Quiz 4 - CNS Flashcards
(169 cards)
1
Q
Describe the breakdown of the nervous system
A
- peripheral nervous system
- central nervous system
2
Q
Describe the 2 divisions of the peripheral nervous system
A
- autonomic nervous system
- somatic nervous system
3
Q
Describe the 2 divisions of the autonomic nervous system
A
- parasympathetic nervous system
- sympathetic nervous system
4
Q
Acetylcholine contains a (tertiary/quaternary) amine which means it (can/cannot) cross the BBB
A
- quaternary
- cannot
5
Q
What 2 main functional groups are found on ACh?
A
- 4* amine
- ester
6
Q
The products of ester hydrolysis include:
A
- acid
- alcohol
7
Q
Where does AChE exist in the myoneural junction?
A
at the motor endplate
8
Q
List the depolarizing NMBAs:
A
succinylcholine
9
Q
List the steroid derivative NMBAs:
A
- rocuronium
- vecuronium
- pancuronium
10
Q
List the benzylisoquinoline derivative NMBAs:
A
- atracurium
- cisatracurium
- mivacurium
- d-tubocurarine
11
Q
What structure is typical of steroid derivative NMBAs?
A
4-ring structure and 4* amine
12
Q
Succinylcholine is 2 of which molecule linked together?
A
ACh
13
Q
Describe ester hydrolysis:
A
ester –> enzyme + H20 –> acid + alcohol
14
Q
Atracurium and cisatracurium produce which metabolite? Through which process?
A
Laudanosine through Hoffman elimination
15
Q
Which 2 processes do Atracurium and Cisatracurium undergo?
A
- ester hydrolysis
- Hoffman elimination
16
Q
Hoffman elimination depends on…
A
pH and temperature
17
Q
NMBAs have a (small/large) Vd. Why?
A
- small
- presence of a charge makes them hydrophilic
18
Q
List the NMBAs eliminated in the plasma:
A
- Atracurium (ester hydrolysis and HE)
- Cisatracurium (ester hydrolysis and HE)
- Mivacurium (plasma ChE)
- Succinylcholine (plasma ChE)
19
Q
List the NMBAs eliminated primarily in the kidney:
- What implication does this have on DOA?
A
- d-Tubocurarine
- Pancuronium
- Pipecuronium
kidney = slow clearance = longer DOA
20
Q
List the NMBAs eliminated primarily in the liver:
A
- Rocuronium
- Vecuronium
21
Q
5 things that affect onset of paralysis:
A
1) dose
2) potency (# of molecules)
3) Keo (chemistry/blood flow)
4) clearance
5) age
22
Q
Describe which has a quicker onset, Roc or Vec? Why?
A
Roc - you have to give more molecules to get it to work (0.6mg/kg = 6x as much as the dose of Vec) which makes the onset faster
23
Q
What effect does a nondepolarizing NMBA have on the ion channel?
A
closes and blocks the channel
24
Q
What effect does a depolarizing NMBA have on the ion channel?
A
opens and blocks the channel
25
List ways to assess postop NM function:
- sustained 5sec head lift
- ability to clench teeth
- negative inspiratory force >-40cmH2O
- ability to open eyes x5 sec
- hand grip strength
- sustained arm/leg lift
- quality of speaking voice
- tongue protrusion
26
A TOF ration of >___% indicates patient is ready for reversal
<90%
27
What TOF ratio was previously the gold standard for reversal?
70%
28
NMBAs that can cause histamine release:
What effect can this have?
- Atracurium
- Mivacurium
- d-tubocurarine +++
- succinylcholine
decreased SVR
29
Which NMBA produces a moderate block on cardiac muscarinic receptors? What effect can this have?
Pancuronium
increase HR
30
Pancuronium effect on HR
increases HR (vagolytic)
31
Onset / duration / reversal of Pancuronium
- onset slower
- DOA intermediate
- not reversed
32
Vecuronium effect on HR, BP
no effects on HR, BP; no histamine release
33
NMBA that requires reconstitution
Vec
34
Rocuronium effect on HR, BP
no effects on HR, BP; no histamine release
35
Ropacuronium effects on HR, BP
minimal effects on HR, BP; no histamine release
36
Ropacuronium was removed from the market due to...
potential for bronchospasm
37
4 problems with depolarizing NMBAs:
1) hyperkalemia
2) increased IOP
3) intragastric pressure
4) muscle pain
38
Drugs that interact with NMBAs:
- inhaled anesthetics
- antibiotics
- Mg
- other NMBA
39
Group of antibiotics that interact with NMBAs
Aminoglycosides (Gentamycin, Tobramycin)
40
Effect that Mg can have on neuromuscular blockade
prolongs it
41
How do acetylcholinesterase inhibitors interact with NMBAs?
increase ACh so it can compete with the NMBA
42
Why might early reversal with neo/glyco not work?
There is a ceiling effect (AChE is an enzyme) and it will take much longer for the patient to recover if it is used up before complete reversal can occur
43
Adverse effects of Neostigmine
- muscarinic effects
--bradycardia
--increased secretions
--N/V
--abdominal cramping
- nicotinic effects
--muscle fasciculations
44
Adverse effects of Glycopyrrolate
- tachycardia
- xerostomia
*less CNS anticholinergic effects than Atropine
45
Sugammadex falls under which class of drugs?
selective relaxant binding agent (SRBA)
46
Sugammadex is a _______. Specifically, Sugar ___-____
cyclodextrin
Sugar gamma-cyclodextrin
47
The core of Sugammadex is (lipophilic/hydrophilic) and the surrounding functional groups are (basic/acidic)
core = lipophilic
functional groups = acidic
48
Sugammadex reverses which NMBAs?
steroidals
49
The functional groups on Sugammadex interact with:
N+ on the steroidal NMBAs
50
The core of Sugammadex interacts with...
the 4 lipophilic rings of steroidal NMBAs
51
Sugammadex effectiveness with NMBAs
Roc > Vec > Pan
NO effect on benzyls or succs
52
Sugammadex (does/not) interact with the cholinergic system
does not
53
The Sugammadex-NMBA complex is excreted through the
kidneys
54
Roc must be in the (central/peripheral compartment) to bind to Sugammadex
central
the equilibrium shifts rapidly to pull Roc from tissues and back into plasma
55
Sugammadex should be dosed based on (IBW, LBW, TBW)
TBW
56
Sugammadex is incompatible with which drug commonle given at the end of surgery?
Ondansetron
57
Sugammadex notably interacts with which drugs?
hormonal contraceptives
58
ACh is made from which 2 substances?
Acetyl CoA and choline
59
ACh is hydrolyzed into which 2 substances?
Acetate and choline
60
ACh is an (inhibitory/excitatory) NT
both
61
There are ___ subtypes of muscarinic receptors
5
62
Stimulation of nicotinic receptors leads to opening of which channels and what effect in the cell?
opens Na+ and K+ channels resulting in depolarization
63
The 2 muscarinic receptors most relevant to anesthesia
M2 and M3
64
Where are M2 receptors located?
- CNS
- heart
- smooth muscle
65
Where are M3 receptors located?
- smooth muscle
- exocrine glands
66
Describe what happens when M2 receptors are stimulated
- Gi protein
- inhibits adenylyl cyclase
- negative inotropic effect --> decreased relaxation of smooth muscle
67
Describe what happens when M2 receptors are stimulated
- Gq protein
- effector = phospholipase C
- results in mobilization of Ca++
- smooth muscle contraction
- exocrine secretion
68
List the direct acting cholinergic agonists
- ACh
- Nicotine
- Muscarine
- Bethanechol
- Pilocarpine
69
ACh and Carbachol are unique in that they are cholinergic agonists that...
act on both muscarinic and nicotinic receptors
70
Succinylcholine is rapidly hydrolyzed by what enzyme?
Plasma/butyryl cholinesterase
71
Which substance does plasma cholinesterase NOT hydrolyze?
acetyl-B-methylcholine
72
Which substance does acetylcholinesterase NOT hydrolyze?
Succinylcholine
73
List the types of drugs that inhibit cholinergic transmission:
- inhibitors of vesicular storage
- inhibitors of release
- nicotinic antagonists
- muscarinic antagonists
- inhibitors of high-affinity choline transport
- inhibitors of pyruvate dehydrogenase
74
List the drugs that enhance or mimic cholinergic transmission:
- nicotinic agonists
- muscarinic agonists
- cholinesterase inhibitors
75
Describe the effects that muscarinic agonists have on the following systems:
- eye
- GI
- bladder
- vascular smooth muscle
- pupil constriction
- increased GI motility
- increased urination
- vascular smooth muscle dilation
76
Describe the effects that muscarinic agonists have on the following systems:
- bronchial smooth muscle
- exocrine glands
- heart
- brain
- bronchoconstriction
- exocrine gland secretion
- negative inotropic, chronotropic, and dromotropic effects on heart
- brain excitation, tremor, hypothermia
77
Describe the effects that AChE inhibitors have on the following systems:
- eye
- GI
- urinary bladder
- bronchial smooth muscle
- pupil constriction
- increased GI motility
- increased urination
- bronchoconstriction
78
Describe the effects that AChE inhibitors have on the following systems:
- exocrine glands
- heart
- skeletal muscle
- brain
- increased exocrine secretion
- negative inotropic, chronotropic, and dromotropic effects on heart
- increased skeletal muscle strength
- brain excitation, tremor, hypothermia
79
List the 5 nerve gases
1) GA (Tabun)
2) GB (Sarin)
3) GD (Soman)
4) VX
5) GF
80
Describe the MOA of nerve gases
potent organophosphate compounds that bind to and inhibit AChE and cause a cholinergic crisis
81
DUMBELLS stands for
diarrhea
urination
miosis
bradycardia
emesis
lacrimation
lethargy
salivation
82
Cholinergic crisis/muscarinic stimulation = what acronym?
DUMBELLS
83
Nicotinic receptor simulation produces which syndrome?
MTWHF syndrome:
muscle pain
tremors
weakness
HTN
fasciculation
84
Describe the 2 steps of nerve gas binding to AChE
1st stage: reversible with pralidoxime
2nd stage: "aging" is irreversible
85
Symptoms of nerve agent poisoning
- confusion
- altered LOC
- seizures
- coma
86
How do organophosphates occupy enzymes?
covalently bonded
87
What is the treatment for nerve gas poisoning?
1) Atropine - counteracts muscarinic effects
2) Pralidoxime (2-PAM) - counteracts nicotinic effects
2) Benzos - counteracts CNS effects
88
MOA of Pralidoxime
reactivates AChE at the NMJ - if the aging process has not occurred within 5 min to 24 hours, depending on the nerve agent
89
Patient monitoring after nerve gas poisoning
- minor symptoms = 6-8 hrs
- 2-PAM administration = ICU
90
Muscarinic agonists are used to treat:
- glaucoma
- postop ileus
- urinary retention
- xerostomia
91
Cholinesterase inhibitors are used to treat:
- glaucoma
- postop ileus
- urinary retention
- myasthenia gravis
- reverse NM blockade
- SVT
- Alzheimer's dz
92
SE of cholinergic agonists:
- hypotension
- bronchoconstriction
- salivation
- miosis
- sweating
- GI discomfort
93
Cholinergic agonists are contraindicated for which patients?
- asthma
- COPD
- peptic ulcer
- urinary obstruction
- GI obstruction
94
List 5 tertiary amines that are anticholinergics:
- Atropine
- Scopolamine
- Pirenzepine
- Dicyclomine
- Tropicamide
95
Ipratroprium is a (4*/3*) amine used to treat _____
4* amine used to treat COPD (prevents bronchoconstriction) as it does not need to cross the BBB
96
Benztropine is a (4*/3*) amine used to treat _____
3* amine used to treat EPS/Parkinson's; is able to cross the BBB
97
List 2 quaternary amines that are anticholinergics:
- Propantheline
- Glycopyrrolate
98
Describe the effects of muscarinic antagonists/anticholinergics on the following body systems:
- eye
- GI smooth muscle
- bladder
- bronchial smooth muscle
- pupil dilation
- decreased GI motility
- decreased urination
- bronchodilation
99
Describe the effects of muscarinic antagonists/anticholinergics on the following body systems:
- exocrine glands
- heart
- brain
- blockade of secretion/gastric acid secretion
- tachycardia, increased dromotrophic effect
- impaired memory, increased excitement
100
What effects does Atropine cause at lower doses (0.5mg)? Higher doses (1.0mg)?
- lower doses = decreased salivation and micturition
- higher doses = increased HR and decreased accommodation
101
Anticholinergic with greatest effect on HR
Atropine (+)
102
Anticholinergic with greatest effect on secretions
Scopolamine (-)
103
Anticholinergic with greatest effect on CNS
Scopolamine (+)
104
Treatment for anticholinesterase poisoning
Atropine
105
6 emesis receptors
- serotonin
- opioid
- CN VIII
- dopamine
- histamine
- muscarinic
106
Effects of anticholinergics on the eye
- increase dilation
- decrease accommodation
107
Closed-angle glaucoma surgical treatment
surgically placed hole in the iris to allow aqueous humor to drain and reduce IOP
108
Receptors involved in the eye
- alpha
- beta
- muscarinic
109
2 drugs used to treat open-angle glaucoma and their effects
- Pilocarpine = cholinomimetic = ciliary muscle contraction
- Timolol = beta blocker = decreased aqueous secretion from ciliary epithelium
110
Side effects of anticholinergics
- urinary retention
- constipation
- tachycardia
- dry mouth
- mydriasis
- inhibition of sweating
- toxic psychosis
111
Structural characteristics of a catechol
OH on 3rd and 4th carbons
112
Rate limiting step of NE synthesis
hydroxylation of tyrosine to DOPA by tyrosine hydroxylase
113
Why doesn't dopamine cross the BBB?
too polar
114
Final step in NE synthesis
hydroxylation of dopamine by dopamine-B-hydroxylase
115
COMT =
catechol-o-methyl transferase
116
NE is an (excitatory/inhibitory) NT
both - depending on the receptor it hits
117
Effect of stimulating A1 receptors
(excitatory)
formation of IP3 and DAG --> increased intracellular Ca2+
118
Effect of stimulating A2 receptors
(inhibitory)
inhibition of adenylyl cyclase --> decreased cAMP
119
Effect of simulating B1 receptors
(excitatory)
simulation of adenylyl cyclase --> increased cAMP
120
Effect of stimulating B2 receptors
(excitatory)
simulation of adenylyl cyclase --> increased cAMP
121
A1 receptor locations
- smooth muscle
(vascular, genitourinary, intestinal, cardiac, and hepatic)
122
A2 receptor locations
- CNS
- platelets
- lipocytes
- smooth muscle
123
B1 receptor locations
- heart
- kidneys
124
B2 receptor locations
- lungs
- blood vessels
- eyes
- uterus
- bladder
- liver
- GI
125
B3 receptor locations
lipocytes (fat mobilization)
126
Effect of making the N on a catecholamine more nonpolar
more B effects
127
List the catecholamines
- Epi
- NE
- Dopamine
- Isoproterenol
128
List the sympathomimetic amines
- Phenylephrine
- Ephedrine
- Methoxamine
- Amphetamine
129
B1-selective agonists
- DoButamine
- Prenalterol
130
B2-selective agonists
- Rotidrine
- Terbutaline
131
Types of drugs that enhance of mimic noradrenergic transmission:
- facilitate release
- block reuptake
- receptor agonists
132
Types of drugs that reduce noradrenergic transmission:
- inhibit synthesis
- disrupt vesicular storage
- inhibit release
- receptor antagonists
133
Phenylephrine acts on which receptors:
A1, maybe some B1
134
Effect of phenylephrine
vasoconstriction
135
NE acts on which receptors:
A1=A2>B1>>>>>B2
136
Epinephrine works on which receptors:
A1>>A2
B1>>B2
*dose dependent*
137
Ephedrine works on which receptors:
A1 (indirect)
B1>>B2 (direct)
138
How does Ephedrine indirectly stimulate the A1 receptor?
simulates endogenous Epi release, Epi then acts on the A1 receptor
139
Dopamine works on which receptors:
A1 + to +++++
B1>>B2
DA1
*dose dependent effects on A1*
140
Effects of low-dose Dopamine
increases renal and mesenteric blood flow
141
Effects of high-dose dopamine
A1 agonist > B1 agonist
142
Dobutamine works on which receptors:
A1 (little bit)
B1>>B2
*inotropism > chronotropism*
143
Isoproterenol works on which receptors:
B1=B2
144
Which adrenergic agonist is most effective at augmenting BP? Why?
Norepi - equally affects A1 venous and A1 arterial receptors more than other agonists
145
Effect that Isoproterenol has on BP and the subsequent effect on HR
decreases BP --> direct (B stim) and indirect (reflex) increase in HR
146
Effect that NE has on BP and the subsequent effect on HR
increases BP --> direct increase and reflex decrease in HR
147
Effect that Phenylephrine has on BP and the subsequent effect on HR
increases BP d/t A1 stimulation --> no direct effect but a reflex decrease in HR
148
Effect that Dobutamine has on BP and the subsequent effect on HR
no effect on BP but a direct increase in HR d/t B1 stimulation
149
Uses of adrenergic drugs
- hypotension
- reduction in regional blood flow
- cardiac applications
- respiratory
- ophthalmic
- uterine relaxation
- decongestant
- CNS uses
- central A2
150
Problems with adrenergic drugs
- HTN
- HoTN
- tachycardia
- ventricular arrhythmias
- infiltration with A agents
- CNS toxicity
151
Metoprolol, Atenolol, and Esmolol work on which receptors:
B1>>>>B2
cardio-selective BUT increase dose = increase B2 effects
152
Propranolol and Timolol work on which receptors
B1=B2
153
Labetalol and Carvedilol work on which receptors
B2=B2>A1>A2
*cause A1 receptor blockade*
154
Butoxamine works on which receptors
B2>>>B1
no practical medical use for it
155
BB with high lipid solubility:
Why is this relevant?
Propranolol
- can cross the BBB and is used to treat migraines
156
MOA of BB for HTN
decrease HR and inhibit RAAS system leading to a reduction in HTN
157
Uses of BB
- HTN
- ischemic heart disease
- cardiac arrhythmias
- glaucoma
- hyperthyroidism
- migraines
- portal HTN
158
First line treatment for chronic HF
ACE + BB
159
3 alpha blocking agents:
1) Phentolamine
2) Phenoxybenzamine
3) Prazosin
160
What happens to the receptor effects when NE and Epi are blocked by Phentolamine
- Phentolamine blocks A receptors
- see an increase in B1 and B2 effects
161
Which drug is a nonselective A blocker?
Phentolamine
- blocks both A1 and A2 receptors
- leads to an increase in B effects (increased HR)
162
Which drugs are selective A blockers?
Prazosin & Phenoxybenzamine
- selectively blocks A1 receptors
- A2 receptors maintain - feedback loop with NE
- normal NE acting on B receptors = less tachycardia
163
Which drug is a noncompetitive A blocker?
Phenoxybenzamine
164
Prazosin, Terazosin, and Doxazosin work in which receptors:
A1>>>>A2
165
Phenoxybenzamine works on which receptors:
A1>A2
166
Phentolamine works on which receptors:
A1=A2
167
Uses of alpha blockers
- pheochromocytoma
- HTN
- peripheral vascular dz
- infiltration of A agents
168
Uses of alpha blockers
- pheochromocytoma
- HTN
- peripheral vascular dz
- infiltration of A agents
- BPH
- make sexual dysfxn
169
Problems with alpha blockers
- **Orthostatic hypotension**
- sedation
- nasal stuffiness
- HF in patients with cardiac dz
