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Pharmocolgy > P5: Drugs and Parasympathetic Nervous System > Flashcards

P5: Drugs and Parasympathetic Nervous System Flashcards

1
Q

Name the two types of cholinergic receptors

A
  • Nicotinic

- Muscarinic

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2
Q

What type of receptors are nicotinic receptors?

A

Ligand gated Na+ channel

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3
Q

What type of receptors are muscarinic receptors?

A

G protein coupled receptors

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4
Q

What are the subtypes for muscarinic receptors?

Where are they found?

A
  • M1 (Many tissues)
  • M2 (Heart)
  • M3 (Many tissues)
  • M4 (CNS)
  • M5 (CNS)
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5
Q

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

A
  • M1 (Gq)
  • M2 (Gi)
  • M3 (Gq)
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6
Q

Where are N1 nicotinic receptors found?

A

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

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7
Q

Where are N2 nicotinic receptors found?

A

Neuromuscular junctions

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8
Q

How does activation of the PsNS affect vision?

A

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

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9
Q

How do muscarinic agonists treat glaucoma? (3)

A
  • Causes contraction of iris circular muscle
  • Which allows aqueous humour drainage via the canals of Schlemm
  • Which reduces intra-ocular pressure
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10
Q

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

A
  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
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11
Q

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

A
  1. Ach binds to M2 receptors in atria and nodes
  2. βγ subunit causes increase in K+ entry
  3. This decreases heart rate
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12
Q

Most blood vessels have which type of innervation?

Parasympathetic or Sympathetic?

A

Sympathetic

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13
Q

Action of ACh on vascular endothelial cells causes what?

A
  • Release of Nitric Oxide via M3 AChR
  • Which induces smooth muscle relaxation
  • Which lowers BP
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14
Q

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

A
  • Salivation
  • Increased bronchial secretion
  • Increased gastro-intestinal secretion
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15
Q

What is Pilocarpine?

A
  • 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
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16
Q

What is Bethanechol?

A
  • M3 receptor selective agonist
  • Orally active
  • Used to assist bladder emptying + enhance gastric motility
17
Q

What is atropine?

A
  • Antagonist at all forms of muscarinic receptors

- Stimulates HR, little effect on arterial BP

18
Q

What do Cholinesterase Enzymes do?

A

Act to metabolise acetylcholine to choline and acetate

19
Q

What are the two types of cholinesterase enzymes?

A
  • Acetylcholinesterase

- Butyrylcholinesterase

20
Q

How do Reversible Anti-Cholinesterase Drugs work?

A
  • Compete with acetylcholine for active site on the anti-cholinesterase enzyme
  • By donating carbamyl group to the enzyme and blocking it
21
Q

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

A
  • Neostigmine
  • Pyridostigmine
  • Physostigmine
  • Donepezil
22
Q

What does Physostigmine treat? (2)

A
  • Glaucoma, aiding intraocular fluid drainage

- Atropine poisoning

23
Q

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

A
  • Ecothiopate (only one in clinical use)
  • Dyflos
  • Parathion
  • Sarin
24
Q

What are some side effects of Ecothiopate?

A
  • Sweating
  • Blurred vision
  • Hypotension
  • GI pain
  • bradycardia
  • respiratory difficulty
25
Q

What type of organophosphates can cross the Blood brain barrier?

A

Non-polar e.g. physostigmine and donepezil

26
Q

Which Anti-Cholinesterase Drugs treat Alzheimers?

And why do they work?

A
  • Donepezil
  • Tacrine
  • ACh is important in learning and memory, relieves symptoms but doesn’t affect degeneration
27
Q

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

SLUDGE BBB

A
  • Salivation
  • Lacrimation (tears)
  • Urination
  • Diaphoresis (sweating)
  • GI motility
  • Emesis (vomiting)
  • Bronchorrhea
  • Bronchoconstriction
  • Bradychardia
28
Q

What nervous system is pupil size under the control of

A

Antagonistic parasympathetic and sympathetic control

tropicamide

29
Q

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

A

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

30
Q

Name some muscarinic effects on the body

A
  • Decreased HR
  • Decreased BP
  • Increased sweating
  • Difficulty breathing
  • Bladder relaxation
  • Enhance gastric emptying
  • Increased salivation and tears
31
Q

Name some typical cholinergic adverse effects

A
  • Sweating
  • impaired vision
  • nausea
  • bradycardia
  • hypotension
  • respiratory difficulty
32
Q

Describe the general mechanism of muscarinic antagonists

A
  • Have no efficacy at muscarinic receptors
  • Act by blocking intrinsic, parasympathetic tone
  • Can lead to excessive sympathetic effects, primary source of toxicity
33
Q

Give examples of muscarinic antagonists and their uses and receptors

A 
Atropine - surgery, non-selective
Hyoscine - motion sickness, slight M1
Ipatropium - Asthma, COPD, non selective
Benzhexol - parkinsonism, M1
Tropicamide - Ophthamology, non selective
34
Q

Effects of atropine?

A

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

35
Q

What are the effects of low dose cholinesterase inhibitors

A

Enhanced muscarinic activity

36
Q

What are the effects of moderate dose cholinesterase inhibitors

A

Further enhancement of muscarinic activity

Increased transmission at all (PNS and SNS) autonomic ganglia

37
Q

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

A

depolarising block at autonomic ganglia

38
Q

Where does physostigmine usually act in the CNS

A

Post ganglionic PNS synapse

39
Q

What is pralidoxime used for

A

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.

Pharmocolgy (22 decks)

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