Pesticides and Organophosphates

kinds of insecticides

• organophosphates / carbamates

• pyrethroids

• organochlorines

• botanical insecticides

types of botanical insecticides

• nicotine

• rotenoids

types of organophosphates

• sarin

• soma

• malathion

• parathion

organophosphates composition

organic compounds that contain phosphorous

carbamates composition

salts or esters of carbamic acid

types of carbamates

• carbaryl

• carbofuran

• aldicarb

• oxamyl

organophosphates and carbamates similarities

share similar MOA and cause similar clinical manifestations

main difference between organophosphates and carbamates

• OPs irreversibly phosphorylate AchE

• carbamates reversibly bind AchE

main MOA of organophosphates and carbamates

inhibition of acetylcholinesterase

effect of the inhibition of AchE

• accumulation of free, unbound Ach at the nerve terminal

• continual stimulation of all cholinergic nerves

PNS effect of inhibition of AchE

stimulation of the muscarinic receptors

SNS and PNS effect of inhibition of AchE

stimulation and subsequent blockade of nicotinic receptor

organophosphate aging

the irreversible process by which the bond between an OP and AChE becomes permanent

cause of organophosphate aging

loss of an alkyl side chain

nature of substituent groups for organophosphate aging

• specificity for the enzyme

• tenacity of binding to the active site

• rate at which the phosphorylated enzyme dissociates

PNS signs and symptoms of organophosphates and carbamates

increased secretions, bronchoconstriction, diarrhea, edema, urination, etc.

SNS & PNS sign and symptoms of organophosphates and carbamates

• tachycardia

• tremors

• muscle weakness

• flaccid paralysis

CNS signs and symptoms of organophosphates and carbamates

• ataxia

• lethargy

• mental confusion

• generalized weakness

• convulsion

psychopathologic signs and symptoms of delayed neurotox

neurologic lesions

2 patterns of signs and symptoms of delayed neurotox

• low vitality and ambition

• premature aging

cause of delayed neurotox

• dying back of degeneration of large diameter axons and their myelinic sheaths

• inhibition of a neuronal, nonspecific carboxylesterase, neuropathic target esterase

examples of low OP toxicities

• LD50 > 1000

  • malathion

  • temephos

  • bromophos

examples of moderate OP toxicities

• LD50 50-1000

  • chlorpyrifos

  • diazinon

  • profenofos

examples of high OP toxicities

• LD50 < 50

  • parathion

  • azinophos-methyl

examples of carbamate low toxicity

• >200

  • carbaryl

examples of carbamate moderate toxicity

• 50-200

  • carbosulfan

examples of carbamate high toxicity

• <50

  • aldicarn

  • carbofuran

diagnosis of organophosphates and carbamates

• case history

• lab evidence

  • plasma pseudocholinesterase

  • RBC cholinesterase

drug therapy for organophosphates and carbamates

• atropine

• pralidoxime 

  • 2-PAM

  • Protopam

• pyridostigmine bromide or physostigmine

• toxogonin or obidoxine

examples of organochlorine

• DDT

• chlordane, aldrin and dieldrin

• chlorinated benzenes/ cyclohexanes

MOA of DDT

• sodium channels are altered

• potassium channels are also affected

• inhibition of ATPase

• inhibition of calmodulin

use of sodium channels

once activated, they close slowly, prolonging the depolarization of the nerve by interfering with the active transport of sodium ions out of the axon

effect of inhibition of ATPase

repolarization inhibited

calmodulin

important in release if neurotransmitters

signs and symptoms of organochlorines

• DDT jitters

• seizures, headache, dizziness, nausea, vomiting, parethesia

DDT jitters

neurons fire impulses spontaneously causing muscles to twitch

MOA of cyclodienes

• acts on the GABA receptor

• prevents chloride ions from entering the neurons

• inhibits Na/ K and Ca/ Mg ATPase

signs of cyclodienes poisoning

• dizziness

• headaches

• myoclonic jerking

• seizures

• convulsions

treatment of chlorinated hydrocarbons

• medical emergency

  • tremors, motor seizures

• decon and supportive

• diazepam or phenobarbitol

• Chloestyramine

  • depending on extent of biliary excretion

MOA of nicotine

• mimics action of Ach

• muscular fasciculations, convulsions, death

• direct effect on brain

  • vomiting and seizures

treatment of nicotine

mecamylamine

moa of rotenoids

blocks electron transport in mitochondria by inhibiting oxidation linked to NADH2

• nerve conduction blockade

2 main types of herbicides

• chlorophenoxy compounds

• paraquat

treatment for paraquat

• gastric lavage followed by activated charcoal

• hemoperfusion

paraquat derivative

bipyridyl derivative

symptoms of paraquat

• dehydration

• electrolyte abnormalities

• low blood pressure

• abdominal pain

• kidney or liver failure

• nausea, vomiting

• pain and/ or swelling of mouth or throat

• heart failure

• lung scarring

• bloody diarrhea

destructive phase of paraquat

• Type I and II damage

• damage to pulmonary capillaries

• early necrosis of terminal bronchioles

• alveolar and interstitial edema

proliferative phase of paraquat

• fibroblasts and collagen synthesis

• intraalveolar fibrosis

types of fungicides

• hexachlorobenzene

• organomercurials

• dithiocarbamates

  • mancozeb

  • maneb

  • ethylene- bisdithiocarbamate

effects of hexachlorobenzene

• black sore

• osteoporosis, porphyria

• pink sore

types of fumigants

• methyl bromide

• phosphine (PHE)

  • chloropicrin

• sulfuryl fluoride

• dibromochloropropane (DBCP)

features of methyl bromide

• nonselective, highly reactive and cytotoxic

• irritating to the respiratory tract

DBCP toxicity

• sterility in males

• >200 ppm pulmonary edema

• centralobular hepatic necrosis

• proximal tubular necrosis