L8 Autonomic Pharmacology

Question 1

What are the principal transmitters in the autonomic nervous system (ANS)?

Answer 1

Acetylcholine and Noradrenaline

These transmitters act upon nAChRs, mAChRs, α- and β−adrenoceptors.

Question 2

What are the two main ways that drugs can target ANS receptors?

Answer 2

Indirectly (synthesis, storage, breakdown) or directly (agonists, antagonists)

Understanding the systems controlled by these receptors helps predict drug action.

Question 3

What is the role of G proteins in receptor signaling?

Answer 3

G proteins modulate effector proteins, which can be ion channels or enzymes

This modulation helps predict cellular effects.

Question 4

What are the effects of Gαs protein activation?

Answer 4

Increases adenylyl cyclase, cAMP levels, and protein kinase A (PKA)

Gαs is considered stimulatory.

Question 5

What does Gαi protein activation lead to?

Answer 5

Decreases adenylyl cyclase, cAMP levels, and protein kinase A (PKA)

Gαi is considered inhibitory.

Question 6

What is cAMP?

Answer 6

A second messenger, moves freely in cytoplasm

Question 7

What are kinases?

Answer 7

Adds phosphates to molecules/proteins

Question 8

Explain how G protein- coupled receptor signalling works

Answer 8

1) Hormone or neurotransmitter binds to receptor which causes a conformational change
2) Activates G heterotrimeric G protein (Gαi/ Gαs)
3) This interacts with adenylyl cyclase
4) Adneylyl cyclase converts ATP to cAMP which activates PKA

Question 9

What effect does Gαq have on intracellular calcium levels?

Answer 9

Increases intracellular Ca2+ levels through phospholipase C

This results in increased IP3 and DAG.

Question 10

What are gαs, gαi and gαq?

Answer 10

They are all different types of G protein alpha subunits

Question 11

What effect does Gβy have in membrane potential?

Answer 11

They can directly influence membrane potential by interacting with and activating ion channels, specifically potassium channels

Question 12

What are the two types of subunits within the Gi protein?

Answer 12

Gαi (inhibitory effects for cAMP)
Gβγ (activates potassium channels)

Question 13

What are the main subtypes of muscarinic receptors?

Answer 13

M1, M2, M3, M4, M5

M1, M3, and M5 are coupled to Gq, while M2 and M4 are coupled to Gi.

Question 14

Which subtypes of muscarinic receptors are coupled to Gq and Gi?

Answer 14

• M1, M3, M5 are coupled to Gq ( Increase calcium conc)
• M2 and M4 are coupled to Gi (inhibitory cAMP) and increases potassium channel opening

Question 15

The effects of Muscarinic actions closely resembles what?

Answer 15

It closely resembles the effects of parasympathetic innervation

Question 16

Where are Muscarinic receptors primarily located?

Answer 16

They are located postsynaptic to the parasympathetic ganglion neuron and in the sweat glands

Question 17

What are Muscarinic receptors?

Answer 17

They are a type of GPCR that are activated by the neurotransmitter acetylcholine

Question 18

Where are M2 (cardiac) located?

Answer 18

M2 receptors are located in nodal tissue and atria.

Question 19

Where are M3 (glandular/smooth muscle) generally located?

Answer 19

• Exocrine glands: salivary, etc
• Smooth muscle: gastrointestinal tract, eye, airways, bladder
• Blood vessels: endothelium

Question 20

What is M3’s (glandular/ smooth muscle) main functional response?

Answer 20

• Gastric, salivary secretion
• Gastrointestinal smooth muscle contraction

Question 21

What is the primary function of M2 muscarinic receptors?

Answer 21

Decreases heart rate and slows atrioventricular conduction (decrease force of atria contraction)

Cardiac inhibition

Question 22

How does M2 decrease heart rate?

Answer 22

• M2 activation via ACh
• Gαi protein activation
• βγ subunits open potassium channels
• Potassium ions move out of the nodal cell into the ECF
• More negative membrane potential which makes it more difficult for cell to reach threshold potential

Question 23

What physiological response is stimulated by M1 and M3 muscarinic receptors?

Answer 23

Contraction of smooth muscle and secretion from exocrine glands

This includes bronchoconstriction and gastrointestinal motility.

Question 24

What is a common effect of muscarinic agonist overdose?

Answer 24

Death from cardiac and respiratory failure

Symptoms may include decreased blood pressure, increased saliva, tearflow and sweating

Question 25

What is atropine and its primary function?

Answer 25

A non-selective muscarinic antagonist that inhibits secretion and relaxes smooth muscle

It can also cause pupillary dilation and modestly increase heart rate.

Question 26

What happens if antihcolinesterase drugs enter the brain?

Answer 26

These drugs will affect ALL cholinergic transmission including CNS

Question 27

What can reverse poisoning by anticholinesterases?

Answer 27

Muscarinic antagonists

Question 28

What are the effects of β1 adrenergic receptor activation?

Answer 28

Increased heart rate and contractility

β1 receptors are coupled to Gαs and located in nodal tissue and ventricular myocytes.

Question 29

What are the main subtypes of adrenergic receptors?

Answer 29

-α1
-α2
-β1
-β2
-β3

All β adrenergic receptors coupple to gαs (muscarinic) and thus increase cAMP levels

Question 30

Where is noradrenaline and adrenaline synthesised from?

Answer 30

Noradrenaline - sympathetic neurons
Adrenaline - chromaffin cells of the adrenal medulla

Question 31

What happens when activation of β1 adrenergic receptors occurs?

Answer 31

• 𝛽1 activation via NA
• Gαs protein activation
• Increases adenylyl cyclase, cAMP and PKA
• This increases phosphorylation of calcium channels
• Increase calcium ions into myocytes
• Increases contraction

NA - norepinephrine

Question 32

What is the role of β2 adrenergic receptors in the respiratory system?

Answer 32

Causes smooth muscle relaxation in the bronchioles by increased PKA

This is important for bronchodilation, especially in asthma treatment.

Question 33

Which drugs can treat hypertension and heart failure?

Answer 33

Adrenoceptor antagonists

These drugs can also alleviate anxiety symptoms.

Question 34

What are the unwanted effects of adrenoceptor antagonists?

Answer 34

Bronchoconstriction - beta blockers are avoided in asthma patients
Cardiac depression - particularly in the elderly

Question 35

Give me 2 examples of adrenoceptor agonists

Answer 35

• Adrenaline
• 𝛃2 selective respiratory system

Question 36

What’s the difference between antagonists and agonists?

Answer 36

Agonist - A substance that binds to a specific receptor and activates it, triggering a biological reponse
Antagonist - A substance that binds to a specific receptor but does not activate it

Question 37

What are the clinical uses of adrenoceptor agonists?

Answer 37

• Adrenaline:
  Cardiac arrest, Anaphylaxis
• 𝛃2 selective respiratory system:
  Bronchodilator to treat asthma

Question 38

What is the function of acetylcholinesterase (AChE)?

Answer 38

Breaks down acetylcholine

This is crucial for terminating cholinergic transmission.

Question 39

True or False: All β adrenergic receptors couple to Gαs.

Answer 39

True

This leads to increased cAMP levels.

Question 40

Fill in the blank: Muscarinic antagonists can be used to reverse poisoning by _______.

Answer 40

Anticholinesterases

These drugs affect all cholinergic transmission.

Question 41

What physiological consequences depend on a drug’s specificity for particular receptors?

Answer 41

The drug’s effects and clinical uses

This includes whether the drug acts as an agonist or antagonist.