Westminster Anticholinesterase

Front 1

___________ is the neurotrasmitter for the entire parasympathetic nervous system (ganglion and effector) and is the neurotrasmitter at the ganglion of the sympathetic nervous system, the adrenal medulla and sweat glands also some nuerons in CNS and somatic nerves in skeletal muscle

Back 1

ACH

Front 2

____________ is the NT at the effector in the sympathetic nervous system

Back 2

norepi

Front 3

__________ amines can be absorbed in the stomach, ________ amines cannot.

Back 3

tertiary

quaternary

Front 4

Parasympathetic Effects(Rest and Digest) of ach?

Back 4

Eye: Contraction to give miosis and near vision
Salivary Glands: Secretion
Heart: Decreased HR, conduction velocity, contraction
Lungs: Bronchoconstriction
Pancreas: Increased insulin secretion
Intestine: Increased Motility and tone
Bladder: Sphincter relaxation and Detrosor contraction

Front 5

_____________ are blocked by the nueromuscular blockers/muscle relaxants

Back 5

Nicotinic Receptors

Front 6

_____________ are blocked by the anticholigergic drugs

Back 6

Muscarinic receptors

Front 7

NMB's increase _________ neurotransmission but not change the __________ neurotransmission

Back 7

nicotinic

muscarinic

Front 8

For Alzheimer's use _________. why?

Back 8

Physostigmine

lipophylic and can cross BBB

Front 9

___________ is the only anticholinesterase not charged in the free base form.

Back 9

Physostigmine

Front 10

All anticholinesterases have carbamates except ____________.

Back 10

Edrophonium

Front 11

____________ binds within the active site because of it’s charge.

Back 11

Edrophonium

Front 12

2 insecticides?

Back 12

malathion (organophosphate)

sevin

Front 13

Catalytic triad?

Back 13

Serine
Histadine
Glutamic acid

Front 14

The __________ does the chemistry on the ester bond on the carbamate.

The chemistry happens on the _______.

Back 14

catalytic triad

serine

Front 15

_________ has a ring structure and is more lipophyllic …..helps orientation

Back 15

Histadine

Front 16

the _______ is negative, and our compounds are positive

Back 16

triad

Front 17

____________ binding is what places ester in correct site to form covalent bond with serine

Back 17

Quaternary amine

Front 18

__________ attacks ach and creates a covalent bond between the ________ of the serine and the _______ of the ester.

Back 18

Acetylcholinesterase

oxygen

carbon

Front 19

__________ forms strong electrostatic and hydrogen bonds with the enzyme.

Back 19

Edrophonium

Front 20

_______ AND _______ form covalent bond to the carbamate carbon of the enzyme

Back 20

Neostigmine/Pyridostigmine

Front 21

Organophosphate derivatives go through process called _______ and form irreversible bonds. (covalent bonds)

Back 21

aging

Front 22

there is no chemistry with?

Back 22

edrophonium

Front 23

Used to treat Myasthnia gravis – auto immune (destroys receptors)?

Back 23

neostigmine

Front 24

anti-Ach reversible mech's?

Back 24

2 hydrolysis steps(ester first, amide second-takes longer….can’t interact w/ ach, this is what causes the reversal) for the reversibles

Front 25

Losing an R group is ________. You could reverse after one aging, but not after two. (suicide inhibition)

Back 25

aging

Front 26

_________ only has one OR group so, it’s dead after one aging

Back 26

Sarin

Front 27

_________ can reverse complete block

Back 27

no dosage

Front 28

if too soon, will make the condition worse. why?

Back 28

This may be that excess Ach causes desensitization like that observed for depolarizing muscle relaxants

Front 29

Plasma concentrations quickly peak followed by a rapid decrease in concentration.

which ones?

Back 29

all

Front 30

absorption-
Poor from gut and across membranes since most are not lipophylic (exception is ________.)

Back 30

physostigmine and organophosphates

Front 31

Vd is?

Back 31

more than would be expected

.7-1.4

Front 32

metabolism?

Back 32

50% neostigmine/30%edrophonium/25%pyridostigmine
Physostigmine hydrolyzed by plasma esterases

Front 33

Elimination
T1/2 ~ 1-2 hr
Clearance greater than _______

Back 33

glomular filtration rate

Front 34

This volume of distribution is ________. Compare to 0.2 to 0.4 for the muscle relaxants. Suggested than must be stored in liver and kidneys but not peripheral tissues

Back 34

large

Front 35

Hepatic metabolism is _______.

Back 35

minor

Front 36

Fastest Onset is _________?

Back 36

Edrophonium

Front 37

Since kinetics nearly equivalent, shows potency difference in affinity for ________.

Back 37

enzyme

Front 38

Duration of Action

Back 38

Parallel with disappearance from plasma
Nearly the same for all compounds
25-50% due to hepatic metabolism
50-75% due to renal clearance
Physostigmine metabolized by plasma esterases
Can be adjusted by dosage
0.043 mg/Kg neostigmine~0.21 mg/Kg pyridostigmine~0.5 mg/Kg edrophonium
Can potentiate a Neuromuscular blockade

Front 39

__________ can prolong duration

Back 39

Liver or renal disease

Front 40

To increase duration of action, can __________ but must be careful

Back 40

give a larger dose

Front 41

Succinylcholine activity prolongs because?

Back 41

So much acetylcholine that increase the initially depolarization and also inhibit psuedocholinesterase activity which is somewhat responsible for elimination of some the neuromuscular blockers (neostigmine and somewhat pyridostigmine can do this and edrophonium has very little anti-psuedocholinesterase activity). Example- mivacurium is metabolised by the psuedocholinesterase. If give neostigmine, the metabolism of mivacuirium is slowed a bit but the reversal still proceeds.

Front 42

factors affecting time to recovery?

Back 42

Choice/dosage of the inhibitor
The muscle relaxant being reversed
Extent of blockade at time of reversal

Front 43

Side Effects, Cholinesterase Inhibitors also effect:

Back 43

Cardiovascular Muscarinic Receptors
Vagal-like bradychardia to sinus arrest
Pulmonary Muscarinic Receptors
Bronchospasm and increased secreations
Cerebral Muscarinic and Nicotinic Receptors
Physostigmine
Diffuse Activation
Gastrointestinal Muscarinic Receptors
Increase paristaltic and gladular secretions
Perioperative bowel anastomotic leakage
Nausea and Vomiting

Front 44

Can be used to antagonize the parasympathomimetic effects (muscarinic)?

Back 44

Atropine/Glycopyrrolate

myesthenia gravis

Front 45

When we increase ________ we are increasing duration

Back 45

dosage

Front 46

Atropine/glycopyrolate=?

Back 46

antimuscarinic

Front 47

Atropine has a _______ onset than glycopyrolate, hence they are paired with other agents based on onset.

Back 47

faster

Front 48

Neostigmine structure?

Back 48

Carbamate*
Quat. amine

Front 49

Pyridostigmin structure

Back 49

Carbamate
Quat. amine

Front 50

Edrophonium structure

Back 50

Quat. amine

Front 51

Physostigmine structure

Back 51

Carbamate
Tert. amine

Front 52

1 non carbamate?

Back 52

Edrophonium

Front 53

can cross BBB?

Back 53

Physostigmine

Front 54

anticholinergic for Pyridostigmine

Back 54

0.05 mg glycopyrrolate**

Front 55

anticholinergic with neostigmine

Back 55

0.2 mg glycopyrrolate
Pregnancy: atropine for fetal bradycardia

Front 56

anticholinergic for Edrophonium

Back 56

0.014 mg atropine**
0.007 mg
(must be given early)

Front 57

anticholinergic for Physostigmine

Back 57

Infrequently needed but should have avail.

Front 58

other uses for neostigmine?

Back 58

Myasthenia Gravis
Urinary Bladder Atony
Paralytic ileus
Intrathecal anesthesia

Front 59

other uses for Physostigmine

Back 59

Central Anticholin. Toxicity
(atropine/scopolamine)
Reverse CNS depression
(benzo’s/volatiles)
Prevent postop. Shivering