Flashcards in Pharmacology Capstone Deck (90):
0
sympathetic nervous system is aka
thoracolumbar
1
parasympathetic nervous system is aka
craniosacral
2
Parasympathetic NT and R
NT=Ach
R=NAchR, MAchR
3
Sympathetic NT and R
NT= NE>epi>Da; Ach
R= alpha, Beta, D, nAchR, mAchR
4
Cholinergic - think?
acetyl choline
muscarinic and nicotinic receptors
5
adrenergic think?
norepinephrine
epinephrine
dopamine
alpha, beta, D receptors
from tyrosine
6
major NT of the parasymp system
Ach
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found at ALL PREganglionic autonomic fibers
Ach
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found at ALL POST ganglionic parasympathetic fibers
Ach
9
found at a few POSTgaglionic sympathetic fibers (WHERE?)
Ach
sweat glands
10
major NT of the sympathetic nervous system
NE
11
found at a vast majority of postganglionic sympathetic fibers
NE
12
synthesis occurs in adrenal medulla and a few neuronal pathways in brainstem
EPI
13
Synthesized in the cytoplasm of neurons
Dopamine
14
Dopamine has actions where?
in the CNS and renal vascular smooth muscle
15
Neurons that release Ach are called
cholinergic neurons
16
Order of steps in cholinergic neurotransmission
Synthesis
storage
release
binding
termination
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Synthesis of Ach
CHOLINE TRANSPORTER transports choline into neurons
dependant on cotransport with NA
CHOLINE ACETYLTRANSFERASE (ChAT) conbines acetyl coenxyme A with choline to make Ach
18
Storage of Ach
ATPase dependent Ach vesicular transporter transports Ach into neuronal vesicles.
19
Release of Ach
AP reaches axon terminal, causes opening of VgCa2+channels
Ca2+enters the neuron
Ca2+ influx promotes fusion of vesicular membrane with cell membrane
Ach is released
the SNARE protein complex is responsible for fusion of the vesicle membrane and synaptic membrane through VAMP and SNAP proteins
20
Binding of Ach to cholinergic receptors
Ach diffuses across the synaptic cleft
binds nachrs which facilitates Na entry into post-gang fiber or release of epi/NE from adrenal medulla
post-synaptic machrs are also activated by ach causing smooth muscle contraction, decrease in HR, glandular secretin etc
Ach can bind to and activate both nachr (+) and machr (-) to modify its own release.
21
activation of prejunctional nAchRs _________ Ach release
stimulates/potentiates
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activation of prejunctional machrs ________further release
inhibits
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Termination of Ach signaling
Acetylcholinesterase cleaves Ach into acetate and choline
acetate diffuses out of the synapse
choline is recycled into the nerve
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What two types of receptors does Ach bind to?
nAchR
mAchR
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Where are NnAchrs found
all ganglia (sym and parasymp) and adrenal medulla (symp)
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where are mAChrs found
smooth and cardiac muscle
gland cells
nerve terminals
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nAchR is what type of a channel
ionotropic (ligand gated ion channel)
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nAchR allows what to pass through the channel
Na
29
mAchR is what type of receptor
metabotrpoic, GPCR
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how many subtypes of muscarinic receptors are there
5
31
what are the predominant smooth muscle muscarinic receptors
M2 and M3
32
what is the predominant muscarinic receptor in cardiac muscle
M2
33
adrenergic transmission, think
catecholamines
(NE, E, Da)
34
principle NT of most of sympathetic post ganglionic fibers and ov certain tracts in CNS
NE
35
major hormone/NT released by adrenal medulla
epi
36
predominant NT of mammalian extrapyramidal system and several mesocortical and mesolimbic neuronal pathways
Dopamine
37
Steps of catecholamine signalling
synthesis
storage
release
binding
termination
38
Synthesis of catecholamines
tyrosine transported into nerve terminal by a Na dependent transporter
trosine--> DOPA->Dopamine->NE->Epi
final step occurs only in the adrenal medulla and in a few epi containing neuonal pathways in the brainstem
39
Storage of catecholamines
vesicular monoamine transporter (VMAT-2) transports Da into the vesicle
promiscuous, can also transport NE, epi, and seratonin across the vesicle membrane
40
reserpine
inhibits VMAT-2, leads to depletion of catecholamines from sympathetic nerve endings.
41
Release of catecholamines
similar to release of Ach after depolarization and influx of Ca2+.
in adrenal medulla, triggering event is release of Ach and its interaction with nAchRs on chromaffin cells to produce localized deppol
42
Binding of catecholamines to adrenergic receptors
diffuse across synaptic cleft and bind to adrenergic alpha and beta receptors
effector organ responses include: contraction, glycogenolysis, gluconeogenesis, relaxation and increased force and rate of cardiac muscle contraction
43
Termination of catecholamine signaling (3 ways)
reuptake into nerve terminals
dilution by diffusion
metabolic transformation
44
major mechanism that terminates the actions of catecholamines
reuptake
45
reuptake of catecholamines
by two neuronal membrane transporters NET and DAT (NE transporter and DA transporter)
46
Dilution by diffusion of catecholamines
diffuseion out of the junctional cleft and uptake ate extraneuronal sites by transporters ENT/ OCT1 and OCT2)
47
Metabolic transformation of catecholamines occurs through what enzymes?
MAO
COMT
48
examples of common sympathetic cotransmitters
ATP,
NPY
49
feedback on prejunctional receptors to inhibit release of each other
NE, NPY, ATP
sympathetics
50
examples of receptors on sympathetic nerve varicosities that also inhibit the release of sympathetic NTs include
M2 and M4, serotonin, PGE2, histamine, enkephalin, DA, and alpha 2
51
examples of receptors on sympathetic nerve varicosities that enhance sympathetic NT release
Beta 2, ang II, nAchR
52
How many subtypes of alpha adrenergic receptors are there?
2 - alpha1 and alpha2
53
THE END RESULT OF ALPHA-1 RECEPTOR ACTIVATION IS
muscle contraction
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smooth muscle contraction results in ______
cardiac muscle contraction leads to ________
(alpha-1)
vasoconstriction
increase in contractile force on the heart
55
exception to alpha-1 rule
gut
activation of alpha 1 receptors and subsequent increas in Ca2+ causes hyperpolarization and muscle relaxation by activation of Ca2+ dependent K+channels
56
ACTIVATION OF ALPHA-2 RESULTS IN
vascular smooth muscle contraction, decreased insulin secretion adna a decreased release of NE (presynaptic alpha-2 receptors)
57
how many subtypes of Beta adrenergic receptors are there
three
B1, B2, B3
58
All B receptors are _____coupled receptors
Gs coupled
59
B1 receptors are found mainly
myocardium
60
ACTIVATION OF BETA-1 RECEPTORS RESULTS IN
increased force and rate of heart contraction and AV nodal conduction velocity
61
B2 receptors are mainly found
smooth muscle and most other sites
62
BETA 2 RECEPTOR ACTIVATION CAUSES
RELAXATION of
vascular, broncial, GU and GI smooth muscle
63
Beta 3 receptors are found
adipose tissue
64
ACTIVATION OF BETA 3 RECEPTORS RESULTS IN
lipolysis
65
triad of symptoms for pheochromocytoma
headache, perspiration, palpitations
66
alpha 1 receptors are found primarily
on sm m surrounding the vasculature
67
alpha 2 receptor primary location is
presynaptic in brain, leading to a decrease in sympathetic outflow
68
alpha 1 receptors are _____coupled
Gq
69
alpha 2 receptors are _____ coupled
Gi, Go
70
Primary tissue locations of adrenergic receptor subtypes
a1
a2
b1
b2
b3
a1 - postjunctional smooth muscle (contraction
a2 - presynaptic neurons, postynaptic tissues and blood platelets
- (ocular, adipose, intestinal, hepatic, renal, endocrine)
b1 - heart (stimulation)
b2 - bronchial, uterine, and vascular smooth muscle (relaxation)
b3 - adipose tissue (lipolysis)
71
centrally acting a2 think....
decrease in sympathetic outflow
decrease in sympathetic tone
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muscarinic think....
increase body fluids
73
how do B2 and mAchR act on sm m surrounding organs
B2=relax
mAchR= contract
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What type of receptor is the Dopamine receptor
GPCR
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how many types of DA receptors are there
five
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DA activates the D1 receptors in _______ whcich increases_____ and causes _____
renal sm. m
CAMP
dilation
77
stimulation of the D1 receptor will result in
vasodilation, natriuresis and diuresis (via renal vascular smooth muscle)
78
At higher concentrations DA can activate _____ and ____ receptors to cause ______ and _______
alpha 1
beta 1
general vascular vasoconstriction
increase in HR
79
decreased sweating cause
increased temperature
80
Smooth muscle of blood vessels is innervated by
sympathetic neurons
NOT parasympathetic neruons
81
how does vascular relaxation happen
need an intact epithelium
stumuli - Ach, physical stimuli, and vasoactive products of inflammation and platelet aggregation (bradykinin, histamine, serotonin, purines, thrombin)
endothelial cells release nitric oxide, which acts on sm m cells
causes vasodilation
Ach activates a mAchr in this scenario
82
three exceptions of mAchRs causing contraction
intestines
urinary bladder
vasculature
83
Baroreceptor reflex
need to add slides for this section but i dont GAFRN
84
Rule of thumb - Alpha 1
stimulate contraction of all smooth muscle
(vascular sm m= vasoconstriction; glandular sm m= secretion)
85
Rule of thumb - Beta2
relax smooth muscle
(vascular sm m - vasodilation)
86
Rule of thumb - muscarinic receptors
contract smooth muscle
87
Increase BP causes ______ baroreceptor firing leading to ______
increased
decrease in sympathetic output
increase in parasympathetic output
88
decreased BP leads to_______baroreceptor firing, resulting in _______
decreased
increase sympathetic discharge
decrease parasympathetic discharge
89