneuropathy?

A

Muscle weakness, ataxia, rear limb paralysis

24
Q

What is the MOA?

A

Irreversible inhibition of cholinesterases

  • Non competitive inhibition
  • aging conformational change in OP- Ach esterase complex that results in increased or irreversible binding of the complex over time
25
Q

What is a clinical sign of over exposure?

A

Lung mucous production and airway obstruction

26
Q

What is a specific lesion to look for?

A

Pulmonary edema

27
Q

What is the laboratory diagnosis like?

A

<50% is suspicious

<25% activity is diagnostic

28
Q

What test is used to for clinical diagnosis?

A

Atropine response test

  • if positive low likelihood of OP poisoning
  • if negative high likelihood of OP poisoning
29
Q

During treatment of OP poisoning what should you avoid?

A

Phenothiazines, aminoglycosides, muscle relaxants, drugs that depress respiration (opioids)

30
Q

What is the treatment of OP poisoning?

A

Atropine

  • main concern with OP toxicity is resp failure (asphyxia and death) from excessive airway secretions
  • Atropine therapy acts to suppress or dry pulmonary secretions

RUSVM Toxicology (23 decks)

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