ANS Pharmacology & Pathophysiology Flashcards
1
Q
How is phenylephrine metabolized?
A
monoamine oxidase (MAO)
2
Q
How is dexmedetomidine metabolized?
A
Liver -CYP450
3
Q
Alpha 2 agonism in the vasculature results in what?
A
Vasoconstriction
4
Q
Which receptor is responsible for inhibiting ADH (diuresis)?
A
Alpha-2
5
Q
Which receptor is responsible for decreasing insulin release from the pancreatic ___________cells.
What increases insulin secretion from these cells?
A
Alpha-2
(Islets/B-Cells)
M3 increases insulin (DM3)
6
Q
What adrenergic receptor increases platelet aggregation?
A
Alpha 2
7
Q
Agonism of which adrenergic receptors produce an antishivering effect?
A
alpha 2
8
Q
Where does dexmedetomidine produce its analgesic effects?
A
alpha-2 receptors in the dorsal horn of the spinal cord
9
Q
Alpha 2: Alpha 1 binding of clonidine vs precedex
A
clonidine 200:1
precedex 1600:1
10
Q
What happens with abrupt clonidine withdrawal?
A
Rebound HTN and tachyarrythmias
11
Q
3 Endogenous catecholamines
A
- Epi
- Norepi
- Dopamine
12
Q
What systemic effects do endogenous catecholamines have on GI tract, lungs, heart, liver, and BP
A
GI- decreased digestion
Lungs- bronchodilation
Heart- increased HR
Liver- converts glycogen to glucose
Increased BP
13
Q
Epi may cause (hyper/hypo) glycemia and (hypo/hyper) kalemia and why?
A
hyperglycemia (stimulation of B2 receptors)
hypokalemia 2nd to transcellular K shift
14
Q
Norepinephrine affects which receptors the most?
A
Alpha 1 and Beta 1
(Low doses = beta 1- increased HR, CO, inotropy, dromotropy
High doses = alpha 1 - systemic vasoconstriction [minus coronaries] and decreased HR)
15
Q
Norepi at high doses causes systemic vasoconstriction by agonizing alpha 1 receptors. Why is the baroreceptor response of bradycardia not as clinically significant as neosynephrine?
A
Because Norepi also has inherent B1 agonizing properties which limits the BRR of bradycardia secondary to alpha-1.
16
Q
Does Norepi cause elevations in glucose?
A
No- or very minimally (minimal effects at b2)
17
Q
What is 1st line therapy in distributive shock states refractory to hypotension?
A
Norepi
18
Q
Low/Moderate/High dose dopamine
-dosages and effects
A
Low 1-2mcg/kg/min : D1 receptors (vasodilation: increased renal and splanchnic blood flow)
Mod 2-10: alpha 1 & beta 1 (increased HR, contractility, and BP)
High 10-20: pure alpha 1 agonism (vasoconstriction)
19
Q
Which dopamine receptors cause direct vasodilation of the renal, GI, coronary, and cerebral blood vessels?
A
Post-synaptic D1
20
Q
Which dopamine receptors inhibit Norepi release causing systemic vasodilation?
A
Pre-synaptic D2
21
Q
3 Places D2 receptors are found
A
- Pituitary gland
- Emetic center
- Kidney
22
Q
Which dopamine receptors are responsible for inducing nausea and vomiting?
A
D2 - chemoreceptor trigger zone
23
Q
Main concern with Levophed
A
Extravasation and skin necrosis
*Central line
24
Q
How do you treat extravasation caused by Levophed? (2 ways)
A
Phentolamine (2.5-10mg diluted in 10mls) > vasodilate
(keep it simple 10mg diluted in 10mls)
Stellate ganglion block (improve blood flow to extremity
25
Where are B3 receptors primarily found and what are they primarily responsible for?
Apidose tissue - thermoregulation and lipolysis
26
What is isoproterenol derived from?
Dopamine
27
Isoproterenol is how much more potent than epi?
2-3x
28
T/F Isoproterenol has no effect on alpha receptors
True!
29
S/E's of Isoproterenol?
Hypotension (B2), SVTs and VTs
(has been largely replaced by transcutaneous or transvenous pacing for this reason)
30
How does isoproterenol work?
It agonizes B1 & B2 receptors leading to increased HR, contractility, and \*vasodilation (hypotension!)
31
What can be used for bradycardia unresponsive to atropine or in a denervated heart?
Isoproterenol
32
How does isoproterenol treat cor-pulmonale? Are there better options?
By enhancing RV contraction (B1), thereby decreasing pulmonary congestion (blood can move forward more easily with a better contracting RV + B2 bronchodilator effects)
\*NO & prostagadin I2 are better
33
What is dobutamine derived from?
Isoproterenol
34
What drug acts as a pharmacologic stress test and how?
Dobutamine
- potent B1 agonist
- increased inotropy and chronotropy
35
What 2 populations should Dobutamine be avoided in and why?
1. Active MI (could extend the MI)
2. Afib (increased conduction velocity through the AV node may trigger RVR)
36
What classification is Dobutamine?
Positive inotrope
\*Not a pressor!
\*Increase in HR, contractility, and CO
37
When is dobutamine a good choice?
Cardiogenic shock and CHF
\*coronary artery vasodilator
\*LV failure improves due to a decrease in SVR
\*RV failure improves due to a decrease in PVR - allowing forward flow)
38
Why is ephedrine considered a controlled substance in some institutions?
It crosses the BBB and has mild stimulating effects centrally
39
What is the black box warning regarding B2 agonists?
The long-acting ones can lead to asthma-related death
(Salmetrol and formoterol)
\*Long term use may lead to downregulation of beta2 receptors resulting in tachyphylaxis and may lead to a hyperresponsive airway
40
2 long-acting Beta 2- agonists
1. Salmeterol
2. Formoterol
41
3 Short-acting beta-2 agonists
1. Albuterol
2. Levoalbuterol
3. Terbutaline
42
What's the problem when people just take their rescue inhaler more instead of being put on a controller?
Increased B2 agonism over time, the B2 selectivity wanes and B1 predominates \> tachycardia and arrhythmias
43
What is the precursor of Epinephrine?
Norepi
44
What adrenergic agonist is metabolized by the liver?
Ephedrine
45
What is the precursor of Norepi?
Dopamine
46
What are the two non-selective alpha antagonists?
1. Phenoxybenzamine
2. Phentolamine
47
What alpha antagonist is used almost exclusively preoperatively to treat pheochromocytoma?
PHEnOxybenzamine
PHEO
(think the one with benz bc you'll need a benzo to manage pheo cases)
48
Best treatment for phenoxybenzamine-induced severe hypotension.
IVF and vasopressin
49
Why can phenoxybenzamine and phentolamine produce reflex tachycardia?
BRR + NE keeps being released but no alpha receptors to bind to \> beta 1 on SA and AV node
50
Which non-selective alpha antagonist:
1. binds reversibly/irreversibly (competitive/noncompetitive)
2. short vs long acting
3. IV vs PO
Phenoxybenzamine - PO/long/non-comp (irreversible)
Phentolamine- IV/short/competitive (reversible)
51
Which drug is used to treat IV extravasation to prevent tissue necrosis?
Phentolamine (2-10mg diluted in 10mls)
| (keep it simple: 10mg in 10mls)
52
Why should you avoid phentolamine in pts with severe CAD?
bc of the BRR resulting in tachycardia
53
Prazosin
- competitive/noncompetitive
- selective/nonselective
competitive
selective- alpha 1
54
What is the only commonly used beta-blocker that is dependent on the kidneys as its primary route of elimination AND metabolism and can accumulate in renal failure?
Atenolol
55
What is the only beta-blocker metabolized by RBC esterases?
Esmolol
56
Treatment of betablocker overdose? (6)
1. Glucagon
2. Calcium
3. PDE III inhibitors
4. Epi
5. Isoproterenol
6. Cardiac pacing
57
Beta-1 selective Betablockers (6)
Metoprolol
Atenolol
Betaxolol
Esmolol
Acebutolol
Bisoprolol
"MAyBE AB"
58
Nonselective Betablockers (6)
Cardivelol
Labetalol
Timolol
Propanolol
Pindolol
Nadolol
(the two with mixed alpha and beta + TPPN)
59
Half life of labetalol
6 hours
60
beta: alpha ratio of labetalol vs carvedilol
labetalol 7:1
carvedilol 10:1
61
Metoprolol bolus dosing and max dose
2.5-5mg
Max 15mg
62
Esmolol duration of action
\<15 minutes
63
Esmolol bolus dosing and infusion dose
10-80mg
50-300mcg/kg/min
64
Which betablocker has intrinsic sympathomimetic effects?
Labetalol
65
Which betablocker has membrane stabilizing effects
Propanolol
(inhibits AP propagation across the cell membrane - kind of like local anesthetics, so has antidysthrymic properties to it)
66
What does abrupt betablocker withdrawal result in?
HTN, tachycardia, myocardial ischemia, and an increase in 1-year mortality
(due to upregulation of receptors)
67
What does nicotine do to acetylcholine?
It enhances its effect
| (Cholinomimetic)
68
What cholinergic agonist is used to identify reactive airway disease in those who don't have clinically apparent signs of asthma?
methaCHOLINE
69
What cholinergic agonist is used selectively for M3 receptors in the GI and urinary tracts and is used to treat non-obstructive urinary retention?
BethanaCHOL
70
Mneumonic for anticholinergic syndrome (5)
Dry as a bone
Red as a beat
Blind as a bat
Hot as a hare
Mad as a hatter
71
What drugs would cause central anticholinergic syndrome and what drug reverses it?
Atropine & Scopolamine
Reverse with PHYSostigimine 1-2mg
72
What are the 3 classes of calcium channel blockers?
1. Dihydropyridines
2. Benzothiazepines
3. Phenylalkyamines
(Ni's & clevidipine)
(Diltazem)
(Verapamil)
73
Which CCBs are best for reducing HR in patients with tachycardia, afib, or aflutter?
Diltiazem & Verapamil
(benozthiazepine & phenylalkyamine)
74
Which CCB would you want to use in a patient with a tachyarrhythmia and a reduced EF? (with the goal of lowering HR will preserving myocardial contractility)
Diltiazem
75
Rank the CCBs in order of greatest impairment of contractility to least:
Nifedipine, Diltiazem, Verapamil, Nicardipine
1. Verapamil
2. Nifedipine
3. Diltiazem
4. Nicardipine
76
Which two CCBs are the best vasodilators for the treatment of HTN from an elevated SVR?
Nifedipine & Nicardipine
77
Which CCB is useful for coronary vasospasm?
Nicardipine
78
Which is the only CCB proven to decrease M&M from cerebral vasospasm?
Nimodipine (PO)
79
What are two class-4 antiarrhythmics?
Verapamil and Diltiazem
\>decrease electrical impulses in the SA and AV nodes
80
What could happen if you give verapamil to a patient on betablockers?
Complete heart block or profound myocardial depression
81
Why is nimodipine useful in cerebral vasospasm and not the other CCBs?
It is more lipophilic and crosses the BBB
\>cerebral vasodilation
82
Which type of calcium channels to calcium-channel blockers target?
L-type calcium channels
83
How does Nitroglycerine work?
It's a direct vasodilator -- dilates coronary arteries and reduces systemic BP (preload\>afterload), supplying more blood flow and less workload
\*liberates nitric oxide from the vascular smooth muscle walls
84
How is nitro metabolized?
by the liver
85
Before giving nitro, what should you think of?
Are they on viagra/sildenafil? \>will become profoundly hypotensive.
86
Dosing of nitro gtt
5-100mcg/min
87
Which nitrodilator primarily reduces preload
Nitroglycerin
88
Which nitrodilator reduces both preload and afterload?
Nitroprusside
89
Which nitrodilator affects mainly arterial smooth muscle?
Hydralazine
90
Why is Sodium Nitroprusside not used in MI?
It will induce coronary steal and redistribute blood flow away from the ischemic tissue
91
What total dose and rate should sodium nitroprusside not exceed and why?
Cyanide toxicity
total dose \< 500mcg/kg
no faster than 2mcg/kg/min
92
How does Hydralazine produce vasodilation?
It activates potassium ATP channels which reduces intracellular calcium.
93
Which nitrodilator preserves preload?
Hydralazine - it doesn't dilate veins
94
Which drug causes hypertrichosis and what is that?
Minoxidil \> Hair growth
95
Where is vasopressin stored and released?
Posterior pituitary
96
Where is vasopressin synthesized?
Hypothalamus
97
What do V1 receptors produce?
intensive vasoconstriction
98
What do V2 receptors produce?
increases ADH and creates more aquaporin channels which insert themselves into the walls of collecting ducts to increase water (not solute) reabsorption
(lowers serum os)
99
Where are V3 receptors located?
Pituitary gland
100
What is first-line therapy for ACE or ARB-induced vasoplegia?
What would be the next best drug after that?
Vasopressin
Methylene Blue
101
What can vasopressin OD cause?
hyponatremia and seizures
(holding onto water, getting rid of solute)
102
Vasopressin bolus dose
1-2 units
103
Infusion rate of vasopressin
0.01-0.1 units/min
104
How long does vasopressin last?
10-30 minutes
105
Two PDE3 inhibitors
1. Milrinone
2. Cilostazol
106
How many moles of ATP can be produced from one mole of glucose?
38
107
What do phosphodiesterases usually do?
Break down cAMP and cGMP
108
How do PDE inhibitors work in general?
They prevent the breakdown of cAMP and cGMP
\>increased concentrations in the cell
\>increased inotropy in the heart
\>vasodilation in lungs and smooth muscle
109
What are the PDE5 inhibitors (3)?
1. sildenAFIL
2. tadalAFIL
3. vardenAFIL
varmints slide in, ta-da! (Dont know how i'm going to remember the whole 5 part with that but ok)
110
Which drug class treats pulmonary HTN and ED?
PDE5 inhibitors
(increases cGMP in the lungs and penis \> smooth muscle relaxation \> increased blood flow)
111
Suffix for PDE4 inhibitors
-ilast
Romflumilast, Apremilast, Ibudilast
112
What are theophylline and methylxanthine classified as?
Nonspecific PDE ihibitors
\>relax airway smooth muscle
\>decrease inflammation
\>Asthma/COPD
113
PDE inhibitors affect what two 2nd messengers?
cAMP & cGMP
(prevent their metabolism/breakdown)
114
What drug is frequently used for weaning pt's off cardiopulmonary bypass?
Milrinone
115
Which specific PDE inhibitor prevents platelet aggregation?
PDE3
116
List the Gq receptors
Alpha-1
Vasopressin-1
Histamine-1
M1/3/5
117
List the Gs receptors
Beta 1 & 2
Vasopressin-2
Histamine-2
Post-synaptic Dopamine 1
118
List the Gi receptors
Alpha-2
Presynaptic Dopamine 2
M2/M4
119
Where is aldosterone secreted by and what does it do?
The adrenal cortex
- sodium and water reabsorption
- K+ excretion
120
ACE inhibitors are 1st line therapies for what 4 conditions?
1. HTN
2. CHF
3. MR
4. LV dysfunction
121
Which drug class is renal protective in diabetics?
ACE inhibitors
122
Why do ACE inhibitors elicit a cough in some people?
What about angioedema?
Because ACE breaks down bradykinins (pro-inflammatory mediator in the lungs)
- ACE inhibitors prevent this breakdown
- more bradykinin = more pulm inflammation = cough
-in most people bradykinin can be broken down by other pathways, but those who do not (possibly genetic component) will develop angioedema
123
Which people are at most risk for angioedema from ACE inhibitors?
African Americans - 4-5x more likely
124
Which ace inhibitor undergoes hepatic metabolism?
Captopril
125
Which ACE inhibitor is a prodrug?
Enalapril
126
What receptor do ARBs target?
AT1 (prevents binding of angiotensin II at that receptor)
127
What happens when an agonist binds to the GABA-A receptor?
An influx of chloride hyperpolarizes the cell membrane and APs aren't generated
128
What receptor do volatile agents primarily target?
GABA-A
129
By which mechanism do volatile anesthetics produce myocardial depression and vasodilation?
By blocking calcium channels in cardiac and VSM.
130
By which mechanism do volatile agents prolong the QT interval?
by inhibiting potassium efflux which normally causes repolarization
131
What enzyme converts angiotensinogen to angiotension I?
Renin
132
What is cardiac output dependent on in the denervated heart?
Stroke volume (Preload)
HR is fixed
133
Which ANS reflex remains intact in the denervated heart and why?
Bainbridge - bc stretch of the SA node directly increases the SA node firing rate
134
What agent can be used to treat carcinoid-like symptoms?
Octreotide
135
What are carcinoid-like symptoms?
bronchoconstriction, diarrhea, headache, flushing, HTN
(think need to emergently have diarrhea but can't bc your in public so you start freaking out and getting HTN, flushed, headache, and then you cant breathe bc u cant hold it in any longer....and your thinking why does this always happen to me- do i have cancer?/carcinoid
136
What is Shy-Drager syndrome now referred to as?
Multiple system atrophy
137
2 Metabolites of ephedrine?
Noreipi & Benzoic acid
138
What drug is a selective alpha-2 receptor ANTAGONIST
Yohimbine
139
How does Methylene Blue produce widespread vasoconstriction?
Bc it inhibits the nitric oxide pathway
140
Max dose of methylene Blue
7mg/kg
141
What is central anticholinergic syndrome treated with?
Physostigmine (Anticholinesterase, inhibits the breakdown of acetylcholine allowing it to build up)
-tertiary amine
142
6 drugs that can induce carcinoid syndrome.
1. Sux
2. Atracurium
3. Thiopental
4. Epi
5. NE
6. Isoproterenol
143
What is carcinoid syndrome?
A life-threatening event seen in patients with carcinoid tumors that release GI peptides and vasoactive substances.
