Cholinergic transmission Flashcards

1
Q

Cholinergic receptors (2)

A
  • type of receptors that get activated when they bind acetycholine
  • Muscarinic (slow) and nicotinic (fast)
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2
Q

Nicotinic receptor sub-types

  1. “Name”
  2. Location
  3. Mechanism
  4. Major functions
A

Nn –> ANS ganglion, Na+-K+ ion channels, depolarizes and evoke an action potential

Nm –> neuromuscular end plate, Na+-K+ ion channels, depolarizes and evoke an action potential

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3
Q

Muscarinic receptor sub-types

  1. “Name”
  2. Location
  3. Mechanism
  4. Major functions
A

M1 –> activation, nerve endings, Gq-coupled, increase IP3 and DAG cascade
M2 –> inhibition, heart and some nerve endings, Gi-coupled, decrease cAMP and activates K+ channels
M3 –> activation, effector cells: smooth muscles/glands/ ednothelium, Gq-coupled, increase IP3 and DAG cascade
M4 –> Gi- coupled, enhanced locomotion
M5 –> Gq

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4
Q

Nicotinic signalling (4)

A
  • receptor sub-types: Nn and Nm
  • made of 5 subunits
  • ligand-gated ion channels
  • Acetylcholine binds to the alpha subunit, causes conformational changes, channel is open, Na+ in and K+ out, depolarization, response
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5
Q

Muscarinic signalling (5)

A
  • 7 transmembrane proteins, one end binds acetylcholine and the other end activates intracellular proteins
  • G-protein coupled receptors
  • G- proteins are made up of 3 subunits (alpha, beta, gamma)
  • bound to GDP when it is inactive, bound to GTP when it is active
  • When the alpha subunit is bound to GTP, it separates from the others and then it is free to interact with other proteins. But, by doing that it used energy and then GTP is converted back to GDP and the subunits come back together.
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6
Q

Cholinergic junction (9)

A
  1. Choline is transported into the pre-synaptic nerve by sodium dependent choline transporter (inhibited by hemicholiniums)
  2. Choline + acetyl coA –> acetylcholine (enzyme: choline acyl transferase)
  3. Acetylcholine is transported to the vesicle by VAT (inhibited by vesamicol)
  4. Release of transmitters
  5. Voltage-sensitive Ca2+ channels open
  6. Increase intracellular Ca2+
  7. Vesicle fuses with surface membrane (inhibited by botulinium toxin)
  8. Acetylcholine is released
  9. Acetylcholine function is terminated by acetylcholinesterase
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7
Q

Cholinergic drugs

-types

A

Direct acting

  1. Muscarinic: choline esters –> acetylcholine and alkaloids –> pilocarpine
  2. Nicotinic

Indirect acting

  1. Organophosphates –> long acting –> ex: parathion
  2. Carbamates –> intermediate to long acting –> ex: neostigmine
  3. Edrophonium –> short acting
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8
Q

Clinical use of muscarinic agonists

  • name
  • what do they do
A

-acetilcholine and pilocarpine

Eye: accomodation for near vision (increase tension in the ciliary muscle), miosis, increase outflow
GI tract: increase secretion and peristalsis, decrease sphincter tone
Bladder: decrease sphincter tone and increase detrusor

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9
Q

Drugs use in open-angle glaucoma

  • name
  • what do they do
A

Pilocarpine - ciliary muscle contraction, opening of trabecular meshwork: increased outflow

Timolol - decreased aqueous secretion from ciliary epithelium

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10
Q

Anticholinesterase drugs (3)

A
  • acetycholinesterase is inhibited –> increase acetylcholine
  • stimulate:
    1. Parasympathetic: cardiac and smooth muscle, gland cells and nerve terminals
    2. Sympathetic: glands
    3. Somatic: skeletal muscle
  • Neostigmine, donepezil, edrophonium, dyflos, pralidoxin
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11
Q

Clinical uses of anticholinesterase drugs (indirect-acting agonists)

  • Names
  • Actions, indications, side effects duration of action
A

-Neostigmine, donepezil, edrophonium

CNS: alzheimer’s disease - donepezil
Eye: glaucoma
GI: increase motility
Anesthesiology: reverse action of non-depolarising neuromuscular blocking drugs
Myasthenia gravis: diagnosis (short acting), treatment (long acting)

Unwanted effects: excessive secretions, bradycardia, hypotension, bronchoconstriction, muscle fasciculations

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12
Q

Irreversible anticholinesterases

  • Names
  • Actions, indications, side effects duration of action
A
  • organophosphates
  • Dyflos, Pralidoxin
  • in agriculture, used as insecticides and antihelminthic agents
  • Dyflos –> used in the treatment of chronic glaucoma
  • Unwanted effects: hypotension, bronchoconstriction, bradycardia, muscle fasciculations, CNS stimulation (convulsions), excessive secretions
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13
Q

Anticholinergic drugs

-classification

A

Antimuscarinic

  1. M1- selective (pirenzepine)
  2. Non-selective (atropine)

Antinicotinic

  1. Ganglion blockers (hexamethonium)
  2. Neuromuscular blockers (tubocurarine)
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14
Q

Antimuscarinic drugs

-stimulate

A

Parasympathetic: cardiac and smooth muscle, gland cells and nerve terminals

Sympathetic: sweat glands

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15
Q

Clinical uses of muscarinic antagonists (antimuscarinic drugs)

  • Names (7)
  • Actions, indications, side effects duration of action
A

-Atropine, Scopolamine, Oxybutynin, Tropicamide, Pirenzepine, Benztropine, Ipratropium

CNS: motion sickness (Scopolamine), Parkinson’s disease (Benztropine)
Eye: dilates the pupil (tropicamide)
Respiratory: asthma, COPD (Ipratropium)
Cardiovascular: bradycardia (atropine)
GI: peptic ulcer (pirenzepine), antispasmodic action (oxybutynin)
Anesthesiology: premedication (atropine)

Unwanted effects: sedation, blurred vision, dry mouth, urinary retention

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16
Q

Nicotine effect

-where does it act

A

-acts on both parasympathetic and sympathetic ganglia

Parasympathetic –> cardiac and smooth muscle, gland cells, nerve terminals

Sympathetic –>. sweat glands, cardiac and smooth muscle, gland cells, nerve terminals, renal vascular smooth muscle

17
Q

Nicotine effect

  • what does it do
  • activation effects
  • clinical use
A

CNS: stimulation
Cardiovascular: tachycardia and hypertension
Respiratory: increase bronchial secretion
GI: nausea, vomiting, increase motility
Salivary glands: increase secretion
Sweat glands: increase secretion

  • more parasympathetic system and less sympathetic system –> more parasympathetic effects (except vascular system)
  • assists giving up smoking
18
Q

Ganglion-blocking drugs

-where does it act

A

-both parasympathetic and sympathetic

Parasympathetic –> cardiac and smooth muscle, gland cells, nerve terminals

Sympathetic –>. sweat glands, cardiac and smooth muscle, gland cells, nerve terminals, renal vascular smooth muscle

19
Q

Ganglion-blocking drugs

  • what does it do
  • inhibitory effects
A

LOOK AT THE TABLE IN THE SUMMARY

20
Q

Neuro-muscular blocking drugs

-classification

A

-block the cholinergic transmission between motor nerve endings and nicotinic receptors on the skeletal muscle

Non-depolarizing drugs

  1. Long action (tubocurarine)
  2. Intermediate action (rocuronium)

Depolarizing drugs - succinylcholine

21
Q

Malignant hyperthermia

A

-massive release of calcium from the sarcoplasmic reticulum, leading to uncontrolled contraction and stimulation of metabolism in skeletal muscle

22
Q

Neuromuscular blocking drugs: nondepolarizing & depolarizing blockers

A
  1. Acetylcholine (normal agonist) –> opens the sodium channel
  2. Nondepolarizing blocker –> competitive antagonists –> bind to the receptor to prevent opening of the channels
  3. Depolarizing blockers –> they mimic acetycholine but they are much more resistant to acetylcholinesterase –> producing persistent depolarization
    Fasciculation (phase I) –> desensitization (phase II) –> muscle relaxation
23
Q

Neuromuscular blocking drugs

  • Names
  • Side effects
A
  • Depolarizing: succinylcholine
  • Non-depolarizing: atracurium, pipecuronium, mivacurium, tubocurarine

Succinylcholine unwanted effects –> bradycardia, arrhythmias, increased intraocular pressue, prolonged paralysis

Non-depolarizing unwanted effects –> hypotension (due to ganglion block and histamine release)

24
Q

Neuromuscular blocking drugs

-reversal blockade

A
  • action of nondepolarizing blockers is reversed by increasing ACh concentration (by cholinesterase inhibitors)
  • paralysis produced by the depolarizing blocker is increased by cholinesterase inhibitors during phase I; during phase II, the block produced by succinylcholine is usually reversible by cholinesterase inhibitors
25
Q

Ganglion blocking drugs

  1. Name
  2. Clinical use
A
  1. Trimetaphan

2. ganglionic blocker in hypertension, as an adjunct to anesthesia, and to induce hypotension during surgery.

26
Q

How parasympathetic system works in the eye? (3)

A
  • Pupil contracts
  • Ciliary muscle constriction
  • Constrictor pupillae contracts –> lens bulges more and reduces focal length
27
Q

Signs or symptoms that are consistent with the diagnosis of botulinum poisoning? (2)

A
  • Inhibits the vesicle fusion with the surface membrane

- Cycloplegia (paralysis of accommodation)

28
Q

Sympathetic vs. Parasympathetic system

A
  • Sympathetic –> reaction to stress –> second neuron is in a specific ganglion
  • Parasympathetic –> activated when body is in rest state –> two neurons in the loop, one in the CNS and one next to the organ
29
Q

Pralidoxime

A

cholinesterase regenerator

30
Q

Atropine – indications (6)

A
  • We need it because it increases the amount of acetylcholine in general
  • Blocks M receptors
  • non selective
  • It is an antimuscarinic drug
  • Stimulation of M receptors –> bradycardia
  • too much acethylcholine –> tachycardia