Autonomic Agents Flashcards
(164 cards)
1
Q
What neurotransmitter is released into the synaptic cleft from the presynaptic neurons in Sympathetic and Parasympathetic systems?
A
Acetylcholine for both.
2
Q
Where are the sympathetic preganglionic fibers located?
A
in paravertebral chains on either side of the spinal column or prevertebral ganglia on ventral surface on aorta. Short preganglionic fibers are very short.
3
Q
Where are parasympathetic preganglionic fibers located?
A
In or near the wall of the organ they innervate. Parasympathetic hanglionic fibers are very long
4
Q
Where are nicotinic receptors located?
A
postsynaptic neurons in ganglia of both parasympathetic nervous system and sympathetic nervous system, adrenal medulla, NMJ, CNS
5
Q
Where are muscarinic receptors located?
A
Organs innervated by PNS, thermoregulatory sweat glands innervated by sympathetic nervous systems, CNS
6
Q
What does the PNS do to the heart rate?
A
Decreases the HR.
7
Q
What enzyme catalyzes the reaction between choline and acetylCoA to form Ach.
A
Choline acetyltransferase (CAT)
8
Q
The neuronal release of Ach into the synapse is inhibited by what toxin
A
Botulinum toxin
9
Q
What organism produces Botulnum toxin?
A
Clostridium botulinum
10
Q
What enzyme degrades Ach
A
Acetylcholinesterase (AChE)
11
Q
What are the breakdown products of Ach?
A
Choline and acetate
12
Q
Where is AChE located in the autonomic nervous system?
A
synaptic cleft
13
Q
What is muscarine?
A
Alkaloid found in various poisonous mushrooms
14
Q
Where are M1 muscarinic receptors found in the body?
A
Nerves, gastric parietal cells
15
Q
Where are M2 muscarinic receptors found in the body?
A
Nerves, cardiac cells, smooth muscle cells
16
Q
Where are M3 muscarinic receptors found in the body?
A
Smooth muscle, exocrine glands, lungs, gastrointestinal tract, eye, bladder
17
Q
Where are M4 muscarinic receptors found in body?
A
CNS
18
Q
Where are M5 muscarinic receptors located in the body?
A
CNS
19
Q
What is the M1 gprotein?
A
Gq coupled, IP3, DAG cascade
20
Q
What is the M2 gprotein?
A
Gi coupled, inhibition of cAMP production, activation of potassium channels
21
Q
What is the M3 gprotein?
A
Gq coupled, IP3, DAG cascade
22
Q
What is the M4 gprotein?
A
Gi coupled, inhibition of cAMP production
23
Q
What is the M5 gprotein?
A
Gq coupled, IP3, DAG cascade
24
Q
Does the PNS directly innervate the vasculature?
A
No. Vascular Tone is determined by the degree of stimulation of adrenergic receptors of the symphathetic nervous system. There are muscarinic receptors located on the vasculature.
25
How can Ach lower blood pressure?
Ach binds to Ach receptors in the vasculature leading to increased synthesis of NO via second messenger pathways. An increase in NO leads to vasodilation.
26
What is another name for NO?
Endothelialderived relaxation factor (EDRF)
27
What amino acid is a precursor to NO synthesis?
Arginine
28
Does AChE have a high affinity for Ach
yes
29
What is the effect of Ach on blood pressure?
decreases arterial and venous blood pressure via NO
30
What is the effect of Ach on Heart rate?
decreases via M2 receptors
31
What is the effect of Ach on salivation?
increases via M3
32
What is the effect of Ach on lacrimation?
Increases via M3
33
What is the effect of Ach on sweating?
Increases via sympathetic stimulation of muscarinic cholinergic receptors
34
What is the effect of Ach on GI secretionGI motility
Increases via M3 receptors
35
What is the effect of Ach on constriction of pupil, bladder detrusor muscle?
Increases via M3 receptors
36
What is the effect of Ach on bladder sphincter tone
decreases, in combination with increased detrusor tone, leads to increasesd urination via M3 receptors
37
What is the effect of Ach on bronchodilation?
Decreases via M3 receptors
38
How does Ach causes miosis?
Increased contraction of the circular muscle in the iris
39
Does Bethanechol have muscarinic activity?
Yes (agonist)
40
Does AchE have a high affinity for Bethanechol?
No, zero affinity. This gives bethanechol a long duration of action.
41
What is the clinical use for bethanechol?
Increases detrusor tone and GI motility
42
Does carbachol have muscarinic activity?
Yes, muscarinic antagonist
43
Does carbachol have nicotinic activity?
Yes, it is also a nictonic agonist
44
Does AChE have a high affinity for carbachol?
No, the enzyme has zero affinity for carbachol.
45
What is carbachol used for?
It is a mitotic agent to reduce Intraocular pressure in emergency settings of glaucoma
46
Does pilocarpine have muscarinic activity?
Yes
47
Does pilocarpine have nicotinic activity?
No
48
Does AChE have a high affinity for pilocarpine?
No, enzyme has zero affinity for pilocarpine
49
Can Pilocarpine cross the BBB?
Yes, because it is a tertiary, uncharged amine
50
Give examples of AChE inhibitors?
Neostigmine, pyridostigmine, physostigmine, edrophonium, rivastigmine, donepezil, galantamine, tacrine
51
What are donepezil, galantamine, rivastigmine, and tacrine used for?
Alzheimertype dementia. They are AChE imhibitors, thereby increasing the levels of Ach in the brain
52
What two AChE inhibitors are quaternary ammonium compounds?
Neostigmine and Pyridostigmine
53
What is the shortacting AChE inhibitor used to diagnose myasthenia gravis and is also used to differentiate myasthenic from cholinergic crisis?
Edrophonium. The trade name is Tensilon, so the test is referred to as the Tensilon test.
54
What reversible AChE inhibitor is used as an antidote in atropine overdose?
Physostigmine, a tertiary amine, is able to cross the BBB to act on the CNS
55
Give examples of irreversible AChE Inhibitors?
Echothiophate, isoflurophate, sarin, malathion, parathion
56
Name an irreversible AChE inhibitor that is used as nerve gas?
Sarin
57
What two AChE inhibitors are used as insecticides?
Malathion, Parthion
58
What is another name for the irreversible AChE inhibitors?
organophosphates
59
How do organophosphates irreversibly inibit AChE
The phosphate group covalently binds to serine hydroxyl group in active site of ACHE, rendering the enzyme permanently inactive
60
What is used to counteract the muscarinic and CNS effects of organophosphate poisoning?
Atropine via competitive inhibition. Atropine binds the muscarinic receptors, outcompeting the increased levels of Ach, preventing overstimulation.
61
What agent is used to reactivate inhibited AChE during organophosphate poisoning?
Pralidoxime (2PAM), prevents aging
62
What are the signs and symptoms of organophosphate poisoning?
SLUDGE: salivation, lacrimation, urinative, diaphoresis, GI motility, Emesis. Parasympathetic overstimulation.
63
Does atropine block nicotinic receptors, muscarinic receptors, or both?
it blocks muscarinic receptors
64
What are pharmacologic actions of atropine?
Mydriasis, cycloplegia, tachycardia, sedation, urinary retention, constipation, dry mouth, dry eyes, decreased sweating, hallucinations, sedation, hyperthermia, delirium, blurred vision, coma (anticholinergic, sympathetic overstimulation)
65
What class of drugs can be used to counteract atropine overdose?
AChE inhibitors
66
What is belladonna?
deadly nightshade plant, named for dilated pupils, blushing of cheeks, and reddening lips making the ladies pretty
67
What does scopolamine differ from atropine?
Scopolamine has a longer duration of action, more potent CNS effects, able to block shortterm memory
68
What is the therapeutic indication of scopolamine?
Motion sickness
69
What emergent medical condition can anticholinergics cause?
closedangle glaucoma
70
What are the signs of Sx of acute closedangle glaucoma?
pain, headache, red eye, photophobia, increased IOP, visual changes, malaise, nausea, vomiting
71
What two anticholinergic agents are quaternary ammonium compounds and used for treatment of asthma and COPD?
Ipratronium and tiotropium. Tiotropium has a long half life compared to ipratronium.
72
Does ipratronium affect airway secretions?
No, unlike atropine, which decreases airway secretions
73
Name three ganglionic blocking agents?
Hexamethonium, mecamylamine, trimethaphan
74
What are ganglionic blocking agents primarily used for?
Lowering blood pressure, blocking autonomic nervous system reflexes, smoking cessation due to blockade of central nicotine receptors
75
Why can ganglionic blockers cause a marked postural hypotension?
Sympathetic tone is blocked, so both arterial and venous dilation occur, lowering blood pressure. Ganglionic blockers also prevent the sympathetically mediated baroreceptor response to suddent decrease in BP.
76
Neuromuscular blocking agents can be grouped into two general categories?
Depolarizing and nondepolarizing
77
Do NMBs work at muscarinic or nicotinic receptors?
Nicotonic receptors (NMJ)
78
What subunit of the nicotinic receptors does Ach bind to?
two alpha subunits
79
Binding of Ach to the nicotinic receptors at the NMJ is required to open which ion channel?
sodium channel
80
What is the most commonly used NMJ?
Succinylcholine, the only depolarizing NMB. Ideal for endotracheal intubation due to its fast onset of action and short duration of action
81
How does succinylcholine work at the NMJ?
It acts as a cholinergic agonist, remains bound to Ach receptor for a prolonged period of time.
82
What happens during Phase I and Phase II of succinylcholine binding to the Ach receptor?
Phase I receptor is depolarized. Phase II receptor becomes resistent to depolarization and a flaccid paralysis ensues.
83
What are the two main uses of succinylcholine?
Relaxing pharyngeal and laryngeal muscles for intubation and used in electroconvulsant shock therapy to prevent muscle breakdown
84
What is the duraction of action of succinylcholine?
48 minutes because of rapid hydrolysis by plasma cholinesterase
85
How is malignant hyperthermia treated?
dantrolene
86
What is the mechanism of action of dantrolene
Inhibits calcium release from sarcoplasmic reticulum of muscle cells, thereby relaxing muscle tone and reducing heat production
87
In what patients does succinylcholine have a prolonged half life?
in the 12500 patients that have a genetic deficiency or an altered form of plasma cholinesterase
88
What is the mechanism of action of nondepololarizing NMBs?
Competitive antagonists of Ach at the NMJ
89
Which drug is the prototype for the nondepolarizing NMBs
Tubocurarine
90
What antidote is used in tubocurarine overdose?
AChE inhibitor, so Ach can compete for binding
91
List in order the muscles that are paralyzed first to last by nondepolarizing NMBs
1. small muscles of face and eye 2. fingers 3. limbs, neck, trunk 4. intercostals 5. diaphragm
92
Give examples of nondepolarizing NMBs
tubocurarine, mivacurium, vecuronium
93
When do you use Nondepolarizing NMBs?
facilitate intubation, relax skeletal muscles during surgery, and facilitate mechanical ventilation in ICU patients
94
What are the major NTs of the sympathetic nervous system?
Epinepherine, norepi, dopamine
95
What a.a. is the precursor to dopamine, epi, and norepi
Tyrosine
96
What 2 enzymes metabolize norepi?
MAO (monoamine oxidase) 2. COMT (Catecholomethyltransferase)
97
What is the mechanism of action of reserpine?
inhibits transport of norepi from neuronal cytoplasm into synaptic vesicles
98
What are common side effects of reserpine?
Depression, sedation
99
What breakdown products of norepi are excreted into urine and can be measured to help diagnose pheochromocytoma?
Vaillymandelic acid, metanepherine, normetanephrine
100
What are the two major classes of adrenergic receptors?
Alpha and Beta receptors
101
What is metabolized by MAO?
Norepi, epi, serotonin, tyramine, dopmaine
102
How does cocaine increase norepi in the synaptic cleft?
inhibits the reuptake of NT back into the presynaptic neuron
103
Where are alpha 1 receptors found?
vascular smooth muscle, papillary dilator muscle, pilomotor smooth muschle, prostate, heart
104
Where are alpha 2 receptors found?
Postsynaptic CNS adrenoceptors, pancreatic beta cells, platelets, adrenergic and cholinergic nerve terminals, vascular smooth muscle, fat cells
105
Where are B1 receptors found?
heart, juxtaglomerular cells
106
Where are B2 receptors found?
Respiratory, uterine, and vascular smooth muscle; skeletal muscle, liver
107
Where are D1 receptors found?
smooth muscle
108
Where are D2 receptors found?
Nerve endings
109
What are local vs systemic affects of alpha2 receptor activation?
local infusion activates alpha2 receptors in vasculature, causing vasoconstriction. Systemic administration activates central alpha2 receptors in locus ceruleus, which inibits norepi release and sympathetic activation. The central effects overwhelm the local effects, resulting in a decreased blood pressure.
110
What are examples of Alpha2 receptor agonists?
Clonidine, alphamethyldopa, guanaenz, guanfacine, dexmedetomidine
111
What are the therapeutic indications of clonidine
Hypertension, severe pain, heroin withdrawal, nicotine withdrawal, migraine prevention
112
What is desmedetomidine used for?
Sedation of intunated and mechanically ventilated patients, prolongation of spinal anesthesia
113
With drugs that activate both alpha and beta receptors, which receptors are generally activated first?
Beta receptors
114
Activation of what type of receptor in the eye leads to contraction of the radial muscle (causing mydriasis)?
alpha1 receptor
115
What is the Gprotein involved with Alpha1 receptors?
Gq
116
What is the Gprotein involved with Alpha2 receptors?
Gi
117
What is the Gprotein involved with B1, B2, D receptors?
Gs
118
What happens when alpha1 receptors are activated?
mydriasis, vasocontriction leading to increased blood pressure, decreased urination, increased glycogenolysis, decreased renin release, ejaculation
119
What happens with alpha2 receptors are activated?
Inhibition of norepi release, inhibition of insulin release, platelet aggregation
120
What happens with B1 receptors are activated?
increased HR, increased conduction velocity, increased force of contraction, increased rein release
121
What happens when B2 receptors are activated?
Vasodilation, bronchodilation, relaxation of uterine, respiratory and vascular smooth muscle, increased insulin secretion, increased potassium uptake, increased glycogenolysis
122
What receptor causes insulin increase? Decrease?
Alpha2 decreases insulin release and B2 increases insulin release
123
Which receptor does epi preferentially bind to at low doses?
B receptors (vasodilation in vasculature)
124
What receptor does epi bind to at high doses
Alpha receptors (vasocontstriction in vasculature)
125
What drug is used in Type 1 hypersensitivity reactions?
Epi
126
Why is epi often given with local anesthetics?
Epi causes vasoconstriction, limiting redistribution of local anestheic away from site of action
127
With low dose epi, which decreases and which increases: SVR, BP systole and diastole, pulse pressure
SVR decreases, Systolic BP increases, Diastolic BP decreases, Pulse pressure increases
128
What receptors are activated by dobutamine?
B1 \> B2
129
What receptors are activated by isoproterenol?
B1 = B2
130
What receptors are activated by dopamine?
D \> B \> A
131
What receptors are activated by pheylephrine?
Alpha 1 \> Alpha 2
132
Does norepi activate B2?
No
133
Activation of dopamine receptors causes what in the mesenteric and renal vasculatuer
vasodilation
134
What is dopamine metabolized to?
Homovanillic acid
135
What is dobutamine used for?
Increases cardiac output in congestive heart failure (CHF), without affecting Renal Blood Flow
136
Tyramine is a breakdown product of what amino acid?
Tyrosine
137
Where is tyramine found?
beer, cheese, salami… soy suace…
138
What enzyme breaks down tyramine?
MAO
139
What can happen if a patient on an MAOI (monoamine oxidase inhibitor) consumed a bunch of fermented cheese?
Hypertensive crisis due to tyramine in the cheese which leads to the release of norepi from storage vesicles in presynatic neurons
140
What is phenylephrine and pseudoephedrine used to treat?
Nasal congestion
141
What are mixed action adrenergic agonists?
release stored epi from nerve terminals and also directly stimulate alpha and beta receptors
142
What are some examples of mixed action adrenergic agonists?
Ephedrine, pseudoephedrine, metaraminol
143
What drug is nonselective competitive antagonist at both alpha 1 and alpha 2 receptors
Phentolamine
144
What drug is a non selective irreversible antagonist at both alpha 1 and alpha 2 receptors?
Phenoxybenzamine
145
What are phentolamine and phenoxybenzamine used for?
to achieve alpha receptor blockade before surgical removal of pheochromocytoma to achieve perioperative blood pressure control, and to prevent intraoperative hypertension from release of catecholamines during surgical manipulation
146
What is the mechanism of action of prazosin
selective alpha 1 antagonist
147
What are prazosin, terazosin, and doxazosin used for?
treating benign prostatic hyperplasia, hypertension
148
This drug is a selective alpha 1 receptor antagonist, used to treat Benign prostatic hyperplasia and has less cardiovascular side effects vs. traditiinal alpha 1 atagonists
Tamsulosin
149
What advantages do selective alpha 1 antagonists have over nonselective alpha 1 antagonists
Less reflex tachycardia
150
What is Yohimbine used for
the alpha 2 receptor antagonist is used to treat posutral hypotension and ED \*erectile dysfunction
151
What is Mirtazapine used for
alpha 2 receptor antagonist is used to treat depression
152
What exambles of B1 selective antagonists
acebutolol, atenolol, bisoprolol, betaxolol, esmolol, metopropol
153
Give examples of nonselective B antagonists
Proranolol, timolol, pindolol, nadolol
154
Give examples of mixed alpha 1beta antagonists
Carvedilol, labetalol
155
What is the name of a Beta antagonist that also blocks K+ channels and is used as an antiarrhythmic?
Sotalol
156
What is intrinsic sympathomimetic activity?
Drugs act as partial agonists and only work when there is increased sympathetic drive, such as with exercise. Less badycardia, less effects on lipid metabolism.
157
What two Beta antagonists have ISA?
Acebutolol, pindolol
158
What happens to exercise tolerance in patients taking Beta Blockers.
decreased exercise tolerance
159
What are main therapeutic indications of Beta Blockers
Angina, arrhhythmias, hypertension, CHF, thrytoxicosis, glaucoma
160
What are non cardiovascular uses of propranolol?
treat stage fright, migraine prophylaxis
161
What betablockers can inhibit the majority of effects caused by thyrotoxicosis (except for what sign)?
Diaphoresis. Sweat glands have muscarinic receptors and are cholinergic rather than adrenergic.
162
What does propranolol do to serum LDL
increases serum LDL
163
Why does propranolol cause vivid dreams?
it crosses the BBB
164
What should B blockers be tapered instead of abruptly discontinued?
Chronic therapy leads to upregulation of beta receptors. Abrupt discontinuation may lead to life threatening cardiovascular rebound effects, tachycardia, hypertension, arrhythmias and deatth
