Exam 2 Everything Autonomic Flashcards

1
Q

How is the peripheral nervous system divided up?

A

Autonomic and somatic nervous systems

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2
Q

How is the autonomic nervous system divided up?

A

Sympathetic and parasympathetic nervous systems

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3
Q

What two neurotransmitters are associated only with the sympathetic nervous system?

A

Epinephrine and norepinephrine

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4
Q

What neurotransmitter is released by both parasympathetic and sympathetic neurons?

A

Acetylcholine

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5
Q

Where do parasympathetic preganglionic neurons synapse with postganglionic neurons?

A

At ganglia near target organ

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6
Q

What neurotransmitter do parasympathetic preganglionic neurons release? What kind of receptors are activated by this neurotransmitter at this location?

A

Acetylcholine; activates nicotinic receptors on postganglionic neurons

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7
Q

What neurotransmitter do parasympathetic postganglionic neurons release? What kind of receptors are activated by this neurotransmitter at this location?

A

Acetylcholine; activates muscarinic receptors on the target organ

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8
Q

Where do sympathetic preganglionic neurons synapse with postganglionic neurons?

A

In the paravertebral sympathetic ganglion, near the spinal cord.

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9
Q

What neurotransmitter do sympathetic preganglionic neurons release? What kind of receptors are activated by this neurotransmitter at this location?

A

Acetylcholine; activates nicotinic receptors on postganglionic neurons

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10
Q

What neurotransmitter do sympathetic postganglionic neurons release? What kind of receptors are activated by this neurotransmitter at this location?

A

Norepinephrine; activates adrenergic receptors on target organs

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11
Q

What autonomic nervous system controls sweat glands?

A

Sympathetic nervous system

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12
Q

The only postganglionic neurons in the sympathetic nervous system that release acetylcholine are in the…

A

sweat glands involved with thermoregulation.

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13
Q

What autonomic nervous system controls the smooth muscle of the renal vascular bed?

A

Sympathetic nervous system

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14
Q

What neurotransmitter do postganglionic sympathetic neurons release at the kidney vascular bed?

A

Dopamine – precursor to NE, causes vasodilation.

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15
Q

What is unique about sympathetic innervation of the adrenal glands?

A

The preganglionic neurons do not synapse in the paravertebral ganglion. Instead, preganglionic neurons synapse directly on the adrenal gland and release acetylcholine to nicotinic receptors. Adrenal glands act like the postganglionic neuron because the release epinephrine.

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16
Q

What are two other names for cholinergic drugs?

A

Muscarinic agonists and parasympathomimetics

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17
Q

What are two other names for muscarinic antagonists?

A

Anticholinergics and parasympatholytics

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18
Q

What are two other names for sympathomimetics?

A

Adrenergics or adrenergic agonists

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19
Q

What are two other names for antiadrenergics?

A

Adrenergic antagonist and sympatholytic

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20
Q

Name three parts of the body where you can find nicotinic receptors.

A

Ganglion, skeletal muscle, and neuronal CNS

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21
Q

How many subunits compose the nicotinic receptor?

A

Five

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22
Q

Where is the M3 muscarinic receptor found?

A

Smooth muscle in glands – causes contraction that releases gland contents

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23
Q

Where is the M2 muscarinic receptor found?

A

The heart – decreases heart rate.

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24
Q

What kind of receptor is a muscarinic receptor?

A

A 7 transmembrane domain GPCR or heterotrimeric G protein receptor

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25
What kind of G alpha subunit do M1, M3, and M5 receptors release?
Gq subunits
26
What net effect does M1, M3, and M5 receptor activation cause?
Activation of protein kinase C (PKC) and increased levels of calcium
27
What effector does the Gq subunit act on once activated by M1, M3, or M5 receptors?
Phospholipase C (PLC) which splits PIP2 into DAG and IP3
28
What kind of G alpha subunit do M2 and M4 receptors release?
Gio subunits
29
What is the net effect of M2 and M4 receptor activation?
Decreased cAMP formation, which decreases PKA activity, and opening of potassium channels.
30
In what major organ are alpha-1 adrenergic receptors located and what is their effect?
In the smooth muscle around arteries -- causes vasoconstriction which increases BP
31
In what major organ are alpha-2 adrenergic receptors located and what is their effect?
In the cardiovascular control center of the brainstem -- they turn off the sympathetic nervous system (?)
32
In what major organ are beta-1 adrenergic receptors located?
The heart
33
In what major organ are beta-2 adrenergic receptors located?
Smooth muscle
34
Alpha 1 adrenergic receptors activate Gq, activating PLC and eventually leading to increased calcium in the cell and activated PKC. What other receptor(s) is alpha 1 similar to?
M1, M3, and M5 receptors
35
What G alpha subunit do alpha-2 adrenergic receptors activate?
Gi
36
What is the net effect of alpha-2 activation?
Decreased levels of cAMP, leading to less kinase activity
37
What G alpha subunit do beta adrenergic receptors activate?
Gs
38
What is the net effect of beta adrenergic activation?
Increased levels of cAMP, leading to increased kinase activity.
39
What receptors in the heart decrease rate and force of contraction?
M2 receptors -- parasympathetic
40
What receptors in the heart increase rate and force of contraction?
B1 > B2
41
What receptors in most arteries and veins cause vasodilation?
Trick question -- only the sympathetic system innervates arteries and veins, and sympathetic stimulation causes vasoconstriction. A decrease in sympathetic activation causes vasodilation.
42
What receptors in skeletal muscle arteries cause vasodilation?
B2 receptors -- sympathetic
43
What receptor causes endothelium to release EDRF?
M3 receptors -- parasympathetic
44
What receptor causes bronchodilation in the lungs?
B2 receptors -- sympathetic
45
What receptor causes bronchoconstriction in the lungs?
M2 and M3 receptors -- parasympathetic
46
What receptor causes relaxation of the bladder wall?
B2 receptors -- sympathetic
47
What receptor causes contraction of the bladder wall?
M3 receptors -- parasympathetic
48
What receptor causes contraction of the ureter and sphincter?
A1 receptors -- sympathetic
49
What receptor causes relaxation of the ureter and sphincter?
M3 -- parasympathetic
50
What parasympathetic receptor plays a role in a pregnant uterus?
M3 receptor
51
In the pregnant uterus, what sympathetic receptor causes relaxation? Contraction?
Relaxation -- B2 (target if premature contractions) | Contraction -- A1
52
What receptor causes erection of the penis?
M3 -- parasympathetic
53
What receptor causes penile ejaculation?
A1 -- sympathetic (sperm flight)
54
In what gland do sympathetic and parasympathetic receptors have the same response?
Salivary gland
55
What two receptors causes increased salivary secretion?
A1 (sympathetic) and M3 (parasympathetic)
56
What receptor causes increased GI secretion?
M2 and M3 -- parasympathetic
57
What receptor inhibits GI secretion?
A2 -- sympathetic
58
What receptors cause both GI wall contraction and GI sphincter relaxation?
M2 and M3 -- parasympathetic
59
What receptor causes contraction of GI sphincters?
A1 receptors -- sympathetic
60
What receptor causes relaxation of GI walls?
A2 and B2 receptors -- sympathetic
61
What receptor causes contraction of hair follicles and goosebumps?
A1 -- sympathetic
62
True or false: All tissues are innervated by both the sympathetic and parasympathetic nervous system
False -- one example is skin, which is innervated only by the sympathetic nervous system
63
What receptor is responsible for inducing sweating for thermal regulation?
M3 -- SYMPATHETIC (only instance)
64
What receptor is responsible for inducing sweating in response to stress?
A1 receptor -- sympathetic
65
What receptor is responsible for causing contraction of the radial muscle in the eye?
A1 receptor -- sympathetic
66
Radial muscle contraction causes pupil...
dilation (mydriasis).
67
Circular muscle contraction causes pupil...
contraction (miosis).
68
What receptor is responsible for causing contraction of the circular muscle in the eye?
M3 receptor -- parasympathetic
69
What receptor is responsible for causing ciliary muscle contraction?
M3 receptor -- parasympathetic
70
Ciliary muscle contraction causes the lens to adjust to ___ vision.
near (short distance)
71
Ciliary muscle relaxation causes the lens to adjust to ____ vision.
far (long distance)
72
What receptor is responsible for stimulating the secretion of aqueous humor in the eye?
B2 -- sympathetic.
73
If an eye doctor wanted to dilate your eye, what two types of agents could he administer?
M3 receptor antagonist (parasympatholytic) to stop contraction of the circular muscle (what they actually do) or A1 receptor agonist (sympathomimetic) to cause contraction of the radial muscle.
74
What receptor increases renin secretion in the kidney?
B1 -- sympathetic
75
List locations and functions of A1 receptors.
Vasoconstriction in arteries and veins, contraction of the ureter and urinary sphincter, penile ejaculation, contraction of the uterus, increased salivary secretion, contraction of sphincters in GI tract, contraction of hair follicles and goosebumps in skin, stimulation of sweating due to stress, contraction of the radial muscle in the eye, metabolic changes in liver and fat
76
List locations and functions of A2 receptors.
Vasoconstriction in veins, relaxation of GI walls, inhibition of GI secretion, decrease in insulin release from the pancreas
77
List locations and functions of B1 receptors.
Increase in the rate and force of contraction in the heart. increase in renin secretion from the kidneys.
78
List locations and functions of B2 receptors.
Vasodilation in smooth muscle vasculature, bronchodilation in the lungs, bladder wall relaxation, uterus relaxation, GI wall relaxation, some minor relaxation of ciliary muscle and minor effects on heart.
79
List locations and functions of M2 receptors.
Decrease in heart rate and force of contraction, bronchoconstriction, increased GI secretion, GI wall contraction, and GI sphincter relaxation.
80
List locations and functions of M3 receptors.
Release of EDRF from endothelium, bronchoconstriction, all parasympathetic responses in GU and GI systems, contraction of the ciliary muscle and circular muscle, and sympathetic sweat secretion in response to heat.
81
What type of agent is atropine?
A long-acting tertiary amine antimuscarinic
82
What type of agent is anisotropine?
A quaternary amine antimuscarinic
83
What type of agent is scopolamine?
A long-acting tertiary amine antimuscarinic
84
Which has higher CNS penetration--atropine or scopolamine?
Scopolamine
85
What type of agent is homotropine?
A short-acting tertiary amine antimuscarinic
86
What type of agent is tropicamide?
A short-acting tertiary amine antimuscarinic
87
Which has a shorter duration of action--homatropine or tropicamide?
Tropicamide
88
What type of agent is procyclidine?
A tertiary amine antimuscarinic used for Parkinsons
89
What type of agent is benztropine?
A tertiary amine antimuscarinic used for Parkinsons
90
What type of agent is glycopyrrolate?
A quaternary amine antimuscarinic
91
What type of agent is propantheline bromide?
A quaternary amine antimuscarinic
92
What type of agent is ipratropium bromide?
A quaternary amine antimuscarinic for COPD
93
What is glycopyrrolate used specially for?
Pre-operative drying up
94
What type of agent is succinylcholine?
Depolarizing neuromuscular blocker
95
What is the duration of action of succinylcholine?
5-10 minutes
96
What type of agent is d-tubocurarine?
Non-depolarizing neuromuscular blocker
97
What type of agent is pancuronium?
Non-depolarizing neuromuscular blocker
98
What type of agent is atracurium?
Non-depolarizing neuromuscular blocker
99
What type of agent is mivacurium?
Non-depolarizing neuromuscular blocker
100
What type of agent is rocuronium?
Non-depolarizing neuromuscular blocker
101
What is the neuromuscular blocker with the shortest duration of action?
Succinylcholine
102
What is the neuromuscular blocker with the longest duration of action?
Pancuronium
103
What drug class is used to relax muscles for surgery, tracheal intubation, control of ventilation, and treatment of convulsions?
Neuromuscular blockers
104
True or false: Neuromuscular blockers have the potential to cross the blood-brain barrier, depending on the structure
False -- all neuromuscular blockers have multiple charged quaternary amines
105
What drug class can be used to treat incontinence, IBS, motion sickness, Parkinson's, and COPD, for pupil dilation and pre-op anti-secretory, and causes cycloplegia?
Antimuscarinics
106
What drugs can treat motion sickness and Parkinson's, and cause drowsiness, mydriasis, and cycloplegia?
Tertiary amine antimuscarinics
107
What type of agent is edrophonium? What can it be used to diagnose?
A reversible, non-covalent acetylcholinesterase inhibitor
108
What type of agent is neostigmine?
A reversible, covalent acetylcholinesterase inhibitor
109
What type of agent is pyridostigmine?
A reversible, covalent acetylcholinesterase inhibitor
110
What type of agent is physostigmine?
A reversible, covalent acetylcholinesterase inhibitor
111
What type of agent is isofluorophate?
An irreversible, covalent acetylcholinesterase inhibitor (organophosphate)
112
What type of agent is echothiophate?
An irreversible, covalent acetylcholinesterase inhibitor (organophosphate)
113
What type of agents are sarin and soman?
Organophosphate nerve gases
114
What type of agents are malathion and diazinon?
Organophosphate insecticides, rapidly inactivated in mammals and birds by esterases
115
What is organophosphate aging?
A partial hydrolysis of the organophosphate bound to the ester that makes it even harder to reverse.
116
What is pralidoxime chloride (2-PAM)? How does it work?
The antidote to organophosphate poisoning (pesticide or nerve gas). It is a very strong nucleophile, so it reacts with the strong electrophile, the organophosphate. Must be given within a few hours.
117
When should you never use a parasympathomimetic (AchE inhibitors or direct acting drugs)?
Asthma, COPD, peptic ulcer, obstruction of the urinary or GI tract
118
What are the side effects associated with cholinergics?
SLUD -- salivation, lacrimation, urination, defecation, sweating, pupil constriction, lower heart rate, and CNS activation (hallucinations, seizures)
119
Why are cholinergics (esp AchE inhibitors) used to treat alzheimers?
Alzheimers causes loss of cholinergic neurons. AchE inhibitors increase the amount of Ach in the brain.
120
What type of agents are tacrine and donepezil?
Reversible, non-covalent AchE inhibitors that enhance cognitive ability in Alzheimers but does not stop disease progression
121
What type of agents are rivastigmine and eptastigmine?
Reversible AchE inhibitors used in Alzheimers that increase cognitive ability but lose effectiveness as disease progresses
122
What type of agent is galantamine?
A reversible competitive AChE inhibitor used in Alzheimers that loses effectiveness as disease progresses.
123
What type of agent is memantine?
A NMDA receptor antagonist that decreases excitotoxicity of glutamate and slows the progression of the disease.
124
What type of agent is carbachol?
A nonselective sympathomimetic that is not sensitive to AChE
125
What type of agent is methacholine?
A nonselective sympathomimetic that is not sensitive to AChE
126
What type of agent is bethanechol?
A selective muscarinic agonist that is not sensitive to AChE
127
What type of agent is pilocarpine?
A selective muscarinic agonist that is not sensitive to AChE
128
What type of agent is varenicline?
A selective nicotinic partial agonist that is not sensitive to AChE
129
A methyl substitution on a direct acetylcholine agonist on an alpha carbon directs selectivity towards which receptor--muscarinic or nicotinic?
Nicotinic
130
What is the structural difference between epinephrine and norepinephrine?
Epinephrine has a methyl group on the nitrogen
131
What is the first molecule created by the slow step in the synthesis of epinephrine from tyrosine?
DOPA
132
In what order are epinephrine, norepinephrine, and dopamine synthesized?
Dopamine, norepinephrine, and epinephrine
133
What is the end product of the metabolism of norepinephrine?
Vanilylmandelic acid (VMA)
134
What two major enzymes are involved in norepinephrine metabolism? Which acts first within the cell?
COMT (catechol o-methyl transferase) and MAO (monoamine oxidase). MAO first in cells (but not necessarily if norepinephrine goes through gut)
135
What endogenous ligand must be present at high levels in order to activate B2 receptors but activates the others at lower levels?
Norepinephrine
136
What is the most nonselective endogenous sympathetic ligand?
Epinephrine
137
What receptor is most strongly triggered by dopamine?
B1
138
What is the main function of an a1 agonist?
Vasoconstriction
139
What type of agent is phenylephrine?
An a1 receptor agonist -- pressor. Susceptible to MAO but not COMT
140
What type of agent is methoxamine?
An a1 receptor agonist -- pressor
141
What type of agent is oxymetazoline?
A partial a1 receptor agonist -- pressor
142
What type of agent is tetrahydrozoline?
A partial a1 receptor agonist -- pressor.
143
What type of agent is naphazoline?
A partial a1 receptor agonist -- pressor
144
What are the risks and uses for the 2-aralkylimidazoline a1 receptor agonists?
Nasal and ophthalmic decongestants -- ionized at physiological pH -- risk of desensitization so <3 day use.
145
What type of agent is clonidine?
A selective a2 receptor agonist
146
What type of agent is guanabenz?
An a2 receptor agonist
147
What type of agent is guanfacine?
An a2 receptor agonist
148
Which has a shorter half-life--guanabenz or guanfacine?
Guanabenz (shortest of a2 agonists)
149
How do a2 agonists decrease blood pressure?
They decrease sympathetic tone, leaded to decreased heart rate, contractility, renin release, and vasoconstriction--all of which act to lower blood pressure.
150
What type of agent is methyldopa?
An a2 receptor agonist prodrug
151
What side effects are associated with a2 agonists?
Sedation, Na+ and water retention, dry mouth, and withdrawal syndrome if stopped suddenly
152
What type of agent is isoproterenol?
A non-selective B receptor agonist, sensitive to COMT but not to MAO.
153
What type of agent is metaproterenol?
A selective B2 receptor agonist, not metabolized by MAO or COMT
154
What type of agent is terbutaline?
A selective B2 receptor agonist, not metabolized by MAO or COMT
155
What is terbutaline used for that metaproterenol is not?
Tocolytic to prevent premature labor
156
What is the primary effect of B2 agonists?
Bronchodilation
157
What are the primary effects of nonselective B agonists?
Bronchodilation, increased CO
158
What type of agent is albuterol (or levalbuterol)?
A selective B2 receptor agonist
159
Which has a longer duration of action--isoproterenol or albuterol and salmeterol?
Albuterol and salmeterol
160
What type of agent is salmeterol?
A selective B2 receptor agonist
161
What type of agent is formoterol?
A selective B2 receptor agonist
162
Are any of the beta agonists sensitive to MAO?
No
163
What beta agonists are sensitive to COMT?
Isoproterenol and dobutamine
164
What two selective B2 agonists are longer acting?
Salmeterol and formoterol (shorter onset)
165
What type of agent is dobutamine?
Potent B1 agonist, a1 agonist and antagonist with short half life--net effect increase contractility in acute HF, shock
166
What is the difference between ephedrine and pseudoephedrine?
They are diastereomers. Pseudoephedrine has less agonist activity but instead acts to reverse the transporter.
167
What are the general types of indirect-acting sympathomimetics?
MAO inhibitors, transporter blockers, transporter reversers
168
What type of agent is amphetamine?
Norepinephrine transporter reverser
169
What type of agent is phenylpropanolamine?
Norepinephrine transporter reverser
170
What type of agent is pseudoephedrine?
Norepinephrine transporter reverser
171
What type of agent is tyramine?
Norepinephrine transporter reverser and norepinephrine synthesis inhibitor
172
What type of agent is ephedrine?
Norepinephrine transporter reverser
173
What are the clinical uses for a norepinephrine transporter reverser?
ADHD, narcolepsy, anorexiant, nasal decongestant
174
What type of agents are cocaine and antidepressants?
Transporter blockers -- increase [NE] in synapse
175
What type of agent is phenelzine?
MAO inhibitor
176
What type of agent is selegiline?
MAO inhibitor
177
True or false: A combination of indirect-acting sympathomimetic drugs is used for effective treatment.
False -- co-administration of indirect-acting sympathomimetics can lead to hypertensive crisis.
178
What substituent makes a sympathomimetic resistant to MAO?
A large alkyl group on the amine
179
A tera-butyl group on the amine for a sympathomimetic increases selectivity for which receptor?
B2
180
What kind of substituent on a sympathomimetic blocks MAO oxidation, increases lipophilicity, and makes the molecule a transporter reverser instead of a direct agonist--beta or alpha?
Alpha methyl substitution -- makes it an amphetamine!
181
A beta hydroxyl on a sympathomimetic does what?
Enhances uptake and storage, makes molecule a direct agonist
182
What groups must be present in order to be susceptible to COMT?
Two catechol hydroxyls on carbons 3 and 4
183
What does moving a hydroxyl on a catechol to create a resorcinol do to receptor selectivity?
Makes it B2 selective.
184
What type of agent is phenoxybenzamine?
The nonselective a1 and a2 receptor antagonist that also blocks acetylcholine, histamine, and serotonin. Only irreversible sympathetic antagonist.
185
What type of agent is phentolamine?
A competitive, nonselective alpha antagonist. Significant reflex tachycardia and also blocks 5-HT receptors and is a muscarinic/histamine receptor agonist.
186
What type of agent is prazosin?
An a1 antagonist (vasodilator)
187
What type of agent is terazosin?
An a1 antagonist (vasodilator)
188
What type of agent is doxazosin?
An a1 antagonist (vasodilator)
189
Put the -zosin drugs in order from shortest half life to longest half life
Prazosin (3h) < terazosin (12h) < doxazosin (20h)
190
What ailment, besides hypertension, do the -zosin drugs treat?
BPH -- relax smooth muscle in prostate and bladder base
191
What major side effect should patients be warned about regarding the -zosin drugs?
Orthostatic hypotension, especially with first few doses
192
What do we do to avoid reflex tachycardia?
Give an a1 antagonist slowly or orally so you do not trip the baroreceptors
193
What type of agent is yohimbine?
An a2 antagonist that increases sympathetic discharge (male impotence?)
194
What are the hallmark structural parts of a beta blocker?
A non-carbon atom in side chain attached to an aromatic ring structure, with a bulky alkyl group on the amine on the other end
195
What type of agent is propranolol?
A non-selecive, lipophilic beta blocker
196
What is the primary way a beta blocker impacts blood pressure?
Decreasing the renin release from the kidney
197
Are the increase in VLDL and decrease in HDL a point of concern with beta blockers?
No -- usually resolves after a month
198
Why should beta blockers be used cautiously in diabetics?
They inhibit the body's response to hypoglycemia
199
Hypertension, angina, cardiac arrhythmias, migraine, stage fright, thyrotoxicosis, glaucoma, and congestive heart failure stage II and III can all be treated by...
Beta blockers.
200
What type of agent is nadolol?
A nonselective but less lipophilic and longer lasting beta blocker
201
What type of agent is timolol?
A nonselective beta blocker
202
What type of agent is pindolol?
A nonselective PARTIAL beta receptor agonist (functions like antagonist)
203
What type of agent is carteolol?
A nonselective PARTIAL beta receptor agonist (functions like antagonist)
204
What type of agent is metoprolol?
A selective B1 receptor antagonist
205
What type of agent is bisoprolol?
A selective B1 receptor antagonist
206
What type of agent is atenolol?
A selective B1 receptor antagonist with low lipophilicity and longer half-life
207
What type of agent is esmolol?
A selective B1 receptor antagonist that is VERY short acting (9 minutes)
208
What type of agent is nebivolol?
A new selective B1 receptor antagonist that also works to produce nitric oxide, both mechanisms producing vasodilation
209
What type of agent is labetalol?
A non-selective B and a1 antagonist -- combination prevents reflex tachycardia
210
What drug is used for hypertensive crisis?
Labetalol
211
What type of agent is carvedilol?
A non-selective B and a1 antagonist -- combination prevents reflex tachycardia. CHF II and III too.
212
What side effects are associated with beta blockers?
Bradycardia, AV block, sedation (esp if lipophilic), withdrawal syndrome, masking symptoms of hypoglycemia
213
When are beta blockers contraindicated?
Asthma, COPD, CHF type IV
214
What type of agent is reserpine?
A catecholamine deplete that blocks the loading of NE into vesicles. Slow onset, may precipitate depression.
215
What type of agent is beryllium tosylate?
An indirect sympatholytic that blocks the fusion of the vesicle or release of NE.