Week 7!! Flashcards
Three drugs increase Rosuvastatin exposure. What are they and what transporters are involved?
Lopanivir, Ritonavir, Cyclosporine. All involve OATP inhibition. Cyclosporine also involved breast cancer resistance inhibition.
_________ stains neuron a golden brown and found more often in older neurons
Lipofuscin
Microglial cells are derived from ___________ which invade the developing nervous system
Mesenchymal
Name three agonists present at NMJ, autnomic ganglia and CNS
Ach, nicotine, carbachol
Name two types of cholinesterases
Acetylcholineesterase, butyrylcholinesterase
Which component of the peripheral nervous system contains the autonomic nervous system?
a) somatic sensory
b) visceral sensory
c) visceral motor
d) somatic motor
c
What are the two important sites on ACHE catalytic center that are blocked by Ache inhibitors?
anionic site and esteric site.
What are the two types of nicotinic receptors and where are they found?
Ganglionic (Nn) found in post-ganglionic neurons. Muscle (Nm) found in skeletal muscle end plates. Both are non-selective cation channels that are depolarized.
Where are alpha 2 receptors found?
Primarily on presynaptic nerve terminals, also vascular smooth muscle
Hydroxyl substitutions on __ and __ positions of the benzene ring tend to enhance beta 2 adrenergic receptor selectivity
3 and 5
__________ aallow oligodendrocytes and Schwann cells to get nutrients through the “jelly wrap” to th axon that is myelinating
Schmidt-Lanterman clefts
Sympathetic fibers travel to targets via what 3 mechanisms?
blood vessels, branches of spinal nerves, sphlancnic nerves
______ are derived from ciliated neuroepithelial cells and line ventricles of brain and central canal of spinal cord
Ependyma
The lesser thoracic sphlancnic nerve comes off from what levels
T10-T11
All preaortic ganglia are named acording to what?
aortic branch in their vicinity
True/False: Presynaptic fibers can go directly to the spinal cord
FALSE HAVE TO GO TO CHAIN YO
_________ are involved in touch, pain, pressure, vibration, temperature and proprioception in skin in the body wall and limbs
general somatic afferent fibers
The spinal cord has the white matter on the ________ whereas the brain has the white matter on the _______
outside, inside
True or false: In the region of the thoracic and abdominal cavities, there is not a lot of mixing of the fibers of the spinal nerves, whereas in the extremities there is, leading to changes in dermatomal delineation
true
What is the heritability eqn?
H = 2 (Cmz - Cdz) [concordance in twins]
Name 4 brain stem and brain areas capable of modulating autonomic nervous system
Brainstem CV and respiratory centers, hypothalamus, cingular cortex, amygdala
_______ is a form of ventricular tachycardia that can most often be due to medications
torsades de pointes
All body wall sympathetic fibers synapse where?
in chain at or near the spinal nerve where they will ultimately distribute to their targets
Describe how Nm receptor activation leads to skeletal muscle contraction
Ach binds to Na+ channel which opens and sets off EPSP
______ is found at synapses between parasympathetic post-ganglionic neurons and their effectors along with at neuromuscular junction in skeletal muscle (somatic nervous system)
Ach
Acetylcholine is made from _________ and __________ by the enzyme _____________
choline, acetyl Coa, acetylcholine transferase
Name the 7 layers that make up the cerebral cortex, from most superficial to least
molecular, outer granular, pyramidal, inner granular, inner pyramidal, polymorphic
The ________ system only innervates viscera in body cavities, glands in head, the eye and erectile tissues
parasympathetic
__________ is a growth disorder characterized by a large size for gestational age, large tongue, abdominal wall defects, and predisposition to embryonic tumors.
Beckwith-Widemann (BWS)
Oligodendrocytes are derived from the ________ while Schwann cells are from __________. Oligo’s actually inhibit axonal growth while Schwann cells participate in regeneration of injured axons.
neuroepithelium, neural crest
Describe what receptors are found in the eye and their actions.
Beta 2, Alpha 1, Muscarinic. B2 causes relaxation of ciliary muscles (allows focus on far objects) and Alpha I contracts radial muscle (dilation of pupils). Muscarinic receptors are involved on parasympathetic side (contracts ciliary and circular muscles)
Describe the mechanism promoted by D2, D3, and D4 receptors.
Gi inhibition of AC. This affects CNS control of motor movement, regulation of prolactin secretion.
_________ converts dopamine to norepinephrine in the presynaptic nerve terminals
dopamine-beta-hydroxylase
For catecholamines with beta carbon subunits, the ________ are the most bioactive form. (Endogenous only exist in this form)
L-isomers
____________ connect neurons, in a chain or sequence, mediate action between sensory-sensory, etc
Interneurons
What is another word for the parasympathetic system?
Craniosacral
What are the main enzymes involved in drug metabolism? What phase are they involved in?
CYP! (cytochrome p450s). Phase I “oxygenases”
______ substitution on beta carbon of methacholine and bethanecol reduces potency at nicotinic receptors and limits hydrolysis by cholinesterases
Methyl
What are drugs transformed to via metabolism (2) and what is the exception
active or inactive metabolites, exception is prodrug which is a medication that after metabolized will turn into pharmacologically active drug
Nicotinic receptors are _______ by nicotine at low doses and ______ at high doses. They are blocked by ______
stimulated, blocked, curare
Name the two families of transporters and 2 examples for each
1) ATP-binding cassette transporters (P-glycoprotein, CFTR); 2) solute carrier transporters (serotonin transporter, dopamine transporter)
The _________ contains the neocortex and has 3 connective tissue sheets that surround CNS and act as buffer
cerebral cortex
_____ administration is usually required for high molecular weight drugs.
IV
______ inhibits disposition of acetylcholine life cycle by inhibiting Ache
Neostigmine
___________ occurs when one chromosome is lost from a trisomy (causes 20% of BWS cases)
uniparental disomy
_______ is process by which a local and stronger effect occurs in sympathetic ganglia while ________ is a more systemic efect
convergence, divergence
_________ receptors are GPCR’s that mediate parasympathetic end-organ//tissue receptors
Muscarinic
True or false: In Turner syndrome, if X is imprinted from father, then the child also has social problems
FALSE - maternal imprinting
The cell bodies of autonomics (visceromotor) are found in the lateral horn (intermediate grey). At what vertebral levels are sympathetic fibers found versus parasympathetic
symp is T1 to L2, parasymp is S2-S4
If a radial nerve fiber goes to up to 5 dermatomes and it is cut, where would the cut need to be to lose sensation in all 5 dermatomes?
close to origin
Name two types of active transport involved in drug absorption
facilitated diffusion? (ability of cell to engulf a drug molecule) and drug transporters (ATP dependent)
_______ inhibits synthesis of catecholamines by inhibiting tyrosine hydroxylase
alpha-methyltyrosine
In the sensory (afferent) division of the PNS, describe the two categories and the types of fibers in each.
a) somatic sensory: general somatic afferent, special somatic afferent; b) visceral sensory: general visceral afferent and special visceral afferent
Sphlancnic nerves that have to go back to chain use _____ to get back to spinal cord
grey ramus
_______ have no underlying basement membrane and have long processes that extend into the hypothalamus where they terminate
Tanycytes
M1 is found in (choose all that apply)
a) smooth muscle
b) exocrine glands
c) CNS neurons
d) vascular endothelium
A,B,C
Which of the following is not a result of adverse effects when a medication is taken with grapefruit juice?
a) excessive sedation with benzodiazepines
b) excessive stimulation with amphetamines
c) increase in rhabdomyolsis with statins
d) symptomatic hypotension with dihydropidine Ca++ antagonists
e) QT interval prolongation with pimozide and tertenadine
b)
_____ are a group of neurons outside CNS whereas ______ are a group of neurons inside CNS
ganglia, nuclei
__________ converts norepinephrine into epinephrine in the chromaffin cells
phenylethanolamine-N-methyltransferase (PNMT)
True/False: Sympathetic chain runs entire length of vertebral column
TRUE, however symp fibers only come from T1 to L2 yo
What are the effects of toxicity by indirect acting muscarinic agonists?
confusion, ataxia, convulsions, coma, resp arrest, CV collapse, weakness, paralysis. Treated by atropine or 2-PAM
_______ inhibits the synthesis step of Ach by blocking the choline transporter
Hemicolinium
____ are the current markers of choice for linkage studies
SNPs
The _________ for acids and bases determines if drugs can be excreted
pH of environment
Cholinergic receptors in autonomic ganglia are __________ whereas at end organs are ___________
nicotinic, muscarinic
____ adminstration may interfere with interpretation of certain diagnostic tests such as CK and is precluded during anticoagulant therapy
intramuscular
The __________ is a large nerve that penetrates diaphragm and travels to collection of cell bodies sitting on celiac trunk called the ________
greater thoracic sphlancnic nerve, cephalic ganglion
________ have long basal processes and line floor of third ventricle with end feet on capillaries. They transport substances from CSF to hypophyseal portal system
Tanycytes
How does beta2 receptor stimulate smooth muscle relaxation
Gs activation of AC. Increase in cAMP inhibits MLCK.
Why is pain from an organ sometime felt in a different part of the body?
Pain fibers from organ synapse on same dorsal horn cell as pain fibers from skin. Convergence of viscerosensory and somatic sensory fibers on same dorsal horn cell.
For a drug given 2X daily, proper dose results in therapeutic levels in ___ days
4
Any fiber leaving the chain and coursing anteromedially is always a _________
sphlancnic nerve
What are the cell bodies of somatomotor fibers found? (GSE and GVE)
ventral horn
In context of drug metabolism, a duplication of a wild type allele may lead to a _________ whereas 2 mutant alleles may lead to a ________
ultrarapid metabolizer, poor metabolizer
_____ fibers do not have an associated ganglia and their cell body is found in the spinal cord.
Somatomotor
________ disrupts disposition of catecholamines by inhibiting COMT
entacapone
A neurotransmitter taken up by presynaptic nerve terminal can be (2)
transported back into vesicles by VMAT, metabolized by MOA
M2 and M4 are found in CNS neurons. Which is also found in cardiac muscle?
M2
True or false: endoneurium is not present in the CNS
TRUE
In the CNS, capillaries are lined by continuous endothelial cells linked by _________, which are the main components of the blood brain barrier.
tight junctions
What are the two types of nerves associated with PNS? Describe the differences in terms of components.
cranial nerves (21) and peripheral nerves (31). CNs different in what they carry, spinal nerves are similar in terms of components but target different areas of the body.
If the trait is __-% genetic, monozygotic twins will be the same as dizygotic twins
0
Serotonin transporter is a target for what?
Selective serotonin uptake inhibitors! (DUH)
Describe the mechanism of M1/M3/M5 receptor activation
Gq activates PLC which produces IP3 and DAG from PIP2 and inc Ca++ concentration
Describe what receptors are found on blood vessels. What are their actions (opposite)
Beta 2 and Alpha 1. B2 relaxes smooth muscle and dilates blood vessels. Alpha I contracts vascular smooth muscles and constricts blood vessels.
70% of cases of Angelman Syndrome and Prader Willi are caused by the same microdeletion on ________
chromosome 15
Most sympathetics to thorax come from ______________ ganglion after synapsing. Heart and lungs are reached by way of ____________. They are called _________
inferior cervical chain ganglion, cardiopulmonary plexus, cardiac nerves
Imadozolines are a class of sympathomimemetics that contain an imidazole moiety. Name two.
oxymetazoline, xylometazoline
________ disrupts disposition of catecholamines by inhibiting MAO
Phenylzine
Which receptors like isoproterenol the most? (may be more than one)
a) alpha I
b) alpha 2
c) beta 1
d) beta 2
C+D
True or False: Restriction enzyme analysis on PCR can differentiation between UPD and microdeletion in Prader Willi Syndrome?
FALSE, FISH or CHIP microarray needed OR haplotyping
Most blood vessels do not receive parasympathetic innervations. In those that do, low doses of Ach causes ______ via activation of muscarinic receptors on vascular endothelial cells. High doses of Ach causes _______ due to activation of these receptors on smooth muscle cells.
vasodilation and hypotension, vasoconstriction and hypertension
Apolar neuroblasts give rise to bipolar neuroblasts which give rise to unipolar neuroblasts which give rise to ______________, that after further development, become a nerve cell or neuron
multipolar neuroblasts
____________ are exogenous compounds that imitate functional responses associated with parasympathetic stimulation
Parasympathomimetics
Sympathetic fibers to head come from _______ and travel up chain as presynaptic fibers then synapse in highest ganglion, ____________ then travel to head structures on blood vessels
T1-T4, superior cervical
Astroblasts and oligodendroblasts are derived from the ____________
glio/spongioblast
__________ inhibits norepinephrine release
guanethidine
Distinguish between primary active transport and secondary active transport
primary is ATP-driven channel. secondary is symport or antiport
BWS is caused by two active copies of IGF-2 gene and/or no active copy of CDKN1C (inhibition of cell proliferation). ______ is expressed only from paternally inherited chromosome, while _____ is expressed only from maternally inherited chromosome
IGF-2, CDKN1C
Where is Beta 2 receptor located and what are the results of its activation?
primarily in smooth muscle (also in liver). Leads to smooth muscle relaxation and glycogenolysis
True or false: Oligodendrocytes proliferate
FALSE
Sympathetic fibers below the diaphragm synapse in the ___________
preaortic ganglia
Sympathetic fibers to body wall travel on every spinal nerve. They reach the sympathetic chain via preganglionic fibers on _____ communicating rami and synapse in chain before leaving on _____ communicating rami and connect to spinal nerve and distribute.
white, grey
Perivascular astrocyte end feet form the _________________
blood-brain barrier
When an axon is regenerated, how is it different?
internodal segments are short, reduced diameter
_________ astrocytes have high GFAP concentration while _______ have flow GFAP concentrations
fibrous, protoplasmic
Describe the receptors found on skin and their effect.
Alpha and Muscarinic. Alpha contract pilomotor muscles. Muscarinic leads to SYMPATHETIC activation of Ach which stimulates generalized sweating (IMPORTANT EXCEPTION!!!)
Cell fate is maintained by differential _________ of DNA
methylation
Name 3 beta-selective direct acting sympathomimemetics
dobutamine, tertabuline, isoprotenelol
Where is Beta 1 receptor primarily located and what are the results of activation?
Heart; inc firing rate (SA node), conduction velocity (AV node), contratility (ventricular muscle), and rate of relaxation (ventricular muscle). Also the kidney where stimulates renin release.
___________ segment is the site of initiation of action potential
initial segment
Describe how M1/M3/M5 activation modulates smooth muscle contraction
IP3 leads to Ca++ release from sarcoplasmic reticulum, DAG activates PKC which stimulates contraction
Neurons are ___________ because of high concentration of neurofilaments (stain with silver)
agryophilic
The ________, which are small fibers coming off the spinal nerve, sever as conduits for the sympathetic autonomic fibers traveling between the spinal cord where they arise and the sympathetic chain where they sometimes synapse
communicating rami
Neurons are unique in that they must form contacts with target cells in order to survive AKA __________
trophic stimuli
Describe how M1/M3/M5 activation modulates blood vessel relaxation
Ca++ binds to calmodulin, stimulates synthesis of eNOS, NO flows across membrane to smooth muscle and inc cGMP which leads to relaxation
Normally, ACH in synaptic vesicle binds to presynaptic membrane via ________ proteins and is then released into synaptic cleft
SNARE
__________ are thrown into folds and possess tight junctions. They cover the surfaces of choroid plexus and produce and secrete CSF.
Choroidal epithelial cells
Where are the cell bodies of visceromotor fibers found?
lateral horn (intermediate grey)
___________ is filled with CSF that surrounds brain and spinal cord. It contains large blood vessels.
Subarachnoid space.
Acetylcholine is rapidly broken down by the enzyme _________ in the neural cleft.
acetylcholinesterase
What are the 5 steps in the life cycle of a neurotransmitter?
1) synthesis, storage, release, receptor interaction, disposition/reuptake
______ is a cholinesterase inhibitor used in treatment of myasthenia gravis, post op and neurogenic ileus, post op and neurogenic urinary retention
Neostigmine
_________ inhibits the release step of Ach by blocking exocytosis via modification of vesicle docking proteins
Botulinum
Name the 3 layers of the cerebellar cortex grey matter
molecular, purkinje cell, granule cell
When plotting concentration on the x-axis and (delta)concentration/delta(time) on y-axis, if the line is straight, the drug is ________
first-order
Where do sympathetic fibers synapse?
in the chain (paravertebral) or prevertebral ganglia (preaortic)
True/False: Spinal nerves supply body cavities
False, only body wall structures. Sphlancnic nerves and vagus supply body cavities.
Which receptors like epinephrine the most? (may be more than one)
a) alpha I
b) alpha 2
c) beta 1
d) beta 2
A+B
True or false: Dendrites lack golgi
TRUE
How are spinal nerves formed?
from ventral and dorsal roots of spinal cord
_________ are involved in stretch, pain, temperature, chemical changes and initiation in viscera. Also nausea and hunger.
general visceral afferent fibers
Describe the parasympathetic effect on the adrenal medulla
There is none, trick question HAHA
True/false: Chemical transmission at some neuroeffector synapses does not involve either norepinephrine or Acetylcholine.
TRUE - nonadrenergic/noncholinergic NANC transmission
Describing the anatomy of autonomic synapses, a transmitter is released from ______ all along the presynaptic nerve axon and post-synaptic receptors are distributed across the entire cell
varicosities
True/False: Drug accumulation in some compartments may be increased well AFTER drug is no longer measured in blood stream
TRUE
What is the most important job of sympathetics?
Regulation of blood flow
Through what two mechanisms do alpha 2 receptors operate?
Inhibits Ca++ (and thus neurotransmitter release) and Gi/0 inhibits AC
______ is induced by smoking tobacco and catalyzes primary metabolism of propanolol and clozapine and inhibited by many fluoroquinolone ABX, fluoxamine, cimetidine
CYP 1A2
Where are the enlargements of the spinal cord located?
cervical and lumbar
A neurotransmitter taken up extraneuronally can be metabolized by (2)
MOA, COMT
What is the equation for bioavailability (F), which measures the effect of liberation and absorption and is important when converting pt from therapy to another
F = AUC / dose
________ are indirect acting cholinesterase inhibitors that cause poisoning due to formation of irreversible covalent bond with esteric site. This poisoning can be treated with ____. This can be reversed via _____ process where an H2O is added at a specific spot strengthening the covalent bond
Organophosphates, 2-PAM, aging
_____ is absent in 7% whites and hyperactive in 30% East Africans. It catalyzes the primary metabolism of codeine, beta blockers, and TCAs but is inhibited by some SSRI’s, Quinidine and Haldol
CYP 2D6
Sympathetics to abdominal viscera leave chain as preganglionic fibers on ______________. They synapse at _________ and travel to post-ganglionic fibers on blood vessels
sphlancnic nerves, pre-vert/pre-aortic ganglia
St. John’s wort contains _____ which stimulates neurotransmitter reuptake inhibition
hyperforin
_________ are cuboidal or columnar cells with cilia, microvilli and gap junctions that circulate and abosrb CSF
Ependymocytes
_______ is found at synapses between sympathetic post ganglionic neurons and their effectors. What are the two exceptions?
Norepinephrine. Two exceptions are the transmitted in sweat glands is Ach and chromaffin cells in adrenal medulla release epinephrine and norepinephrine.
______ and different levels explain individual differences in drug clearance
small nuclear polymorphisms
SNAPs and VAMPs are two types of SNARE proteins. Name examples.
VAMP - synaptobrevin, SNAPs - syntaxin, SNAP25
Describe the process of ion trapping.
Deionized drug is more likely to be taken back into the body. So alkalinizing urine with sodium bicarbonate to a pH level that matches the pKA of the drug would mean 50% of the drug is ionize and not available for reabsorption
Parasympathetic NS goes as far as the ______________
left colic flexure
M5 is found in (choose all that apply)
a) smooth muscle
b) exocrine glands
c) CNS neurons
d) vascular endothelium
D,A
Name two mixed acting sympathomimetics
ephedrine, phenylpropanolamine
Name the four types of neuroglia
astrocytes, oligodendrocytes, microglia, ependyma
Each muscle fiber receives input from a single ____________, however this structure can innervate many muscle fibers
motor neuron
The ________ is shrink wrapped onto spinal cord
pia matter
Where do sympathetic fibers exit the cord?
Ventral root
______________ neurons bypass the cell body or soma and are the sensory neurons of the DRG and most CNS ganglia. They include a split axon and no dendrites.
Pseudounipolar
What are the effects of acute toxicity by direct acting Nicotinic agents?
convulsions, coma, respiratory arrest, respirartory paralysis, HTN, cardiac arrhythmias
What similar action do M1/M3/M5 possess?
formation of Ip3 (increasing intracell Ca++) and DAG (activates PKC)
Name six differences between oligodendrocytes and Schwann cells
1) cell body of oligo not closely associated with myelin sheath like ScC; 2) each oligodendrocyte provides myelin to several axons while ScC only provide to one; 3) no basal lamina associated with myelin sheath in CNS; 4) myelinated axons in CNS lack a supporting connective tissue; 5) in Schwann cells, cytoplasm is retained in myelin; 6) in CNS, surface of node is contacted by astrocyte processes; while in PNS this is ScC processes
The autonomic nervous system consists of 2 synaptic connections. Describe.
Between first (pre) and second (post) neurons. Between post and effector cell.
___________ is a neurotransmitter at postganglionic sympathetic neuroeffector junctions in the kidney and certain CNS synapses
Dopamine
True or false: If muscle has only one segmented area of the spinal cord, you’ll lose entire muscle from damage to that one area.
True, but not common for muscle to only have one segmented area
True/False - There are no synaptic connections in sensory fibers
TRUE
Where are alpha I receptors found?
Located in smooth muscle and glandular tissue, causes smooth muscle contraction
Once Ach is broken down, choline can be recycled by transport back into presynaptic nerve terminal by Na+ - dependent ____________ where it can be used to make more Ach
choline transporter (CHT)
What type of protein are adrenergic receptors?
GPCR
What similar action do M2/M4 possess?
Activate K+ channels via hyperpolarization and inhibit AC (leading to decrease in cAMP)
What is the formula for maintenance dose?
(dosing rate / F) * dosing interval
6 agonistic drugs disrupt receptor interaction in catecholamine life cycle. Name them.
Oxymetazoline, Phenylephrine, Clonidine, Ispropterenol, Dobutamine, Tertbutaline
True or false: Sympathetic fibers traveling to body wall have to synapse at same level of structure they are traveling to
FALSE
Name the three connective tissue layers that cover the brain
dura matter, arachnoid membrane, pia matter
What happens when you cut a ventral/dorsal root?
The muscles/area connected to the peripheral nerves coming from the root will be affected - but will not be dead during to having more than one nerve innervating them
_______ sphlancnics come off chain and will synapse closer to superior or inferior hypogastric plexus
Sacral
Ach is transported into vesicles by ___________
vesicle associated transporter
Describe what receptors are found in the stomach and intestines and general functions.
Beta 2, alpha 2, general alpha, general muscarinic. Beta 2 and alpha 2 release motility and tone. Alpha contracts sphincter. Muscarinic has opposite effects and stimulates glandular secretion.
True or False: Uniparental disomy causes more cases of Angelman syndrome than Prader Willi Syndrome
FALSE, 25% PWS, <5% AS
While the post-ganglionic rami are found from C1-S4 levels, the preganglionic rami of the sympathetic system are only found between ______
T1-L2
50-60% of cases in BWS are due to loss of methylation at _____ while 10% of cases are due to mutations in ______
DMR2, CDKN1C
Most of the sympathetic fibers to pelvis come from abdominal cavity and pass to pelvis via _________
hypogastric nerves
Cells of the perineurium are joined by tight junctions forming the ____________
blood-nerve barrier
In ______ elimination, a constant amount of drug is eliminated per unit time, whereas in _______ elimination the amount of drug eliminated per unit time is proportion to concentration (constant %)
Zero order, first order
Describe how activation of a beta1 receptor leads to increased contractility in ventricular muscles.
Gs activation of AC. Leads to increased cAMP which activates PKA to open Ca++ channels. Ca++ flows into SR.
What is a the equation for finding the slope of a constant rate (-kel)
y2-y1/x2-x1
_____ family is responsible for metabolism of most calcium channel blockers, benzodiazepines, HIV protease inhibitors, HMG-CoA reductase inhibitors, cyclosporine, non-sedating antihistamines, ciaspride and is present in GI tract and liver
CYP3A
_______ do not follow first order elimination. These drugs are nephrotoxic.
aminoglycosides
A protonated base is going to be ________ whereas an protonated acid is going to be _______
charged, uncharged
_______ is used for post op and neurogenic ileus, postop urinary retention
Bethanecol
Huntington’s Disease is linked to a different ____ allele (repeat expansion) in each form
G8
What is the formula for steady state concentration?
Css = FXD/Cl X dosing interval
True or false: Dendrites do not contain Nissl components
FALSE THEY DO
________ increases Cephradine exposure 3.6X fold via organic anion transporter (OAT) inhibition
Probenecid
Describe what receptors are found in the lungs.
Beta 2 and muscarinic. Beta 2 stimulates relaxation of bronchial smooth muscle and dilation of airways. Muscarinic does opposite and stimulates secretion from bronchial glands.
What are the two types of docking proteins involved in Ach release? What is the stimulus for vesicular fusion?
Synaptosome associated proteins (SNAPs) and vesicle associated proteins (VAMPs), Ca++ intake by vesicle
_____ is absent in 1% of whites and African Americans. It is involved in the primary metabolism of most NSAIDs, S-warfarin and phenatoin and inhibited by fluconazole.
CYP 2C9
Purkinje ____ are found in the cerebellar cortex whereas purkinje ____ are found in the heart
cells, fibers
Which receptors likes norepinephrine the least? (may be more than one)
a) alpha I
b) alpha 2
c) beta 1
d) beta 2
D
Describe the mechanism of M2/M4
Gi/o inhibits AC and opens K+ channels
What are the three types of metabolic reactions
oxidative, hydrolytic, conjugative
Where are the cell bodies of sensory fibers found? (SSA and GSA)
dorsal root ganglia
________ is found at synapses between pre- and post- ganglionic neurons in ALL autonomic ganglia
Ach
_________ is the process by which chromosomes are “stamped” with a memory of the parent from whom it came from during gametogenesis
Genomic Imprinting
Describe what two receptors are primarily found on heart tissue. What are their actions at the ventricular muscle, SA node, and AV node.
B1 (Symp) and M2 (Parasymp). On ventricular muscle, B1 inc contractility (inotrophic) while M2 antagonizes symp response. On sinoatrial node, B1 inc HR, M2 dec (chronotrophic). On AV node, B1 inc conduction velocity, M2 dec (dromotrophic)
____________ are the smallest of neuroglial cells and have wavy branches with spines. They are scattered throughout CNS and inactive in normal CNS
Microglia
_____________ is the process of epigenetic programming of metabolism during the prenatal and neonatal periods. In utero exposures (chemicals, diet) can affect the risk of development of chronic disease in later life
metabolic imprinting
A lack of balance between microglia and astrocyte interaxn can lead to CNS-directed __________
autoimmunity and inflammation
The _________ encloses the entire nerve whereas the _______ encloses each fascicle and the ________ surrounds individual nerve fibers
epineurium, perineurium, endoneurium
The greater thoracic sphlancnic nerve comes off from what levels
T5-T9
Visceral afferent sensory fibers involved in reflexes and pain can travel with parasympathetics and be involved in general feeling of _________ and activate reflex action of autonomics
malaise
________ disrupts disposition of catecholamines by inhibiting reuptake
amphetamines
What are the 4 inducers of the CYP3a system?
carbamazepine, rifampin, rifabutin, St. John’s wort
What test can be ordered to improve diagnostic accuracy in a repeat expansion disorder?
PCR!!!!
___________ involves study of several family members in order to infer the presence of a disease causing change (mutation) in a gene by identifying the genetic DNA markers that are CO-INHERITED with gene of interest
linkage testing
The _________ produces the ependyma and epithelium of choroid plexus
neuroectoderm
What is an important exception to the two neuron rule in the autonomic nervous system?
Chromaffin cells in the adrenal medulla - preganglion cells synapse directly with these to initiate release of epi into bloodstream
5 antagonistic drugs disrupt receptor interaction in catecholamine life cycle. Name them.
Phentolamine, prasozin, tohimbine, propanolol, metropolol
True/False: Target cells may receive input from multiple post-synaptic neurons
True
If the pH is below the pKa, the ratio of dissociated:associated form will be _______ whereas it will be ____ if the pH is above the pKA
less than 1, more than 1
Name three indirect acting sympathomimemetics (CLUE they are involved with disposition aspect of catecholamine synthesis)
amphetamine, phenylzine, entacapone
Describe the general visceral motor efferent fibers
Involved in motor innervation of smooth muscle, cardiac muscle, and glands. Involved in autonomic nervous system.
What types of enzymes make up Phase II of drug metabolism?
Transferases!
Describe the steps in dopamine synthesis (4)
Tyrosine taken up from diet into presynaptic nerve terminal –> converted to DOPA via tyrosine hydroxylase (RLS). —-> converted to dopamine via dopamine decarboxylase.–> transferred into vesicles via vesicular monoamine transporter (VMAT)
When classified by cell process ________ neurons are the most abundant. They are motor neurons and include pyramidal cells and purkinje cells.
Multipolar
Nerve fibers are grouped into _____ by connective tissue sheathers, containing myelinated and unmyelinated fibers
fascicles
________ are derived from monocytes and are the smallest and least numerous neuroglia. They are phagocytic cells that respond to injury.
Microglia
Describe the effects of M2/M4 activation
slows heart rate, inhibits contractility of ventricular myocytes
Cranial nerves carry sensory fibers but synapse at ________ rather than dorsal root ganglia
cranial nerve ganglia
True or False: In multifactorial/polygenic diseases, the relative risk is higher if the proband is of the more commonly affected sex
FALSE - less commonly affected, indicates higher genetic load
The ________ is the main structural component of a peripheral nerve and consists of an axon, myelin sheath and Schwann cells
nerve fiber
In salivary glands, sympathetic and parasympathetic responses are ______
complimentary
Visceral afferent sensory fibers can also travel with sympathetic fibers and where they carry information related to _____. This is generally more localizable than that carried by parasympathetics
Pain
______ increases Metformin exposure 1.4X via organic cation transporter (OCT) inhibition
Cimetidine
___________ cells insulate the motor end plate
Schwann
Microglia produce ________ capable of recruiting leukocytes across blood-brain barrier to initiate neuroimmunogic diseases
chemoattractants
Varying what three things can impact concentration of a drug in plasma (Cp)?
absorption, dose, elimination rate
True or false: Ganglion cells of visceromotor fibers do not have a synapse
TRUE
What is a complication of subcutaneous administration?
possible pain or necrosis at site
____________ are exogenous compounds that imitate functional responses produced by Ach at cholinergic receptors
Cholinomimetics
_____ inhibits vesicular monoamine transport and thus the storage part of catecholamine life cycle
Resperpine
_________ inhibits the storage step of Ach by blocking the vesicle associated transporter
Vesamicol
Name the 5 drugs that affect receptor interaction in acetylcholine life cycle.
Bethamicol, Nicotine, Atropine, Trimethapan, D-tubocuranine
Parasympathetic fibers travel on __________ and __________. They NEVER travel to their target on a spinal nerve.
Cranial nerves, pelvic sphlancnic
Sympathetic and parasympathetic systems usually oppose each other. What are three important exceptions?
Piloerector muscles, sweat glands, most blood vessels (all symp)
The most common CYP enzyme is _____ and it metabolizes the most drugs. The CYP that metabolizes the 2nd largest amount of drugs is _____
3A4, 1A2
In multifactorial/polygenic diseases, the recurrence risk will change from population to population and from family to family due to difference in ___________
genetic load
All nicotinic receptors contain at least two ____ subunits where Ach binds
alpha
Where is beta 3 receptor found and what are the results of its activation?
Primarily in adipocytes, causes lipolysis via Gs activation of AC
What is the Henderson-Hasselbach equation?
pH= pKa + log [A-]/[HA] for acid; pH = pKa + log [B]/[BH+]
True/False: Parasympathetic fibers do not travel on branches of spinal nerves.
TRUE - nothing to do with blood flow of skeletal muscles or innervation of body wall
____________ is a potent inhibitor of intestinal cytochrome CYP 3A4-mediated drug metabolism (responsible for first pass metabolism of many medications)
Grapefruit juice!
Describe special visceral efferent nerves
Misnomer, under somatic motor or “branchiomotor,” still involved in innervating striated skeletal muscle under voluntary control, cranial nerves are example
What is the formula for loading dose?
Css X Vd / F (bioavailability)
Where is the collateral ganglion located?
aorta
An _________ position is where the axon terminal faces a dendritic spine
Axospinous
True or false: Synapses in autonomic ganglia are simple 1:1 relays
FALSE
Through what mechanism do alpha I receptors initiation smooth muscle contraction?
Gq activation of PLC. PLC leads to formation of IP3 and DAG –> inc intracellular Ca++ –> Ca++ binds calmodulin –> activates MLCK –> MLC phoshorylated –> contraction
The parasympathetic fibers usually have _____ preganglionic neurons and ____ postganglionic neurons, while the opposite is true for sympathetic fibers
long, short (closer to body wall
_______ are structures in which cell bodies of sensory neurons reside. There are no _________ in these ganglia
dorsal root ganglia, synaptic
________ cover neurons, the inner surface of the pia matter and every blood vessel of the CNS
end-feet
What is the formula for kel?
Cl/Vd
Some sympathetic fibers to thorax come directly off thoracic chain ganglia after synapsing and are known simply as __________
thoracic sphlancnic nerves
A mutation in a gene active only the paternal derived chromosome was inherited from the father (on the paternal chromosome). Will the mutant allele be expressed in the individual? What if its inherited from mother?
YES! from dad and NO! from mom
___________ fibers involved in hearing, vision, equilibrium
special sensory afferent
Explain how alpha 2 receptor activation leads to vasoconstriction
Inhibition of AC reduces cAMP levels. cAMP normally inhibits MLCK. MLCK is free to phosphorylate MLC’s which leads to contraction and thus vasoconstriction of vascular smooth muscle
________ confer resistance to DM while mutations in ________ account for about 40% of heritability in US
HLADQ, HLA DR3 and DR4
__________ are the largest glial cells and contain long-branched cytoplasmic processes with vascular end feet
Astrocytes
Some spinal nerves leave the cord and travel alone (intercostals), whereas others merge adjacent spinal nerves and form a ______ which become _______
plexus, peripheral nerves
Muscarinic receptors are activated by _______ and inhibited by ______
muscarine, atropine
Ependymal cells contain abundant mitochondria and are attached to each other via ___________
belt desmosomes
Describe what receptors are found in the urinary bladder and their actions.
Beta 2, Alpha 1. B2 causes detrusor relaxation. Alpha I contracts the internal sphincter. (Parasympathetic system contracts detrusor and relaxes sphincter which promotes voiding)
What do the dorsal rami AKA posterior cutaneous branches supply?
motor and sensory to skin of back and true back muscles (GSA, GVE, GVA - no GSE bc no skeletal muscle in skin)
Describe what receptors are found on salivary glands and their effects.
Beta and Muscarinic. Beta causes a weak increase in amylase secretion. Muscarinic causes pronounced increase in H2O and K+ secretion.
Name 4 direct acting alkaloid cholinomimetics
lobeline, nicotine, muscarine, pilocarpine
Direct acting sympathomimemetics consist of two moieties. What are they?
A catechol and an ethylamine side chain
Astrocytes divide in response to injury and form scar tissue in a process called _______
gliosis
Several drugs result in increased Digoxin exposure due to inhibition of p-glycoproteins. Which is NOT one of these drugs?
a) Quinidine
b) Dronedarone
c) Rifampin
Rifampin - dec Digoxin exposure via p-gp INDUCTION
_____________ neurons are short single axon neurons with no dendrite and include photoreceptor cells
Unipolar
The peripheral nervous system, carries cranial nerves and spinal nerves that are composed of what two categories of components?
a) sensory vs motor; b) visceral, somatic or special
When drug given for first time, will expect to wait at least ____ half lives before drug at steady state
4
A _________ can eliminate time to steady state drug (in comparison to a therapeutic dose)
loading dose
____________ have small cell bodies, few delicate processes and no cytoplasmic filaments and are found along myelinated nerves surrounding neuronal cell bodies in the CNS
Oligodendrocytes
____ is absent in 20-30% of Asians, 3-5% of whites and is primary metabolism of diazepam, pheytoin and omeprazole. It is inhibited by omeprazole, isoniazid, and ketoconazole
CYP 2C19
As the pH increases or decreases by one unit relative to pKa, the radio of dissociate form to associate form changes by factors of ____
10
__________ astrocytes contain long slender processes and contain white matter and cytoplasmic filaments. ________ astrocytes have short, thick processes with many branches and contain grey matter and no cytoplasmic filaments.
fibrous, protoplasmic
What are the effects of toxicity by direct acting muscarinic agents?
SLUDGE (Salivation, Lacrimation, Urination, Defecation, Gastric Distress, Emesis)
The first neuron in sacral spinal cord exits with cranial nerves or on ventral root of S2-S4 and the 2nd neuron in or near the wall of the organ and is part of the ________
enteric nervous system
How does beta2 receptor stimulate glycogenolysis in the liver?
Gs activation of AC. Increase in cAMP leads to increase in PKA which leads to glucose production
_________ are involved in all aspects of drug absorption, distribution, metabolism and excretion. They can also be a source of drug-drug interactions.
Transporters
True or false: In first order elimination, a steady state cannot be reached
False, IN NON-FIRST ORDER
M3 is found in (choose all that apply)
a) smooth muscle
b) exocrine glands
c) CNS neurons
d) vascular endothelium
A,B,C,D
What is the equation for half life in terms of kel (elimination rate)?
t 1/2 = 0.693/kel
What is the formula for dosing rate?
Css X Cl / F
At the neuromuscular junction, ___________ is released at presynaptic nerve terminal and post-synaptic receptors are found only at the ________. Responses are rapid and all-or-none.
neurotransmitter, end plate
Name two alpha-selective direct acting sympathomimemetics
Phenylephrine, methyldopa
Competition between CYP enzymes lead to _________
adverse drug reactions
What cranial nerves carry sympathetics?
3,7,9,10
The greater, lesser and least thoracic sphlancnic nerves pierce diaphragm as preganglionic fibers and synapse on _______ then go to targets on blood vessels
collateral ganglia
If a trait is 100% genetic, ________ will be 100% concordant, and _________ will be 50% concordant
monozygotic twins, and dizygotic twins
Viscera in general are supplied by ___________ from S2-S4 spinal cord segments
pelvic sphlancnic nerves
The regeneration process starts but is aborted by two things in the CNS. What are they?
Absence of endonerium and lack of proliferation of oligodendrocytes
What 4 fibers do all spinal nerves generally contain?
GSA, GVA, GSE, GVE ** both motor fibers are in all spinal nerves.
COMT is found in what two places?
smooth muscle cells and liver
The simple cuboidal cells responsible for the production and maintenance of CSF are derived from ependymal cells and called the __________
choroid plexus
Describe the two categories of the motor (efferent) division of the CNS and the types of fibers in each
a) somatic motor: general somatic efferent, special visceral efferent; b) visceral motor: general visceral efferent (ANS)
What is the principal duty of somatic motor fibers?
innervation of striated skeletal muscle under control
Where are the cell bodies of post-ganglionic neurons found?
Autonomic ganglia (also where synaptic connections between pre and post terminals made)
True or false: Neurons can receive lots of afferents but will only have one efferent
TRUE
____________ neurons are found only in retina, OLFACTORY MUCOSA, and inner ear
bipolar
_____________ is determining which one of each pair of alleles are in synteny (were inherited together on a contiguous piece of a chromosome)
haplotyping
What are the effects of chronic toxicity by direct acting Nicotinic agents?
addictive properties of smoking, inc incidence of peptic ulcers
Sympathetics to viscera in body cavities are called ________
sphlancnics
If the pH of a solution is 6, and the pKA is 7, the ratio of [A-]/[HA] will be
0.1 or 1/10
There is an increased prevalence of what two disorders in pregnancies conceived by IVF?
Angelman and Beckwith-Widemann (BWS)
True or false: Axon hillock contains no nissl bodies and is the origin of neurofilaments and neurotubules
TRUE
A dermatome is an area of skin innervated by a single _________
spinal nerve, includes dorsal and ventral ramus
What do the ventral rami AKA as lateral and anterior cutaneous branches supply?
motor and sensory to skin and muscles of trunk and limbs (except for that is which supplied by dorsal rami)
Describe the mechanism promoted by D1 and D5 receptors.
Gs stimulation of AC. In vascular smooth muscle this leads to relaxation.
Any fiber leaving the chain and coursing posterolaterally is always a __________
communicating ramus
Many tumors that overexpress P-Gly are resistance to chemotherapy. Why?
P-glycoproteins export many drugs out of cells
Explain how alpha 2 receptor activation inhibits release of norepinephrine from postganglionic neurons
Neurotransmitter binds alpha 2 –> Beta y binds Ca++ channels and blocks –> Ca++ does not enter so vesicle stays negative –> No NT released
How do sympathetic fibers reach their targets?
on sphlancnic nerves, spinal nerves or blood vessels
The lateral horn is generally not seen in the ____ portion of the cord due to small numbers of cell bodies
sacral
Name four direct acting choline esters
Bethanecol, Methacholine, Carbachol, Ach
During gametogenesis, enzymes are expressed that erase/remove all of the methylations on DNA except what?
metabolic and environmental methylations
Name two types of passive transport involved in drug absportion
Paracellular transport (filtration through aq channels) and diffusion
Joined end feet processes coating the pia matter form collectively the _______________
glia limitans
Both parasympathetic and sympathetic systems play role in controlling the visceral and head structures, but only ________ control the body wall. What is the one exception?
sympathetics; exception is arteries associated with external genitalia (ie in erection) are innervated by parasympathetic
____ receptor activation leads to neuronal excitation
Nm
In general, sympathetic fibers to targets above the diaphragm (OTHER than body wall) synapse in the ________
sympathetic chain
_________ receptors are ligand-gated ion channels and primary receptor at all autonomic ganglia along with postsynaptic receptor at NMJ.
Nicotinic
_________ stains neurons a brown-black and may represent older neurons
Melanin
