Autonomics Pharmacology Flashcards
(34 cards)
Anatomy of ANS
- autonomous (independent, not under conscious control)
- CO, blood flow, digestion
- afferent (sensory) inputs which send information into CNS
- Output through reflex arcs of varying size and complexity
SNS
- sympathetic
- efferent arises from thoracolumbar outputs (preganglionic terminate in ganglia (paravertebral chains) and post ganglionic fibers innervate peripheral tissues (post ganglionic fibers are long)
- SYmpathetic actions are broad and diffuse;
- Recruited in times of stress
- Cardiac stimulation, increase blood glucose, cutaneous vasoconstriction
Adrenal medulla
Modified sympathetic ganglion
-Receives symp preganglionic fibers and releases epinephrine and norepinephrine into blood
PNS
Craniosacral outputs
- preganglionic fibers terminate in parasympathetic ganglia (typically close to peripheral end organ)
- Post ganglionic fibers originate in ganglia and innervate organs (shorter post ganglionic fibers)
- Produces energy conservation, tonic activity
- Major underlying tone at most end organs (not vasculature)
- Slowing of heart, stimulate digestion
Enteric nervous system
- walls of GI system
- Third division of ANS
- Myenteric plexus (plexus of auerbach) and submucous plexus (plexus of meissner)
- Preganglionic PNS and postganglionic SNS inputs
Parasympathetic post ganglionic neurons are ____
Cholinergic; release acetylcholine
Predominant post ganglionic sympathetic mediators are ____
- Post ganglionic sympathetic neurons release Norepinephrine
- Adrenals release epinephrine
All preganglionic neurons release
Acetylcholine via nicotinic receptors
Co-transmitters
- Ach + vasointestinal peptide
- NE + neuropeptide Y
- Peptides provide long lasting, slowly developing activation of post synaptic target tissue
Acetylcholine
- Synthesized by choline acetyltransferase (ChAT)
- Acetyl-CoA synthesized in mitochondria, choline transportedinto neurone
- ACh transported into small clear vesicles
- Release of transmitter is calcium dependent (influx via action potentials) (blocked by botulinum toxin)
- ACh binds to receptors on post synaptic membrane
Acetylcholinesterase
AChE catabolizes ACh
- Breaks ACh into choline and acetate
- Duration of 1/2 life of ACh is short because high affinity of AChE to ACh
- pseudoAChE (butyrylcholinesterase) in other tissues as well (RBCs) break down ACh so the amt of ACh in blood stream and tissues is not high
Formation of NE
NE product in SNS (in adrenal, EPI)
-Conversion ot tyrosine to dopa is rate limiting (via tyrosine hydroxylase)
-Dopa converted to dopamine via dopa decarboxylase
-Dopa converted to NE via dopamine beta hydroxylase
-Storage inhibited by reserpine
-Release blocked by guanethidine and bretylium
-Uptake 1 transports cats into neuron (inhibited by cocaine)- not broken down, but taken up
-
Reserpine
Inhibits VMAT and prevents storage of catelcholamines
Cocaine
Inhibits uptake 1 of NE- so NE stays in synaptic cleft longer
Tyramine and amphetamines
Enter via uptake 1 and displace NE
Two enzymes that degrade catecholamines
- Monoamine oxidase (MAO) in mitochondria of nerve terminal
- Catechol-o-methyl transferase (COMT) in postjunctional cell
- Metabolize catecholamines to VMA (excreted in urine and can be used to measure sympathetic activity)
Muscarinic receptors
- G protein receptors
- Respond to ACh
Nicotinic receptors
- Ion channels, gate K and Na
- Respond to ACh
Adrenoreceptors
- Respond to catecholamines
- Alpha and beta adrenoreceptors
- Differ based on how they respond to catecholamines
Nonadrenergic, Noncholinergic Neurons (NANC)
- Use peptides, NO, purines
- Important in GI and GU system fxn
Central integration
- Midbrain and medulla
- Integrate information from sensory inputs and higher CNS influence
- Output by SNS and PNS and endocrine system are integrated
Dual innervation
- Opposing actions at end organs (eye)
- No cholinergic innervation of peripheral vasculature (no parasympathetic tone!)
- Peripheral vasculature does have cholinergic receptors that can be activated pharmacologically by ACh , mediated by NO and elicits vasodilation (but does not mimic parasympathetic activity)
Modification of MAP
- Mean arterial pressure
- Main variable that is controlled by ANS
- Altering MAP will stimulate compensatory reactions by ANS- increased peripheral resistance (sympathetic control), tachy/bradycardia
Presynaptic regualtion
- Autoreceptors on presynpatic neuron terminals (inhibiting vesicular release)
- Heterologous action
