Drugs and ANS

Question 1

Where can we target drugs to alter ANS activity?

Answer 1

Points of chemical communication:
Presynaptic receptors
Post synaptic receptors
Inactivation of transmitter
Reuptake of transmitter (neuronal/non neuronal)
Degradation of transmitter

Question 2

Steps of neurotransmission

Answer 2

Synthesis and vesicle storage of transmitter
depolarisation via action potential
Influx of Ca2+
Vesicles fuse with membrane and release to synaptic cleft
Diffuse to post synaptic membrane and interact with receptors (pre and post)
Re uptake or degradation

Question 3

Acetylcholine synthesised from

Answer 3

Acetyl Co A + Choline = acetylcholine (+co enzyme A)

Question 4

Enzyme used to synthesise Ach

Answer 4

Choline acetyltransferase (CAT)

Question 5

Acetylcholine degradation

Answer 5

acetylcholine –> acetate + choline

Question 6

Enzyme used for acetylcholine degradation

Answer 6

(acetyl)cholinesterase (AchE)

Question 7

How are drugs targeted to cholinergic sites?

Answer 7

nAchR in autonomic ganglia structure is different to nAchR at neuromuscular junction
can get ganglion-blocking drug

Question 8

Ganglion blocking drug

Answer 8

Trimethaphan

in hypertensive emergencies or induce hypo in surgery

Question 9

How can Ach action be enhanced?

Answer 9

Using AchE inhibitors

Question 10

When are AchE inhibitors used?

Answer 10

Pyridostigmine for Myasthenia Gravis

Donepezil for Alzheimers

Question 11

Problem with mAchR agonists/antagonists

Answer 11

Not many selective ones
Effect all subtypes (M1-M5) so side effects limit use

(eg decrease HR, cause bronchoconstriction and increase sweating/salivation)

Question 12

What is SLUDGE syndrome?

Answer 12

Parasympathetic mAchR system overly stimulated 
Salivation
Lacrimation
Urination
Defectation
GI upset
Emesis

Question 13

Causes of SLUDGE

Answer 13

Drug overdose
Magic shrooms
Organophosphate poisoning (parathion)
Nerve agents (sarin, VX)

Question 14

What do organophosphate poisoning and nerve agents do?

Answer 14

Covalently modify acetylcholinesterase

Ach levels rise = continued stimulation of mAchR

Question 15

Sludge treatment

Answer 15

Atropine

Pralidoxime

Question 16

mAchR agonists

Answer 16

Pilocarpine (treat glaucome)

Bethanechol (stimulate bladder emptying)

Question 17

mAchR antagonists for asthma/COPD

Answer 17

Ipratropium

Tiotropium

Question 18

mAchR antagonists for overactive bladder

Answer 18

Tolterodine
Darifenacin
Oxybutynin

Question 19

mAchR antagonists for IBS/post op nausea

Answer 19

Hyoscine (aka Scopolamine)

Question 20

Sympathetic neuroeffector junction

Answer 20

postganglionic neurones = branches axonal network with bulges (VARICOSITIES)
These are specialised site for Ca2+ dependent release of noradrenaline from vesicles

Question 21

Noradrenaline synthesis

Answer 21

Tyrosine –> DOPA –> dopamine –> Noradrenaline

Question 22

What happens in adrenal medulla to noradrenaline?

Answer 22

Converted to adrenaline via phenylethanolamine N-methyltransferase)

Question 23

How is noradrenaline released?

Answer 23

Ca2+ dependent exocytosis

Question 24

What does noradrenaline do once released?

Answer 24

interacts with post-synaptic adrenoreceptors to signal effector tissue
Interacts with pre-synaptic adrenoreceptors to provide negative feedback to stop release

Question 25

How is NA removed from cleft?

Answer 25

By high affinity Na+ dependent transporter (NET aka Uptake 1) back to presynaptic terminal
If not recaptured by Uptake 1:
Uptake 2 = low affinity, non neuronal mechanism

Question 26

What happens to NA once back in presynaptic terminal?

Answer 26

Packaged back into vesicles
Any not packaged metabolised by:
- monoamine oxidase (MAO)
- catechol-O-methyltransferase (COMT)

Question 27

B2 receptor agonists

Answer 27

Salbutamol 
treat asthma (reverse bronchoconstriction)

Question 28

Why is B2 selectivity important?

Answer 28

if just broad beta receptor agonist there are possible cardiovascular side effects (+ve inotropic and chronotropic)

Question 29

Drugs for hypertension

Answer 29

a1 adrenoreceptor antagonist (Doxazosin)

B1 adrenoreceptor antagonist (atenolol)