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143 Cards in this Set

  • Front
  • Back
The circadian rhythm of autonomic function originates where?
suprachiasmatic nucleus (SCN) in the hypothalamus
The circadian rhythm of autonomic function is entrained by light falling on what?
melanopsin-containing retinal ganglion cell dendrites (not rods or cones) in the eye
stretch-sensitive mechanoreceptors in the carotid arteries transmit information via what nerve?
glossopharyngeal
sretch sensitive mechanoreceptors in the aorta transmit information via what nerve?
vagus
stretch sensitive receptors transmit information to where in CNS?
nucleus tract solitarii (NTS) in the posterior medulla.
Excitatory neurons from the nucleus tract solitarii (NTS) innervate what?
the dorsal motor nucleus
Inhibitory neurons of the nucleus tract solitarii (NTS) innervate what?
Excitatory neurons innervate the dorsal motor nucleus of the vagus, where parasympathetic outflow is regulated.

Inhibitory neurons, using gamma- aminobutyric acid (GABA) as neurotransmitter, innervate areas in the ventrolateral medulla from which sympathetic outflow is regulated. The most important such site is the rostral ventrolateral medulla (RVLM).
Destruction of the NTS or its afferent input can lead to what?
the syndrome of baroreflex failure--acute period of dramatic hypertension, followed by wide swings in blood pressure
Efferent parasympathetic outflow to the cardiovascular system goes through what nerve?
vagus nerve.
Glossopharyngeal neuralgia?
(glossopharyngeal syncope)
disorder post 9th cranial nerve damaged

Paroxysms of severe throat pain with hypotension and bradycardia occur.

Attacks are due to massive spontaneous afferent discharges of the glossopharyngeal nerve, providing excessive input into the NTS, and eliciting parasympathetic activation and sympathetic withdrawal.
Efferent sympathetic outflow from the RVLM travels in the ____tract to the intermediolateral column of the spinal cord.
bulbospinal
The primary neurochemical mediator of both sympathetic and parasympathetic preganglionic neurons is what?
acetylcholine (ACh).
The primary mediator of sympathetic postganglionic fibers is usually ____, but at least some sympathetic postganglionic fibers to sweat glands are ____
norepinephrine (NE), cholinergic (acetylcholine).
Neurotransmitter of parasympathetic postganglionic fibers is what?
acetylcholine.
Epinephrine is found in the ____, the central nervous system and the ____
adrenal medulla

para-aortic bodies (organs of Zuckerkandl).
____ is a neurochemical mediator in the central nervous system and probably also in some neurons in the superior cervical ganglion and the kidney.
Dopamine
name the catecholamines
Norepinephrine, epinephrine and dopamine
sympathomimetic amines
norepinephrine, epinephrine, adrenaline plus drugs that resemble them
what is cotransmission ?
multiple neurotransmitters commonly exist within one neuron, and they may be differentially released
P2 receptor
ATP acts directly on receptor (purinergic)
P1 receptor
adenosine acts on receptor (ATP post metabolism)
Acetylcholine (ACh) is synthesized by what?
choline acetyltransferase
choline acetyltransferase catalyzes what reaction?
the transfer of an acetyl group from acetylcoenzyme A to choline
What is the rate limiting step of ACh synthesis?
the choline transporter into the neuron
botulinum toxin acts by what biochemical mechanism
blocking the release of acetylcholine
hydrolysis of ACh into choline and acetic acid is catalyzed by which enzyme
acetylcholinesterase
acetylcholinesterase (true cholinesterase) is found where?
near cholinergic neurons and in red blood cells
non-specific cholinesterase (pseudocholinesterase or butyrylcholinesterase) is found where?
in plasma and in some organs but not in the red blood cell or the cholinergic neuron.
clinical effect of pseudocholinesterase deficiency
some drugs such as succinylcholine (used during anesthesia) which are normally broken down by pseudocholinesterase, are very poorly metabolized by this variant enzyme. Such patients may have prolonged muscle paralysis from succinylcholine
the rate-limiting step in NE synthesis and is located in which cell compartment?
the cytoplasm
the rate limiting step of NE synthesis is what reaction & enzyme?
Tyrosine hydroxylase (tyrosine to dopa)
During increased sympathetic stimulation, dopa production is increased in what ways?
a) more enzyme is synthesized, and b) the physical properties of the enzyme are altered (allosteric activation) so that affinity for tyrosine is increased and affinity for end products like NE is reduced
what is a clinically useful inhibitor of tyrosine hydroxylase? Why significant enzyme?
metyrosine (a-methyl-p-tyrosine).

rate limiting step of NE synthesis
Dopa decarboxylase "aromatic-L-amino acid decarboxylase" (dopa to dopamine) is found in what cell compartment of what tissues?
cytoplasm of many nonneural as well as neural tissues
carbidopa clinical usefulness
Peripheral (non-neuronal) dopa decarboxylase inhibition when one is trying to prevent formation of peripheral dopamine during dopa therapy of Parkinsonism
Dopamine-ß-hydroxylase catalyzes what reaction? what metal contained by enzyme?
dopamine to norepinephrine

copper
treatment of Dopamine-ß-hydroxylase deficiency
dihydroxyphenylserine (DOPS), which is decarboxylated directly into norepinephrine by dopa decarboxylase, thus restoring the appropriate neurotransmitter
symptoms of Dopamine-ß-hydroxylase deficiency
lifelong orthostatic hypotension, and ptosis of the eyelids. Their sympathetic neurons contain large quantities of dopamine, but little or no norepinephrine.
Phenylethanolamine-N-methyltransferase (norepinephrine to epinephrine) is restricted to where?
adrenal medulla, the brain and the organ of Zuckerkandl
inhibition and stimulation of Phenylethanolamine-N-methyltransferase (norepinephrine to epinephrine)
inhibited by physiological concentrations of epinephrine

Glucocorticoid increases enzyme activity.
monoamine oxidase (MAO) breaks down what neurotransitter?
norepinephrine
acetylcholine stimulates release of NE from postganglionic neuron via what receptor
nicotinic receptor
nicotinic receptor function in sympathetic system?
accepts acetylcholine from preganglionic sympathetic neuron.

Stimulates release of norepinephrine
a2-receptors
reduce release of additional norepinephrine
b2-receptors
increase release of norepinephrine
which modulatory receptor reduces release of additional norepinephrine?
presynaptic a2-receptors
Which modulatory receptor increases release of additional norepinephrine?
b2-receptors
substances that increase norepinephrine release in selected tissues via a nicotinic receptor
angiotensin, and acetylcholine
substances that decrease norepinephrine release via a muscarinic receptor in selected tissues
1 dopamine
2 histamine
3 serotonin
4 adenosine
5 PGD2
6 PGE2
7 acetylcholine
uptake I
reuptake of catecholamines into the neuron via norepinephrine transporter
uptake II
uptake of catecholamines into extraneuronal tissue
inhibitors of monamine oxidase
pargyline, tranylcypromine, and selegiline (Deprenyl®)
Monoamine oxidase function, location
converts catecholamines to their corresponding aldehydes

located in the outer membrane of mitochondria as well as extraneuronally
Catechol-o-methyltransferase (COMT) function and location
converts NE into normetanephrine and epinephrine into metanephrine

found especially in liver and kidney.
intervention which results in acetylcholine precursor transport blockade?
hemicholinium
interventions which promote acetylcholine release?
choline, black widow spider venom (latrotoxin)
intervention which prevents acetylcholine transmitter release?
botulinum toxin
intervention which prevents ACh storage?
vesamicol
Interventions which result in cholinesterase inhibition?
physostigmine, neostigmine
intervention which inhibits tyrosine hydroxylase
metyrosine, used to treat pheochromocytoma
intervention which inhibits dopa decarboxylation
carbidopa
intervention which inhibits Dopamine-ß-hydroxylase
disulfiram
interventions which inhibit monamine oxidase
pargyline, tranylcypromine, selegiline
intervention which prevents norepinephrine storage
reserpine
interventions which cause initial release of NE leading to depletion of catecholamine
guanethidine, guanadrel
intervention which blocks NE release
bretylium
intervention which block the norepinephrine transporter
(Uptake I)
cocaine, tricyclic antidepressants
intervention which inhibits Catechol-o-methyltransferase
entacapone
intervention which blocks uptake II of catecholamine
glucocorticoids
motor neuron -< skeletal muscle

Name:
neurotransmitter/receptor type of skeletal muscle
ACh

nicotinic
pregang symp -< postgang symp

Name:
neurotramsmitter and receptor type
ACh
nicotinic
Medulla Oblongata a2

NE what response?
Reduced sympathetic outflow
Pupil a1

--NE what response?
Mydriasis (radial muscle contraction)
Heart b1

NE what response?
Acceleration, contractility increase
Arterioles a1,a2

NE what response?
Constriction
Arterioles b2

NE what response?
Dilation
Veins a1,a2

NE what response?
Constriction
Bronchial Muscle b2

NE what response?
Relaxation
Uterus b2

NE what response?
Relaxation
Bladder Sphincter a1

NE what response?
Contraction
Platelet a2

NE what response?
Aggregation
Salivary Glands a1,a2

NE effects?
Viscous secretion
Pilomotor Muscles a1

NE effects?
Contraction (horripilation, "chill bumps")
Gastrointestinal Muscle a1,a2,b2

NE effects?
Relaxation
Spleen Capsule a1
Contraction
Pancreas a2

NE effect?



NE effects?
Reduced insulin
Pancreas ß2
NE effect?
Increased insulin
Liver a1, b2

NE effect?
Hyperglycemia
Adipose Tissue b1, b3

NE effect?
Lipolysis
Adipose Tissue a2

NE effect?
Reduced lipolysis
Adipose Tissue b3

NE effect?
Heat production
Kidney a2

NE effect?
Sodium conservation, reduced renin
White Blood Cells b2

NE effect?
Demargination
Norepinephrine is especially potent at which adrenoreceptors.
a1 and at b3
Epinephrine has relatively more activity at which adrenoreceptors than does norepinephrine.
b2
a1-agonists
phenylephrine, methoxamine, norepinephrine
eccrine sweat glands are stimulated by what neurotransmitter
ACh
Bladder sphincters are contracted by stimulation of what receptor
a1-stimulation
Phenylephrine (Neosynephrine®) and methoxamine are far more potent in stimulating which receptors
a1-receptors
How are Phenylephrine (Neosynephrine®) and methoxamine used clinically?
hypotensive states

locally to cause mydriasis

nasal congestions

Phenylephrine is occasionally used to restore paroxysmal atrial tachycardia to normal sinus rhythm (via baroreceptor-mediated enhancement of vagal tone).
how does Norepinephrine differs from phenylephrine in receptor stimulation
greater capacity to stimulate b1-adrenoreceptors as well as a1-adrenoreceptors
Epinephrine clinical use
to support blood pressure, especially during anaphylaxis
a1-blockers, 4
1 prazosin
2 phentolamine
3 tolazoline
4 phenoxybenzamine
prazosin receptor stimulation
selectively block the a1- receptor
Phentolamine clinical use
competitive nonselective alpha adrenergic receptor antagonist

used to determine whether a given level of hypertension is catecholamine-mediated.

helpful in diagnosing pheochromocytoma at the bedside.
Phenoxybenzamine clinical use
medical management of pheochromocytoma.
Phentolamine mechanism
competitive, short-acting a-antagonist.
Phenoxybenzamine mechanism
noncompetitive, long-acting a-antagonist
Prazosin mechanism
selective blocks a1-receptors without blocking the a2-receptors that mediate feedback inhibition of norepinephrine synthesis/release
Prazosin clinical use
hypertension and in congestive heart failure.
The major problems in prazosin use
prazosin syncope," fainting that occasionally occurs on standing 2-4 hours after the first oral dose

tendency toward reduced efficacy with chronic use
a2-agonists
clonidine, guanabenz, guanfacine, and a-methylnorepinephrine
The most important effects of a2-agonists
presynaptic a2- stimulation mediates feedback-inhibition of norepinephrine release
intracellular effect of activation of beta-adrenoreceptor
synthesis of cAMP by adenylyl cyclase

**The hormone-receptor ("liganded receptor") interacts with a stimulatory guanine nucleotide-binding regulatory protein (Gs), which then activates the adenylyl cyclase.
intracellular effect of activation of alpha-2 receptor (M2 receptor)
inhibition of adenylyl cyclase


**regulatory protein (Gi) also binds to GTP
interaction of Gi leads to inhibition of adenylyl cyclase. The Gi regulatory protein sometimes also interacts with ion channels to activate (K+ channels) or inhibit (voltage-gated Ca++ channels) them
intracellular receptor for cAMP
cyclic AMP-dependent protein kinase (protein kinase A)

When activated by cyclic AMP, the kinase phosphorylates a variety of cellular proteins and regulates their activities.
intracellular effect of alpha 2 receptor activation
Ca++ release-> calmodulin-dependent enzyme activation

DAG--> protein kinase C

**activation of a membrane-bound phospholipase C (PLC). Phospholipase C hydrolyzes a membrane phospholipid, phosphatidylinositol-4,5-biphosphate (PIP2), resulting in the formation of diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (IP3). IP3 causes the release of Ca2+
what drug stimulates brainstem a2 receptors and binds to imidazoline receptors and reduces sympathetic outflow to cardiovascular system?
Clonidine
reason for methyldopa use as antihypertensive
its metabolite, a-methylnorepinephrine, stimulates a2 receptors
Causalgia
pain syndrome that develops in the joints especially after nerve injuries
only widely available, relatively specific a2-antagonist
yohimbine
mechanism of yohimbine
By blocking a2-adrenoreceptors in the medulla, it increases sympathetic outflow

By blocking presynaptic a2-adrenoreceptors in the periphery, it enhances norepinephrine release
Isoproterenol mechanism
stimulates both b1- and b2-receptors
clinical uses of beta2 agonist (none is perfectly selective)
asthma and cessation of premature labor
dobutamine mechanism
relatively selective b1-agonist
dobutamine clinical uses
cardiac stimulation
such as in pulmonary edema, coronary bypass post-op
b3 adrenoreceptor funciton
mediates heat production and energy expenditure in adipose tissue.

sensitive to norepinephrine, not easily blocked
Propranolol mechanism
competitive inhibitor of sympathomimetic amines at both the b1- and b2- receptor
propranolol affects on heart rate, contractility, and BP
In persons on no medication, propranolol reduces heart rate, contractility and blood pressure
propranolol affect on AV conduction
slowed
propranolol effect on bronchial tone
increased
propranolol contraindications
in asthmatics and in patients with chronic obstructive pulmonary disease.
propranolol use
to reduce heart work in patients with angina pectoris and

treat ventricular arrhythmias

antihypertensive agent probably by reducing renin production.

produces subjective improvement in thyrotoxicosis

subjective improvement in certain anxiety states
Metoprolol mechanism
relatively selective blocker of the b1-receptor
Atenolol mechanism
relatively selective blocker of the b1-receptor
timolol clinical use
eye drops are used in glaucoma patients to reduce intraocular pressure
Atenolol clinical use
given once daily in managing hypertension.
Fenoldopam mechanism
specific for D1
D1 receptors effects
mediate vasodilatation in the coronary, cerebrovascular, renal, and mesenteric vascular beds
D2 receptors effects
cause emesis and inhibition of prolactin
Tyramine mechanism
enters noradrenergic neurons via the norepinephrine transporter and displaces NE from the "labile pool" (non-stored NE) and into the synaptic cleft onto postsynaptic receptors
foods which are dangerous for patients on inhibitors of monoamine oxidase
patients on inhibitors of this enzyme (e.g., pargyline) may have profound hypertension from over-indulgence in tyramine-containing foods.
--such as cheddar cheese, certain wines, marmite, country ham, and broadbeans (fava beans).
diagnosis and localization of Horner's syndrome
documenting that an a1-adrenoreceptor agonist (phenylephrine) will dilate the patient's constricted pupil.

Hydroxyamphetamine, a tyramine-like agent, will also dilate the pupil if the neuron innervating the iris is intact (that is, if the lesion is more central). If the most peripheral nerve is the damaged one, hydroxyamphetamine will not work.