7. Cholinoceptor Antagonists

Question 1

What is the difference between affinity and efficacy?

Answer 1

Affinity
• ability to bind to receptor
• rapid and reversible
• agonists and antagonists
• not antagonists blocking a channel pore

Efficacy
• ability to stimulate an effect
• only agonists

Question 2

Where can nicotinic ACh receptors be found?

Answer 2

All autonomic ganglia

Question 3

What are nicotinic receptor antagonists also known as?

Answer 3

Ganglion-blocking drugs

Question 4

What are the 2 actions of nicotinic receptor antagonists?

Answer 4

• Block the nicotinic receptor (ion-channel linked receptor)

* Block the channel itself

Question 5

What is Hexamethonium?

Answer 5

• Nicotinic-receptor antagonist
• Blocks both the receptor and channel pore
• Anti-hypertensive
• Vasodilation - blocked sympathetic tone in vessels
• Decreased renin - less aldosterone released

Question 6

Which nicotinic antagonists is used clinically?

Answer 6

• Trimetaphan
• IV during surgery to induce hypotension
• Reduces chance of blood loss
• Short acting
• Selective - only blocks the receptor

Question 7

What does use-dependent block describe?

Answer 7

• Degree of block is proportional to opposing stimulation
• Any drug that blocks an ion channel tends to present with this
• More agonist => more open channel => more effective block (as it’s more accessible to the antagonist)
• However, it is nearly always incomplete - can never get complete block

Question 8

How can you overcome antagonisms of a nicotinic receptor (not channel)?

Answer 8

• Add more ACh

* Competitive

Question 9

Do ganglion-blocking drugs produce sympathetic or parasympathetic effects at rest?

Answer 9

• Sympathetic

- parasympathetic is dominant at rest, and this is blocked

Question 10

What are the side effects of ganglion-blocking drugs?

Answer 10

• Pupil constriction interference (dilation)
• Bladder dysfunction
• Decreased GI tone
• Decreased saliva production
• Impaired sweating capacity
• Decreased exocrine secretions

Question 11

What poison comes from the krait snake and how does it act?

Answer 11

• Alpha-bungarotoxin
• Most potent toxin at the nicotinic receptor
• Irreversible (covalent forces)
• Targets both the autonomic and somatic (skeletal) nervous system receptors
• Paralysis

Question 12

How are muscarinic receptor antagonist different to the nicotinic receptor antagonists?

Answer 12

• More selective
• Only influence (block) parasympathetic function
• Muscarinic receptors only found at end of parasympathetic nerves (end sympathetic innervating sweat glands)

Question 13

What are the effects of 2 muscarinic receptor antagonists (normal + toxic dose)?

Answer 13

Atropine
• Normal dose: little effect
• Toxic dose: mild restlessness
• Less M1 selective

Hyoscine
• Normal dose: sedative, amnesia
• Toxic dose: CNS depression or paradoxical CNS excitation
• Greater permeation into CNS due to lipid solubility

Question 14

What happens if you add a muscarinic receptor antagonist into the eye (and which one is used)?

Answer 14

• Tropicamide is an opthalmic drug
• Causes pupil dilation
• Parasympathetic usually constricts the pupil and this is blocked

Question 15

How can muscarinic receptor antagonists be used in surgery?

Answer 15

• Anaesthetic premedication
• Reverses constriction in lungs => bronchodilation => assists inhalation of anaesthetic for surgery
• Dries up salivary secretions - reduced risk of aspiration
• Counteracts slowing effects (e.g. HR) by anaesthetic
• Hyoscine is sedative - calms patient

Question 16

What causes motion sickness and how do muscarinic antagonists affect this?

Answer 16

• Sensory mismatch between visual system and labyrinth (balance + posture)
• Make activate vomiting centre if it doesn’t match - cholinergic
• Hyoscine can prevent the cholinergic system from activating the vomiting centre

Question 17

How can muscarinic receptor antagonists be used in Parkinson’s disease?

Answer 17

• Dopaminergic neurones originate from the substantia nigra and project down to the striatum
• Modulation of fine control of movement
• Dopamine is released in the striatum and binds to D1 receptors on striatal neurones
• Muscarinic receptors (M4) impair D1 receptor function
• Parkinson’s - loss of dopaminergic neurones, reduced D1 activation
• M4 not down-regulated
• Muscarinic antagonists block this inhibitory effect

Question 18

How can muscarinic receptor antagonists be used in respiratory diseases?

Answer 18

• Parasympathetic constricts the airways
• Local administration of MRAs can act as bronchodilators
• Ipratropium bromide is a derivative of atropine
- positive charge, can’t enter systemic circulation

Question 19

How can muscarinic receptor antagonists be used in GI diseases?

Answer 19

• In IBS, parasympathetic NS activates gut motility and secretions
• Symptoms are due to hyperactive gut - diarrhoea
• MRAs slow down the gut and decrease motility and secretions
• M3 receptor antagonists used

Question 20

What are the unwanted side effects of muscarinic receptor antagonists?

Answer 20

• Inability to sweat - impaired thermoregulation
• Decreased salivary/exocrine secretions
• Cycloplegia - decreased ability to adjust visual focus
• CNS disturbance

Question 21

Where is atropine mainly seen and how is it treated?

Answer 21

• Children who accidentally eat atropa belladonna berries
• Bethanechol (agonist) or physostigmine for treatment
• Physostigmine blocks acetylcholinesterase - increasing ACh in synapse
• More abundant drug will produce the greater effect if competing

Question 22

How does Botulinum toxin work?

Answer 22

• Diffuses into parasympathetic nerves
• Prevents ACh vesicles from fusing with membrane - blocks SNARE complex proteins
• ACh exocytosis prevented

Question 23

How can botox be used clincally?

Answer 23

• Paralyse skeletal muscle in diluted, less potent form to remove wrinkles locally
• Injection into sweat and salivary glands to control secretions