Cholinoceptor Antagonists

Question 1

define affinity

Answer 1

y is the ability to bind to a receptor – both agonist and antagonist.

Question 2

define efficacy

Answer 2

is the ability to induce a biological response – agonist only.
o i.e. ACh has efficacy for the muscarinic acetylcholine receptor.

Question 3

where are nicotinic receptors always present?

Answer 3

Nicotinic receptors are present at ALL autonomic ganglia.

Question 4

what are nicotinic receptor antagonists also called?

Answer 4

Also called ganglion blocking drugs

Question 5

what are the two groups of cholinoreceptors?

Answer 5

nicotinic
-present on all autonomic ganglia

muscarinic
-present within the effector organs of the parasympathetic nervous system as well as the sweat glands innervated by the SNS

Question 6

how can the ganglion blocking drugs act to work?

Answer 6

there are two ways in which you can interfere with an ion-channel linked receptor; blocking the receptor or the ion channel itself.

GBDs can act to both antagonise the receptor AND/OR physically block the ion-channel itself.

GBDs block the ion channel thus preventing ions from moving through the channel pore.

Question 7

what does use-dependent block mean?

Answer 7

Use-dependant blocks – the drug works best when the channel is open so the more the receptor is used, the more it is blocked. Opposite to most with the more agonist meaning the less effective the drug is.
More agonist present = more opportunity for the antagonist to block the channel. But hence these drugs only result in incomplete block.

Question 8

define incomplete blocking

Answer 8

Incomplete blocking – Ion-channel blockade is only partial (as some ions still pass through).

Question 9

do all GBD have affinity?

Answer 9

Some GBDs do NOT have affinity as some types DON’T bind to the receptor, just block the ion-channel itself.

Question 10

examples of GBDs

Answer 10

Hexamethonium

Trimetaphan

Question 11

what are the effects of GBD on the body

Answer 11

CVS effects; hypotension – blood vessel vasoconstriction inhibited and kidney renin secretion inhibited (so no AngII).
§ Smooth muscle effects; pupil dilation, decreased GI-tone, bladder dysfunction, bronchodilation.
§ Exocrine secretions; decreased secretions.

Question 12

why do GBDs cause hypotension?

Answer 12

reduced renin secretion from the kidney

vasodilation

*the more dominant pathways lost

Question 13

clinical use of hexamethonium

Answer 13

Hexamethonium – the first anti-hypertensive drug used but LOTS of side effects as very general.
o Primarily an ion-channel blocker (so not a lot of affinity).

Question 14

clinical use of trimetaphan

Answer 14

Trimetaphan – used for when you want hypotension during surgery, IV-administered, short acting.
o Primarily a receptor antagonist (so has affinity).

Question 15

what is a-bungarotoxin?

Answer 15

a-bungarotoxin is an example of a GBD that is irreversible (used by snakes).
o This drug binds mainly to somatic nicotinic receptors (NRs) whereas the GBDs above bind to autonomic NRs.

Question 16

what are muscarinic receptors antagonists?

Answer 16

Muscarinic Receptor Antagonists (MRAs):
§ This is mainly a PNS antagonist as the only muscarinic receptor in the SNS is found in sweat glands.
o So expect mainly inhibition of PNS.

Question 17

what are two types of MRAs?

Answer 17

Two examples of MRAs are:
o Atropine.
o Hyoscine.

Question 18

what are the CNS affects of atropine?

Answer 18

Atropine:
§ Normal dose – little effect.
§ Toxic dose – mild restlessness à agitation.

Question 19

what are the CNS effects of hyoscine?

Answer 19

Hyoscine:
§ Normal dose – sedation, amnesia.
§ Toxic dose – CNS depression or paradoxical CNS excitation (associated with pain).
· Possibly due to a greater permeability through the BBB into the brain.

Question 20

what are the ophthalmic effects of MRAs and what is the drug used?

Answer 20

Tropicamide:

§ Used in examination of the retina – causes dilation/miosis.

Question 21

how can MRAs be used in anaesthetic pre-medication? what are the effects?

Answer 21

The MRAs block the PNS and so block; bronchoconstriction (so bronchodilates), watery secretions (more thick secretions decreases chance of aspirations), decreased HR and contractility (protect the heart from slowing effects of other drugs) and also sedates the patient

Question 22

what can the hyoscine patch be used in?

Answer 22

Inhibits the muscarinic receptors in the vomiting centre so the sensory mismatch (from a mismatch from what the eyes see and what the labyrinth reports in balance) cannot induce vomiting when suffering from motion sickness.

Question 23

how can MRAs be used in Parkinson’s disease?

Answer 23

Neurological – Parkinson’s Disease – lack of dopamine in the CNS:
o MRA drug:
§ In Parkinson’s disease, the substantia nigra neurones are lost which usually produce dopamine for the striatum. The lack of dopamine gives the Parkinson’s disease symptoms. However, a muscarinic receptor antagonist drug decreases the negative inhibition on release of dopamine into the striatum from another source meaning dopamine can continue to be released into the striatum.

Question 24

what effects can ipratropium bromide have?

Answer 24

Ipratropium Bromide:
§ Used for Asthma and COPD as it causes bronchodilation.
§ Similar molecular shape to atropine but has an extra nitrogen-containing polar group attached that allows it to linger more in the lungs as it cannot cross the mucosa as easily as atropine would.

Question 25

what GI effects can MRA drugs have?

Answer 25

Treats irritable bowel syndrome as the MRA decreases GI tone and secretions.

Question 26

what are the unwanted effects of muscarinic receptor antagonists?

Answer 26

Hot as hell – decrease in sweating and thermoregulation defects.
§ Dry as a bone – decreased secretions.
§ Blind as a bat – cyclopegia (paralysis of eye muscles so no accommodation).
§ Mad as a hatter – CNS disturbance (i.e. tremors etc.).

Question 27

what drug would you administer to treat an atropine overdose?

Answer 27

bethanechol
ecothiopate
physostigmine

Question 28

what is botulinum toxin?

and what does it do?

Answer 28

One of the most toxic proteins know.
§ Botulinum binds to the ACh vesicles and stops them docking with the inner membrane.
o Forms SNARE complexes.