auto ganglionic blockers

sympathetic NS has _________ outflow, with ganglia ________ from target organs

parasympathetic NS has __________ outflow, with ganglia ________ from target organs

symp= thoracolumbar; far from target/ close to spine

para= cranial sacral; close to target organ/ further from spine

paravertebral vs prevertebral ganglia

- both sympathetic

Paravertebral ganglia= close to spinal cord (sympathetic chain) give rise to post ganglionic fibers

prevertebral= front of aorta/ abdomen; "collateral" ganglia

what kind of receptors are found in ganglia?

nicotinic ACh receptors= ligand-gated (ACh) channels that become permeable to sodium (major) and calcium (minor) when activated

when nicotinic receptors are activated by a ligand (ACh), what do they become permeable to

1. primarily sodium

2. secondarily calcium

t/f: nicotinic receptor subunits have low diversity amongst ganglia

false. subunit composition is very diverse among nicotinic receptors in CNS and ganglia

when ACh is released from pregang neurons, it activates nicotinic receptors leading to _________ of postgang neurons and ______

a. hyperpolarization

b. depolarization

c. repolarization

b. depolarization

= excitatory post synaptic potential (EPSP)

Excitatory post synaptic potential (EPSP)

after ACh activates nicotinic receptor-> small post synaptic potential that makes the neurons more likely to fire an action potential (decays over time, need large EPSP for AP)

t/f: IPSP and secondary slow EPSPs are not mediated by nicotinic neuronal receptors

true, mediated by M2 and neuropeptides

summarize the electrophysiology of ganglionic transmission (how is neuronal electricity mediated? one receptor or multiple?)

- negative resting potential

- ACh binds= depolarization= EPSP may lead to action potential if threshold reached (mediated by Nn)

- IPSP follows action potential (mediated by M2, then EPSP follows (mediated by M1)

- late slow EPSP mediated by neuropeptides

predominant tone of arterioles/veins

sympathetic

predominant tone of heart, eye, GI, urinary bladder

parasymp

hexamethonium

blocks the CHANNEL associated with Nn receptors, blocking ganglionic transmission

(does not reach CNS)

trimethaphan

competes w ACh for ACh binding site on Nn receptors, blocking ganglionic transmission

(does not reach CNS)

mecamylamine

competes w ACh for ACH binding site on Nn receptors, blocking ganglionic transmission (same as trimethaphan)

BUT this can get through BBB and enter CNS!!!

which ganglionic blocker can get past BBB and reach CNS due to its lipophilicity?

mecamylamine

what would happen to a patient with normal cardiovasc function if given a ganglionic blocker?

- ganglionic blocker would stop transmission of both parasymp and symp

arterioles, veins, sweat glands (sympathetic)= vasodilation, drop in bp, postural hypotension, blood pooling= lower CO, anhidrosis

heart, GI, bladder, salivary, eye (para)= tachycardia, atony in GI/bladder, xerostomia, cycloplegia

why would ganglionic blockers lead to mild tachycardia and lower cardiac output

-heart has parasympathetic predominant tone, so blocking it would increase HR

- veins have symp tone, blood pooling means not enough reaching heart= lower CO

t/f: ganglionic blockers block both Nn and Nm

false. only Nn (neuronal)

t/f: nicotine has potential opposing effects on Nn seen as receptor stimulation and receptor desensitization

true. if too much nicotine, it may desensitize Nn receptors (protective effect), or it may work and stimulate receptors

(remember ACh has AChE to prevent too much, but nicotine is exogenous so we can have too much)

what were ganglionic blockers initially used as?

lower bp, treat acute hypertensive crisis (but too many side effects, not rlly used now)