Autonomic drugs: Cholinesterase inhibitors

Question 1

cholinesterase inhibitors effects

Answer 1

profound effects skeletal muscle, autonomic system and brain

Question 2

what are the two binding sites on cholinesterase enzyme important for drug action?

Answer 2

anionic

esteratic

Question 3

why hydrolysis acetylcholine?

Answer 3

AChE

-block parasympathetic system and somatic system

Question 4

how is the anionic site formed?

Answer 4

by ring systems of Trp and Phe binds ACh

Question 5

how is the esteratic side formed?

Answer 5

by Ser, His, and Glu hydrolyses ester

Question 6

ACh is hydrolysed

Answer 6

rapidly

25,000 molecules/sec

Question 7

is the inhibitor neostigmine hydrolyzed?

Answer 7

Yes, but carbamate portion remains on the Ser to block further hydrolysis for a few hours

Question 8

edrophonium

Answer 8

• simple quarternary alcohol, no ester, lasts for 2 days
• binds to anionic site
• duration few mins, must inject, can’t take orally
• organophosphate block AChase

Question 9

medical use of cholinesterase inhibitors?

Answer 9

Alzheimer’s

• most common cause of dementia in old age
• improper processing beta amyloid protein-> beta-amyloid 42, toxic
• loss of cholinergic neurons in brain
• treated with donepezil

Question 10

ACh inhibitors neostigmine used to

Answer 10

increase GI activity postoperatively

• quaternary but effective p.o.
• no CNS effects

Question 11

Myasthenia gravis

Answer 11

skeletal muscle weakness

• autoimmune loss receptors
• loss 2/3 receptors-> symptoms
• more common in women
• neostigmine effective: increase in muscle strength

Question 12

drugs used for MG

Answer 12

• edrophonium for diagnosis, injection and short duration of action (sometimes neostigmine used)
• pyridostigmine p.o. for treatment: longer duration of action than neostigmine

Question 13

important amino acids in AChE

Answer 13

• Glu237
• Phe338
• His440
• Ser203
• Trp86

Question 14

catonic cholinesterase inhibitors

Answer 14

act on anionic site

• edrophonium 4N
• donepezil 3N

Question 15

carbamate ester cholinesterase inhibitors

Answer 15

rivastigmine 3N
physostigmine 3N
neostigmine 4N
pyridostigmine 4N

Question 16

insecticides

Answer 16

chlorpyrifos

malathion: specific for insects
- non medical cholinesterase inhibitors
- block cholinesterase
- block esteratic site

Question 17

nerve gases

Answer 17

soman

Question 18

toxicicty from cholinesterase

Answer 18

asphyxia

Question 19

four factors for asphyxia

Answer 19

bronchoconstriction
increased secretions: can drown in own secretion
skeletal muscle paralysis
CNS depression: at a high dose

Question 20

Acronym for symptoms

Answer 20

DUMBELS 
Diarrhea
Urination
Muscle weakness, miosis
Bronchoconstriction
Excitation
Lacrimation
Seizures, sweat, salivation

Question 21

treatment of toxicity

Answer 21

because increasing acetylcholine in body:

1. atropine: block parasympathetic
2. For skeletal muscle: pralidoxime (2-PAM) (Protopam)
   - blocks anionic site from quaternary charge

Therapy quickly
May require prolonged therapy

Question 22

what does atropine not help with in toxicity

Answer 22

skeletal muscle paralysis

-PAM does

Question 23

what does Pralidoxime not help with in toxicity

Answer 23

CNS depression

-quaternary, won’t get to brain

Question 24

Malathion for pediculosis capitis

Answer 24

common in school children

• person contact transmision
• vector for typhus, trench fever, relapsing fever
• small ovoid gray nits (ova) and mature lice both respond to malathion

Question 25

what are pyridostigmine and edrophonium also used to diagnose?

Answer 25

distinguish between MG and cholinergic crisis

• too much ACh-> get weakness
• MG: edrophonium will make them feel better
• cholinergic: edrophonium will make worse because already too much drug there

Question 26

Acronym for parasympathetic

Answer 26

SLUG

Salivation, Lacrimation, urination, GI