sympathetic nervous system

Question 1

where are a1, a2, B1 and B2 (also B3) adrenoceptors located

Answer 1

SNS: post-ganglionic neurone to effector organ, adrenal medulla to effector organ

Question 2

what do adrenoceptor agonists do

Answer 2

mimic actions of noradrenaline or adrenaline by binding to and stimulating adrenoceptors

Question 3

what type of receptor are adrenoceptors

Answer 3

type 2 (G-protein coupled receptor)

Question 4

secondary messengers of a1

Answer 4

PLC, IP3, DAG

Question 5

secondary messengers of a2

Answer 5

downregulate cAMP so Gi (negative feedback receptor)

Question 6

secondary messengers of B1

Answer 6

upregulate cAMP

Question 7

secondary messengers of B2

Answer 7

upregulate cAMP

Question 8

where are adrenoceptor agonists used principally

Answer 8

CVS, eyes, lungs

Question 9

eye: adrenoceptor, importance and effect

Answer 9

a1, important, dilation; B, vaguely important, aqueous humour production by ciliary body

Question 10

trachea and bronchioles: adrenoceptor, importance and effect

Answer 10

B2, vaguely important, dilation

Question 11

liver: adrenoceptor, importance and effect

Answer 11

a1 and B2, very important, glycogenolysis and gluconeogenesis

Question 12

adipose: adrenoceptor, importance and effect

Answer 12

a1 and B1, important, lipolysis

Question 13

kidney: adrenoceptor, importance and effect

Answer 13

B1, important, increased renin secretion

Question 14

ureters and bladder: adrenoceptor, importance and effect

Answer 14

B2, vaguely important, detrusor relaxation; a1, important, trigone and sphincter contraction

Question 15

salivary glands: adrenoceptor and effect

Answer 15

a/B, thick and viscous secretions

Question 16

skin: adrenoceptor, importance and effect

Answer 16

a1, very important, piloerection; increased sweating (cholinergic)

Question 17

heart: adrenoceptor, importance and effect

Answer 17

B1, important, increased rate and contractility

Question 18

GI: adrenoceptor and effect

Answer 18

a/B, decreased motility and tone, sphincter contraction

Question 19

blood vessels to skeletal muscle: adrenoceptor, importance and effect

Answer 19

B2, important, dilation

Question 20

blood vessels to skin, mucous membranes and splanchnic area: adrenoceptor, importance and effect

Answer 20

a1, very important, constriction

Question 21

what endogenous agonists can activate all adrenoceptors

Answer 21

noradrenaline and adrenaline

Question 22

relative selectivity for noradrenaline of adrenoceptors

Answer 22

a1 = a2 > B1 = B2; still selective to both

Question 23

relative selectivity for adrenaline of adrenoceptors

Answer 23

B1 = B2 > a1 = a2; still selective to both

Question 24

noradrenaline metabolism, release and uptake

Answer 24

tyrosine -> noradrenaline by enzymatic steps (incl. in vesicle) -> action potential promotes exocytosis -> has effect -> removed from synpase by transport proteins into tissue (a2 is presynpatic receptor and inhibits noradrenaline release, suppressing SNS) or nerve

Question 25

5 directly acting SNS adrenoceptor agonsists and relevant adrenoceptor

Answer 25

adrenaline (non-selective), phenylephrine (a1), clonidine (a2), dobutamine (B1), salbutamol (B2)

Question 26

why is adrenaline used in anaphylaxis treatment and relevant adrenoceptors

Answer 26

opens airways (B2 - bronchodilation); causes vasoconstriction (a1) and so increases TPR and blood pressure (as histamine acts as vasodilator); increases heart rate (B1 - tachycardia); suppresses mediator release from mast cells (B receptors present); stomach cramps prevented as SNS effect relaxes gut motility etc.

Question 27

5 other clinical uses of adrenaline and relevant adrenoceptors

Answer 27

in asthma (B2: IM, SC; bronchodilation and mediator release); acute bronchospasm associated with chronic bronchitis or emphysema (B2); cardiogenic shock - sudden inability of heart to pump sufficient oxygen-rich blood (B1); spinal anaesthesia (a1: maintains blood pressure by vasoconstriction); local anaesthesia (a1: vasoconstricts - prolongs action to stop it getting into systemic circulation)

Question 28

5 locations of unwanted actions of adrenaline (non-selective)

Answer 28

secretions, CNS (minimal), CVS, GIT (minimal), skeletal muscle

Question 29

unwanted actions of adrenaline (non-selective) on secretions

Answer 29

reduced, thickened mucous

Question 30

unwanted actions of adrenaline (non-selective) on CVS, including if overdose

Answer 30

tachycardia, palpitations, arrhythmias; cold extremities (vasoconstriction), hypertension; overdose - cerebral haemorrhage, pulmonary oedema

Question 31

unwanted action of adrenaline (non-selective) on skeletal muscle

Answer 31

tremor (typically due to noradrenaline)

Question 32

example of a selective a1 adrenoceptor agonist, and relevant adrenoceptor selectivity

Answer 32

phenylephrine: a1>>a2>>>B1/B2; chemically related to adrenaline

Question 33

clinical uses of phenylephrine

Answer 33

nasal decongestant, vasoconstriction, mydriatic (pupil dilation)

Question 34

why mght phenylephrine be used as a decongestant

Answer 34

vasoconstriction, so less white cell invasion and oedema into sinus (which is mucous)

Question 35

phenylephrine relative duration in peripheral vs central

Answer 35

more resistant to COMT (peripheral enzyme) not MAO (central enzyme), so longer lasting in peripheral tissue

Question 36

example of a selective a2 adrenoceptor agonist, and relevant adrenoceptor selectivity

Answer 36

clonidine: a2>>a1>>>B1/B2

Question 37

how does clonidine work

Answer 37

a2 agonist so negative feedback, preventing noradrenaline release, looking like SNS antagonism

Question 38

sympathomimetics treating glaucoma: cause and consequence

Answer 38

caused by increase in intraocular pressure due to poor drainage of aqueous humour produced by cilliary body by blocked venous drainage channels; if untreated, permanently damages optic nerve, causing blindness

Question 39

sympathomimetics: which 2 areas are targeted by sympathomimetics to cause decreased glaucoma risk

Answer 39

in cilliary body, agonise a1 to cause vasoconstriction (restricts blood flow and thus aqueous humour production by limiting fluid loss), and agonise a2 to cause decreased humour formation; don't activate B1 with agonist as this stimulates aqueous humour production

Question 40

3 clinical uses of clonidine

Answer 40

treat glaucoma; treat hypertension and migraine (possible link); reduce sympathetic tone

Question 41

how does clonidine reduce sympathetic tone and therefore blood pressure

Answer 41

stimulates a2 adrenoceptor of presynpatic neurone, inhibiting noradrenaline release; central action in brainstem within baroreceptor pathway to reduce symapthetic outflow

Question 42

example of a selective B adrenoceptor agonist, and relevant adrenoceptor selectivity

Answer 42

isoprenaline: B1=B2>>>>a1/a2; chemically related to adrenaline

Question 43

isoprenaline resistance to degradation and uptake and relevant location

Answer 43

more resistant to MAO and uptake 1 so used in brain not peripherally

Question 44

clinical uses of isoprenaline

Answer 44

cardiogenic shock, acute heart failure, myocardial infarction

Question 45

why might B2 receptor stimulation be a problem using isoprenaline

Answer 45

stimulates vasodilation in vascular smooth muscle in skeletal muscle, resulting in fall in venous blood pressure, triggering tachycardia via baroreceptor stimulation (reflex tachycardia)

Question 46

example of a selective B1 adrenoceptor agonist, and relevant adrenoceptor selectivity

Answer 46

dobutamine: B1>>B1>>>a1/a2

Question 47

clinical use of dobutamine

Answer 47

cardiogenic shock

Question 48

why is dobutamine used to treat cardiogenic shock

Answer 48

lacks isoprenaline's reflex tachycardia, and has a plasma half life of 2 minutes as rapidly metabolised by COMT so acute effect

Question 49

example of a selective B2 adrenoceptor agonist, and relevant adrenoceptor selectivity

Answer 49

salbutamol (ventolin): B2>>B1>>>a1/a2

Question 50

salbutamol resistance to degradation

Answer 50

synthetic catecholamine derivative with relative resistance to MAO and COMT

Question 51

2 clinical uses of salbutamol

Answer 51

treatment of asthma, treatment of threatened premature labour

Question 52

how does salbutamol treat asthma

Answer 52

B2 relaxation of bronchial smooth muscle; upregulates cAMP, leading to hyperpolarisation as K+ efflux so harder for action potential to be triggered, causing muscle relaxation; inhibition of release of bronchoconstritor substances from mast cells

Question 53

how does salbutamol treat threatened premature labour

Answer 53

B2 relaxation of uterine smooth muscle

Question 54

side effects of salbutamol use

Answer 54

reflex tachycardia, tremor, blood sugar dysregulation