Br Pharmacology: Cholinoceptor-Activating And Cholinesterase Inhibitors

Front 1

What is cholinergic crisis?

Back 1

excessive activation of cholinoceptors leading to muscle weakness and parasympathetic signs

Front 2

What is cyclospasm?

Back 2

paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation

Front 3

What is myasthenia crisis?

Back 3

1) defined as weakness from acquired myasthenia gravis (MG) that is severe enough to necessitate intubation or to delay extubation following surgery. The respiratory failure is due to weakness of respiratory muscles.
2) people with myasthenia experience acute worsening of symptoms from inadequate cholinomimetic treatment

Front 4

What is organophosphate aging?

Back 4

the organophosphate bound to cholinesterase is chemically modified and becomes firmly bound

Front 5

How doe Gq function? Which recptors activate this pathway?

Back 5

1) M1 and M3 and M5
2) Gq activates phospholipase C releasing DAG and IP3. DAG modulates protein kinase C leading to secretion and IP3 releases calcium stores

Front 6

Which M receptor is linked to Gi? What is it's effect?

Back 6

1) M2
2) Gi inhibits adenylyl cyclase

Front 7

Which M receptor is coupled with the Betagamma subunit of the G protein to K+ channels in the heart and elsewhere?

Back 7

M2
Note: M2 facilitates opening of this channel

Front 8

Which muscarinic receptors are important in the CNS?

Back 8

M4 and M5

Front 9

What type of G protein is M1 and what does it cause? M2? M3?

Back 9

1) Gq increases IP3 and DAG
2) Gi decreases cAMP
3) Gq increases IP3 and DAG

Front 10

What type of G protein is M4 and what does it cause? M5?

Back 10

4) Gi decreases cAMP
5) Gq increases IP3 and DAG

Front 11

Does ACh act on N, M or both? Bethanechol? Carbachol? Pilocarpine? Nicotine?

Back 11

1) both
2) M
3) both
4) M
5) N

Front 12

Do indirect acting cholinesterase inhibitors act on N, M or both?

Back 12

both

Front 13

Parasympathetics do NOT innervate blood vessels. How does vasodilation occur with muscarinic agonists?

Back 13

M receptors on endothelial cells produce NO which is part of endothelium derived relaxing factor

Front 14

What is the physiologic effect on heart of giving someone small amounts of direct-acting muscarinics?

Back 14

1) tachycardia follow by vagal discharge causing bradycardia

Front 15

What is an effect when given a muscarinic agonist that is a sympathetic response?

Back 15

thermoregulatory sweating

Front 16

What are clinical uses of direct acting nicotinic agonists?

Back 16

only as skeletal muscle relaxant

Front 17

If given a nicotinic agonist where is sympathetic activity observed? parasympathetic?

Back 17

1) sympathetic constriction of blood vessels
2) increased motility and secretion in gut

Front 18

What are muscarinic toxic effects?

Back 18

1) CNS stimulation
2) miosis
3) spasm of accommodation
4) bronchoconstriction
5) Increased GI/GU motility
6) Increased secretory activity
7) vasodilation

Front 19

What are nicotinic toxic effects?

Back 19

1) convulsions followed by depression
2) ganglionic stim then block
3) fasiculations then paralysis

Front 20

Which muscarinic drugs have little CNS stimulation?

Back 20

1) choline esters
2) pilocarpine

Front 21

What can bethanechol be used to treat? What is its action?

Back 21

1) postop and neurogenic ileus
2) urinary retention
3) Action: activates smooth muscle

Front 22

What can carbachol be given for? What is its action?

Back 22

1) glaucoma
2) pupillary contraction
3) decreased IOP
4) Action: activates pupillary sphincter and cilliary muscle

Front 23

What can nicotine be given for? What is its action?

Back 23

1) smoking cessation
2) slow action compared to cigarettes

Front 24

What can neostigmine be given for?

Back 24

1) postop and neurogenic ileus
2) urinary retention
3) MG
4) reversal of neuromuscular blockade (postop)

Front 25

What can neostigmine, edrophonium and pyridostigmine be given for?

Back 25

1) MG

Front 26

What is physostigmine used to treat?

Back 26

1) glaucoma
2) atropine overdose

Front 27

What is the MOA of carbamate and organophosphate?

Back 27

1) bind and undergo hydrolysis
2) acidic phosphate or carbamate group remains attached
3) prevents hydrolysis of ACh

Front 28

How long do carbamates act? organophosphates?

Back 28

1) 2-8 hours
2) days to weeks

Front 29

where in the body do cholinesterase inhibitors typically not have an effect?

Back 29

blood vessels

Front 30

What are 3 organophosphates used in medicine? What are their uses?

Back 30

1) malathion (scabicide)
2) metrifonate (antihemlminthic)
3) ecothiophate (anit-glaucoma)

Front 31

What is edrophonium used for?

Back 31

1) differentiating MG from cholinergic crisis
2) in cholinergic crisis edrophonium will continue to weaken muscles

Front 32

What is the most toxic cholinesterase inhibitor? How is it treated? what symptoms will remain?

Back 32

1) parathion
2) atropine
3) atropine has no effect on nicotinic receptors so still have muscle effects and some autonomics

Front 33

What is an example of a regenerator that can be given to reverse effects of cholinesterase inhibitors?

Back 33

1) pralidoxime
2) Note this can reverse nicotinic signs atropine can't

Front 34

Which cholinesterase inhibitors are prodrugs?

Back 34

1) malathion - malaoxan
2) parathion - paraoxon

Front 35

How are the side effects of cholinesterase inhibitors different than direct agonists?

Back 35

Same except for:
1) vasodilation is uncommon
2) bradycardia more common than tachycardia
3) CNS stim is common

Front 36

which 2 cholineserase inhibitors primarily effect the CNS leading to convulsions?

Back 36

1) physostigmine
2) organophosphates

Front 37

What does DUMBBELSS stand for?

Back 37

D - diarrhea
U - urination
M - miosis
B - bronchoconstriction
B - bradycardia
E - excitation of muscle and CNS
L - lacrimation
S - salivation
S - sweating

Front 38

What are examples of muscarinic agonists?

Back 38

1) muscarine
2) bethanechol
3) carbachol
4) pilocarpine

Front 39

What are examples of nictonic agonists?

Back 39

1) nicotine
2) carbachol
3) succinylcholine

Front 40

Alcohol cholinesterase inhibitor?

Back 40

1) edrophonium

Front 41

What are examples of carbamates?

Back 41

1) neostigmine
2) pyridostigmine
3) physostigmine

Front 42

What are examples of organophosphates?

Back 42

1) parathion
2) malathion
3) sarin
4) metrifonate
5) echothiophate

Front 43

This agent has greater affinity for muscarinic receptors and used for postoperative and neurogenic ileus and urinary retention

Back 43

Bethanechol

Front 44

Only direct acting agent that is very lipid soluble and used in glaucoma

Back 44

Pilocarpine

Front 45

This agent used to treat dry mouth in Sjögren's syndrome

Back 45

Cevimeline

Front 46

Carbamate with intermediate action, used for+A1170 postoperative and neurogenic ileus and urinary retention

Back 46

Neostigmine

Front 47

Treatment of atropine overdose and glaucoma (because lipid soluable). Enters the CNS rapidly and has a stimulant effect, which may lead to convulsions

Back 47

Physostigmine

Front 48

Treatment of myasthenia gravis

Back 48

Pyridostigmine
Note: does not penetrate CNS

Front 49

Antiglaucoma organophosphate

Back 49

Echothiophate

Front 50

Associated with an increased incidence of cataracts in patients treated for glaucoma

Back 50

Long acting cholinesterase inhibitors

Front 51

The most frequent cause of acute deaths in cholinesterase inhibitor toxicity

Back 51

Respiratory failure

Front 52

Treatment of choice for organophosphate overdose

Back 52

Atropine