W3 - 11 Autonomic Pharmacology II

Question 1

How is sympathetic function mediated?

Answer 1

Effects mediated via noradrenaline from postganglionic fibres, or adrenaline from the adrenal medulla

Question 2

What is the exception to sympathetic effects mediated by NAd or Ad?

Answer 2

Sweat glands are cholinergic

Question 3

What are sympathetic effects?

Answer 3

Increase in heart rate and contractility
Vasoconstriction (a) and vasodilation (b)
Bronchodilation
Decreased gut motility
Piloerection
Glycogenolysis and gluconeogenesis
Renin secretion

Question 4

What action do sympathetic nerves have on blood vessels?

Answer 4

Nerves run in the outside of the blood vessel, regulating smooth muscle tone. Almost all autonomic control of blood vessels is by sympathetic nerves,

Question 5

What adrenoceptors are there?

Answer 5

alpha adrenoceptors - a1 and a2 - vascular
beta adrenoceptors - b1 (cardiac), b2 (vascular) b3

Question 6

Give agonists for each adrenoceptor

Answer 6

Phenylephrine and midodrine- a1 agonist
Clonidine - a2 agonist
Dobutamine - b1 agonist
Salbutamol - b2 agonist
Mirabegron - b3 agonist

Question 7

Give example antagonists for a1 and b1 adrenoceptors

Answer 7

Doxazosin - a1
Metoprolol - b1

Question 8

What effects on the heart do b-adrenoceptor activation have?

Answer 8

Increased heart rate
Increase contractility rate
Increased automaticity
Fast relaxation and recovery

Question 9

What effects on intracellular pathways do b-adrenoceptor activation have?

Answer 9

More Ca2+ entry and increase Ca2+ sensitivity
Faster repolarisation
Increase sodium potassium ATPase activity

Question 10

What are the clinical uses of adrenaline (b/a agonist) in the CVS?

Answer 10

Used to treat asystole, ventricular fibrillation and other severe arrhythmias
Anaphylaxis
Locally causes vasoconstriction (a1), commonly used in LA

Question 11

How does adrenaline affect arrhythmias?

Answer 11

b/a agonist
Increases ability of the heart to generate spontaneous rhythm

Question 12

How does adrenaline help anaphylaxis?

Answer 12

b/a agonist
During anaphylaxis, blood pressure falls and airways constrict. Adrenaline effects on the heart will increase HR and contractility, and bronchodilate the lungs.
Fast acting - helpful in emergency. In epi-pens.

Question 13

What is the clinical use of dobutamine?

Answer 13

B1 agonist
Used to treat cardiogenic shock

Question 14

What is salbutamol used for?

Answer 14

Asthma (bronchodilation of the airways) or delay of premature labour (relaxes smooth muscle)

Question 15

What is salbutamol?

Answer 15

Selective B2 receptor agonist

Question 16

What are side effects of salbutamol?

Answer 16

Tachycardia, arrhythmia, tremor

Question 17

How can salbutamol be taken?

Answer 17

Usually given as inhaled aerosol or powder. Oral or intravenous.

Question 18

What is terbutaline salmererol?

Answer 18

Selective b2 receptor agonist, same as salbutamol but for more severe asthma.
Given by aerosol. Longer acting. Same side effects

Question 19

What is phenylephrine?

Answer 19

a1 agonist

Question 20

What is phenylephrine used to treat and how?

Answer 20

Treats nasal congestion.
Upper respiratory tract infection causes blood vessels to dilate here, leading to increase in mucous production and tissue fluid, giving a sense of congestion. This vasoconstriction it and decreases symptoms.

Question 21

What is doxazosin?

Answer 21

a1 antagonist

Question 22

What does doxazosin cause?

Answer 22

a1 antagonist causes vasodilation (by blocking sympathetic vasoconstriction), drops TPR by opposing resting tone, lowering blood pressure

Question 23

What is doxazosin used to treat?

Answer 23

Hypertension (severe after ACE inhibitors or b-adrenoceptor antagonists)
Raynaud’s syndrome (inappropriate or excessive cutaneous vasoconstriction)

Question 24

Give examples of beta blockers

Answer 24

b-adrenoceptor antagonists
Propranolol - b1/b2
Metoprolol, atenolol - b1

Question 25

What effect do beta blockers have (b adrenoceptor antagonists)?

Answer 25

Decrease work done by the heart by slowing heart, decreasing contractility and decreasing ability to be spontaneously active
Anti-platelet aggregation

Question 26

What are beta blockers used to treat?

Answer 26

Angina, heart failure, cardiac arrhythmias, hypertension

Question 27

What is carvedilol and what is it used for?

Answer 27

Mixed b and a adrenoceptor antagonist
Used to treat heart failurw

Question 28

What terminates the action of noradrenaline once it is released from a sympathetic nerve terminal?

Answer 28

Action is terminated by recycling or update through the noradrenaline transporter (NAT) and back into nerve terminals

Question 29

What packages NA into vesicles?

Answer 29

VMAT - vesicular monoamine transporter

Question 30

What breaks down NA?

Answer 30

Monoamine oxidase (MA) and catechomethyl transferase (COMT)

Question 31

Neuronal uptake of NAd mediated by NAT is a secondary active transporter (requiring sodium and chloride ions). What drugs can block these effects? (Drugs affecting reuptake)

Answer 31

Blocked by cocaine and tricyclic antidepressants eg imipramine

Question 32

What peripheral side effects come from inhibiting NAT?

Answer 32

Won’t reuptake NAd, so it stays in the junctional cleft for longer and can activate its receptors, amplifying sympathetic transmission: increase HR, cause increased risk of cardiac arrhythmias thus increased risk of cardiac death and amplifies sympathetic vasoconstriction (excessive) of the upper airways, which can cause ischaemia. Snorting cocaine can cause nasal septal defect.

Question 33

What drugs affect the release of NA?

Answer 33

Indirectly acting sympathomimetic amines - eg tyramine, ephedrine, amphetamine (speed)

Question 34

What is the action of drugs affecting release of NA (sympathomimetic amines)?

Answer 34

They cause reversal of NA transport through NAT, causing release of NA.
They displace NA from sympathetic terminals. These drugs are also substrates for NAT, and will switch the configuration of NAR so that it is more likely to transport NA out of the cell, so it no longer takes it up but releases NA.

Question 35

Why are they indirectly acting sympathomimetic amines?

Answer 35

Acts in the nerve terminals to cause the release of NA, which will cause action on the adrenoceptors. So systemic action will then amplify sympathetic transmission.

Question 36

What drugs might affect synthesis of NA?

Answer 36

Carbidopa - used in treatment of Parkinson’s disease

Question 37

What drug is used for hypertension in pregnancy?

Answer 37

Methyldopa
Drops central sympathetic drive and thus decreases BP, safe for baby.

Question 38

Which drugs affect metabolism?

Answer 38

Blockers of monoamine oxidase (MAO) - MAOIs
COMT - blocked by entacapone

Question 39

What are the cardiovascular effects of catecholamines?

Answer 39

NA should activate beta receptors in the heart, but when injected, it drops heart rate. This is because the increase in peripheral resistance causes an increase in BP, causing a baroreceptor mediated fall in sympathetic tone, causing a net fall in heart rate.