Vasoconstrictors - Pharm 2 Flashcards
1
Q
Stimulation of presynaptic Alpha-2 receptors results in _________ of NE release from the nerve ending
A
inhibition
2
Q
SNS has a thoracolumbar origin of ___ to ___
A
T1-L2
3
Q
Preganglia are near the _____ ______
A
spinal cord
4
Q
Postganglia secete ________ which act on ______ fibers
A
norepinephrine / adrenergic
5
Q
NOREPINEPHRINE: Dopamine enters the ________ vessel. Dopamine beta hydoxylase converts dopamine to _________. An _____ _______ releases NE from the synaptic vessel.
A
synaptic / norepinephrine / action potential
6
Q
Norepinephrine signal termination is accomplished by what?
A
Reuptake, dilution by diffusion, Metabolism by MOA and COMT
7
Q
Most of norepi is being recycled and some of norepinephrine is being _____ down
A
broken
8
Q
Alpha-1
A
periphery
9
Q
Beta-1
A
heart
10
Q
Beta-2
A
periphery
11
Q
Alpha-2
A
central
12
Q
When norepinephrine is binds with beta-1 G-proteins cause ________ changes. Review slide 8
A
confomrational
13
Q
Review slide 9 for alpha 1 and 2 with norepi
A
Review slide 9
14
Q
Alpha-1 Postsynaptic receptor
A
Activation increases intracellular calcium, smooth muscle contraction, periphereral vasoconstriction, Bronchoconstriction, inhibits insulin secretion, stimulates glycogenolysis and gluconeogenesis, mydriasis, GI relaxation
15
Q
Alpha-2 receptors: Presynaptic in the PNS
A
decreases entry of calcium into the cell AND limits the release of norepinpehrine
16
Q
Alpha-2 receptors: Postsynaptic in the CNS
A
sedation, decreased sympathetic outflow, decreased BP, platelet aggregation
17
Q
Beta-1 Postsynaptic receptor
A
increases HR, increases conduction velocity, increases myocardial contractility
18
Q
Beta-2 postsynaptic receptor
A
stimulation leads to smooth muscle relaxation, peripheral vasodilation, decreases BP, bronchodilation, increases insulin secretion, increases glycogenolysis and gluconeogensis, decreases GI mobility
19
Q
PNS is CRANIOSACRAL origin. Which CN?
A
III, V, VII, X
20
Q
The PNS is preganglia near _______ or innervation
A
organs
21
Q
PNS postganglia secrete _______ and act on _______ fibers
A
acetylcholine / cholinergic
22
Q
Acetylcholine activates both arms of the _______
A
ANS
23
Q
Review slide 15
A
acetylcholine and calcium mediated action potential
24
Q
SNS stimulation of the heart results in
A
increased HR, increased conduction velocity, increased automacity, increased contractility
25
SNS stimulation of the bronchial smooth muscle results in
relaxation
26
SNS stimulation of the GI tract results in
decreased motility, decreased secretion, sphincter contraction
27
SNS stimulation of the gallbladder results in
relaxation
28
SNS stimulation of the urinary bladder results in
smooth muscle relaxation and spincger contraction
29
SNS timulatioin of the uterus and ureters
contraction
30
SNS stimulation of the eye
mydriasiss
31
SNS stimulation of the Liver
glycogenolysis and gluconeogensis
32
SNS stimulation of the pancreas
Decreased beta cell secretion (decreased insulin)
33
SNS stimulation of the salivary glands
increased secretion
34
SNS stimulation of Sweat glands
increase
35
PNS stimulation of heart
Decreased HR, decreased conduction velocity, slight decrease in contractility
36
PNS stimulation of the bronchial smooth muscle
contraction (resting state)
37
PNS stimulation of the GI tract
Increased motility, increased secretion, sphinter relaxation
38
PNS stimulation of the galllbadder
contraction
39
PNS stimulation of the urinary bladder
smooth muscle contraction, spincter relaxation
40
PNS stimulation of the uterus
variable
41
PNS stimulation of the ureter
relaxatioin
42
PNS stimulation of the eye
miosis
43
PNS stimulation of the liver
glycogen synthesis
44
PNS stimulation of the salivary gland
marked increase in secretion
45
PNS stimulation of sweat glands
increases
46
Extended exposure to agonists reduces the number, but not their response. Results in tachyphylaxis.
down regulation
47
Chronic depletion of catecholamines or use of antagonists increases the number of receptors, but not their SENSITIVITY. May account for withdrawal syndrome with beta blockers.
Up Regulation
48
OCCURS RAPIDLY. Inability of the receptor to bind G protein (alter the function of the receptor)
Receptor uncoupling
49
OCCURS more SLOWLY. Movement of receptors from the cell surface to intracellular compartments.
Sequestration
50
Rapidly diminishing response to successive doses of a drug, rendering it less effective. The effect is common with drugs acting on the nervous system
Tachyphylaxis
51
T/F There is a residual basal activity of the ANS
TRUE
52
Uncontrolled release of catecholamines due to an adrenal gland tumor that results in constant SNS stimulation
pheochromocytoma
53
Catecholamines are considered both _______ and _________
neurotransmitters and hormones
54
Catecholamines act on _______ receptors
adrenergic
55
Catecholamines have both the ____ and ____ group
catechol and amine
56
Sympathomimetics, which means they mimic the SNS, they do not all have to be _________.
catecholamines
57
Sympathomimetics are classified according to their selectivity for stimulating ____ and/or _____ receptors
alpha / beta
58
INDIRECT-ACTING sympathomimetics are considered synthetic ___________. They work by causing release of endogenous neurotransmitter _________ from ______sympathetic nerve endings
non-catecholamines / norepinephrine / postganglionic
59
DIRECT-ACTING sympathomimetics are ________ and ________
catecholamines and synthetic non-catecholamines
60
All sympathomimetics are derived from __________
B-phenylethylamine
61
Presence of hydroxyl groups on the 3 and 4 position of the benzene ring of the B-phenylethylamine creates a catachol. Drugs with this composition are _______
catecholamines
62
Sympathomimetics are most often used as _____ ________ to improve cardiac contractility OR ________ to elevate blood pressure from unacceptable low levels.
positive inotrope / vasopressor
63
The only time a vasopressor should be used is when the patient's blood pressure must be increased __________ to avoid pressure-dependent reductions in organ perfusion with subsequent ischemia
immediately
64
Other uses for sympathomimetics
treatment of brnochospasm in the asthmatic patient, management of anaphylaxis, addition to local anesthetic to slow systemic absorption of local anesthetic from site of infiltration or injection
65
Metabolism of Catecholamines: All drugs containing the 3,4 dihydroxybenzen (catecholamines) structure are rapidly inactivated by ____ and ______
MAO and COMT
66
Monamine oxidase (MAO) is an enzyme present in liver, kidneys, GI tract that ________ oxidative deamination
catalyzes
67
Catechol-o-transferase (COMT) ________ the hydroxyl group of catecholamines
methylates
68
Reupatake of catecholamines: Inhibition of this uptake mechanism produces a greater potentiation of effects of ________ than does inhibition of either enzyme (MAO or COMT)
Epinephrine
69
Non-catecholamines are only metabolized by ______
MAO
70
Synthetic non-catecholamines are not involved in _______
reuptake
71
Metabolism of non-catecholamines: Since they lack a 3-hydroxyl group they are not metabolized by ______. They are dependent on _______ for metabolism. Metabolism is often _______ than that of catechols. Therefore, inhibition of MAO may PROLONG their DOA. Patients on MAO inhibitors may manifest exaggerated responses when treated with SYNTHETIC NON-CATECHOLAMINES
COMT / MAO / Slower
72
T/F Parkinson's patients may be on MAOB inhibitors and PTSD patients as well may be on TCAs which are MAO inhibitors so may have exaggerated responses to synthetic non-catecholamines
TRUE
73
Reflex changes from vasoconstrictors
decreasede HR, Decreased conduction, occasionally decreased contractility
74
If the heart feels like it is pumping against a high pressure, you may see a reflex of _______
decreased HR
75
Vasoconstrictors non-cardiac effects
bronchodilate, glycogenolysis, insulin, renin, pituitary hormone, CNS stimulation
76
Risk of end organ damage and mortality increases with time. So MAP <65 when can we see end organ damage?
13-28 minutes
77
MAP <50 for how long will usually result in end organ damage?
1 minute
78
Other indications for vasoconstrictors include anaphylactic shock, intracardiac __ to ___ shunts, and hypovolemia after adequate fluids
R to L
79
Vasoconstrictors contraindications / complications
Can worsen LV faliure, Can exacerbate RV failure, can decrease renal blood flow, can mask hypovolemia
80
Natural catecholamines
epi, norepi, dopamine
81
Epinephrine is a natural catecholamine that stimulates what?
alpha-1, beta-1, beta-2 receptors
82
Most potent activator of Alpha-1 receptors and is 2-10x more potent than norepi
epinephrine
83
______ has the most potential for side effects because it stimulates everything
epi
84
T/F Norepinephrine at any dose stimulates alpha-1
TRUE
85
Epinephrine ______ lipolysis and glycogenolysis, and _______ secretion of insulin
increases / inhhibits
86
Epi decreases renal blood flow even in the absence of changes in ________. It is a potent renal vasoconstrictor which relates to it's _____ effect. It also stimulates _____ release (indirect effect)
systemic BP / alpha-1 / renin
87
Low dose Epi (1-2 mcg/min)
stimulate alpha-1 receptors in the skin, mucosa, and hepatorenal system while Beta-2 receptors are stimulated in skeletal muscle.
88
Low dose Epi (1-2 mcg/min), Beta-2 effects in peripheral vasculature _________. The net effect is decreased SVR and distribution of blood to skeletal muscle. MAP essentially ______
predominates / stays the same
89
Intermediate dose epi (4mcg/min)
BETA-1 / increases HR and contractility and increases CO. Increased automacity may lead to dysrrhythmias
90
High dose epi (>10mcg/min)
ALPHA-1
91
_____ is the most potent activator of alpha-1 receptors. At high doses (>10mcg/min) it is a potent vasoconstrictor including cutaneous, splanchninc and renal vascular beds. No significant effect on _____ ______. Used to maintain myocardial and cerebral perfusion. _______ bradycardia can occur
epi / cerebral arterioles / reflex
92
Only __ to __% of anything inhaled actually makes it into the lungs and subsequentally the blood stream
12 to 15%
93
Racemic epi is a mixture of levo- and dextrorotary isomers that constrict edematous mucosa. It is used to treat severe _____ and post extubation or traumatic airway ______.
croup / edema
94
Racemic epi treatment lasts ___ to ____ and should observe the patient for ___ after treatment to watch for rebound
30 to 60 min / 2 hours
95
Epinephrine side effects
hyperglycemia, mydriasis, platelet aggregation, sweating, headache, tremor, nausea, arrhythmias
96
With epinephrine there are no CNS effects noticed with initial doses but tremors, shakiness, and jitters after _________ use.
prolonged
97
Looks and smells like EPI, but it's really beta-1 light, get improved CO, improved contractility, and maintain conduction velocity, but not a significant change in HR
Norepinephrine
98
Endogenous catecholamine that is responsible for maintaining BP by adjusting the SVR. It Increases systolic, diastolic and MAP.
Norepinephrine
99
Norepinephrine is a potent vasoconstrictor or renal, mesenteric and cutaneous vascular beds. Ths vasoconstriction may _______ renal blood flow and cause _______. May lead to mesenteric ______. Peripheral hypoperfusion can lead to _______ of digits.
decrease / oliguria / infact / gangrene
100
Norepi alpha and beta effects
primarily alpha-1 Agonist | Beta-1 effects are overshadowed by its Alpha-1 effects | Beta-2 effets are minimal to none
101
With norepi, CO may increase at ____ doses. _______ doses may decrease CO because of increased afterload and baroreceptor-mediated reflex bradycardia and could result in refractory hypotension
low / high
102
T/F there are case reports of tachyphylaxis with norepinephrine when used for a long time
TRUE
103
T/F Norepi has more metabolic effects than epi
FALSE, It has LESS metabolic effects than epi and they are only seen at larger doses
104
Review slides 60-63
Cardiac effects of Epi vs. norepi
105
Dopamine: Beta and Alpha receptor effects (10-20 mcg/kg/min)
At doses over 5 mcg/kg/min causes NE to be released contributing to cardiac stimulation (precursor). At doses over 10 mcg/kg/min ALPHA effects start to predominate.
106
With Dopamine, at doses of >20 mcg/kg/min, it is mainly ______ receptor effects
alpha
107
Dopamine has no effect on ________ status. Dopamine given IV does not cross the ______. Increased mania, decreased schizophrenia, ADHD, and PD, so monitor mental status
pulmonary / BBB
108
Synthetic noncatecholamine with direct and indirect actions. Principle effect is indirect. It works on both alpha-1 and beta receptors.
ephedrine
109
With epehdrine, ______ stimulatioin may evoke arrhythmia, particularly in a sensitized myocardium.
beta
110
Ephedrine relies primarily on _______ for metabolism.
MAO
111
Alpha-1 effects of ephedrine is coming from the release of ______ from storage vessicles in the CNS
Norepi
112
The principle mechanism of ephedrine is increased _______ ______
myocardial contractility
113
Epehedrine causes _________ greater than ___________ constriction which increases preload and with increased HR and myocardial contractility, it increases CO (beta-1 receptor action). IT INCREASES SBP AND DBP as a result.
venoconstriction / arteriolar constriction
114
With ephedrine, _________ can occur. Can start having negative feedback at alpha-2 receptors and will stop the release of _________.
Tachyphalxis / norepinephrine
115
Ephedrine preserves or _______________ uterine blood flow
increases
116
Ephedrine is also a bronchial smooth muscle _______
relaxant
117
Ephedrine dose is 2.5-25 mg IV. What is the onset and duration?
onset 1 min | Duration: 5-10 min
118
PO dose of ephedrine
25-50 mg PO or IM
119
Ephedrine is like ________, but BP response is less intense and lasts LONGER
epi
120
E-meds are everything
epi and ephedrine hit everything
121
Side effects of epehedrine
HTN, insomnia, urinary retention, headache, weakness, tremor, palpitations, psychosis
122
Synthetic non-catecholamine that is a direct alpha-1 agonist
phenylephrine
123
Increases PVR when CO is adequate
phenylephrine
124
May be used to improve coronary perfusion pressure without chronotropic side effects
phenylephrine
125
T/F Phenylephrine is ok to use in pregnant patients
TRUE
126
Other uses for phenylephrine
drug induced priapism, mydriatic agent, nasal decongestant
127
Phenylephrine causes a reflex _______. Decreases renal and _______ blood flow. Increases ________ artery resistance and pressure. NO DYSRRHYTHMIAS as a direct effect.
bradycardia / splanchnic / pulmonary
128
Phenylephrine dose, onset, duration, infusion
dose: 50-100 mcg bolus or drip | onset: 1-2 min | duration: 5-10 min | infusion: 10-20 mcg/min
129
Phenylephrine is like ________ but less potent and longer lasting
norepinephrine
130
Onset of epi and norepi is _________ while onset of ephedrine and phenylephrine is ______.
immediate / 1-3 min
131
Duration of epi and norepi is ______ while ephedrine is_____ and phenylephrine is ________
5-15 min / 15-20 min / 10-20 min
132
Review slide 76
chart comparison of catecholamines
133
Arginine vasopressin is formerly known as
ADH
134
Posterior pituitary hormones
AVP (arginine vasopressin), DDAVP, Oxytocin
135
Review potency on slide 79
Appears DDAVP is most potent
136
Vasopressin has vasopressor effects as well as _____ effect
antidiuretic
137
Vasopressin stimulates V1a receptors causing intense _______ ________
arterial vasoconstriction
138
Vasopressin in the renal collecting ducts increases the permeabilty of cell memranes resulting in the passive reabsorption of water which is the ____ effect
V2
139
Used to PRESERVE cardiocirculatory homeostasis in patients with advanced vasodilitory shock
vasopressin
140
Patients who have failed of resistant to conventional vasopressor therapy may benefit from _________
vasopressin
141
Unlike catecholamines, effects of arginine vasopressin are preserved during _____ and severe ______
hypoxia and severe acidosis
142
Studies mention that when someone is acidotic and hypoxic, __________ still works so consider using it first
vasopressin
143
In animal studies, vasopressin is associated with
better blood flow to vital organs, bettery delivery of cerebral oxygen, better chance of resuscitation and better neurologic outcome HOWEVER, human data is lacking
144
Catecholamines may not work well in an acidic environment associated with ____
CPR
145
EPI increases myocardial oxygen consumption which can contribute to risk of developing post-resuscitation _____ and arrhythmias
MI
146
Vasopressin is at least effective as ____, may have fewer adverse side effects than ____, and therefore is a reasonable alternative to _____ in the treatment of cardiac arrest
Epi / epi / epi
147
Cardiac dysrhythmias from vasoconstrictors is usually from _____ stiimulation
beta
148
Pure alpha agonsists can activate _______ and possible decrease CO
baroreceptor reflex-mediated bradycardia
149
Antihypertensives may decrease the pressor response to _______ acting drugs OR enhance the response to _______ acting drugs (denervation hypersensitivity)
indirect / direct
150
TCAs and MAOIs increase the availability of endogenous __________. Exaggerated response with ______ acting agents.
norepi / indirect
151
With TCAs and MAOIs interacations with vasoconstrictors will be worse in the first 14-21 days of therapy and then a ________ __________ of receptors occurs.
down regulation
152
With someone on TCAs and MAOIs what vasoconstrictors would you use?
It's okay for them to continue their meds but you would use a DIRECT acting drugs at a DECREASED dose
153
_______ is the primary way we get rid of our catecholamines.
reuptake
154
Make sure you use combo agents with both alpha and beta blockade for someone with cocaine use. What are examples of these drugs?
coreg and labetolol
155
Cocaine facts
interferes with reuptake of catecholamines. Both exogenous and endogenous catecholamines exhibit enhanced effects. Produces central and peripheral sympathetic stimulation, resulting in vasoconstriction, tachycardia, and potentially and arrhythmias. Acute toxicity may best be mananged with adrenergic blockade (labetolol with alpha and beta effects)
156
How long before surgery should ephedrine or pseudoephedrine be stopped
at least 24 hrs prior to surgery
157
Treatment for extravasation
phentolamine
158
Alpha 1 and 2 agonist. It is a peripheral vasodialtor that treats skin necrosis secondary to norepi, epi and dopamine.
phentolamine
159
Giapreza AKA
Angiotensin II
160
Increases blood pressure in adults with septic shock or other distributive shock who do not adequately respond to available therapies.
Giapreza
161
Increases aldosterone and causes to hold on to fluids and increases BP. Used when failing norepi, vasopressin, and full of fluids. However this is a last resort and can cause >10% chance of DVT, arterial thrombosis, and prophylactic treatment for blood clots should be used.
Giapreza
