Autonomic Pharmacology

Question 1

What are the principle NTs in the ANS?

Answer 1

Acetylcholine
Noradrenaline

Question 2

How is the CNS connected to sweat glands?

Answer 2

CNS -> ACh (nic) -> ACh (mus) -> sweat glands (sympathetic system)

Question 3

How is the CNS connected to blood vessels?

Answer 3

CNS -> ACh (nic) -> NA -> blood vessels (sympathetic)

Question 4

How is the CNS connected to the adrenal medulla?

Answer 4

CNS -> ACh (nic) -> adrenal medulla (sympathetic)

Question 5

How is the CNS connected to salivary glands?

Answer 5

CNS -> ACh (nic) -> ACh (mus) -> salivary glands (parasympathetic)

Question 6

Which receptors do ACh and NA act on?

Answer 6

nAChRs, mAChRs, alpha and beta adrenoreceptors

Question 7

What is cAMP?

Answer 7

Second messenger
Moves freely in cytoplasm

Question 8

What are kinases?

Answer 8

Add phosphates to molecules/proteins

Question 9

What do G-Alpha-S proteins do?

Answer 9

Stimulatory G protein that changes cAMP and protein kinase A levels
- Increases adenylyl cyclase activity
- Increases [cAMP]
- Activates protein kinase A (PKA)

Mediated by alpha G protein subunits

Question 10

What do G-Alpha-i proteins do?

Answer 10

Inhibitory G protein that changes cAMP and protein kinase A levels
- Decreases adenylyl cyclase activity
- Decreases [cAMP]
- Decreases PKA

• Increased K+ channel opening

Question 11

What do G-Alpha-q proteins do?

Answer 11

Increases intracellular Ca2+ levels through Phospholipase C enzyme
- Increases PLC
- Increases IP3 + DAG
- Increases [Ca2+] + Protein kinase C (PKC)

Mediated by alpha G protein subunits

Question 12

Which G protein subunits mediate Gi action?

Answer 12

Alpha - Inhibits adenylyl cyclase
Beta-Gamma - Activates K+ channels

Question 13

What type are muscarinic receptors?

Answer 13

Cholinergic

Question 14

Where are muscarinic receptors located structurally?

Answer 14

Postsynaptic to parasympathetic ganglion neurones and sweat glands

Question 15

Which mAChR subtypes couple to Gq proteins?

Answer 15

M1, M3, M5

Question 16

Which mAChR subtypes couple to Gi proteins?

Answer 16

M2, M4

Question 17

Where are M2 receptors found?

Answer 17

Heart - Nodal tissue and Atria
Widely distributed in CNS

Question 18

Where are M3 receptors found?

Answer 18

Exocrine glands - e.g. salivary
Smooth muscle - GI tract, eye, airways, bladder
Blood vessels - endothelium

Question 19

What response do M2 receptors cause?

Answer 19

Cardiac inhibition
- Decreased heart rate
- Slowing of AV conduction
- Decreased force of contraction (atria only)

Question 20

What response do M3 receptors cause?

Answer 20

Gastric, salivary secretion
GI smooth muscle contraction

Question 21

What is the mechanism for decreasing heart rate?

Answer 21

• M2 receptor activation via ACh
• Gai protein activation
• By subunits open K+ channels
• Increased K+ moving out of nodal cell
• More negative membrane potential (hyperpolarisation)

Question 22

What does M1 and M3 AChR activation cause?

Answer 22

Stimulates contraction of smooth muscle
- Bronchoconstriction
- GI motility
- Bladder voiding - urination
Stimulates secretion from exocrine glands?
- Mucus in lungs
- Lacrimal glands - tears
- Salivary glands
- Sweat glands

Question 23

What are the effects of muscarine?

Answer 23

• Decrease blood pressure
• Increase saliva
• Increase tearflow
• Increase sweating
• Abdominal pain
• Nausea
  Overdose = death from cardiac + respiratory failure

Question 24

What is atropine?

Answer 24

Non-selective mAChR antagonist
- Blocks all muscarinic receptors

Question 25

What effects does atropine have?

Answer 25

- Inhibition of secretion from glands - Smooth muscle relaxant - Pupillary dilation - Modest increase in HR - Decrease GI motility and acid secretion

Question 26

What are cholinomimetic drugs?

Answer 26

Drugs acting indirectly to enhance cholinergic transmission

Question 27

What are the properties of Anticholinesterase drugs?

Answer 27

- Prevents ACh breakdownby AChE - Long acting (irreversible) - Affects all cholinergic transmission including CNS e.g. nerve gas (sarin), pesticides - Muscarinic agonists can be used to reverse poisoning by anticholinesterases

Question 28

Whare are the receptors for NA?

Answer 28

GPCRs - Found on tissues responding to postganglionic sympathetic neurones

Question 29

Where do all B adrenergic receptors couple to?

Answer 29

G-alpha-s - Thus increase cAMP levels

Question 30

How is heart rate increased?

Answer 30

1) NA released from sympathetic neurones 2) B1 adrenergic receptor activation via NA 3) G-alpha-s protein activation 4) Increases adenylyl cyclase 5) Increase cAMP 6) Increase PKA 7) Increase phosphorylation of calcium channels - increases time open for 8) Increase Ca2+ into myocytes 9) Increased contraction

Question 31

Where are B1 adrenergic receptors located?

Answer 31

Nodal tissue and ventricular myocytes (cardiac muscle cells)

Question 32

What is the mechanism for bronchiole smooth muscle contraction?

Answer 32

1) Adrenaline released from chromaffin cells 2) Activates B2 adrenergic receptors n bronchial smooth muscle cells 3) G-alpha-s protein activation 4) Increases adenylyl cyclase 5) Increases cAMP 6) Increases PKA 7) Phosphorylation of smooth muscle cell machinery 8) Bronchodilation

Question 33

What are the clinical uses of adrenoceptor agonists?

Answer 33

Adrenaline (non-selective) CV system: - Cardiac arrest - Anaphylaxis B2 selective Respiratory system: - Bronchodilator to treat asthma: - Salbutamol

Question 34

What are the clinical uses of adrenoceptor antagonists?

Answer 34

Treat: - Hypertension - Heart failure - Somatic anxiety symptoms Unwanted effects: - Bronchoconstriction - beta blockers avoided in asthma patients - Cardiac depression