Lecture 10 - Tutorial II: PNS & CNS

Question 1

What is the MOA of Cholinergic transmission?

Answer 1

Mechanism of action:
Acetylcholinestrase inhibition leading to ACh
accumulation and overstimulation of PNS and
CNS cholinergic receptors = cholinergic crisis

Question 2

Question 3

Answer 3

Toxicants are anti-acetylcholinesterase. Ach is not quickly removed or NM junction b/c enzyme that breaks it down is inhibited. Ach binds to many receptors on post0sn cleft –> mass activation of cholinergic receptors.

Question 4

What is the difference between OPs and Carbamates?

Answer 4

1. OPs form a strong covalent bond with AChE
    Bond is initially reversible
    Becomes irreversible after “aging”
    Aging results from loss of an alkyl group
2. Carbamates form weaker bonds with AChE
    Reversible
    No aging

Question 5

What are the clinical signs?

Answer 5

• A combination of signs:
   Muscarinic
   Nicotinic
   CNS
• NOT ALL signs will be seen in all animals
  and signs will vary over time (see videos)
• Death often due to respiratory failure
   Bronchoconstriction, bronchorrhea
   Paralysis of respiratory muscles
   Central respiratory depression
• Sometimes sudden death is the only sign

Question 6

How do you diagnose?

Answer 6

1. History and clinical signs
2. ATROPINE TEST
    LOW dose (pre-anesthetic dose: 0.02 to 0.04
   mg/kg)
    Not a particularly good test for horses  ILEUS
3. If no atropinization (i.e., no responses such as
   tachycardia, mydriasis, reduced glandular
   secretions, etc):
    Very likely AChE inhibitor, e.g., OP is present
4. AChE activity
    Whole blood: >50% decrease indicates exposure;
   >75% decrease is diagnostic
    Brain
    Retina
5. Chemical analysis for OPs
    Rumen/stomach contents
    Liver, skin, wool, urine, etc.
6. Necropsy
    Usually non-specific
    May see pulmonary changes

Question 7

What is the treatment plan?

Answer 7

1. Initiate ASAP. Stabilize patient first
    Secure airway and ventilate if necessary
    Administer supplemental oxygen
    Secure venous access and collect blood for lab
   tests
    Administer isotonic IV fluids to support perfusion
   and blood pressure
    Control seizures

Question 8

How would you decontaminate?

Answer 8

–> Induce emesis for recent (<1h) oral exposures
if no contraindications exist

–> Administer activated charcoal @ 1-5g/kg.

–> Administer a carthartic

–> Gastric/enterogastric lavage
–> For dermal exposure bathe animal with
warm water and mild hand dishwashing
detergent

Question 9

Decontamination via emesis in dogs and cats?

Answer 9

1. Dogs
   - Hydrogen peroxide
   - MOA: Local irritation of oropharynx and gastric lining
   - Apomorphine
   - MOA: Centrally acting, stimulates dopamine receptors in chemoreceptor trigger zone (CRTZ)
2. Cats
   - Xylazine
   - MOA: Centrally acting, stimulates α2-adrenergic
   receptors in CRTZ
   - Dexmedetomidine
   - MOA: Centrally acting, stimulates α2-adrenergic
   receptors in CRTZ

Question 10

Decontamination via activated charcoal ?

Answer 10

 Regarded as a “universal antidote” in the Tx of
toxicoses
 It is a highly porous material with an enormous
surface area relative to its weight
 Adsorption of substances onto activated
charcoal is reversible because substances bind
to it by weak bonds
 Typically, there is rapid adsorption and slow
desorption

Question 11

Administer a cathartic?

Answer 11

 Sorbitol (comes mixed with activated charcoal
(ToxiBan)) or saline cathartic (Mg or Na salts)
 Avoid Mg salts due to CNS depressant effect of Mg
 Usually not necessary for OP toxicosis because
patients often have diarrhea
 Sorbitol (osmotic cathartic) draws water to GI tract
 Accelerates toxicant transit through GI tract and
decreases time for absorption
 Decreases time for desorption of toxin from
activated charcoal
 Saline cathartics stimulate GI motility

Question 12

Gastric/enterogastric lavage

Answer 12

 For ingestion of large amounts of OP before
emesis has occurred or if emesis is
contraindicated
 May need to take scout radiograph to assess
presence or absence of ingesta if substantial
amount of time has elapsed since ingestion

Question 13

Dermal exposure

Answer 13

Activated charcoal is indicated in dermal
exposure because grooming leads to oral
exposure

Question 14

How is atropine an antidote?

Answer 14

 Atropine
 Competes with ACh for muscarinic receptors
and blocks them
 Very little effect at nicotinic sites
 Dosing:
 Much higher doses than pre-anesthetic dose
 IV, IM or SC. Dosage varies with animal species
 Repeat as needed
 Don’t over-atropinize

Question 15

Answer 15

When atropine given it binds to post-syn receptors and then the recptors are no longer avalable to bind to ACh. Reduces stimulation of cholinergic receptors and reduces signs of toxicosis. Atropine does not bind to ? so it does not mimic ? of toxicosis.

Question 16

Answer 16

When atropine given it binds to post-syn receptors and then the recptors are no longer avalable to bind to ACh. Reduces stimulation of cholinergic receptors and reduces signs of toxicosis. Atropine does not bind to ? so it does not mimic ? of toxicosis.

Question 17

How is 2-Pralidoxime (2-PAM) used as an antidote?

Answer 17

 For OPs, not CMs
 Best when used in conjunction with atropine
 Combines with the OP and removes it from AChE
 Reactivates AChE
 Give early, prior to aging
 IV or IM. Can repeat administration
 Can quickly reverse nicotinic signs
 Also reverses muscarinic and CNS signs
 Not recommended for carbamates toxicosis

Question 18

Answer 18

How 2Pam reactivateds Achesterase that has been deact by phosphorylatin following phosphory exoposre.
2PAM removed organophosphate from ACTemzyne and binds the OP. This reactivates the enxyme and the OP boudn to 2 PAm is excreted.

Question 19

Question 20

Symptomatic and Supportive Tx

Answer 20

 Give diazepam or short-acting barbiturate for
seizures/convulsions
 Artificial respiration and supplemental oxygen
 Give IV fluids
 Treat hyperthermia. Cooling techniques include
spraying dog with cool water or immersing dog in
cool water; wrapping dog in cool, wet towels;
convection cooling with fans; and evaporative
cooling (e.g., applying isopropyl alcohol on foot
pads, groin, and under the forelegs)