cholinergic neurons Flashcards
Acetylcholine (ACh) is a common ____
neurotransmitter
_____neurons are those that utilize ACh
Cholinergic
Neurotransmission Six sequential steps:
Synthesis Storage Release Binding of ACh to receptor Degradation in synaptic cleft Recycling of choline and acetate
Black widow spider venom causes all ACh stored in synaptic vesicles to ____
empty
ACh ____ inhibitors will block the degradation and increase time ACh is acting on postsynaptic receptors
esterase
______ toxin blocks release of vesicle content (ACh)
Botulinum
Two families distinguished on basis of their different affinities for agents that mimic the action of ACh (parasympathomimetics):
what are they?
Nicotinic
Muscarinic
this cholinergic receptor is ligand-gated ion channels whose activation causes a rapid (millisecond) increase in cellular permeability to Na+ and Ca++, depolarization, and excitation
Nicotinic
this cholinergic receptor is GPCRs with slower (still few seconds to minutes) responses
Muscarinic
muscarinic receptors may be either excitatory or inhibitory, and they are not necessarily linked to changes in _____
ion permeability
muscarinic receptors are Located primarily (but not exclusively) at the ________ of the parasympathetic nervous system
neuroeffector junction
muscarinic receptors: Five subclasses: M1-5 but only 3 have been functionally characterized
what are first three?
M1: gastric parietal cells
M2: cardiac cells and smooth muscle
M3: bladder, exocrine glands, smooth muscle
for muscarinic receptors what do you need to recognize to identify it
Recognize muscarine (alkaloid present in certain poisonous mushrooms)
for nicotinic receptors what do you need to recognize to identify it
Recognize nicotine
Nicotine at ____stimulates
[low]
Nicotine at _____ inhibits
[high]
Nicotine at [low] stimulates and at [high] inhibits, due to _______
desensitization
nicotinic receptors locations
CNS
Adrenal medulla
Autonomic ganglia
NMJ
Direct-Acting Cholinergic Agonists are also known as ____.
parasympathomimetics
what do Cholinergic Agonists do?
Mimic the effects of ACh by binding directly to cholinergic receptors
Some drugs preferentially bind to muscarinic receptors and are termed ______
muscarinic agents
As a group, Cholinergic Agonist show little _____ so their use is limited
specificity
Indirect-Acting Cholinergic Agonists Inhibit _______ which degrades ACh
acetylcholinesterase (AChE)
Indirect-Acting Cholinergic Agonists Subtypes are______ and are used as nerve agents and pesticides
organophosphates
Cholinergic Agonists Effects
DUMBBELSS
Diarrhea Urination Miosis Bronchorrhea** Bradycardia** Emesis Lacrimation Sweating Salivation**
Cholinergic Agonists Effects
SLUDGEMM
Salivation Lacrimation Urination Diarrhea GI upset** Emesis Miosis Muscle spasms**
Cholinergic Antagonists are also known as?
cholinergic blockers, parasympatholytics, or anticholinergics
what do Cholinergic Antagonists do?
Bind to ACh receptors but do NOT trigger the usual receptor-mediated response
Compared to cholinergic agonists, Cholinergic Antagonists have many more ______.
therapeutic applications
Cholinergic Antagonists- Three main groups/uses based on specific site of action:
- Muscarinic receptors of the parasympathetic nerves (aka: antimuscarinic agents)
- Nicotinic receptors of the sympathetic and parasympathetic ganglia
- Nicotinic receptor on skeletal muscle (aka: neuromuscular blockers)
____ Cause inhibition of all muscarinic functions
Antimuscarinic Agents
Antimuscarinic Agents, Also block the few sympathetic neurons that are_______ (i.e., sweat and salivary glands)
cholinergic
Antimuscarinic Agents Have little to no action at _______ (i.e., lack NMJ and autonomic ganglion activity)
nicotinic receptors
ABCDs of anticholinergic effects
Anorexia Blurry vision Constipation/ Confusion Dry Mouth Sedation/ Stasis of urine
Anticholinergic Effects
- Hot as a hare: increased body temperature
- Blind as a bat: mydriasis (dilated pupils), blurred vision
- Dry as a bone: dry mouth, dry eyes, decreased sweat, constipation, urinary retention
- Red as a beet: flushed face
- Mad as a hatter: confusion/delirium/euphoria
- Bloated as a toad: constipation, urinary retention, ileus
- And the heart runs alone: tachycardia
MANY drugs have anticholinergic effects that are not the main ____
MOA
MANY drugs have anticholinergic effects that are not the main MOA, examples?
antihistamines, opioid analgesics, antipsychotics, antidepressants, antiemetics, muscle relaxants
this is Often considered the prototype anticholinergic drug
Atropine
Atropine CV uses
Bradycardia: blocks parasympathetic activity which leads to an increased HR (dose-dependent action)
Atropine uses
Bradycardia
OP Poisoning
Secretions: pre-anesthesia drying of secretions
Eye: results in persistent mydriasis, unresponsiveness to light, cycloplegia
Atropine ADR
in general think anti-SLUDGE
