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BDS1 > Pharmacology of cholergenic transmission > Flashcards

Pharmacology of cholergenic transmission Flashcards

1
Q

what is acetylcholine?

A

neurotransmitter

- charged signalling molecule that is very soluble in water and is very flexible

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2
Q

why is Ach charged

A

due to acetyl end

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3
Q

what does Ach do

A

released from nerves at synapses and acts on postsynaptic target cells

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4
Q

what three systems is Ach a neurotransmitter in

A

somatic - NMJ
autonomic - ganglionic synapses and parasympathetic neuroeffector synapses
CNS

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5
Q

what distinguishes the two families of cholinergic receptors

A

nicotine

muscarine

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6
Q

describe nicotinic receptors

A

ionotropic (ligand gated ion channels - allows direct binding of Ach)

  • main categories are autonomic ganglionic and muscle
  • made up of 5 sub units with 2 alpha groups to which the Ach binds
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7
Q

describe muscarinic receptors

A 
metabotropic (coupled to ion channels, transported and enzymes by G proteins
5 types (M1-5) 1,2,3 are important in peripheral tissues
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8
Q

what is similar and different between nicotinic and muscarinic receptors

A

pre synaptic mechanisms (synth, storage and release of ach) are similar but post synaptic are very different depending on the type of target cell

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9
Q

pre synaptic events in cholinergic neurotransmission

A
  • ach synthesised from choline and acetyl coenzyme A by the action of choline acetyl transferase
  • ach is stored in synaptic vesicles that are released by the process of exocytosis triggered by a rise in intracellular Ca conc within nerve terminal
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10
Q

which drugs act pre-synaptically to inhibit cholinergic neurotransmission
–must affect either storage synthesis or release

A

synth - hemicholiniums
storage - AH5183
release - botulinum toxin

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11
Q

where is botulinum toxin from

A

clostridium botulinum - found in uncooked foods and its ingestion gives rise to botulism

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12
Q

what is the lethal dose of botox in mice

A

10^-12 g

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13
Q

what do the toxin in botox do

A
  • cause death due to paralysis of respiratory muscles

- toxin destroys key proteins involved in exocytosis

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14
Q

what is botox currently used to treat?

A

blepharospasm - involuntary tight closure of the eyelids

and in cosmetic medicine

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15
Q

what is botox being developed for use

A

hyperhidrosis - excessive sweating, bladder hyperactivity, migraine, spasticity associated with MS and cerebral palsy

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16
Q

post synaptic events in cholinergic transmission

A

-ach diffuses across synaptic cleft and activates either nicotinic or muscarinic receptors depending on synapse involved
ach broken down by acetylcholine esterase

17
Q

what does AchE do

A

destroys ester bonds in Ach and choline part is taken back up into the nerve and recycled

18
Q

clinical uses of drugs acting at nicotinic receptors

A
  • no uses of nicotinic receptor agonists
  • muscle relaxants
  • ganglion blockers
19
Q

how do drugs work as muscle relaxants

A

reversible competitive antagonists

  • bind to receptor but do not open the associated channel
  • prevent Ach activating the receptor
20
Q

what are effects of drugs acting as ganglion blockers?

A

reduction in blood pressure

these drugs are mostly used experimentally

21
Q

example of ganglion blocker and its use

A

trimetaphan - reduces bleeding during surgery

22
Q

what do muscarinic receptor agonists do

A

mimic the effect of the parasympathetic NS

- act as parasympathoMIMETICS

23
Q

what do muscarinic receptor antagonists do

A

block the effects of the parasympathetic NS

- act as parasympathoLYTICS

24
Q

what are some parasympathetic agonist effects?

A

reduction of HR
stimulation of gut and bladder
contraction of bronchi
constrict pupils

25
Q

clinical uses of muscarinic receptor agonists

A

pilocarpine - eye drops used in treatment of glaucoma
- also used to detect CF from a sweat test
bethanacol - used as stimulant laxative and to treat urinary retention

26
Q

clinical uses of muscarinic receptor antagonists

A

atropine - bradychardia
tropicamide - dilate pupils
ipratropium - asthma COPD

27
Q

what drugs can inhibit AchE

A

neostigmine

edrophonium

28
Q

what is neostigmine used for

A

AchE inhibitor
to clinically reverse the effects of reversible, competitive antagonists muscle relaxants t skeletal NMJ
- can also be used in myasthenia gravis

29
Q

what AchE inhibitors have been shown to benefit Alzheimer’s

A

donepezil

rivastigmine

BDS1 (21 decks)

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