Cholinergic Agonist Flashcards
Name the neurons which use Ach as neurotransmitter
- Preganglionic fibres terminating in Adrenal Medulla.
- The autonomic ganglia ( both parasympathetic and sympathetic)
- The post ganglionic fibers of the parasympathetic division.
- The postganglionic sympathetic division of sweat glands.
Name Direct acting Cholinergic Agonists
Ach Bethanechol Carbachol Cevimeline Pilocarpine
(Aisay beth Kr sewiyan pilo)
Indirect Cholinergic Agonists reversible
Ambenonium Donepezil Galantamine Neostigmine Pyridostigmine Physostigmine Rivastigmine Tacrine
(Aam do, galay nai paro, phr rivaj takrain.)
Indirect Cholinergic Agonist irreversible.
Echothiophate
Reactivation of Acetylcholinesterase
Pralidoxime
Cholinergic neurons also innervate the muscles of -
____ cells
Somatic
Patients with Alzheimer disease have a significant loss of ______ neurons in the temporal lobe and entorhinal cortex.
Cholinergic
Most of the drugs to treat Alzheimer’s disease are
Acetylcholinesterase inhibitors
Neurotransmitter in Cholinergic neurons involve six sequential steps:
- Synthesis
- Storage
- Release
- Binding of Ach to receptor
- Degradation of neurotransmitter in the synaptic cleft
- Recycling of choline and acetate
What is the synaptic cleft?
The space b/w nerve endings and Adjacent receptors located on nerves or effector organs
____ is transported from the extracellular fluid into the cytoplasm of the cholinergic neuron by energy dependant carrier system that co transports Sodium.
Choline
Drug that can inhibit the transport of Choline
Hemicholinium
Choline has a quaternary nitrogen and carries a permanent ____ charge
Positive
The uptake of chine is a _____ step in Ach synthesis.
Rate limiting step
________ catalyzes the reaction of choline with acetyl coenzyme A (CoA) to from ACh in cytosol
Choline acetyl transferase
Acetyl Coa is derived from mitochondria and produced by:
Pyruvate Oxidation
Fatty acid Oxidation
ACh is packed and stored into _______ by an active transport process coupled to the efflux of protons.
Presynaptic Vesicles
The neurotransmitter in vesicles appear as beadlike structures, known as
Vericosities
Explain release of ACh
- Action potential propagated by voltage sensitive sodium channel arrives at nerve ending
- Voltage sensitive Calcium channels on presynaptic membrane open.
- Increase in intracellular Calcium conc.
- Elevated Ca levels promote fusion of synaptic vesicles with cell membrane.
- ACh released in synaptic space.
Release of ACh can be blocked by
Botulinum Toxin
Toxin in black widow venom causes:
causes all ACh stored in synaptic vesicles to empty into synaptic gap
Post synaptic Cholinergic receptors on irgan surface are divided into:
Muscarinic rec
Nicotinic rec
AChE decomposes ACh to
Acetate & Choline
Butyryl cholinesterase
Pseudocholinesterase
Does not play significant role in ACh termination
What is recycling of Choline
Choline may be captured by a sodium coupled high affinity uptake system that takes the molecule back into the neuron. They are again acetylated to ACh
Muscarinic receptors belong to _____ of protein Coupled Receptors.
Class G
In addition to ACh, Muscarinic rec also show affinity for
Muscarine
An alkaloid, in certain poisonous mushrooms
Muscarinic rec show weak affinity for
Nicotine
classes of Muscarinic receptors
M1 M2 M3 M4 M5
classes of Muscarinic receptors
M1 M2 M3 M4 M5
All 5 classes of M rec are found on
Neurons
M1 rec is specifically found on:
Gastric Parietal Cells
M2 rec found on
Cardiac cells & Smooth muscles
M3 rec found on
Bladder
Exocrine Gland
Smooth Muscle
At High conc. Muscarinic drugs may show some activity on
Nicotinic receptor
Pirnzepine is ______receptor antagonist
M2
On rapid infusion , Pirenzepine produces the following side effect
Reflex Tachycardia
Darifenacin is a competitive M3 antagonist used for
Overactive Bladder
At present no clinically important agents interact solely with:
M4 & M5
Nicotinic receptor is composed of ___ units
5
Nicotinic rec function as a
ligand gated ion channel
Nicotine at low concentration ____ and at high concentration ____ the nicotinic rec.
Stimulates,
Block
Nicotinic rec are located in
CNS
Adrenal Medulla
Autonomic ganglia
Neuromuscular junction NMJ
Ganglionic rec are selectively blocked by
Hexamethonium
NMJ rec are specifically blocked by
Tubocurarine