Pharmacology Of The Sympathetic NS

Question 1

What receptors are present at ganglions?

Answer 1

Cholinergic nicotinic

Question 2

What is the main neurotransmitter of the sympathetic NS?

What are the exceptions?

Answer 2

Noradrenaline

Sweat glands - muscarinic (ACh)

Adrenal medulla - nicotinic (ACh)

Question 3

What are some alpha sympathetic effects?

Answer 3

Mydriasis (a1)

Decreased salivation (a1)

Arteriole constriction (a1)

Gluconeogenesis

Smooth muscle relaxation in GI tract

GI tract and bladder sphincter contraction (a1)

Question 4

What are some beta sympathetic effects?

Answer 4

Ciliary muscle relaxation

Increased heart rate via SAN (b1)

Increased heart contractile force (b1)

Bronchodilation (b2)

Gluconeogenesis (b2)

Smooth muscle relaxation in GI tract and bladder (b2)

Skeletal muscle relaxation (b2)

Question 5

Why do we not target the CNS with drugs?

Answer 5

Must pass blood-brain barrier

Likely to have widespread effects

Question 6

What 5 processes in sympathetic neuroeffector junctions be affected by drugs?

Answer 6

Noradrenaline synthesis

Noradrenaline storage

Noradrenaline release

Post-synaptic adrenergic receptor activation

Termination of signalling

Question 7

What enzyme metabolises unprotected monoamines?

Answer 7

Monoamine oxidase (MAO)

Question 8

What are some examples of monoamines?

Answer 8

Noradrenaline

Dopamine

Serotonin

Question 9

How is noradrenaline taken into vesicles?

Answer 9

Vesicular monoamine transporter (VMAT)

Question 10

What drug inhibits noradrenaline storage?

Answer 10

Reserpine

Question 11

How does reserpine work?

Answer 11

Blocks VMAT so noradrenaline isn’t taken up into vesicles

Noradrenaline metabolised by MAO

Question 12

What reserpine used to treat?

Answer 12

Hypertension

Question 13

What drug is used to inhibit noradrenaline synthesis?

Answer 13

a-methyl-tyrosine

Question 14

How does a-methyl-tyrosine work?

Answer 14

Competitive inhibitor against tyrosine

Inhibits tyrosine hydroxylase

Blocks formation of DOPA (from tyrosine)

Question 15

What is a-methyl-tyrosine used for clinically?

Answer 15

Decrease blood pressure in phaechromocytoma (adrenal gland tumour)

Question 16

How is noradrenaline transported back into the varicosity after release?

Answer 16

“Uptake 1” channels

Question 17

How do drugs inhibit noradrenaline storage?

Answer 17

Enter varicosity via “uptake 1” channels

Displace noradrenaline in pre-synaptic vesicles

Noradrenaline metabolised by MAO

Question 18

What drugs can be used to inhibit noradrenaline release?

Answer 18

Guanethidine

Clonodine

Amphetamine

Tyramine

Ephedrine

Question 19

How is release of noradrenaline usually regulated?

Answer 19

After release of noradrenaline, noradrenaline binds to a2 adrenoceptor on pre-synaptic membrane

Inhibits further noradrenaline release by a negative feedback system

Question 20

What is another name for the a2 adrenoceptor?

Answer 20

Autoreceptor

Question 21

How does clonodine work?

Answer 21

a2 adrenoceptor agonist

Mimics effect of high [NA] in synaptic cleft

Question 22

How do amphetamine/tyramine/ephedrine affect noradrenaline release?

Answer 22

Enter varicosity via “uptake 1” channels

Compete with noradrenaline to enter vesicles via VMAT

Noradrenaline leaks into cleft

Question 23

What is the secondary effect of amphetamine?

Answer 23

Inhibits MAO

Question 24

What type of receptor are adrenoceptors?

Answer 24

7TM GPCR

Question 25

What G-protein is coupled to a1 adrenoceptors?

Answer 25

Gq

Question 26

What G-protein is coupled to a2 adrenoceptors?

Answer 26

Gi

Question 27

What G-protein is coupled to b adrenoceptors?

Answer 27

Gs

Question 28

Where are a1 adrenoceptors mainly found?

Answer 28

Post-synaptic smooth muscle

Question 29

What does activation of a1 adrenoceptors cause?

Answer 29

Activation of PLC, IP3, DAG signalling Constriction and secretion

Question 30

What does activation of a2 adrenoceptors cause?

Answer 30

Inhibition of adenylyl cyclase Reduced cAMP so less PKA stimulated Inhibit neurotransmitter release

Question 31

What do a-blockers do?

Answer 31

Block sympathetic vasoconstriction tone To decrease blood pressure

Question 32

What is the important side effect of non-selective a-blockers?

Answer 32

Severe reflex tachycardia

Question 33

Why are a2-blockers not used?

Answer 33

Too widespread

Question 34

What are a1-blockers used as?

Answer 34

Antihypertensive agents (treat hypertension)

Question 35

Give an example of an a1-blocker

Answer 35

DOXAZOSIN Tamsulosin

Question 36

What are some side effects of a1-blockers?

Answer 36

Postural hypotension Diarrhoea Nasal congestion

Question 37

Where are b1 adrenoceptors mainly found?

Answer 37

Cardiac muscle

Question 38

What does activation of b1 adrenoceptors cause?

Answer 38

Stimulation of adenylyl cyclase Increase cAMP Increase force and rate of heart contractions

Question 39

Where are b2 adrenoceptors mainly found?

Answer 39

Smooth and skeletal muscle Vasculature and airways

Question 40

What does activation of b2 adrenoceptors cause?

Answer 40

Stimulate adenylyl cyclase Increased cAMP Smooth muscle relaxation (bronchodilation, vasodilation) (Glycogen mobilisation in liver)

Question 41

What type of drug is labetolol?

Answer 41

a1 and b blockers

Question 42

What does labetolol do overall?

Answer 42

Reduce arterial blood pressure

Question 43

What is an example of a b-selective blocker?

Answer 43

Propanolol

Question 44

What is propanolol used to treat?

Answer 44

Disturbances in cardiac rhythm MI Angina

Question 45

What are b1-selective blockers often called?

Answer 45

Cardio-selective blockers

Question 46

What is an example of a b1-blocker?

Answer 46

Atenolol

Question 47

Why are b1-blockers better than b-blockers?

Answer 47

Fewer side effects

Question 48

What are some adverse effects of b-blockers?

Answer 48

Fatigue (due to decreased cardiac output) Reduced peripheral blood flow BRONCHOCONSTRICTION Increased risk of cardiac failure Risk of HYPOGLYCAEMIA (patients on insulin therapy)

Question 49

What are b2-agonists used for?

Answer 49

Asthma

Question 50

What is an example of a b2-agonist?

Answer 50

Salbutamol

Question 51

What does salbutamol do to treat asthma?

Answer 51

Promotes bronchodilation | Also induces premature labour

Question 52

What are catecholamines metabolised by?

Answer 52

MAO Catechol-O-methyl transferase (COMT) - in both neuronal and non-neuronal tissue

Question 53

Where is MAO(A) found? (5)

Answer 53

CNS Lung endothelium Liver GI tract Placenta

Question 54

Where is MAO(B) found? (2)

Answer 54

CNS Blood platelets

Question 55

What are some examples of MAO inhibitors?

Answer 55

Phenylzine Moclobemide (A) Selegiline (B)

Question 56

What is moclobemide selective for?

Answer 56

MAO(A)

Question 57

What is selegiline selective for?

Answer 57

MAO(B)

Question 58

Why is it dangerous to eat cheese/yogurt or drink wine when taking MAO-inhibitors?

Answer 58

Tyramine Degraded by MAO usually Tyramine not degraded but converted into noradrenaline Hypertensive crisis