Autonomic Pharmacology Flashcards
Describe the differences between somatic motor neurons and autonomic motor neurons.
Somatic:
- originate from the ventral horn of the spinal cord
- myelinated neuron from the spinal cord to effector cell (skeletal muscle)
- does not have a ganglion
- Ach transmission at the NMJ
Autonomic:
- originates from the later horn of the spinal cord
- most preganglionic neurons are myelinated, howver, post-ganglionic neurons are not myselinated
- Ach transmission at autonomic ganglion. Ach or NE at the end of postganglionic neuron.
- Ach or NE causes: contraction of smooth muscle or cardiac muscle, stimulation or inhibition of grandular secretion.
Detail the arrangment of the autonomic nervous system.
Note: Parasympathetic NS has a long preganglionic fiber, but a short postganglionic fiber. This is because the ganglion of the PNS are found within or nearby the walls of the organs that they innervate. The sympathetic system on the other hand maintains short preganglionic fibers, but long postganglionic fibers. The ganglion of the SNS is mostly found within the prevertebral or paravertebral sites on either side of the spinal cord.
Note Dopamine and its receptors on renal vascular smooth muscles.
Detail the general orientation of the GI tract. Include the locations of the Meissner’s plexus and the Myenteric plexus.
Detail the steps of cholinergic transmission. Include terms such as Acetylcholine esterase, botulinum toxin, vesicle-associated transporter, choline transporter, SNARE and SNAP, Choline acetyltransferase (ChAT), and vesicle-associated membrane proteins (VAMPs).
- CHT: Choline transporter that transports choline into the nerve terminal
- Acetyl-CoA is produced from mitochondria within the nerve terminal.
- ChAT: Choline acetyltransferase (the R.L. step of Ach biosynthesis) binds acetyl-CoA with choline to form Ach. This occurs within the nerve terminal
- VAT: vesicle-associated transporter will transport Ach from the cytoplasm into vesicles.
- VAMPs- vesicle-associated membrane proteins will align the vesicle with the release site, helping to coordinate the release of NTs
- Calcium ion influx via N-type calcium channels.
- Calcium interacts with VAMP (synaptotagmin), which triggers the fusion of the vesicle and opens pores into the synapse. Recall. Botulinum toxin blocks the release of Ach by altering fusion proteins.
- SNARE and SNAP proteins interact with vesicle to release NTs
- Once in the synapse, Ach can either be degraded by AchE, reuptaken back into the presynaptic nerve terminal, or act on nicotinic/muscarinic Ach receptors.
Describe the pathway for catecholamine synthesis. Note the required amino acid.
Tyrosine is the required amino acid for the biosynthesis of catecholamines (Dopamine, NE, and Epi). Tyrosine hydroxylase is the rate limiting step for catecholamine synthesis. Tetrahydrobiopterin, ionized iron, and molecular oxygen regulate TH.
What drug can be used to block the rate limiting enzyme in catecholamine synthesis?
Metyrosine
An inhibitor of the enzyme tyrosine 3-monooxygenase, and consequently of the synthesis of catecholamines. It is used to control the symptoms of excessive sympathetic stimulation in patients with pheochromocytoma.
What drug is responsible for depletion of catecholamine NTs from storage sites?
Reserpine (VMAT- vesicular monamine transporter)
Reserpine is used to treat high blood pressure. It also is used to treat severe agitation in patients with mental disorders. Reserpine is in a class of medications called rauwolfia alkaloids. It works by slowing the activity of the nervous system, causing the heartbeat to slow and the blood vessels to relax.
Cocaine can block what mechanism of norepinephrine transmission?
Cocaine blocks the reuptake of NE via the NET (Norepinephrine transporter)
By what mechanims can norepinephrine’s transmission be terminated? What two enzymes are used in the metabolization of NE?
NE termination is achieved by simple diffusion away from the receptor site with eventual metabolism in the kidneys and liver OR by reuptake into the nerve terminal by NET.
COMT (catechol-O-methyltransferase and MAO (monoamine oxidase) metabolize NE and Epi. The final products of both are VMA, however, NE is first converted into normetanephrine, while Epi is converted into metanephrine, then VMA.
Describe adrenergic transmission.
Describe the mechanism of action of the drug Vesamicol.
Vesamicol is an experimental drug, acting presynaptically by inhibiting acetylcholine (ACh) reuptake into synaptic vesicles and reducing its release. Vesamicol may have applications for the treatment of adenocarcinoma in situ of the lung.
Describe the major autonomic receptor types:
Autoreceptors are presynaptic receptors that respond to the primary NT substance released by the nerve ending. Describe how Alpha-2 receptors act as autoreceptors:
Alpha-2-receptors acts as a negative inhibitor of NE release. When NE is released at the terminal, alpha-2-receptors will inhibit inward calcium currents, thereby inhibiting the release of additional NE NT.
Recall, however, that presynaptic beta receptors facilitates release of NE from some adrenergic neurons.
Define heteroreceptors:
Heteroreceptors are terminal receptors for other transmitters that may act either to stimulate or inhibit release at that terminal (e.g., a cholinergic receptor on a DA nerve terminal).
