Cardiovascular drugs Flashcards
(224 cards)
1
Q
BP =
A
CO x TPR
2
Q
A pipe problem insinuates what type of issue with BP?
A
TPR
3
Q
A pump problem implies what type of issue with BP?
A
CO
4
Q
If your BP was low due to poor TPR, what drug class would be the best remedy?
A
Vasopressors
5
Q
If your BP was low due to poor CO, what drug class would you use to remedy the problem?
A
Inotropes
6
Q
By what means do inotropes increase CO to increase BP?
A
They improve contractility.
7
Q
By what means do vasopressors increase TPR (SVR) to increase BP?
A
They increase vascular tone.
8
Q
How does vasodilation affect cardiac filling pressures?
A
Vasodilation decreases cardiac filling pressures.
9
Q
How does cardiac failure affect filling pressures?
A
Cardiac failure increases filling pressures.
10
Q
By what means does spinal/epidural anesthesia cause hypotension?
A
They wipe out the SVR.
11
Q
If your patient is undergoing an AAA and their CVP doubles during surgery, what do you suspect?
A
The heart is failing, and the CVP is likely increasing due to some kind of backup in flow.
12
Q
How would spinal/epidural administration affect CVP?
A
Spinals and epidurals decrease SVR, which decreases cardiac filling pressures (therefore manifesting as a decrease in CVP).
13
Q
How does calcium aid in causing muscular contraction in the heart?
A
Ca++ binds to troponin-C, a protein that sits on the surface of tropomyosin. Once troponin is bound, there is a conformational shift that allows the removal of tropomyosin from the actin surface. Once actin is exposed, myosin can bind to it. This is called cross-bridge cycling.
14
Q
Where is intracellular Ca++ stored?
A
In the sarcoplasmic reticulum
15
Q
The sarcoplasmic reticulum is in contact with the cell membrane via:
A
T-tubules
16
Q
What spurs Ca++ release from the SR?
A
Electrical signals enter the SR from the cell membrane via T-tubules, exciting the SR and spurring the release of Ca++ into the cell. Ca++ release is a positive feedback loop in that the initial release of Ca++ encourages further release of Ca++ within the cell.
17
Q
How does intracellular Ca++ reenter the SR to be stored?
A
Via nonvoltage-dependent Ca++ channels called ryanodine receptors
18
Q
What are ryanodine receptors?
A
Nonvoltage-dependent Ca++ channels on the surface of the SR that regulate the reentry of Ca++ into the SR
19
Q
When does relaxation of the cardiac tissue occur?
A
Relaxation takes place when Ca++ is pumped back into the SR via ATPase
20
Q
What enzymes allow Ca++ to be pumped back into the SR through ryanodine receptors?
A
ATPase
21
Q
Ca++ is not only pumped back into the SR after contraction; it is also pumped out of the cell. What mechanism is responsible?
A
Ca++ is pumped out of the cell via Na+/K+ ATPase and Na+/Ca++ exchange
22
Q
What two processes remove Ca++ to the extracellular space?
A
First, Na+ is pumped into the cell via Na+/K+/ATPase pump. Then Ca++ is pumped out of the cell along with Na+ via Na+/Ca++ exchange.
23
Q
What defines inotropy?
A
The quantity of intracellular Ca++
The maximum amount of tension the heart can develop
24
Q
What term relates to the maximal amount of tension the heart can develop?
A
Inotropy
25
What term relates to the quantity of Ca++ within the cardiac cell?
Inotropy
26
What term relates to the rate of Ca++ delivery?
Chronotropy
27
What term relates to the rate of contraction?
Chronotropy
28
What is chronotropy?
The rate of contraction defined by the rate of Ca++ delivery
29
What is lusitropy?
The rate of muscle relaxation defined by the removal of intracellular Ca++
30
What term relates to the removal of intraceullar Ca++?
Lusitropy
31
What term relates to the rate of muscle relaxation?
Lusitropy
32
What determines the rate of contraction?
The rate of Ca++ delivery
33
What determines the rate of relaxation?
The rate of intracellular Ca++ removal
34
What determines the maximal tension that can develop in the heart?
Quantity of intracellular Ca++
35
What molecule is an important second messenger in muscle contraction?
cAMP
36
How will an increase in cyclic AMP affect muscle contractility?
It will increase intracellular Ca++ release, which increases contractility.
37
What role does cyclic AMP play in contractility?
cAMP is a second messenger that spurs SR to release Ca++.
38
What receptors are known as "effectors of SNS"?
Adrenergic receptors
39
Medications that work by activating adrenergic receptors are known as:
sympathomimetics
40
What effect is mediated by alpha 1 receptors?
Vasoconstriction
41
Alpha 1 receptors mediate what effect?
Vasoconstriction
42
What class of adrenergic receptors are involved in vasoconstriction?
Alpha adrenergic receptors
43
Which alpha adrenergic receptors are involved in inhibition of presynaptic NE release?
Alpha 2 receptor
44
Effects of alpha 2 receptor activation include
Vasoconstriction
| Inhibition of presynaptic NE release
45
T/F: alpha 1 adrenergic receptor activation inhibits presynaptic release of NE.
False; alpha 2 action
46
T/F: alpha 2 adrenergic receptors are strictly involved in vasoconstriction.
False; alpha 2 receptor activation causes vasoconstriction, but it also causes inhibition of NE release.
47
Effects of beta 1 receptor activation?
Increased myocardial chronotropy + inotropy
48
What class of adrenergic receptors increase myocardial inotropy when activated?
Beta receptors
49
Activatation of B1 receptors causes:
Increased myocardial chronotropy + inotropy
50
Activation of which beta receptor causes increase in myocardial chronotropy?
B1 receptor
51
Which type of adrenergic receptor is involved in vasodilation in vessels and lungs?
B2
52
B2 causes vasodilation in:
vessels and lungs
53
T/F: alpha2 receptors cause vasodilation.
False; alpha2 receptors causes vasoconstriction. B2 receptors cause vasodilation in vessels and lungs.
54
What type of beta receptor acts strictly on the heart?
B1 receptors
55
What does it mean to say that B1 receptor activation increases myocardial chronotropy and inotropy?
It increases HR + contractility of the heart.
56
If you wanted to fix a "pump" problem, you would adminster a drug that worked on which variety of adrenergic receptor?
Beta
57
If you wanted to fix a "pipe" problem, you would adminsiter a drug that worked on which variety of adrenergic receptor?
Alpha
58
T/F: both B1 and B2 serve to increase HR.
True.
59
What types of drugs activate alpha and beta adrenergic receptors?
Sympathomimetics
60
T/F: All clinically used catecholamines work via adrenergic receptors and are therefore sympathomimetics.
True
61
Are catecholamines sympathomimetics?
All of the catecholamines that we use in the clinical setting are sympathomimetics.
62
What two structures make up a catecholamine?
Catechol ring + ethylamine tail
63
Ethylamine + catechol =
Catecholamine
64
T/F: catecholamines are made up of an ethylamine ring and a catechol tail.
False: catechol ring and ethylamine tail
65
The ethylamine tail of a catecholamine has wait nitrous molecule attached to it?
NH2
66
T/F: All catetcholamines are endogenous.
False; some catecholamines are synthetic.
67
Are catecholamines endogenous or synthetic?
Both.
68
Are all sympathomimetics catecholamines?
No, but for our purposes, all catecholamines are sympathomimetics.
69
Name some examples of endogenous catecholamines:
Norepi, epi, dopamine
70
Name some examples of synthetic catecholamines:
Isoproteronol
| Dobutamine
71
All catecholamines work via what type of receptor?
Adrenergic receptor
72
Mechanism of action of beta agonists?
Beta agonists bind to beta receptors on the cell membrane, stimulating adenylyl cyclase. Activated adenylyl cyclase then converts ATP to additional cAMP, enhancing Ca++ release from the SR and increasing contractility.
73
By what means do beta agonists increase contractility (inotropy) in the heart?
Beta agonists bind to beta receptors, activating adenylyl cyclase and triggering synthesis of cAMP from ATP. Increased concentrations of cAMP encourages higher amounts of Ca++ release from SR, increasing contractility.
74
What is the primary method of activating beta receptors?
Catecholamines
75
What catecholamines act as beta agonists?
Epi, norepi, dobutamine, and isoproteronol
76
T/F: epinephrine is the most clinically effective beta agonist.
False; no B-agonist has been proven to be more effective than another.
77
T/F: epinephrine activates alpha and beta receptors equally.
True.
78
What must you keep in mind when choosing to treat with catecholamines.
Each catecholamine will effect alpha and beta adrenergic receptors differently, so you must decide which effects you want and which you must avoid.
79
What is an appropriate rate for a norepi drip?
1-20 mcg/min
80
What is an appropriate rate for a dopamine drip?
2-20 mcg/kg/min
81
What is an appropriate rate for an epinephrine drip?
1-20 mcg/min
82
What is an appropriate rate for a dobutamine drip?
2-10 mcg/kg/min
83
What is an appropriate rate for an isoproterenol drip?
1-5 mcg/min
84
Which catecholamine drips are weight dependent?
Dobutamine
| Dopamine
85
1-20 mcg/min
Epi or norepi
86
2-20 mcg/kg/min
Dopamine
87
2-10 mcg/kg/min
Dobutamine
88
1-5 mcg/min
Isoproterenol
89
Which catecholamine is a strong non-selective beta agonist with no effects on alpha?
Isoproterenol
90
Does isoproterenol have greater affinity for B1 or B2 receptors?
Equally strong affinity for both
91
Isoproterenol only works on what type of adrenergic receptors?
Beta
92
Based on receptor activation, what type of drug is norepi?
A vasopressor and an inotrope
93
Is norepi a stronger vasopressor or a stronger inotrope?
A stronger vasopressor
94
Which catecholamine has no B2 effects, meaning it does not cause vasodilation in the lungs or vessels?
Norepi
95
Which catecholamine has an equally strong effect on beta 1, beta 2, and alpha 1 receptors?
Epi
96
Which inotropes also have vasopressive effects? Which is stronger in that regard?
Dopamine + dobutamine; dopamine is a stronger vasopressor than dobutamine
97
Name some adverse effects of norepinephrine.
Norepi acts on B1 and A1 receptors. Its strong effects on A1 receptors can increase SVR so much that CO decreases.
98
Which catecholamine is the agent of choice in anaphylaxis?
Epi
99
Which catecholamine is prone to causing arrythmias?
Epi
100
T/F: norepi is arrhythmogenic.
False; epi is arrhythmogenic.
101
Which catecholamine is largely indirectly acting?
Dopamine: mild inotrope and moderate vasopressor
102
Which catecholamine is prone to causing moderate tachycardia?
Dobutamine
103
Dobutamine may cause:
moderate tachycardia
104
Which catecholamine is prone to causing severe tachycardia, arrhythmias, and decreased SVR?
Isoproteronol. It is a strong beta agonist, which may increase HR to the point of arrhythmia and decreased SVR.
105
Adverse effects of isoproteronol:
Severe tachycardia
Arrhythmias
Decreased SVR
106
What do phosphodiesterases do?
They break down cyclic nucleotides like cAMP and cGMP.
107
T/F: phosphodiesterases only break down cAMP.
False; break down cGMP as well
108
What are cyclic nucelotides?
Second messengers that activate protein kinases and open ion channels.
109
What do cyclic nucleotides open? What do they activate?
Open ion channels
| Activate protein kinases
110
If cyclic nucleotides activate protein kinases and open ion channels, what do phosphodiesterases do?
They break down cyclic nucleotides and therefore prevent the activation of protein kinases to open ion channels.
111
How many PDE families are known?
11
112
T/F: PDE families include a vast number of cell types.
True.
113
Name three common PDE III inhibitors.
Amrinone
Milrinone
Enoximone
114
What type of drug is amrinone?
PDE III inhibitor
115
What type of drug is milrinone?
PDE III inhibitor
116
What type of drug is enoximone?
PDE III inhibitor
117
Enoximone is a:
PDE III inhibitor
118
Milrinone is a:
PDE III inhibitor
119
Amrinone is a:
PDE III inhibitor
120
Loading dose of amrinone?
Infusion rate?
Duration?
LD: 1 mg/kg
IR: 2-10 mcg/kg/min
Duration: 2 hours
121
Loading dose of milrinone?
Infusion rate?
Duration?
LD: 0.05 mg/kg
IR: 0.5 mcg/kg/min
Duration: 30 minutes
122
Loading does of enoximone?
Infusion rate?
Duration?
LD: 0.5 mg/kg
IR: 10 mcg/kg/min
Duration: 1 hour
123
Which PDE III inhibitor is excreted by the liver?
Enoximone
124
Enoximone is excreted by the
liver.
125
Where do Ca++ sensitizers work?
Work on the interaction of troponin and Ca++ or the response of the myofilaments to Ca++ binding
126
What is the major benefit to using Ca++ sensitizers instead of catecholamines or PDE inhibitors?
Ca++ sensitizers do not increase intracellular Ca++ levels, so they are less arrythmogenic and do not increase O2 consumption.
127
PDE family 1 is found where? What do they regulate?
They are found in smooth muscle cells, likely regulating proliferation in vascular tissue.
128
Which family is found in smooth muscle cells? What is its action there?
PDE 1
| Likely regulates proliferation in vascular tissue
129
PDE family 3 is found where?
Type A is found in CV system and platelets.
| Type B is found in liver/adipose and may be activated by insulin.
130
Which PDE family is of most interest for this topic?
PDE 3, Type A
131
Where is Type A PDE 3 family found?
CV system + platelets
132
Where are PDE 4 found?
In inflammatory cells
133
Which PDE family may play a role in COPD and arthritis?
PDE 4
134
What is the most prominent family of PDE? Where are they found?
PDE 5; found in the penis
135
T/F: PDE inhibitors work synergistically with B agonists.
True
136
T/F PDE inhibitors work synergistically with B antagonists.
False; work synergistically with B agonists
137
Effects of PDE inhibitors in cardiac myocytes?
They inhibit the breakdown of cAMP, which increases cAMP concentrations to increase Ca++ release to incrase contractility.
138
T/F: PDE inhibitors have effects both in cardiac myocytes and in vascular tissue.
True
139
What are the effects of PDE inhibitors in vascular tissue?
Increase cyclic nucleotides to cause smooth muscle relaxation
They decrease PA pressures and decrease SVR
140
PDE inhibitors are known as
inodilators because of their inotropic effects in the heart and their vasodilator effects in vascular tissue
141
Effect of PDE inhibitors on PA pressures?
Decrease PA pressures
142
What class of drug is effective in management of pulmonary hypertension?
PDE inhibitors
143
What effects do PDE inhibitors have on SVR
Increased cyclic AMP in vascular tissue causes smooth muscle relaxation and decreases SVR
144
T/F: PDE inhibitors have a strictly inotropic effect.
False
145
By what PDE family do PDE inhibitors cause vasodilation?
PDE 3
146
Conventional inotropes are known as:
Ca++ mobilizers
147
T/F: Ca++ sensitizers increase O2 consumption.
False; they do not increase the amount of Ca++ in the cell, so they do not add any work to the cell
148
What are the benefits to the fact that Ca++ sensitizers do not increase Ca++ levels in the cell?
Less arrhythmogenic
| Do not increase O2 consumption
149
Any drug that ends in "-endan" is a:
Ca++ sensitizer
150
Name two Ca++ sensitizers.
Pimobendan
| Levosimendan
151
Which Ca++ sensitizer is used as a longterm treatment for CHF?
Pimobendan
152
Pimobendan is used as a long term treatment for
CHF
153
T/F: Levosimendan increases troponin-C affinity to Ca++.
False; it does nothing to affect affinity of Ca++ to Troponin C; instead, it binds to Troponin C to stabilize the troponin/Ca++ conformational change
154
How does Levosimendan aid in contractility?
It binds to troponin in a Ca++-dependent manner and stabilizes the troponin/Ca++ conformational change
155
How do Ca++ levels affect action of levosimendan?
The more Ca++ present, the more stabilizing activity of levosimendan.
156
Which increases O2 consumption more, milrinone or levosimendan.
Levosimendan does nothing to increase Ca++ levels in the cell, so it does not increase O2 consumption as much as milrinone, a PDE III inhibitor.
157
What is the overall goal of vasopressors?
To increase SVR
158
Two groups of vasopressors?
Non-catecholamines
| Catecholamines
159
Within the vasopressor realm, what are the two kinds of non-catecholamines?
Sympathomimetics
| Non-sympathomimetics
160
T/F: cAMP is an important second messenger for alpha receptors within the vasculature.
F; cAMP is only significant in myocardial activity.
161
What is the second messenger for alpha receptors on vasculature?
IP3-DAG pathway
162
By what means does A1 receptor activation increase intracellular Ca++ concentration? What is the effect?
Activation triggers the IP3-DAG pathway, which increases Ca++ concentration and causes smooth muscle relaxation.
163
A1 receptors are present where?
On systemic and pulmonary vasculature
164
A1 receptors are present on what vasculature?
Systemic and pulmonary
165
What catecholamine has the most prominent affects on A1 receptors?
Norepi
166
Which catecholamine has greater effects on A1 receptors, dopamine or epi?
They have equal effects
167
Which catecholamine has no effect on alpha 1 receptors?
Isopropenterol
168
Name two non-catecholamine sympathomimetics:
Phenylephrine
| Methoxamine
169
What type of drug is phenylephrine?
Pure, direct acting a agonist
170
Is phenylephrine a catecholamine?
No, it is a non-catecholamine
171
IV bolus of phenylephrine?
Time of onset?
Duration?
Infusion rate?
Bolus: 1-2 mcg/kg
Onset: 30 s
Duration: 2-3 minutes
IR: 25 - 100 mcg/min
172
Is the phenylephrine drip rate weight-dependent?
No, it is 25-100 mcg/min.
173
What type of drug is methoxamine?
Pure, direct acting A agonist
174
T/F: methoxamine is a catecholamine.
False; it is a non-catecholamine.
175
Bolus of methoxamine?
Onset?
Duration?
Bolus: 5-10 mg
Onset: 1 minute
Duration: 5-10 minutes
176
Which is longer acting, phenylephrine or methoxamine?
Methoxamine
177
What type of drug is ephedrine?
An indirect acting alpha agonist
| A non-catecholamine sympathomimetic
178
Which non-catecholamine sympathomimetic causes NE release from neurons?
Ephedrine
179
Issue with chronic use of ephedrine?
Ephedrine prevents the reuptake of NE into neurons via granules yet perpetuates the release of NE from neurons. Therefore, NE stores are eventually depleted.
180
T/F: ephedrine has no beta activity.
False; it has very little beta activity, but it does have beta activity.
181
What inactivates ephedrine in the liver?
MAO in liver inhibits ephedrine.
182
What inactivates ephedrine in the liver?
MAO
183
What population group may experience prolonged effects of ephedrine? Why?
Those who are on MAO inhibitors (anti-depressants) because MAO inactivates ephedrine in the liver; without that inactivation step, expect a prolonged effect.
184
How is ephedrine excreted?
40% is excreted unchanged in the urine
185
What percentage of ephedrine is excreted unchanged in the urine?
40%
186
Ephedrine is contraindicated in what patient population?
Those on MAO inhibitors, a type of antidepressant.
| Prolonged effect of ephedrine could deplete NE stores.
187
What type of drug is vasopressin?
A non-sympathomimetic vasopressor
188
T/F: vasopressin has strong alpha adrenergic activity.
False; it works on V recepors
189
Does vasopressin utilize alpha receptors?
No
190
Name a drug that is a non-sympathomimetic vasopressor.
Vasopressin
191
By what means does vasopressin cause vasoconstriction?
Activation of V1 receptors
192
Which drug acts on V1 receptors? What is the action of V1 receptors?
Vasopressin
| V1 receptors release Ca++ to cause SM contraction
193
Second messenger in vasopressin mechanism of action?
DAG-IP3
194
What types of drugs utilize DAG-IP3 as a second messenger?
Those that work on alpha receptors and v-receptors.
195
Where are V1 receptors located? V2? V3?
V1: vascular smooth muscle
V2: kidneys
V3: CNS
196
Where are V2 receptors located? Their activation results in?
Located in the kidney.
| Activation results in increased water permeability and dilatation of renal endothelium
197
Activation of what V receptor results in increased water retention and dilalation of renal endothelium?
V2 receptors
198
Activation of what V receptor results in increased ACTH release?
V3
199
Where are V3 receptors located?
Pitutarity gland (CNS)
200
T/F: the principle role of vasopressin is regulation of vascular tone.
False; more important effects in V3 and V2 receptors than in V1 receptors.
201
Physiological level of vasopressin the body:
5-10 pmol/L
202
What disorder can cause vasopressin levels to double or triple in the body?
Onset of sepsis
203
Affect of onset of sepsis on vasopressin levels?
Doubles/triples
204
What happens to vasopressin levels as sepsis continues (no longer onset phase)?
Vasopressin levels decrease dramatically to 1/3 of normal levels.
205
What is a proper infusion rate to replace vasopressin the event of prolonged sepsis or CPB?
4-6 units/hr infusions
206
When might you give your patient a vasopressin drip of 4-6 units/hr?
In the event of prolonged sepsis or CPB
207
Where are alpha receptors located?
In periphery and in lungs
208
Vasopressin causes intense vasoconstriction. What are some risks that comes with that?
Myocardial ischemia
Decreased CO
Mesenteric ischemia
Digital necrosis
209
Why might vasopressin be beneficial in the case of pulmonary HTN?
Its effects are less severe in pulmonary vasculature because V receptors are not in the lungs
210
What may you give if your patient's MAP is below 50 mmHg and they are on a norepi drip of greater than 35 mcg/min?
Methylene blue
211
Methylene blue may treat what problem associated w/ high rates of norepi infusion?
Refractory vasodilation
212
Why does a norepi infusion cause refractory vasodilation?
It has strong alpha effects
213
T/F: methlyene blue may be administered in the event that your patient has very low MAPs with a high infusion rate of norepi, but only as a rescue measure.
True.
214
Why is methylene blue effective in the treatment of refractory vasodilation?
NO activates guanylate cyclase to increase levels of cGMP in the body and cause smooth muscle relaxation. Methylene blue inhibits guanylate cyclase, preventing the proliferation of cyclic nucelotides.
215
Methylene blue inhibits:
guanylate cyclase
216
Guanylate cyclase is inhibited by:
Methylene blue
217
To treat refractory vasodilation, what bolus dose of methylene blue should you give?
Over what amount of time?
Bolus: 1.5 - 2 mg/kg
| Give over 10-60 minutes.
218
Methylene blue adminsitration causes minimal side effects at what dose limit?
<2 mg/ kg
219
What are mild side effects you may see in your patient upon administration of methylene blue?
Transient decrease in SpO2 monitoring
| Mild skin and urine discoloration
220
High doses of methylene blue may cause:
hyperbilirubinemia + hemolytic anemia
221
What population should never receive methylene blue? Why?
Patients on SSRIs shouldn't receive methylene blue because it may cause serotonin syndrome.
222
What symptoms define serotonin syndrome?
Hypotension
Tachycardia
Hyperthermia
223
Your 24 yo patient presents with BP 65/40, HR 100, 92 SpO2, and a rash. What do you suspect? How should you treat it?
Anaphylaxis
| Treat with epinephrine.
224
High CVP indicate what issue, pump or pipe?
High CVP indicates that the heart isn't pumping like it should. Give a beta agonist to remedy.
