Vasoconstrictors Flashcards
1
Q
The sympathetic nervous system originates from where?
A
Thoracolumbar origin (T1-L2)
Preganglia near spinal cord
2
Q
Postganglia adrenergic fibers secrete what?
A
Norepinephrine
3
Q
How is norepinephrine synthesized?
A
Dopamine enters the synaptic vessel
Dopamine beta hyroxylase converts dopamine to NE
An action potential releases NE from the synaptic vessel
4
Q
What 4 things cause the signal termination of release of NE?
A
Reuptake: recycling and putting back where it came from
Dilution by diffusion
Metabolism: Monamine oxidase (MAO) and catechol-o-methyltranserase (COMT)
5
Q
What are the 4 adrenergic receptors?
A
Alpha 1: periphery (helps us in fight or flight response)
Alpha 2: central (negative feedback loop in response to agonist)
Beta 1: heart
Beta 2: other smooth muscle
6
Q
Activation of Alpha 1 postsynaptic receptor causes:
A
- Activation increases intracellular calcium
- smooth muscle contraction
- peripheral vasoconstriction
- bronchoconstriction
- inhibits insulin secretion
- stimulates glycogenolysis and gluconeogenesis
- mydriasis
- GI relaxation
7
Q
Stimulation of Alpha-2 receptors causes what -
Presynaptic in PNS
Postsynaptic in CNS
A
Presynaptic in PNS: decreases entry of calcium into the cell. Limits the release of norepinephrine
Postsynaptic in CNS: sedation, decreased sympathetic outflow, decreased BP, platelet aggregation
negative feedback loop
8
Q
Stimulation of beta 1 post-synaptic receptor causes what?
A
Increased HR
Increased conduction velocity
Increased myocardial contractility
9
Q
Stimulation of Beta 2 postsynaptic receptor causes what?
A
Smooth muscle relaxation Peripheral vasodilation Decreases BP Bronchodilation Increases insulin secretion Increases glucogenolysis and gluconeogenesis Decreases GI mobility
10
Q
The parasympathetic nervous system originates from where?
A
Craniosacral origin (III, V, VII, X)
Preganglia near organs of innervation
Postganglia secrete acetylcholine (ACh) —> cholinergic fibers
11
Q
Acetylcholine activates which arms of the ANS?
A
Both
SNS and PNS
12
Q
What makes up acetylcholine?
A
Choline + acetyl CoA
13
Q
ACh is deactivated by what
A
Acetylcholinesterase
14
Q
Acetylcholine has a __________ mediated action potential
A
Calcium
15
Q
What are the 2 cholinergic receptors?
A
Nicotinic
Muscarinic
16
Q
SNS stimulation of GI tract does what?
PNS stimulation of GI tract does what?
A
SNS: decreases motility secretions, sphincter contraction
PNS: increases motility, secretions, sphincter relaxation
17
Q
SNS stimulation of coronary arteries does what?
A
Alpha: constriction
Beta: relaxation
18
Q
SNS of skeletal muscle arterioles
A
Alpha: constriction
Beta: relaxation
19
Q
Down regulation of effector cell receptors happens why?
A
Extended exposure to agonists reduces the number, but not their response. Results on tachyphyaxis
20
Q
Up regulation of effector cell receptors is caused by what?
A
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
21
Q
T/F receptor uncoupling occurs gradually over time
A
False
Occurs rapidly
22
Q
This is the movement of receptors from the cell surface to intracellular compartments.
Occurs more slowly
A
Sequestration
23
Q
This is the movement of receptors from the cell surface to intracellular compartments, but then destroyed
A
Downregulation
Prolonged process
24
Q
This refers to residual basal activity of the autonomic system
A
Tone
25
What is pheochromocytoma?
Uncontrolled release of catecholamines due to an adrenal gland tumor - constant SNS stimulation
26
These are both neurotransmitters and hormones, and act on adrenergic receptors.
Catecholamines
27
Norepinephrine is primarily a ____________ and epinephrine is primary a __________
NE: neurotransmitter
Epi; hormone
28
These compounds resemble catecholamines except that hydroxyl groups are not present in both the 3 and 4 positions of the benzene ring
Sympathomimetics
Mimic SNS
They are classified according to their selectivity for stimulating alpha and/or beta receptors
29
What are indirect-acting sympathomimetics?
- Synthetic non-catecholamines
- Release endogenous neurotransmitter NE from postganglionic sympathetic nerve endings
*ephedrine is an example
30
What are direct-acting sympathomimetics?
Catecholamines and synthetic non-catecholamines
31
T/F: Sympathomimetics can be both naturally occurring and synthetic.
True
32
T/F: All catecholamines are sympathomimetics
True
33
T/F: All sympathomimetics are catecholamines
FALSE
Not all sympathomimetics are catecholamines
34
What are the 2 most common uses for sympathomimetics?
- positive Inotrope to improve cardiac contractility
| - vasopressor to elevate BP from unacceptable levels
35
T/F: vasopressors are first line treatment for low BP
FALSE
They are a last resort
36
What are 3 other uses of sympathomimetics?
1. Treatment of bronchospasm in the asthmatic pt
2. Management of anaphylaxis
3. Addition to LA to slow systemic absorption of LA from site of infiltration or injection
37
What influences the response evoked by the sympathomimetics?
The anatomical distribution of alpha and beta adrenergic receptors
38
Does NE have significant or minimal effects on airway resistance?
Minimal
Adrenergic receptors in bronchial smooth muscle are mostly beta-2 and thus not stimulated by this catecholamine
39
What are 2 potent bronchodilators as a result of their ability to activate beta-2 receptors?
Epinephrine
Isoproterenol
40
What 2 enzymes metabolize catecholamines?
```
Monoamine oxidase (MAO)
-enzyme present in liver, kidneys, GI tract that catalyze oxidative deamination
```
Catechol-o-transferase (COMT)
-methylated the hydroxyl group of catecholamines
**if its a catecholamine its metabolized by both, if its not a catecholamine its just metabolized by MAO
41
Does inhibition of the reuptake mechanism or inhibition of MAO and COMT cause a greater potentiation of epinephrine
Reuptake mechanism
42
The reuptake mechanism causes ________ presence of unchanged catecholamines in urine
Minimal
43
T/F: oral administration of catecholamines is effective
FALSE
Metabolism of these compounds in GI mucosa and liver before reaching systemic circulation
44
Acceptable routes of administration of epi
Sub-Q
| IV
45
Routes of administration for dopamine
IV
46
Synthetic non-catecholamines are dependent on what for metabolism?
MAO
Not metabolized by COMT bc lack a 3-hydroxyl group
47
Which is faster, metabolism of catechols or non-catechols?
Catechols is faster than non-catechols
48
Pts on MAO inhibitors may manifest ________ responses when treated with synthetic non-catecholamines
Exaggerated
49
What are 2 hemodynamic effects of vasoconstrictors?
- increase arterial resistance and afterload (increase SVR and usually MAP)
- increase venous return (increase preload and CO)
50
What are some reflex changes that can occur with vasoconstrictors?
Decreased HR
Decreased conduction
Occasionally decreased contractility
51
What are 4 non-cardiac effects of vasoconstrictors?
- Bronchodilate
- Glycogenolysis
- Insulin, renin, pituitary hormone
- CNS stimulation (low lipid solubility)
52
What are indications of use of vasoconstrictors?
Decreased arterial resistance (hypotension)
- iatrogenic
- physiologic
CPR
- restore perfusion pressure to vital organs
- used in conjunction of other appropriate cardiac drugs
Other indicators
- anaphylactic shock
- iatracardiac R —> L shunts
- hypovolemia
53
According to study in Anesthesiology - risk of end organ damage and mortality increase with time
- MAP <65 for ______________ minutes
- MAP <50 for ______________ minutes
MAP <65 for 13-28 minutes
| MAP <50 for 1 minute
54
What are 4 contraindications/compilations of vasoconstrictors?
Can worse LV failure
Can exacerbate RV failure
Can decrease renal blood flow
Can mask hypovolemia
55
What are the 3 natural catecholamines?
Epinephrine
Norepinephrine
Dopamine
56
Epi stimulates what receptors?
Alpha 1
Beta 1
Beta 2
**most potent activator of alpha 1 receptors. 2-10x more potent than NE**
EPI = everything
57
What are some uses of epinephrine?
Asthma, anaphylaxis, cardiac arrest, bleeding, and prolong regional anesthesia
58
Does epi increase or decrease lipolysis and glycogenolysis?
Increases
It also inhibits the secretion of insulin.
Can see increase in BG due to the stress of surgery
59
What does epinephrine do to renal blood flow?
It decreases renal blood flow even in the absence of changes in systemic BP
- potent renal vasoconstrictor (alpha-1 effect)
- stimulates renin release (indirect effect)
60
What happens with low doses of epi (1-2 mcg/min)?
Primarily beta-2 effects
-stimulates alpha-1 receptors in the skin, mucosa, and hepatorenal system while bets-2 receptors are stimulated in skeletal muscle
- Beta-2 effects in peripheral vasculature predominate
- net effect is decreased SVR and distribution of blood to skeletal muscle
- MAP remains essentially the same
61
What happens with intermediate doses (4 mcg/min) of epinephrine?
Primarily beta-1 effects
Increased HR and contractility and increased CO
Increased automaticity - may lead to dysrhythmias
62
What happens with high doses (>10 mcg/min) of epinephrine?
Primarily alpha-1 effects.
Potent vasoconstrictor including cutaneous, splanchnic and renal vascular beds (no significant effect on cerebral arterioles)
Used to maintain myocardial and cerebral perfusion
Reflex bradycardia can occur
63
What is the most potent activator of alpha-1 receptors?
Epinephrine
64
This is a mixture of levo- and dextrorotatory isomer that constrict edematous mucosa.
What is it used to treat?
Racemic epinephrine
Used to treat sever croup and post-extubation or traumatic airway edema
*treatment lasts 30-60 minutes. Observe for 2 hours after treatment to watch for rebound
65
What are side effects of epinephrine?
No CNS effects
Hyperglycemia, mydriasis, platelet aggregation, sweating, HA, tremor, nausea, arrhythmias
*monitor BG, RR, O2 sats, HR, and BP
66
This is an endogenous catecholamine responsible for maintaining BP by adjusting SVR.
Norepinephrine
Increases systolic, diastolic, and mean arterial pressure
67
T/F: Norepinephrine is a potent vasoconstrictor of renal, mesenteric, and cutaneous vascular beds
TRUE
- may decrease renal blood flow and cause oliguria
- may lead to mesenteric infarct
- peripheral hypoperfusion can lead to gangrene of digits
68
How does norepinephrine effect the alpha and beta receptors?
Primarily and alpha-1 agonist
Beta-1 effects are overshadowed by its alpha-1 effects
Beta-2 effects are minimal
69
How does norepinephrine affect CO?
CO may increase at low doses.
Higher doses CO may decrease because of increased afterload and baroreceptor-mediated reflex bradycardia
May see refractory hypotension
70
T/F: Norepinephrine has more metabolic effects than epinephrine
FALSE
LESS metabolic effects than epi
71
This endogenous catecholamine has similar effects as epi - different doses affect different receptors.
Dopamine
72
Is ephedrine a catecholamine?
No. It’s a synthetic noncatecholamine
73
Is ephedrine direct or indirect acting?
Principle effect is indirect - causes release of norepi from vessels.
74
What receptors does ephedrine work on?
Alpha-1 and beta receptors.
75
Ephedrine’s principle mechanism is to increase myocardial contractility. How does this occur?
Venoconstriction is greater than arteriolar constriction —> increases preload and with an increased HR and myocardial contractility, increases CO (beta-1 receptor action)
-increases SBP and DBP as a result
76
Can tachyphylaxis occur with ephedrine?
YES
77
How does ephedrine affect uterine blood flow and bronchial smooth muscle
It preserves or increased uterine blood flow
Bronchial smooth muscle relaxant
78
Side effects of ephedrine
HTN, insomnia, urinary retention, HA, weakness, tremor, palpating, psychosis
*monitor BP, pulse, UO, and mental status
79
T/F: phenylephrine is a synthetic catecholamine
FALSE
It’s a synthetic non-catecholamine
80
Phenylephrine affects what receptors?
Direct alpha-1 agonist
- increases preload > afterload
- small beta-1 effect
Increases PVR when CO adequate
May be used to improve coronary perfusion pressure with out chronotropic side effects
81
What are some other uses for phenylephrine?
Drug induced priapism
Mydriasis agent
Nasal decongestant
82
What are some side effects of phenylephrine?
Reflex bradycardia
Decreases renal and splanchnic blood flow
Increases pulmonary artery resistance and pressure
*no dysrrhythmias as a direct effect
83
Which catecholamine is phenylephrine similar to?
Like norepinephrine, but less potent and longer lasting
84
What are the 3 posterior pituitary hormones ?
1. Arginine vasopressin (formally known as ADH)
2. DDAVP (desmopressin)
3. Oxytocin (pitocin)
85
Place 3 posterior pituitary hormones in order of most to least for their antidiuretic effects, and then their vasopressor effects
Antidiuretic: DDAVP > arginine vasopressin > oxytocin
Vasopressor effects: arginine vasopressin > DDAVP > oxytocin
86
Vasopressin stimulates what receptors?
V1a: causing intense arterial vasoconstriction
V2: in renal collecting ducts —> increases permeability of cell membranes resulting in the passive reabsorption of water
87
This is used to preserve cardiocirculatory homeostasis in pts with advanced vasodilatory shock
Vasopressin
88
T/F: Effects of catecholamines are preserved during hypoxia and severe acidosis
FALSE
The effects of arginine vasopressin are preserved during hypoxia and severe acidosis
89
What are 2 advantages of vasopressin over epinephrine?
1. Epi increases myocardial O2 consumption
| 2. Catecholamines may not work well in an acidic environment associated with CPR
90
T/F: There is significant human data showing the benefit of vasopressin
FALSE
Human data lacking
91
3 Benefits of vasopressin shown in animal studies
1. Better blood flow to vital organs
2. Better delivery of cerebral oxygen
3. Better chance of resuscitation and better neurologic outcome
92
T/F: vasopressin is at least as effective as Epi, may have fewer adverse effects than Epi, and therefore is a reasonable alternative to Epi in treatment of cardiac arrest.
TRUE
93
Name 3 adverse effects/drug interaction of vasoconstrictors
1. Cardiac dysrhythmias (Beta stimulation)
2. Pure alpha agonists can activate baroreceptor reflex-mediated bradycardia and possible decrease CO
3. Antihypertensives may decrease the pressor response to indirect acting drugs, or enhance the response to direct acting drugs (denervation hypersensitivity)
94
This class of medications can increase the availability of endogenous norepinephrine
Tricyclics antidepressants and MAO Inhibitors
95
You can have an exaggerated response to direct or indirect acting agents when using tricyclic antidepressants and MAO inhibitors
INDIRECT
96
The exaggerated response to indirect acting agents while on tricyclic antidepressants and MAOI is worse in the first _______ days of therapy
14 - 21
* Ok to continue these drugs in the perioperative period.
* Use a decreased dose of direct acting drugs
97
How does cocaine effect the re-uptake of catecholamines?
It interferes with it.
Both exogenous and endogenous catecholamines exhibit enhanced effects.
Produces central and peripheral sympathetic stimulation resulting in vasoconstriction, tachycardia, and potentially arrhythmias
98
Cocaine acute toxicity is bestmanaged with what?
Adrenergic blockade
Labatelol with both alpha and beta effects
*don’t just give a beta blocker bc alpha stimulation will still be occurring.
99
This weight loss drug may contain ma huang and can cause tachyphylaxis from depletion of endogenous catecholamine stores.
Ephedra
100
This medication is given when there is extravasation of IV during administration of vasoconstrictors
Phentolamine
Alpha 1 and 2 antagonist
Peripheral vasodilator
Treats skin decors is secondary to NE, dopamine and epi
101
This drug is synthetic human angiotensin II
Giapreza
