Autonomic Pharmacology

Question 1

What neurotransmitters do Sympathetic neurones release?

Answer 1

ACh preganglioninc

NA post ganglionic

Question 2

What neurotransmitters do parasympathetic neurones release?

Answer 2

ACh pregangioninc acts on neruonal nAChR’s

ACh postganglionic acts on muscarinic AChR’s

Question 3

What are nAChR’s?
How do they work?
What is the dfference between those found the somatic NS and those used in the ANS?

Answer 3

5 subunit ligand gated ion channels
binding of ligand results in a conformational change rotation of hydrophobic R groups to inside of membrane allowing Na+ ions to flow through causing depolarisation

Neuronal nAChR’s have different protein subunits making the receptor compared to those found on SK muscle in the somatic NS

Question 4

What is hexamethonium?
What class it it?

Answer 4

Was a drug that had been used that targeted only neuronal nAChR’s

Non-Competitive antagonist
blocked all autonomic transmission

Question 5

Why are muscarinic receptors important?

Answer 5

Modulate postganglioninc PNS transmission

Question 6

What are muscarinic receptors

Answer 6

GPCR’s

5 subtypes M1-M3 are the most important in the ANS

Question 7

Where are msucarinic receptors found?

Answer 7

On smooth muscle
cardiac muscle
glands

Question 8

What is the effect of activation of muscarinic receptors bu ACh or muscarinic agonists on smooth muscle?

Answer 8

Causes contraction of smooth muscle in the Gi tract

Causes vasodilation in some blood vessels that have PNS innervation e.g those of the head and neck due to release of endothelium derived relaxing factor (NO) on receptor activation

Question 9

What is the effect on activation of muscarinic receptors on glands and cardiac muscle?

Answer 9

Glands increased secretion

Cardiac muscle decreased heart rate and cardiac output

Question 10

Give two examples of muscarinic agonists

Answer 10

muscarine

pilocarpine

Question 11

what are muscarinic agonists also referred to as?

Answer 11

Parasympathomimetics

as they mimic the effects of PNS innervation

Question 12

What is muscarine poising what are the symptoms

how is it treated?

Answer 12

muscarine found in may mushrooms

high doses activation of muscarinic R’s

bradycardia resulting in a fall in blood pressure

Increased gut motility

Bronchoconstriction pupillary constriction

Treatment is a muscarinic antagonist e.g. atropine (competitive antagonist)

Question 13

What is pilocarpine when is it used?
How is this drug given?
How does it work?

Answer 13

Muscarinic agonist

Used to treat glaucoma

Applied to the eye (topical)

Acts on M3 causes contraction of the ciliary muscles which opens drainage pore allowing the aqueous humour to drain decreasing IOP

Question 14

Give two examples of a muscarinic antagonists

Answer 14

Atropine

Ipatropium

Question 15

What are the uses of muscarinic antagonists in treatment of Asthma?

Answer 15

Ipratropium inhaled

binds to muscarinic receptors preventing bronchoconstriction and bronchosecretion that is a PNS action

Question 16

How can msucarinic antagonists be used in the treatment of Bradycardia?

Answer 16

Binds to muscarinic R’s on cardiac muscle preventing activation thus preventing the slowing of heart rate

Leads to an increase in Cardiac output and contractility

Question 17

How can muscarinic antagonists be used in relation to the eye?

Answer 17

used to dilate pupils
opposes papillary constriction when light hits the eye allowing optometrists to look at the back of the eye

tropicamide (topical antagonist)

Question 18

Where are alpha 1 adrenoceptors found
what does activation of them cause?
What type of G Protein does the intracellular signal transduction cascade rely on?

Answer 18

Smooth muscle
Decreases Gi motility
Cause vasoconstriction
Gq GPCR acts on phospholipase C

Question 19

Where are Alpha 2 adreoceptors found?
what does activation of them cause?
What type of G Protein does the intracellular signal transduction cascade rely on?

Answer 19

CNS including the brainstem midbrain spinal cord cerebral cortex
Activation causes an increase in blood pressure blocks NA release from PNS
Gs acts of adenyl cyclase

Question 20

Where are beta 1 adrenoceptors located?
what does activation of them cause?
What type of G Protein does the intracellular signal transduction cascade rely on?

Answer 20

Cardiac muscle
Increased contractility and cardiac output
Gs

Question 21

Where are B2 adrenoceptors located?
what does activation of them cause?
What type of G Protein does the intracellular signal transduction cascade rely on?

Answer 21

Lots of places notably on bronchi causing relaxation of smooth muscle allowing for vasodilation and on smooth muscle of blood vessels supplying the heart and blood vessels –> Dilation in sympathetic activity

Gs

Question 22

Where are B3 adrenoceptors located?
what does activation of them cause?
What type of G Protein does the intracellular signal transduction cascade rely on?

Answer 22

Urinary bladder
cause relaxation of smooth muscle
Gs

Question 23

Give the name of an alpha adrenoceptor agonist? How does it work (hint is nasal decongestion)

Answer 23

Phenylephrine (Agonist)

Used as a nasal decongestant
causes vasoconstriction of blood vessels supplying nasal mucosa therefore less mucus produced

Question 24

What is used when local anaesthetics are adminstered?

Answer 24

Adrenaline or NA

act agonists causing local vasoconstriction and therefore localisation of LA

Question 25

Give an example of a alpha adrenoceptor antagonist and its use?

Answer 25

Tamsulosin

used in Benign prostatic hyperplasia

Antagonsit therefore causes relaxation of smooth muscle of prostrate and urinary sphincter making urination easier

Question 26

Give an example of an B adrenoceptor agonist and its use?

Answer 26

Salbutamol

used in treatment of asthma as it results in bronchodilation?

Question 27

How can beta agonists be used in the treatment of cardiogenic shock

Answer 27

Increase heart rate and contractility rising blood pressure

Question 28

Give an example fo a B adrenoceptor antagonist?

When is it used clinically and how?

Answer 28

Metoprolol (most things ending with olol)

Used to treat hypertension, arrhythmias
targets B1 decreasing cardiac output

Question 29

How is postgaglioninc sympathetic neruotranmission terminated?

Answer 29

Usign Noradrneline transporters that transport NA back into the postganglionic neurone

Question 30

Give an examples of NAT inhibitors?

Answer 30

Cocaine and tricyclic antidepressants

Question 31

how do NATi work?

Answer 31

Prevent the transport of NA back into postganglionic neurone

NA inhibitor signal is not terminated causing constant sympathetic stimulation

Question 32

What are the effects, and side effects of NATi inhibitors like cocaine?

Answer 32

Effects prolonged sympathetic stimulation

Euphoria and excitement as dopamine and serotonin neurotransmitters also prevented of being transported back into neurones in CNS

Taccycardia increased blood pressure

Question 33

What are mono amine oxidase inhibitors

Answer 33

Block monamine oxidase enzymes that usually break down NA intracellularly

Question 34

What is the use of MAOi?

And how do they work?

Answer 34

Antidepressants

Increase the presence of NA dopamine and serotonin (5HT) in brain

Question 35

What are the side effects of MAOi’s?

Answer 35

Postural hypotension
weight gain
restlessness
insomnia
cheese reaction

Question 36

What are indirectly acting sympathetic amines?

Answer 36

Enter sympathetic postganglionicn nerones via NAT and then displace NA intracellulary resutling thorough the reversal of the NAT

Causes long lasting effects of NA
bronchodillation vasoconstriction increased blood pressure

Question 37

what is the cheese reaction?

Answer 37

Interaction between MAOi’s
and indirectly acting sympathetic amines?

amine cause an increase in amount of NA in cytosol and then the MAOi’s prevent breakdown of this NA therefore more is displaced

causes sever hypertension episodes