Pharm SNS/PSNS
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SNS | thoraco-lumbar
pre-ganglonic: short axon into prevertebral chain
post-ganlionic: long axon to organs
widely spread system
one neuron can go to MULTIPLE places
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Exception to SNS ganglia | adrenal glands
long pre and short post
neuron that goes here ONLY goes here
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PSNS | brain stem and sacral cord
long pre and short post
very restrictive; one neuron to one place
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Acetylcholine (Ach) | used by PRE-ganglionic axons
agonist for NICOTINIC receptor
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Norepinephrine (NE) | major transmitter for SNS
activates alpha 1/2 > beta 1 (mixed adrenergic agonist)
used for hypotension
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Exception to NE for SNS | adrenal gland; chromaffin cell is post ganglia and releases Ach whcih which stimulates Epinephrine
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Flow of transmitter signaling SNS | Ach --> nicotinic --> NE --> Alpha/beta
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PSNS and somatic | cholinergic system
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Flow of transmitter signaling for heart (PSNS) | Ach --> nicotinic --> Ach --> muscarinic
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Flow of transmitter signaling for somatic | Ach --> nicotinic --> Ach --> nicotinic
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In the SNS terminal, what is dopamine converted to? | NE
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What causes the "lipid bubble" containing NE to move to the surface and open into the synapse? | Ca++
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Uptake 1 | NE transporter; pulls NE out of the synapse and back into terminal where MAO breaks it down
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receptors that exist in tissues but DO NOT have direct innervation | Extra junctional
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this receptor is activated to slow the system down because of too much NE; type of feedback inhibition | pre-synaptic alpha 2
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Enzymes that degrade trasnmitters | COMT
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Predominant tone belongs to which system? | PSNS; exception is blood vessels
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Low concentrations of NE will have high affinity for what? | Alpha
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Epinephrine | beta 1/2 >> alpha 1/2 (mixed adrenergic agonist)
used for: asthma, anaphylactic shock, cardiogenic shock, and prolongs actions of local anesthetics
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Low concentrations of Epi have high affinity for what? | beta 1/2
BUT, if dose increases 10x then alpha (dilate) will out-power beta (constrict)
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Dopamine | alpha 1 and beta 1 (mixed adrenergic agonist)
CNS functions
was once used to treat CHF
indirectly acting adrenergic agonist
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pseudoephedrine | alpha and beta (mixed adrenergic agonist)
used for colds
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Phenylephrine | selective alpha 1 agonist
used for hypotension, bradycardia, and as decongestant
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Methoxamine | selective alpha 1 agonists
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Clondine | selective alpha 2 agonist
centrally acting anti hypertensive
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A patient with high SNS activity will have? | HYPERtension
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Isoproternol | beta 1/2
non selective beta agonist
cardiac transplants
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Dobutamine | Selective beta 1 agonist
low doses will increase force of contraction but NOT heart rate
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metaproterenol | selective beta 2 agonist
treats asthma
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albuterol | selective beta 2 agonist
asthma: 1/2 life 6-7 hrs
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salmetrol | selective beta 2 agonist
asthma: 1/2 life 12 hrs
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Phentolamine | non-selective alpha 1/2 antagonist
used for OD of alpha agonists; used in pts with pheochromocytoma
Side effects: orthostatic hypotension, tachycardia, PSNS effects
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Prazosin and silodosin | selective alpha 1 anatagonists
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terazosin | selective alpha 1 antagonist
anti hypertensive agent
water soluble
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Propanolol, Nadolol, Timolol and Pinolol | Non-selective beta antagonists
Tx: HTN, angina, MI, arrhythmia, stage fright, glaucoma, tremor, migraine, and anxiety
contraindication: asthma attack in those with asthma
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Labetalol and carvedilol | non selective beta antagonists
also work on alpha 1
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Tyramine | dietary substance
indirectly acting adrenergic agonost
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ephedrine | indirectly acting adrenergic agonist
can also bind to beta receptors
increase SNS activity
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amphetamine | indirectly acting adrenergic agonist
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Indirectly acting agonists | DO NOT bind to receptors but produce effects that look like SNS agonists
cause increase in NE release; more rapid
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Uptake blockers | cocaine
tricyclic antidepressants
amphetamine (high doses)
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MAO inhibitors | pargyline and tranylcypromine
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What could cause increase in BP in those taking MAO inhibitors? | Tyramine
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Cholinergic receptors are? | nicotinic and muscarinic
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what has no clinical use? | Ach as muscarinic agonist
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Bethanechol | choline esther; M agonist
effects mostly on GI and urinary systems when administered orally or subQ
prevents urinary retention
side effects: over-stimulation of M receptors
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carbachol | choline esther; M and N agonist
produce miosis(constrict) druing ocular surgery
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Pilocarpine | alkaloid; M agonist
NO N effects
used topically to treat glaucoma
somewhat selective for salivary glands
used for Sjorgen's syndrome
Side effects: over-stimulation of M receptors
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Atropine and Scopolamine | Belladonna alkaloids; M anatagonists (selective)
used when PSNS tone is desirable
pre-op use for reduction of salivation/bronchial secretions
treat poisoning by AchE inhibitor
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Atropine toxic actions | dry as a bone, hot as a pistol, red as a beet, blind as a bat, and mad as a hatter
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Cholinesterase (AchE inhibiotrs) | agents used to enhance transmission at cholinergic junctions
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carbamates | bind to the esteratic site of AchE (reversible)
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Physostigmine | carbamate
readily penetrates CNS
drug of choice to treat poisoning with atropinic agents
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Neostigmine | carbamate
does NOT penetrate CNS
used to treat myasthenia gravis
used as antidote for overdose of "curare-like" drugs
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edrophonium | carbamate
short acting
diagnostic agent used to test for myasthenia gravis
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Donepezil (aricept) | carbamate
short term fix for alzheimer's
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Organophosphates | irreversibly phosphorylate serine hydroxyl at active site of AchE
ex: insecticides and nerve gases
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what is the only way to restore function after exposure to organophosphates? | make new enzymes; could take 2-3 weeks
antidote for insecticide= 2-pralidoxine (2-PAM)
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Botulinum toxin (Botox) | prevents Ach release from cholinergic neurons
AP occurs, but nothing happens and muscle is paralyzed
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What is used in surgery to promote skeletal muscle relaxation? | Neuromuscular (NMJ) blocking agents
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Tubocurarine | NMJ blocker
long duration
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Pancuronium | NMJ blocker
intermediate duration
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Succinylcholine | NMJ blocker
used for setting bones
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How are NMJ blockers reversed? | With AchE
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terbutaline | beta 2 agonist
used for premature labor to relax uterus
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