28. Drug Action on Acetylcholine Flashcards
Describe the structure of acetylcholine.
Two groups: acetyl and choline
Describe what acetylcholine is responsible for in the CNS.
In the CNS, acetylcholine and associated neurons form a cholinergic system –> causes excitatory neurons.
* acetylcholine modulates various neurons in the brain to control motivation, arousal, and attention.
Describe the responsibility of acetylcholine in the PNS.
Acetylcholine is a major neurotransmitter in the autonomic nervous system.
* acetylcholine plays an excitatory role leading to the activation of muscle constriction.
Explain the function of acetylcholine in the heart.
Acetylcholine dilates blood vessels, increaes bodily secretions, and slows the heart rate.
Explain the function of acetylcholine in the eye.
Acetylcholine results in constriction of pupil and increases the outflow of fluid from eye.
List the possible results of excess acetylcholine production.
- over constriction
- cramps
- muscular fasciculation
- over fluid
- lacrimation
- blurry vision
List the possible effects of regular acetylcholine balance.
- memory and learning
- muscle constriction
- outflow of fluid from eye
List the possible effects of not enough acetylcholine.
- loss of memory
- alzheimer’s disease
- less movement
- lambert-eaton mayasthenic syndrome
- less fluid from eye
- glaucoma
- estropia
Explain the roles of drug action on acetylcholine.
- altering biosynthesis of acetylcholine in presynaptic neuron.
- altering release of acetylcholine from a presynaptic neuron to a synaptic cleft
- altering reuptake of acetylcholine back to presynaptic neuron
- altering degradatino of acetylcholine in a synaptic cleft
What are the 3 major phases that lead to ACh in the synaptic cleft?
- Biosynthesis
- Storage
- Release
- Degradation
- Reuptake
Explain the steps of ACh biosynthesis.
- Choline is uptake into presynaptic neuron by Na+-dependent choline transporter (CHT). Rate-limiting step of ACh biosynthesis
- AcCoA is released from mitochondria.
- Acetylcholine is synthesized from AcCoA and choline by choline acetyltransferase (ChAT).
Explain the process of ACh storage in the presynaptic neuron.
Acetylcholine is uptaked by vesicle acetylcholine transporters (VATs) coupled with proton efflux.
* uptake can be inhibited by drugs like vesamicol
Explain how ACh is released into the synaptic cleft.
- Vesicles move to the presynaptic terminal –> which enforces Ca2+ channel open and uptake of Ca2+ into the neurons.
- Ca2+ ions activate the vesicles to fuse with the presynaptic membrane and release acetylcholine into synaptic cleft – exocytosis
Explain the process of acetylcholine degradation.
ACh in the synaptic cleft is quickly broken down into acetic acid and choline by acetylcholinesterase (AChE).
Explain the process of ACh reuptake.
Choline can be retaken into the presynaptic neuron by Na+-dependent choline transporter (CHT) to start a new cycle.
Describe the negative feedback mechanism of ACh release.
ACh binds to muscarinic receptor (M2, M4) on the presynaptic membrane –> results in inhibition of Ca2+ uptake and ACh release by negative feedback mechanism.
List the reversible AChEIs.
- Donepezil
- Rivastigmine
- Galantamine
- Pyridostigmine
- Edrophonium
What is the irreversible AChEI discussed.
Echothiophate
Describe Alzheimer’s disease.
Progressive neurologic disorder that causes the brain to shrink (atrophy) and brain cells to die.
* most common cause of dementia – a continuous decline in thinking, behavioral and social skills that affects a person’s ability to function independently.
Describe the association between ACh, AChEIs, and alzheimer’s disease.
ACh is essential for processing memory and learning.
* Deterioration of ACh in the CNS is associated with onset of Alzheimer’s Disease
* AChEIs may improve neuropsychiatric symptoms –> inhibit binding of ACh to ACh-esterase.
Describe Lambert-Eaton Myasthenic Syndrome (LEMS).
- rare hereditary condition resulting from defect at the junction where nerve stimulates muscle activity –> muscle weakness.
Explain how lack of ACh leads to LEMS.
The neuron is unable to release enough ACh for normal muscle functino due to autoantibodies attacking Ca2+ channels.
* insufficient Ca2+ influx into presynaptic terminal results in reduced exocytosis of ACh.
* AChEIs may improve symptoms of muscle weakness
* ex. pyridostigmine
Explain the Edrophonium test for LEMS.
Edrophonium is a readily reversible competitively short-acting acetylcholinesterase inhibitor.
* prevents breakdown of ACh at the neuromuscular junction.
If edrophonium is injected
* muscle strength improved –> possible Myathenia gravis
Explain glaucoma and its association to ACh.
Glaucoma is a group of eye conditions that damage the optic nerve because of an abnormally high pressure in the eye.
* ACh reduces eye pressure by increases the facility of outflow
* occurs when there is a lack of ACh
* drug: echothiophate
Match the drug to the drug action, target protein, and therapeutic indication.
