ANS and Cholinergics Flashcards
What are the lengths of the pre-ganglionic and post-ganglionic neurons in the PSNS division? What do they release?
Pre-ganglionic: lightly myelinated, long, release ACh
Post-ganglionic: un-myelinated, short, and release ACh
What are the lengths of the pre-ganglionic and post-ganglionic neurons in the SNS? What do they release?
Pre-ganglionic: lightly myelinated, short, release ACh (onto post-ganglionic neuron or adrenal medulla)
Post-ganglionic neurons: un-myelinated, long, releases NE
What are the functions of the SNS?
“fight or flight”
- increases the activity of effector organs to use energy
- activated during exercise or when threatened
- shunts blood to skeletal muscles and heart
- bronchioles dilate
- liver releases glucose
- pupils dilate
“E division” → exercise, excitement, emergency, embarrassment
What are the functions of the PSNS?
“Rest and digest”
- promotes energy storage, maintenance activities
- lowers blood pressure, heart rate, and respiratory rate
- increases GI activity
- pupils are constricted and lenses accommodated for close vision
“D Division” → digestion, defection and diuresis
What are the pharmacodynamic effects of cholinergic agonists?
Agonists attach to the cholinergic receptor and activate PSNS functions; acyloxy group binds to esteric site through hydrogen binding and quaternary ammonium group binds to anionic site
What are the physiological effects of cholinergic agonists?
- decreased heart rate via M2 receptors, downstream K+ channels open and impair depolarization
- bronchoconstriction; smooth muscle shifted into constricted state and fluid secretion is increased
- increased GI tract activity; secretion of acid increased, muscle contraction of peristalsis increased
- increased urination; bladder sphincter is relaxed
What is the MOA for reversible cholinesterase inhibitors?
- Quaternary nitrogen is attracted to the anionic site if the enzyme
- Ester portion of the inhibitor moves close to catalytic site
- Enzyme becomes carbamylated which prevents enzyme from interacting with ACh
- Hydrolysis occurs slowly (~10-20 min) causing reversible inhibition of the enzyme
What is the MOA for irreversible cholinesterase inhibitors?
Mechanism is the same except instead of acylating the enzyme, a phosphate ester is formed; bond is extremely stable to subsequent hydrolysis → active enzyme never reforms
What are the components and function of nicotinic acetylcholine receptors?
Nicotinic receptors are pentameric ligand-gated ion channels; the subunits form a pore
Activation occurs from ACh binding to the α subunit
Functions as an ion channel for sodium
What is the MOA of varenicline?
Varenicline is a partial agonist selectively for alpha4-beta2 nicotinic acetylcholine receptors
Results in release of dopamine which decreases craving and withdrawal
What is the MOA of nicotine?
Main psychoactive component of tobacco
Agonist for nicotinic receptors; when it binds, depolarization occurs, leads to increased SNS activity and secretion of catecholamines from adrenal glands
Subsequently desensitizes receptors and more receptors are built, possibly contributing to withdrawal symptoms
- increased dopamine release contributes to addictive qualities
- increased ACh release may contribute to enhanced cognition and attention
- increased NE release may contribute to stimulation and arousal
***likely that multiple receptors are involved
What is the MOA of non-depolarizing neuromuscular blockers and what is an example of one?
These are nicotinic receptor antagonists; they prevent the NMJ from depolarizing
Ex: tubocurarine
What is the MOA of depolarizing neuromuscular blockers and what is an example?
These are nicotinic receptor agonists; they do a really good job activating the receptors so that they’re “always on” and this prevents muscle contraction → flaccid paralysis
Ex: succinylcholine
What is the general structure of a cholinergic antagonist?
Many naturally occurring anticholinergics are tertiary or secondary amines, some may be quaternary ammonium compounds
NECESSARY to have a positively charged nitrogen so that they can bind to the receptor
All are neutral, competitive antagonists
What are the physiological effects of cholinergic antagonists?
Eyes: pupils dilate, accommodation is impaired
Lungs: bronchoconstriction and fluid secretion is inhibited
Heart: tachycardia, not so much do to with BP
GI: All types of secretions are blocked, GI motility and gastric emptying is reduced
Genitourinary: smooth muscle relaxed and motility reduced
CNS: sedation, (high doses is excitement, agitation, hallucinations and delirium), modest tremor reduction in Parkinsons, reduce N/V
