Cholinergic Pharmacology II

Question 1

Describe the actions of Nicotine as the dose increases.

Answer 1

At small doses, the actions of nicotine are central. Larger doses stimulate ganglia.

Question 2

What are the 4 effects of nicotine on autonomic ganglia?

Answer 2

It causes increased PNS and SNS activity.

• rise in BP
• tachycardia
• inhibition of gastric motility
• increased salivation and bronchial secretion

Question 3

Name a ganglionic blocking drug of the nACh receptor

Answer 3

Hexamethonium

Question 4

What are the effects of Hexamethonium on the Cardiovascular System?

Answer 4

Effects are mainly due to inhibition of the SNS.

• Skin vasodilation
• Loss of cardiovascular reflexes
• Loss in BP

Question 5

What are the effects of Hexamethonium on the Gastrointestinal system?

Answer 5

Effects are mainly due to inhibition of the PNS.

- reduction of secretion and motility of the GI tract leading to constipation

Question 6

What are the effects of Hexamthonium on the Genito-Urinary System?

Answer 6

• Block of PNS leads to erection failure
• Block of SNS leads to inhibition of ejaculation
  Net result is impotence in men

Question 7

What are the effects of Hexamethonium on the Eye?

Answer 7

Effects are mainly due to inhibition of the PNS.

• Loss of accommodation as iris sphincter muscles and ciliary muscles no longer contract
• Loss of pupillary reflex causes photophobia

Question 8

State three uses of neuromuscular junction blocking drugs

Answer 8

• muscle paralysis for intubation
• muscle relaxation in abdominal surgery
• assist ventilation in intensive care

Question 9

What are the two classes of NMJ blockers?

Answer 9

Competitive blockers and Depolarizing Blockers

Question 10

What are the features of Competitive block?

Answer 10

• causes relaxation of muscle without preliminary excitation
• the block can be reversed by anticholinesterases
• Myasthenia Gravis sufferers are more sensitive to this
  block

Question 11

Give an example of a Competitive Blocker

Answer 11

Tubocurarine

Question 12

What are the features of Depolarizing Blockers?

Answer 12

• they are agonists of nACh receptors
• they cause initial fasciculation of the muscle fibres
• block is enhanced by anticholinesterases
• Myasthenia Gravis patients are insensitive to the block
• can cause hyperkalaemia

Question 13

Give an example of a Depolarizing Blocker

Answer 13

Suxamethonium

Question 14

How is Suxamethonium metabolised in the body?

Answer 14

By plasma cholinesterase

Question 15

Name three other drugs that are neither Competitive or Depolarizing blockers that affect the transmission of an ACh mediated synapse.

Answer 15

Botulinum Toxin - blocks the release of ACh
Hemicholinium - competitively inhibits uptake of choline
Streptomyocin - blocks Ca2+ so prevents ACh release

Question 16

What are the two main types of cholinesterase?

Answer 16

Acetylcholinesterase and Butyrylcholinesterase

Question 17

What are the features of Butyrylcholinesterase?

Answer 17

• it is soluble and found in plasma

- it’s unspecific but will hydrolyse butyrylcholine like substances faster than Ach

Question 18

What is the Dibucaine Screening Test?

Answer 18

A blood test to asses the sensitivity of the enzyme Butyrylcholinesterase to its inhibitor Dibucaine.

Question 19

Describe the two binding sites on Acetylcholinesterase

Answer 19

The catalytic site contains a reactive serine OH group

The anionic site binds the cationic ammonium group of ACh

Question 20

What are the three stages involved in the hydrolysis of ACh by AChE?

Answer 20

1) The ACh binds to the two sites on AChE
2) The acetyl group on ACh transfers onto the OH serine
3) The choline dissociates followed by spontaneous hydrolysis of the acetylated serine OH releasing acetic acid

Question 21

Name the three classes of Anticholinesterases and their mechanism of action

Answer 21

Short acting - e.g Edrophonium. bind only to the anionic site forming ionic bonds
Medium acting - e.g. Neostigmine. bind to both sites and form an ester bond with the OH serine
Long acting - e.g. DFP. Irreversibly bind to the OH serine due to phosphorylation

Question 22

What are the main effects of anticholinesterases on autonomic ganglia?

Answer 22

Effects mainly on the PNS

• increased secretions (salivation, sweating)
• increased GI motility results in vomiting and diarrhoea
• decrease in intraocular pressure (due to increased contraction of eye muscles)
• bronchoconstriction

Question 23

What are the main effects of anticholinesterases on the neuromuscular junction?

Answer 23

Initial facilitation of transmission followed by depolarizing neuromuscular block (due to excess ACh)

Question 24

What are the clinical uses of anticholinesterases?

Answer 24

• treatment of glaucoma
• treatment and diagnosis of Myasthenia Gravis
• reversal of competitive neuromuscular block

Question 25

What is the danger involved with organophosphates and how can their effect be reversed?

Answer 25

- they can cause demyelination due to inactivating the enzyme involved in myelination - cholinesterase can be reactivated by oxime compunds