Pharm 9.1 Flashcards
1
Q
norepinephrin is an
A
adrinergic neurotransmitter (except in sweat glands)
2
Q
Epinephrine is hormone secreted by
A
the adrenal madula
3
Q
Dopamine a neurotransmitter is found in
A
the basal ganglia, limbic system, CTZ, and anterior pituitary
4
Q
difference btw norepinephrine and epiephrine
A
NE is an NT secreted by neurons and does not act on beta 2 rec, Epi is a hormone secreted by adrenal medulla and acts on all recptros (low dose acts on beta rec)
5
Q
Epinephrine, norepinephrine, and dopamine (catecholamines) synthesized form
A
tyrosine
6
Q
what is the rate limiting step in the synthesis of catecholamines
A
tyrosine hydroxylase
7
Q
Fates of NE
A
binds alpha 1 rec post synaptically, binds alpha 2 rec presynaptically for auto inhibition, gets metabalized by MAO in axoplasm and COMT in snapse, reuptake back into primary neuron
8
Q
tyrosine to dopamine happens in
A
axoplasm
9
Q
dopamine is stored in
A
vesicles to prevent degredation
10
Q
dopamine to NE in
A
vesicles
11
Q
transport of dopamien into vesicles is inhibited by
A
reserpine
12
Q
release of NT from axon termila is caused by
A
influx of ca causing fusion of the vesicle with the cell membrane
13
Q
release of catecholamine vesicle is blocked by
A
guanethidine and bretylium
14
Q
reuptake of catecholamines is inhibited by
A
cocain and imipramine
15
Q
where is dopamine beta hydroxylase
A
dopamine beta hydroxilase is in vesicles to convert dopamine to NE
16
Q
how is Ne coverted to Epi
A
by PNMT (phenylethanolamine N methyltransferase) only in the adrenal medulla bc epinephrine is important in flight, fright, fight
17
Q
granules take up dopamine from the
A
cytoplasme
18
Q
conversion of dopamine to NE occurs in granules by
A
dopamine beta hydroxylase
19
Q
where are the granules
A
in the adrenergic termina (NE is stored in them)
20
Q
how are NE and other catecholamines released
A
exocytosis in response to stimulatory signal
21
Q
indirectly acting amines like tyramine and amphetamines induce
A
release of NE by displacing it from the nerve endings
22
Q
efficient mechanism of release of NE
A
uptake of Ca
23
Q
the most important mechanism for the ermination of the NE action
A
axonal uptake–>i.e. reuptake
24
Q
what ihibits reuptake
A
cocaine and imipramine
25
NE can bind all receptors EXCEPT
BETA 2
26
metabolism of NE occurs by two enzyme systmes
MAO and COMT
27
MAO
monoamine oxidase
28
COMT
catechol-O-methyl transferase
29
NE is acted upon by MAO in the
axoplasm
30
COMT acts on NE when
NE it diffuses out in circulation, mainly in the liver and in the blood stream
31
MAO-A is present
in the nerve/liver mainly or anywhere
32
MAO-A metabolizes
NE, 5HT, tyramine
33
MAO-A inhibitors
Phenelzine, Tyranylcypromine (antidepressants)
34
MAO-B is present in the
Brain
35
MAO-B metabolizes preferentially
dopamine
36
MAO-B inhibitor
Selegiline (antiparkinson)
37
COMT inhibitors
Tolcapone, Entacapone
38
Tolcapone is
long acting
39
Entacapone is
Short acting
40
major metabolites excreted in the urine are
VMA (Vanillyl mandelic acid), metanephrine, and dihydroxy mandelic acid
41
when do you see an increase in adrenergic metabolites
pheochromocytoma - tumor of adrenal gland
42
does metabolism play a significant role in the termination of action of NE?
NO
43
what inteferes with the synthesis of catecholamines by intefering with tyrosine hydrolase
Metyrosine
44
what causes a blockade of storage in granule or granular uptake of catecholamines
Reserpine
45
what causes Displacement of NE from vesicles
amphetamine, tyramine (indirect sympathomimetic agents)
46
what causes Prevention of release of catecholamines
bertylium, guanethidine
47
wht causes block of reuptake at nerve terminal of chatecholamines
cocaine and imipramine
48
adrenergic receptors
alpha beta dopamine
49
aplpha receptors
alpha 1 (usually post synaptic) , alpha 2 (usually pre synaptic)
50
beta receptors
beta 1, 2, 3
51
dopamine receptors
D1, D2
52
type of receptors that adrenergic receptors are
g-proteins coupled receptors
53
adrenergic receptors act by either
increasing or decreasing syn of cAMP OR through IP3, DAG, and Ca2+ as second messengers
54
alpha 1 is a
Gq - inc PLC --> inc IP3, DAG, Ca2+
55
alpha 2 is a
Gi - dec Adenylyl cyclase --> dec cAMP
56
beta1/2 and D1 receptors are
Gs - inc Adenylyl cyclase --> inc cAMP
57
alpha 1 subtypes
A B D
58
alpha 2 subtypes
A B C
59
where do you find the alpha 1 subtype
SM of urethra -- use drugs targetting this recptors in obstructions in BPH
60
alpha 1 on
eye (radial/dialator) muscle, Arterioles (skin, viscera), Veins, Bladder trigone and sphincter, Male sex organs, Liver, Kidney
61
alpha 1 in eye/dialator muscle
contraction - mydriasis
62
alpha 1 in the arterioles (skin, viscera)
contraction - incTPR - inc diastolic pressure - inc afterload --want to shunt blood away from the skin and viscera and more available for the heart
63
alpha 1 in the veins
contraction - inc venous return - inc preload
64
alpha 1 bladder trigone and sphincter
contraction - urinary retension
65
alpha 1 in male sex organs
vas deferens - ejaculation
66
alpha 1 in liver
inc glycogenolysis
67
alpha 1 in kidney
dec renin release
68
alpha 2 receptors are found in
prejunctional nerve terminals, platelets, pancrease
69
alpha 2 in prejunctional never terminals
dec transmitter release and NE synthesis
70
alpha 2 in platelets
aggregation - makes sense bc in fight or flight you want to prevent bleeding out
71
alpha 2 in pancreas
dec insuline secretion
72
beta 1 in the
heart, Kidney
73
beta 1 in the SA node
inc HR - positive chronotropy
74
beta 1 in the AV node
inc conduction velocitiy (positive dromotropy)
75
beta 1 in artiral and ventricular muscle
in force of contraction (positive inotropy), conduction velocity, CO and oxygen consumption
76
beta 1 in His-Purkinje
inc automaticity and conduction velocity
77
beta 1 in Kidney
inc renin release
78
beta 2 in the
blood vessels, uterus, bronchioles, skeletal muscle, liver, pancres
79
beta 2 in the blood vessels
vasodialation - dec TPR - dec diastolic pressure - dec afterload
80
beta 2 in the uterus
relaxation
81
beta 2 in the bronchioles
dialation
82
beta 2 in the skeletal muscle
inc glycogenolysis - contractility (tremor)
83
beta 2 in the liver
inc glycogenolysis
84
beta 2 in the pancreas
inc insuline secretion
85
what receptor is most important for glycogenolysis
beta 2 then alpha 1
86
D1 peripheral receptor actos on
renal, mesenteric, coronary vasculature, causing vasodialation, inc renal blood flow, inc GFR, inc Na secretion(natriuresis)
87
slective agonist of Alpha 1 receptors - alpha 1 mimetics
phenylephrine, methoxamine
88
selective antagonist of alpha 1 receptors
prazosin, doxazosin, tamsulosin (on alpha 1A)
89
alpha 2 receptor agonsit
clonidine, guanfancine, methyldopa
90
alpha 2 antagonist
yohimibine
91
beta receptors
beta 1, 2, 3
92
beta 1 rec
on heart
93
beta 2 on
SM
94
beta 3 on
fat cells (adipocytes)
95
selective beta 1 agonist
dobutamine
96
slective beta 1 antagonist
atenolol, metoprolol
97
beta 2 receptors are mostly
not innervated
98
selective beta 2 agonsit
albuterol (salbutamol), salmenterol (longer acting), terbutaline
99
selective beta 2 antagonist
butoxamine
100
why would a beta 2 antaganist be used
treat bronchospasm (w/ butoxamine) bc remember beta 2 dialate, they are the enemies of alpha 1 that constrict
101
classification of adrenergic drugs
direct, indirect, mixed
102
direct actiong adrenergic drugs
epinephrine, norepinephrine, phenylephrine (beta 1), albuterol (beta 2)
103
indirect acting adrenergic drugs
acts by releasing NE, Tyramine, Amphetamine
104
Mixed acting adrenergic drugs
Ephedrine, Phenylpropanolamine (not on market bc caued stroke after it was in cough mixture)
105
naturally occuring catecholamines includes
epinephrine, norepinephrine, dopamine
106
catecholamines sturcture
catechol moiety and an ethylamine side chain
107
catecholamines are rapidly inactivated by
MAO and COMT (inactivation starts from the gut)
108
the catecholamine epinephrine acts on
alpha 1, alpha 2, beta 1, beta 2
109
the catecholamine norepinephrine acts on
alpha 1, alpha 2, beta 1
110
the catecholamine isproterenol acts on
beta 1, beta2, like epinephrine on steroides bc it vasodialates and decreases heart rate? And there is a reflex tachycardia
111
the catecholamine dobutamine acts on
beta 1
112
the catecholamine dopamine acts on
D1 ( beta 1 and alpha 1 at high doses)
113
the non-catecholamines that work on alpha 1 only
oxymetazolin, phenylephrine, methoxamine
114
non catecholamines that work on beta 2 only
albuterol, pirbuterol, terbutaline, salmeterol, formeterol
115
non catecholamines that acts more on beta 2 than beta 1
metaproterenol
116
non catecholamines that work on alpha and beta
ephedrine, psuedoephedrine
117
action of alpha 1 agonists
inc TPR, inc BP, potential reflex bradycardia, no change in pulse pressure
118
when could you use an alpha 1 agonist
tachycardia
119
action of beta 2 agonists
beta 1 actions increase HR, SV, CO, and pulse pressure, beta 2 actions decrease TPR and BP, overall increase/widening in pulsepressure
120
normal SV is
70 ml/beat
121
Epinephrine is a potent activator of
alpha and beta adrenergic receptors and have prominent cardiovascular effects
122
Epinephrine is involved in the sympathetic
fight flight fright
123
epinephrine on beta 1 receptors in CVS
inc rate of depolarization in cardiac myocytes, inc inotropy, inc chronotropy, inc CO, inc in BP
124
how does activating beta 1 receptors in CVS lead to faster depolarization
cardiac myocytes always leak out potassium, but activation of beta 1 receptors closes the potassium gates faster, depolarizing the SA-AV purkinje, increasing the rate of contraction and heart reate
125
when is activating beta 1 receptors important
asystole (no contraction)
126
epinephrine on alpha 1 receptors in CVS
at high dose causes vasoconstriction (vasopressor effect) via alpha 1, but at low does epi causes vasodialation (vasodepressor effect) via beta 2, produces a biphasic response
127
biphasic response
different effect based on dose
128
Dale's vasomotor reversal (Epinephrine Reversal)
when alpha 1 receptors are blocked, epinephrine will produce hypotension because of unmasking of beta 2 receptor activation
129
low dose epiniephrine
beta 1 and beta 2 stimulation
130
high dose epinephrine
alpha 1, beta 1(beta2) stimulation ---but beta 2 effect is masked
131
high dose epinephrine on alpha 1
inc TPR, inc BP, potential reflex bradycarida
132
high dose epinephrine on beta 1
inc HR, inc SV, inc CO, inc pulse pressure
133
high dose epinephrine on beta 2
dec TPR, dec BP ---> masked at the high dose
134
epinephrine on beta 2 receptors in Respiratory system
bronchodialation
135
alpha 2 receptors work by
stimulating Gi path, decreasing cAMP, stimulating nitric oxide release
136
anaphylaxis
bronchospasm + anaphylactic shock or low BP
137
how is Epinephrine used in anaphylaxis
beta 2 action decreases bronchospasm increasing partial pressure of O2; alpha 1 action increases CO, systolic BP, pulse pressure, tissue perfusion; decrease in eosinophil count reducing anaphylatoxin release
138
Gs
increases cAMP that inhibits MLCK (myosin light chain kinase)
139
Epinephrine metabolic effect
hyperglycemia, lipolysis
140
hyperglycemia by epinephrine
inc glycogenolysis in muscle and liver (beta 2), inc in gluconeogenesis (due to inc release of glucagon -( beta 2), dec insulin secretion (alpha 2)
141
lipolysis by epinephrine
beta 3 - inc cAMP in adipose tissue stimulating hormone sensitive lipase, leading to hydrolysis of TGs to FFA and glycerol
