parasympathetic nervous system

Question 1

what can replicate muscarinic effects

Answer 1

muscarine (selective agonist of mAChR)

Question 2

at low doses, what can abolish muscarinic effects

Answer 2

antagonist atropine

Question 3

what branch of PNS do muscarinic actions correspond to

Answer 3

PSNS

Question 4

after atropine blockade of muscarinic actions, what can larger doses of ACh induce effects similar to

Answer 4

those caused by nicotine (more ACh required to stimulate nAChR)

Question 5

where are muscarinic receptors found

Answer 5

in PSNS at effector organ; in SNS at effector organ of sweat gland

Question 6

where are nicotinic receptors found

Answer 6

in between pre and post ganglion in ANS (pre: long and post: short in PSNS; pre: short and post: long in SNS); at skeletal muscle after motor neurone in somatic

Question 7

3 main subtypes of muscarinic receptor and location; general property of muscarinic receptors

Answer 7

M1: salivary glands, stomach parietal cells, CNS; M2: heart (if vagus activated); M3: salivary glands, bronchial/visceral smooth muscle; sweat glands; eye [M4 and M5 in CNS]; generally muscarinic are excitatory (M2 is inhibitory)

Question 8

what receptor are muscarinic receptors

Answer 8

G-protein coupled receptor

Question 9

what G-protein coupled receptor (type 2) is M1, M3 and M5, and what are the secondary messengers

Answer 9

Gq (stimulatory); IP3 DAG (upregulate)

Question 10

what G-protein coupled receptor (type 2) is M2 and M4, and what is the secondary messenger

Answer 10

Gi (inhibitory) cAMP (reduced production)

Question 11

what type of receptor are nicotinic receptors

Answer 11

ligand gated ion channels (type 1)

Question 12

what subunits can be present in nicotinic receptors

Answer 12

α β γ δ ε

Question 13

in nicotinic receptors, what does subunit combination determine

Answer 13

ligand binding properties

Question 14

nicotinic receptor: muscle type in NMJ in somatic nervous system

Answer 14

2α β δ ε

Question 15

nicotinic receptor: ganglion type in ANS

Answer 15

2α 3β (similar to CNS but tend to be pre-synaptic)

Question 16

strength of ACh effects in nicotinic receptors

Answer 16

relatively weak, so higher concentration required; most reponse is a Na+ influx so excitatory

Question 17

muscarinic cholinergic target systems

Answer 17

eye, salivary glands, sweat glands, lungs, heart, gut, bladder, vasculature

Question 18

3 muscarinic effects in eye and purpose

Answer 18

contraction of ciliary muscle (allowing lens to bulge so more convex, accomodating near vision), contract sphincter pupillae (constrict pupil (miosis) and improves drainage of intraocular fluid), lacrimation (tears)

Question 19

how does contraction of sphincter pupillae reduce intraocular pressure and thus the risk of glaucomas

Answer 19

opens pathway for aqueous humour (produced by ciliary bodies), allowing it to bathe lens and cornea (nutrients and oxygen), and allowing drainage via the canals of Schlemm; in glaucomas, iris becomes ruffled, so rate of drainage decreases due to channel occlusion, increasing intraocular pressure and causing blindness (cholinomimetic drugs flatten iris, increasing rate of drainage again)

Question 20

2 muscarinic effects in heart

Answer 20

decreased cardiac output (as decreased atrial contraction), decreased heart rate (bradycardia)

Question 21

how does ACh cause decreased cardiac output (negative inotropic effect)

Answer 21

binds to M2 AChR in atria and nodes (SAN and AVN) -> downregulates cAMP -> decreases Ca2+ entry

Question 22

how does ACh cause decreased heart rate (negative chronotropic effect)

Answer 22

binds to M2 AChR in atria and nodes (SAN and AVN) -> downregulates cAMP -> increases K+ efflux

Question 23

how do muscarinic effects decrease TPR in vasculature

Answer 23

most have no PSNS innovation, so ACh binds to M3 AChR on vascular endothelial cells to stimulate NO generation and release -> NO induces vascular smooth muscle relaxation (vasodilation)

Question 24

effect of muscarinic effects causing decreased heart rate, cardiac output and vasodilation on blood pressure

Answer 24

sharp drop

Question 25

muscarinic effects of non-vascular smooth muscle that does have PSNS innovation: lung, gut and bladder

Answer 25

opposite so contracts (excitatory): lung: bronchoconstriction; gut: increased peristalsis and motility; bladder: increased emptying

Question 26

4 muscarinic effects in exocrine glands: salivary, bronchial, GI and sweat

Answer 26

salivation, increased bronchial constriction, increased GI secretions (incl. gastric HCl production), increased SNS-mediated sweating

Question 27

symptoms of muscarinic effects

Answer 27

decrease heart rate and BP, increase sweating, difficulty breathing, bladder contraction, GI pain (contraction of smooth muscle), increased salivation and tears

Question 28

2 typical agonists at muscarinic receptors (directly acting cholinomimetic drugs)

Answer 28

choline esters e.g. bethanechol; alkaloids e.g. pilocarpine

Question 29

2 examples of muscarinic receptor antagonists

Answer 29

atropine, hyoscine (very similar structures)

Question 30

physiological responses influenced by muscarinic receptor antagonists

Answer 30

PSNS innervation, so influences: constriction of pupil, ciliary muscle, trachea and bronchioles, contraction of detrusor and relaxation of trigone and sphincter, copious and watery secretions, decreased heart rate and contractility, increased GI motility, tone and secretions; SNS innervation: increased sweating [limits/inhibits/does opposite of all of these]

Question 31

CNS effect of atropine at normal dose

Answer 31

little effect

Question 32

CNS effects of atropine at toxic dose

Answer 32

mild restlessness and agitation (less M1 selective, CNS excitation)

Question 33

CNS effects of hyoscine at normal dose

Answer 33

depressive effect so sedation, amnesia

Question 34

CNS effects of hyoscine at toxic dose

Answer 34

CNS depression or paradoxical CNS excitation (associated with pain) due to greater permeation into CNS and brain as passes through BBB more readily, or more M1 selective (influence at therapeutic dose)

Question 35

opthalmic clinical uses of muscarinic receptor antagonist tropicamide

Answer 35

examination of retina (dilation) by paralysing cilliary muscle in iris

Question 36

anaesthetic clinical uses of muscarinic receptor antagonists

Answer 36

blocks constriction of trachea and bronchioles (dilates if inhaling anaesthetic); blocks copious, watery secretions (prevents secretions going back down airways); blocks low heart rate and contractility (protect against slowing effects of other drugs); sedation (hyoscine)

Question 37

neurological clinical uses of muscarinic receptor antagonists

Answer 37

motion sickness due to cholinergic sensory mismatch (eyes saying one thing, labyrinth saying another; cholinergic nerve to vomiting centre and induces nausea); treated with hyoscine patch (controls eye movements to maintain vision whilst in motion so no mismatch)

Question 38

Parkinson’s disease clinical uses of muscarinic receptor antagonists

Answer 38

loss of dopaminergic neurones from substantia nigra to striatum (less dopamine binding to D1 so less fine muscle movement from basal ganglia); dopamine produced at lower level so D1 not sufficiently stimulated; M4 receptors suppress D1 receptors to provide control, so by antagonising M4 receptor it becomes blocked, so D1 receptor becomes more responsive even though less dopamine produced, so cholinergic/dopaminergic more balanced in basal ganglia, reducino Parkinson’s symptoms

Question 39

respiratory clinical uses of muscarinic receptor antagonists

Answer 39

asthma/obstructive airways disease by blocking constriction of trachea and bronchioles; atropine (typical) and ipratropium bromide (specific to asthma as attempt to localise effect to lungs to reduce side effects: N+ so polar so less likely to cross lipid membranes)

Question 40

GI clinical uses of muscarinic receptor antagonists

Answer 40

irritable bowel syndrome by being M3 receptor antagonist (selective to reduce side effects); blocks increased GI motility, tone and secretions

Question 41

4 unwanted effects of muscarinic receptor antagonists

Answer 41

decreased sweating and thermoregulation so very hot; decreased secretions so very dry; cycloplegia (paralysis of the ciliary muscle causing loss of lens curvature and near vision) so blind; CNS disturbance and agitation