P5: Drugs and Parasympathetic Nervous System Flashcards
Name the two types of cholinergic receptors
- Nicotinic
- Muscarinic
What type of receptors are nicotinic receptors?
Ligand gated Na+ channel
What type of receptors are muscarinic receptors?
G protein coupled receptors
What are the subtypes for muscarinic receptors?
Where are they found?
- M1 (Many tissues)
- M2 (Heart)
- M3 (Many tissues)
- M4 (CNS)
- M5 (CNS)
What type of G protein is each subtype of muscarinic receptor? (First 3 only)
- M1 (Gq)
- M2 (Gi)
- M3 (Gq)
Where are N1 nicotinic receptors found?
Post-ganglionic neurones in both the parasympathetic and sympathetic nervous systems
Where are N2 nicotinic receptors found?
Neuromuscular junctions
How does activation of the PsNS affect vision?
Activation of the PsNS causes contraction of ciliary smooth muscle, for near vision
How do muscarinic agonists treat glaucoma? (3)
- Causes contraction of iris circular muscle
- Which allows aqueous humour drainage via the canals of Schlemm
- Which reduces intra-ocular pressure
Explain how a muscarinic agonist can decrease cardiac output (4)
- Ach binds to M2 receptors in atria and nodes
- α (Gi) subunit causes a decrease in cAMP levels
- This decreases Calcium ion entry
- This decreases cardiac output
Explain how a muscarinic agonist can decrease heart rate (3)
- Ach binds to M2 receptors in atria and nodes
- βγ subunit causes increase in K+ entry
- This decreases heart rate
Most blood vessels have which type of innervation?
Parasympathetic or Sympathetic?
Sympathetic
Action of ACh on vascular endothelial cells causes what?
- Release of Nitric Oxide via M3 AChR
- Which induces smooth muscle relaxation
- Which lowers BP
What does stimulation of muscarinic receptors on exocrine glands cause? (3)
- Salivation
- Increased bronchial secretion
- Increased gastro-intestinal secretion
What is Pilocarpine?
- 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
What is Bethanechol?
- M3 receptor selective agonist
- Orally active
- Used to assist bladder emptying + enhance gastric motility
What is atropine?
- Antagonist at all forms of muscarinic receptors
- Stimulates HR, little effect on arterial BP
What do Cholinesterase Enzymes do?
Act to metabolise acetylcholine to choline and acetate
What are the two types of cholinesterase enzymes?
- Acetylcholinesterase
- Butyrylcholinesterase
How do Reversible Anti-Cholinesterase Drugs work?
- Compete with acetylcholine for active site on the anti-cholinesterase enzyme
- By donating carbamyl group to the enzyme and blocking it
Give some examples of reversible anti-cholinesterase drugs (4)
- Neostigmine
- Pyridostigmine
- Physostigmine
- Donepezil
What does Physostigmine treat? (2)
- Glaucoma, aiding intraocular fluid drainage
- Atropine poisoning
Give some examples of irreversible anti-cholinesterase drugs (4)
- Ecothiopate (only one in clinical use)
- Dyflos
- Parathion
- Sarin
What are some side effects of Ecothiopate?
- Sweating
- Blurred vision
- Hypotension
- GI pain
- bradycardia
- respiratory difficulty
What type of organophosphates can cross the Blood brain barrier?
Non-polar e.g. physostigmine and donepezil
Which Anti-Cholinesterase Drugs treat Alzheimers?
And why do they work?
- Donepezil
- Tacrine
- ACh is important in learning and memory, relieves symptoms but doesn’t affect degeneration
List the symptoms of organophosphate poisoning (used in insecticides or nerve agents)
SLUDGE BBB
- Salivation
- Lacrimation (tears)
- Urination
- Diaphoresis (sweating)
- GI motility
- Emesis (vomiting)
- Bronchorrhea
- Bronchoconstriction
- Bradychardia
What nervous system is pupil size under the control of
Antagonistic parasympathetic and sympathetic control
tropicamide
How does Non vascular smooth muscle with parasympathetic innervation respond to muscarinic effects
Contraction
Lungs = bronchoconstriction
Gut = increased peristalsis
Bladder = increased bladder emptying
Name some muscarinic effects on the body
- Decreased HR
- Decreased BP
- Increased sweating
- Difficulty breathing
- Bladder relaxation
- Enhance gastric emptying
- Increased salivation and tears
Name some typical cholinergic adverse effects
- Sweating
- impaired vision
- nausea
- bradycardia
- hypotension
- respiratory difficulty
Describe the general mechanism of muscarinic antagonists
- Have no efficacy at muscarinic receptors
- Act by blocking intrinsic, parasympathetic tone
- Can lead to excessive sympathetic effects, primary source of toxicity
Give examples of muscarinic antagonists and their uses and receptors
Atropine - surgery, non-selective Hyoscine - motion sickness, slight M1 Ipatropium - Asthma, COPD, non selective Benzhexol - parkinsonism, M1 Tropicamide - Ophthamology, non selective
Effects of atropine?
Pupil dilation, loss of light responsiveness, impairment of near vision - ophthalmic surgery
Prevents salivation and mucus secretion, bronchorelaxant - surgical uses
What are the effects of low dose cholinesterase inhibitors
Enhanced muscarinic activity
What are the effects of moderate dose cholinesterase inhibitors
Further enhancement of muscarinic activity
Increased transmission at all (PNS and SNS) autonomic ganglia
What are the effects of high dose (toxic) cholinesterase inhibitors
depolarising block at autonomic ganglia
Where does physostigmine usually act in the CNS
Post ganglionic PNS synapse
What is pralidoxime used for
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.
