7 - Autonomic Pharmacology 2

Question 1

nicotinic ACh receptors consist of ___ _____ subunits. These subunits can be assembled to form a diverse range (alpha __ -__, beta __-__, __, __, __)

Answer 1

five subunits

alpha 1-10
beta 1-4
gamma
2 weird signs

Question 2

the subunits forming peripheral skeletal muscle nicotinic receptors are__, __, __, __, __/__

Answer 2

alpha 1, alpha 1, beta 1, gamma, weird/weird

Question 3

the subunits forming peripheral ganglionic nicotinic receptors are__, __, __, __, __

Answer 3

B4,B4,B4, A3,A3

Question 4

the subunits forming CNS nicotinic receptors are__, __, __, __, __

or

__, __, __, __, __

Answer 4

A4,A4,B2,B2,B2

A7 times 5

Question 5

in cholinergic transmission at presynaptic neurone, what generates ACh from the precursor choline? and what causes degradation of ACh one it has had its fffect on post synaptoc receptors?

Answer 5

choline acetyltransferase (CAT)

degradation to acetate and choline by acetylcholinesterase

you then get the reuptake and reuse of choline

Question 6

in cholinergic trasnmission, transmission is rapidly degraded to ___ and___

Answer 6

acetate and choline

Question 7

what does ACh binding to nicotinic receptors do in presynaptic ?

Answer 7

opens the channel and results in the influx of Na causing depolarisation

Question 8

the amount of depolarisation depends on the amount of ____ acting on the nicotinic receptors - what is his called?

Answer 8

neurotransmitter

graded depolarisation/excitatory post-synaptic potential

Question 9

what are the three muscarinic receptors (parasympathetic) ? and where are they found?

Answer 9

M1,M2,M3 on the effector cell (e.g. smooth muscle, gland cell)

Question 10

what is the mneumonic for remembering the post ganglionic receptors ? Kiss (QISS) quick (QIQ)

Answer 10

alpha1 – Gq
alpha2 – Gi
beta1 – Gs
beta2 – Gs

M1 – Gq
M2 – Gi
M3 – Gq

Question 11

Gq - _____ of phospholipase __

Gi - inhibition of ____ ____ ; opening of __ channels

Gs - stimulation of ___ ____

Answer 11

Gq - stimulation of phospholipase C

Gi - inhibition of adenylyl cyclase; opening of K channels - slows discharge of APs

Gs - stimulation of adenylyl cyclase

Question 12

what does activation of M1, M2, M3 do to the body ?

Answer 12

M1- increased acid secretion in the stomach

M2 - decreased heart rate

M3 - increased secretion of saliva and contraction of VISCERAL smooth muscle in lungs

NOTE: VASCULAR smooth muscle is indirectly relaxed by M3 receptor activation

Question 13

what is the precursor for noradrenaline (NA) in nerve terminal of post-ganglionic neurone

Answer 13

L-tyrosine

Question 14

what are the adrenoceptor subtypes?

Answer 14

Alpha 1,2 and Beta 1,2

Question 15

sympathetic division - reuptake of Na by transporters occurs by two uptake methods

1. NA is metabolised by _____ ___ to metabolites in the ___ ___ of ___ ____ neurone
2. NA is metabolised by ___- __- ________ in the ___ cell (e.g. ___ and ___ ___ cells)

Answer 15

1. NA is metabolised by monoamine oxidase (MAO) in the nerve terminal of post-ganglionic neurone
2. NA is metabolised by Catechol-O-methyltransferase (COMT) in the effector cell (e.g. cardiac and smooth muscle cells )

Question 16

what does activation of A1,A2,B1,B2 do to the body ?

Answer 16

A1 - Gq- contracts vascular smooth muscle

A2 - Gi - inhibits NA release

B1 - Gs - increased rate and force of heart

B2 - Gs - relaxes bronchial and vascular smooth muscle

Question 17

______ ______ mediate negative feedback inhibition of transmitter release

Answer 17

presynaptic autoreceptors

Question 18

what are the pre-synaptic autoreceptors in the nerve terminals of post ganglionic parasympathetic neurones? and sympathetic neurones?

Answer 18

parasympathetic - M2

sympathetic - alpha 2

Question 19

what do the presynaptic autoreceptors actually do?

Answer 19

inhibit Ca release - so less neurotransmitter is released

Question 20

how does cocaine work?

Answer 20

it has a very similar structure to NA - so uptake 1 will bind cocaine but cocaine inhibits U1 so NA cannot be metabolised by MAO and Na lvels in the synaptic cleft rise resulting in increased adrenoceptor stimulation

Question 21

what are the effects of cocaine on the body? these are largely the same for amphetamine too

Answer 21

causes vasocontriction (alpha 1) and cardiac arrhythmias (beta 1)

Question 22

how does amphetamine work ?

Answer 22

It is a substrate for U1 but unlike cocaine it will enter the noradrenergic terminal (U1 will take it up) and then it will block MAO.

It also enters the synaptic vesicle and displaces NA into the cytoplasm which leads to U1 running backwards and pumping NA out of the cell into the cleft

Question 23

prazosin is a selective ___,____ of _____. It does not block ___, ___ or ___

Answer 23

prazosin is a selective, competitive, antagonist of alpha 1 and does not block A2,B1,B2

Question 24

what are the clinical uses of prazosin?

Answer 24

anti-hypertensive - it is a vasodilator

Question 25

atenolol is a selective ___,____ of _____. It does not block ___, ___ or ___

Answer 25

atenolol is a selective competitive antagonist of B1, does not block B2,A1 or A2

Question 26

what are the clinical uses of atenolol?

Answer 26

used as an anti-anginal and anti-hypertensive agent

Question 27

salbutamol is a selective ___ of _____. It does not block ___, ___ or ___

Answer 27

salbutamol is a selective agonist of B2. It does not block B1, A1 or A2

Question 28

what are the clinical uses of salbutamol?

Answer 28

bronchodilator in asthma

Question 29

atropine is a competitive _____ of ____ ___ receptors, does not block ______ ____ receptors. It blocks all _____ receptors equally

Answer 29

atropine is a competitive antagonist of muscarinic ACh receptors, does not block nicotinic ACh receptors. It blocks all muscarinic receptors equally

Question 30

what are the clinical uses of atropine?

Answer 30

used to reverse bradycardia following MI