P5: Drugs and Parasympathetic Nervous System

Question 1

Name the two types of cholinergic receptors

Answer 1

• Nicotinic

- Muscarinic

Question 2

What type of receptors are nicotinic receptors?

Answer 2

Ligand gated Na+ channel

Question 3

What type of receptors are muscarinic receptors?

Answer 3

G protein coupled receptors

Question 4

What are the subtypes for muscarinic receptors?

Where are they found?

Answer 4

• M1 (Many tissues)
• M2 (Heart)
• M3 (Many tissues)
• M4 (CNS)
• M5 (CNS)

Question 5

What type of G protein is each subtype of muscarinic receptor? (First 3 only)

Answer 5

• M1 (Gq)
• M2 (Gi)
• M3 (Gq)

Question 6

Where are N1 nicotinic receptors found?

Answer 6

Post-ganglionic neurones in both the parasympathetic and sympathetic nervous systems

Question 7

Where are N2 nicotinic receptors found?

Answer 7

Neuromuscular junctions

Question 8

How does activation of the PsNS affect vision?

Answer 8

Activation of the PsNS causes contraction of ciliary smooth muscle, for near vision

Question 9

How do muscarinic agonists treat glaucoma? (3)

Answer 9

• Causes contraction of iris circular muscle
• Which allows aqueous humour drainage via the canals of Schlemm
• Which reduces intra-ocular pressure

Question 10

Explain how a muscarinic agonist can decrease cardiac output (4)

Answer 10

1. Ach binds to M2 receptors in atria and nodes
2. α (Gi) subunit causes a decrease in cAMP levels
3. This decreases Calcium ion entry
4. This decreases cardiac output

Question 11

Explain how a muscarinic agonist can decrease heart rate (3)

Answer 11

1. Ach binds to M2 receptors in atria and nodes
2. βγ subunit causes increase in K+ entry
3. This decreases heart rate

Question 12

Most blood vessels have which type of innervation?

Parasympathetic or Sympathetic?

Answer 12

Sympathetic

Question 13

Action of ACh on vascular endothelial cells causes what?

Answer 13

• Release of Nitric Oxide via M3 AChR
• Which induces smooth muscle relaxation
• Which lowers BP

Question 14

What does stimulation of muscarinic receptors on exocrine glands cause? (3)

Answer 14

• Salivation
• Increased bronchial secretion
• Increased gastro-intestinal secretion

Question 15

What is Pilocarpine?

Answer 15

• Selective agonist at muscarinic receptors
• Partial agonist for many muscarinic receptors - less effective on GI smooth muscle and heart
• Not broken down by acetylcholinesterase
• Treatment for glaucoma + xerostomia

Question 16

What is Bethanechol?

Answer 16

• M3 receptor selective agonist
• Orally active
• Used to assist bladder emptying + enhance gastric motility

Question 17

What is atropine?

Answer 17

• Antagonist at all forms of muscarinic receptors

- Stimulates HR, little effect on arterial BP

Question 18

What do Cholinesterase Enzymes do?

Answer 18

Act to metabolise acetylcholine to choline and acetate

Question 19

What are the two types of cholinesterase enzymes?

Answer 19

• Acetylcholinesterase

- Butyrylcholinesterase

Question 20

How do Reversible Anti-Cholinesterase Drugs work?

Answer 20

• Compete with acetylcholine for active site on the anti-cholinesterase enzyme
• By donating carbamyl group to the enzyme and blocking it

Question 21

Give some examples of reversible anti-cholinesterase drugs (4)

Answer 21

• Neostigmine
• Pyridostigmine
• Physostigmine
• Donepezil

Question 22

What does Physostigmine treat? (2)

Answer 22

• Glaucoma, aiding intraocular fluid drainage

- Atropine poisoning

Question 23

Give some examples of irreversible anti-cholinesterase drugs (4)

Answer 23

• Ecothiopate (only one in clinical use)
• Dyflos
• Parathion
• Sarin

Question 24

What are some side effects of Ecothiopate?

Answer 24

• Sweating
• Blurred vision
• Hypotension
• GI pain
• bradycardia
• respiratory difficulty

Question 25

What type of organophosphates can cross the Blood brain barrier?

Answer 25

Non-polar e.g. physostigmine and donepezil

Question 26

Which Anti-Cholinesterase Drugs treat Alzheimers? And why do they work?

Answer 26

- Donepezil - Tacrine - ACh is important in learning and memory, relieves symptoms but doesn't affect degeneration

Question 27

List the symptoms of organophosphate poisoning (used in insecticides or nerve agents) SLUDGE BBB

Answer 27

- Salivation - Lacrimation (tears) - Urination - Diaphoresis (sweating) - GI motility - Emesis (vomiting) - Bronchorrhea - Bronchoconstriction - Bradychardia

Question 28

What nervous system is pupil size under the control of

Answer 28

Antagonistic parasympathetic and sympathetic control | tropicamide

Question 29

How does Non vascular smooth muscle with parasympathetic innervation respond to muscarinic effects

Answer 29

Contraction Lungs = bronchoconstriction Gut = increased peristalsis Bladder = increased bladder emptying

Question 30

Name some muscarinic effects on the body

Answer 30

- Decreased HR - Decreased BP - Increased sweating - Difficulty breathing - Bladder relaxation - Enhance gastric emptying - Increased salivation and tears

Question 31

Name some typical cholinergic adverse effects

Answer 31

- Sweating - impaired vision - nausea - bradycardia - hypotension - respiratory difficulty

Question 32

Describe the general mechanism of muscarinic antagonists

Answer 32

- Have no efficacy at muscarinic receptors - Act by blocking intrinsic, parasympathetic tone - Can lead to excessive sympathetic effects, primary source of toxicity

Question 33

Give examples of muscarinic antagonists and their uses and receptors

Answer 33

``` Atropine - surgery, non-selective Hyoscine - motion sickness, slight M1 Ipatropium - Asthma, COPD, non selective Benzhexol - parkinsonism, M1 Tropicamide - Ophthamology, non selective ```

Question 34

Effects of atropine?

Answer 34

Pupil dilation, loss of light responsiveness, impairment of near vision - ophthalmic surgery Prevents salivation and mucus secretion, bronchorelaxant - surgical uses

Question 35

What are the effects of low dose cholinesterase inhibitors

Answer 35

Enhanced muscarinic activity

Question 36

What are the effects of moderate dose cholinesterase inhibitors

Answer 36

Further enhancement of muscarinic activity | Increased transmission at all (PNS and SNS) autonomic ganglia

Question 37

What are the effects of high dose (toxic) cholinesterase inhibitors

Answer 37

depolarising block at autonomic ganglia

Question 38

Where does physostigmine usually act in the CNS

Answer 38

Post ganglionic PNS synapse

Question 39

What is pralidoxime used for

Answer 39

Treats organophosphate binding, but after a few hours the acetylcholinesterase cannot be saved, It cannot enter the CNS so doesn't affect the central symptoms of organophosphate poisoning.