Pesticides: Carbamates Dr. Bergfelt

Question 1

Hx of Carbamates (CM)

Answer 1

Physostigmine 1st carbamate isolated then neostigmine (these are drugs we use today!)

Carbaryl - 1st carbamate insectiside, broad spectrum insect control, very low mammalian oral & dermal toxicity

Aldicarb - most toxic of CMs synthesized to mimic structure of ACh

More readily degraded than OP, not as lipid soluble

DO NOT undergo storage activation

Question 2

Toxicokinetics of CM

Answer 2

Do NOT penetrate CNS - effects mostly respiratory

DOES NOT require hepatic bioactivation - which makes more toxic than some OP in very young pts

Faster onset/shorter duration than OP

Question 3

MoA of CM

Answer 3

REVERSIBLE inhibition of ACh!

Competative inhibition (mass action)

CM-ACh dissociates more rapidly than OP-ACh

Important consequences compared to OPs:
Limits the duration of carbamate poisonings
Greater span between symptom-producing effects and lethal
doses
May invalidate the measurement of blood cholinesterase
activity as a diagnostic index as it disassociates rapidly enough
not to be detected

Question 4

CS of CM

Answer 4

Similar to OP

SLUD

Salivation

Lacrimation

Urination

Diarrhea

death usually from resp failure

Question 5

Dx of CM toxicity

Answer 5

Lab Dx:

Cholinesterase levels - Drug residues may not be detectable in tissues, blood or secretions b/c of rapid metabolism

Clinical Dx:

Hx, atropine response test

Question 6

Tx of CM

Px

Answer 6

• *Atropine** – same as for OPs
• *Oximes or 2-PAM not reliably effective against carbamates**
• Reversible binding reduces benefit*
• *Contraindicated with Carbaryl (Sevin) - can potentially increase the carbamylation process**

Px: good if tx soon, if not severe CS may survive w/o tx