8: Toxicants Affecting the Nervous System 3

where is Ach?

EVERYWHERE

most common neurotransmitter in the body

Ach

hints at cholinesterase inhibitors

if there is a hole, something comes out of it. if it can be wet, it will be wet

how to remember muscarinic signs

sludge or dumbels

S (sludge)

salivation

L (sludge)

lacrimation

U (sludge)

urination

D (sludge)

defecation

G (sludge)

GI pain

E (sludge)

emesis

D (dumbels)

defecation/diaphoresis

diaphoresis

sweating

U (dumbels)

urination

M (dumbels)

miosis (pupil constriction)

B (dumbels)

bronchospasm/bronchorrhea

E (dumbels)

emesis

L (dumbels)

lacrimation

S (dumbels)

salivation

how to remember nicotinic signs

match

M (match)

muscle fasciculations, tremors, paresis, paralysis

A (match)

adrenal medulla stimulation

T (match)

tachycardia

C (match)

cramping

H (match)

hypertension

what signs do we see with cholinesterase inhibition?

BOTH MUSCARINIC AND NICOTINIC SIGNS

organophosphates are used in what?

insecticides, fuel, lubricants, chemical warfare

what does organophosphates inhibit?

Ach

how are organophosphates absorbed?

GI/respiratory tract, skin

3 manifestations of OP toxicosis IN ORDER

1. acute cholingergic syndrome 2. intermediate syndrome 3. OPIDN

OPIDN

organophosphate-induced delayed neuropathy

OP toxicity time (acute cholingergic syndrome: stage 1)

few mins-hours

treatment of OP toxicity (acute cholinergic syndrome: stage 1)

2-PAM and atropine ASAP

OP toxicity time (intermediate syndrome: stage 2)

1-4 days (24-96 hrs)

MOA of OP toxicosis (intermediate syndrome: stage 2)

excess Ach at NMJ downregulates postsynaptic AchRs (receptors).

signs of OP toxicosis (intermediate syndrome: stage 2)

muscle weakness, cranial nerve palsies, respiratory paralysis

treatment of OP toxicosis (intermediate syndrome: stage 2)

supportive care (ventilation)

how long do signs of (intermediate syndrome: stage 2) OP toxicosis last?

1-3 weeks

over time, what do OPs cause?

aging of Ach

once Ach has aged, can we use 2-PAM drug?

NO, new Ach must be synthesized by body

what drug CAN we use with aged Ach?

atropine

2-PAM

pralioxime

if Ach is aged, what will eventually develop?

OPIDN

is OPIDN treatable/reversible?

NO

time onset of OPIDN

10-21 days

signs of OPIDN (3rd stage OP toxicity)

pain, tingling, weakness in pelvic limbs, unsteady gait, limb paralysis

Tx of OPIDN (3rd stage OP toxicity)

supportive care, physical therapy, rehabilitation

do all OPs cause aging of NTE?

NO

true or false: aging of NTE is DOSE-DEPENDENT

TRUE

can NTE aging be treated with 2-PAM?

NO

NTE

neuropathy target esterase

true or false: different OPs age at different rates

TRUE

fastest OP to age

SARIN (minutes) - most dangerous

summary of aged Ach

2PAM doesn't work, use atropine

summary of aged NTE

OPIDN can develop

do carbamates cause aging?

NO

what do carbamates cause?

acute cholinergic syndrome

is there an intermediate or OPIDN stage with carbamates?

NO

what are carbamates used in?

insecticides/herbicides/fungicides

treatment for carbamate toxicity

ATROPINE ONLY

what type of drug is atropine?

anti-cholinergic

SIDE EFFECTS OF ATROPINE

secretion drying, mydriasis, arrhythmias, flushing, confusion, hallucination, ileus

low dost test

atropine challenge test

what does it mean if the low dose test is POSITIVE?

if HR DOES NOT rise significantly - OP/carbamate PRESENT

what does it mean if the low dose test is NEGATIVE?

if HR GOES UP A LOT - OP/carbamate ABSENT

what species should we use EXTREME CAUTION in with atropine?

horses

what can atropine do to horses?

cause fatal ileus (inhibition of GI motility)

organochlorine pesticides

DDT, aldrin, endosulfan, lindane

DDT

dichloro-diphenyl-trichloroethane

OCP

organochlorine pesticides

OCP MoA

act at NERVE AXON, interfere with Na/K gates

signs of organochlorine pesticides

hyperexcitability, resulting in seizures, tremors, paresthesias, ataxic gait, etc

paresthesias

feeling something that is not there (tingling/burning)

true or false: nicotine causes nicotinic signs (remember match)

TRUE

pyrethrin/pyrethroids

permethrin, allethrin, (IF IT ENDS IN THRIN, ITS ONE OF THESE)

what are pyrethrins derived from?

chrysanthemums

pyrethrin MoA

Na channel blocker

how is pyrethrin cleared?

metabolixed thru glucoronidation pathway (ABSENT IN CATS)

true or false: pyrethrin exposure (especially concentrated) is FATAL TO CATS

TRUE

immediate treatment of cats for pyrethrin

WASH WITH DAWN DISH SOAP MULTIPLE TIMES

where is pyrethrin commonly seen? why do cats get it so much?

topical DOG flea/tick treatments. people use it on cats not knowing

signs of cat with pyrethrin toxicity

profuse drooling, vomiting, tremoring, hyperexcitability, agitation, seizures, weakness, dyspnea