Lecture 15- ANS (2)

Question 1

neurotransmission is a

Answer 1

common site of drug action

Question 2

basic steps in NT

Answer 2

1. Uptake of precursors
2. Synthesis of transmitter
3. Vesicular storage of transmitter
4. Degradation of transmitter
5. Depolarisation by propagated AP
6. Depolarisation-dependent influx of Ca2+
7. Exocytotic release of transmitter
8. Diffusion to post-synaptic membrane
9. Interaction with post-synaptic receptors
10. Inactivation of transmitter
11. Re-uptake of transmitter
12. Interaction with pre-synaptic receptors

Question 3

cholinergic system is used in both

Answer 3

sympathetic and parasympathetic (preganglionic- nicotinic receptors)

Messenger post ganglionically in the parasympathetic NS

Question 4

synthesis of acetyl choline by

Answer 4

acetylcholinetransferase

Question 5

acetylcholine degradation by

Answer 5

acetylcholinesterase

Question 6

diet supplies us with an adequare supply of

Answer 6

choline

Question 7

acetyl coA

Answer 7

key intermeidate of metabolism

Question 8

choline is…..

Answer 8

recycled

Question 9

Nicotinic AChRs at autonomic ganglia and the NMJ

Answer 9

differ in structure

Question 10

some drugs have actions that act selectively at autonomic ganglia e.g.

Answer 10

Ganglion-blocking drugs

Question 11

ganglion blocking drug e.g.

Answer 11

trimethaphan

Question 12

trimethaphan

Answer 12

used in hypertensive emergencies and to produce controlled hypotension during surgery (not used regularly anymore)

Question 13

few subtype selective … agonists or antagonists are available

Answer 13

mACHr

Question 14

mACHr antagonist tolterodine (one of the few and newer agents which show tissue selectivity( used to treat)

Answer 14

overactive bladder

Question 15

action of endgenous rleeased ACh can also be released by

Answer 15

AChE inhibitors

e. g. Pyridostigmine
e. g. donepezil

Question 16

e.g. Pyridostigmine

Answer 16

treats myasthenia gravis

Question 17

e.g. donepezil

Answer 17

alzheimers treatment

Question 18

A relative lack of selectivity of cholinerrgic drugs means that

Answer 18

unwanted side-effects often limit their usages

e.g. non-selective, mACH receptors agonists is likely to cause autonomic side effects

• Heart rate and cardiac output decrease
• Smooth muscle: increase bronchoconstriction and GI tract peristalsis
• Exocrine glands: increase sweating and salvation

Question 19

SLUDGE syndrome

Answer 19

a mneumonic for the pathoglogical effects indicative of paraysmpathetic nervous system

Question 20

outline SLUDGE

Question 21

SLUDGE is encoutnered in cases of

Answer 21

• Drug overdose
• Ingestion of magic mushrooms
• Organophosphorus insecticides (parathion) or nerve fades (sarin)
  *

Question 22

Sarin and parathion action

Answer 22

covalently modify ACHesterase to irreversibly deactivate the enzyme and raise acetylcholine levels

Question 23

SLUDGE caused by

Answer 23

chronic stimulation of muscarinic acetylcholine receptors, in organs and muscle innervated by the parasympathetic NS

Question 24

SLUDGE can be treated with

Answer 24

Atropine

Pralidoxime

Anti-cholinergic agents

Question 25

mAChR agonists examples

Answer 25

Pilocarpine- treat glaucoma Bethanechol- stimulate bladder emptying

Question 26

mAChR antagonists

Answer 26

* Ipratropium and tiotropium are used to treat some forms of asthma and COPD * Tolterodine, darifenacin and oxybutynin used to treat overactive bladder

Question 27

Vast majority of post ganglionic sympathetic neurones are

Answer 27

adrenergic- utilising noradrenaline as chemical transmitter

Question 28

Post-ganglionic sympathetic neurones

Answer 28

possess a highly branching atonal network with numerous varicosities, each of which is a specialised site for calcium dependent NA release

Question 29

synthesis of noradrenaline occurs where

Answer 29

Synthesised within the adrenal medulla

Question 30

synthesis of noradrenaline

Answer 30

Precursor- tyrosine—\> DOPA —\> dopamine (taken up by vesicles and then conversion) —\> NA

Question 31

how is noradrenline converted to adrenaline

Answer 31

by phenylethanolamine N- methyltransferase

Question 32

90% of NA rleeased at cleft is

Answer 32

repacked and recycle (sodium/ NA cotransporter)

Question 33

noradrengeric transmission

Answer 33

1. NA diffuses across the synaptic cleft and interacts with adrenoreceptors in the post-synaptic membrane to initiate signalling in the effector tissue 2. NA interacts with presynaptic adrenoreceptors to regulate processes within nerve terminal e.g. NA release 3. NA has only a very limited time in which to influence pre and post synaptic adrenoreceptors as it rapidly removed from the synaptic cleft by NA transporter proteins

Question 34

noradrenergic transmission **termination**

Answer 34

Uptake 1: NA actions are terminated by re-uptake into the pre-synaptic terminal by Na+ dependent, high affinity transporter Uptake 2: NA not re-captured by Uptake 1 is taken up by a lower affinity, non-neuronal mechanism

Question 35

metabolism of NA not reuptaken by vesicles in the pre-synaptic terminal

Answer 35

Within the pre-synaptic terminal NA not taken up into vesicles is susceptible to metabolism by two enzymes 1. Monoamine oxidase (MAO) 2. Catechol-O-methyltransferase (COMPT)

Question 36

subtype selctive adrenorecptor agonists and antagonists are

Answer 36

used clinically

Question 37

B2-adrenoreceptor-selective agonists (salbutamol) used in

Answer 37

asthma to oppose bronchoconstriction

Question 38

why is B-adrenoreceptor selectivity of salbutamol important

Answer 38

limits possible CVD side-effects (e.g. positive inotropic and chronotropic actions)