Pharmacology 2 Flashcards
1
Q
The ability of LA’s to block the conduction of nerve fibers depends on what three factors?
A
the nerves being blocked, chemical structure, and physiochemical properties of the LA
2
Q
What is the functional unit of peripheral nerves?
A
axon
3
Q
What is the function of Schwann cells?
A
support and insulate axons
4
Q
What are nodes of Ranvier?
A
segments of axon that do not contain myelin, where conduction is propagated.
5
Q
What is the primary site of action of LA’s and where are they located?
A
Na channels, in the nodes of ranvier.
6
Q
What is saltatory conduction?
A
action potentials jumping between nodes of Ranvier
7
Q
Describe the difference myelin makes in nerve conduction.
A
Myelinated nerves are larger, conduct impulses faster, and are more difficult to block.
8
Q
What are the three layers of connective tissue of nerves?
A
Epineurium - outer
perineurium
endometrium - inner
9
Q
Which connective tissue layer holds fascicles together to form a peripheral nerve?
A
epineurium
10
Q
What is the resting membrane potential of peripheral nerves?
A
-70 to -90mV
11
Q
What is the primary mechanism that creates the ionic gradient for electrical potential?
A
Na-K/ATPase
12
Q
What equation expresses the charge created by the K concentration gradient?
A
Nernst
13
Q
Besides K, what ions have a minor role in establishing intracellular resting membrane potential?
A
Na and Cl
14
Q
What happens to membrane potential when an electrical impulse is generated?
A
Na channels open, and membrane potential reaches +20 mV then the concentration reverses. Na channels close, K channels open. Na is removed by the NaK/ATPase (3 Na out, 2 K in)
15
Q
What state of Na channels do LA’s bind?
A
Open and inactive.
Not the closed state.
16
Q
What is the guarded receptor or modulated receptor hypothesis of LA’s?
A
LA’s preferentially bind to Na channels when they are in the resting or open states.
17
Q
What is a use-dependent or phasic block?
A
LA’s work faster as the Na channels is repetitively depolarized.
The more frequently the channel is stimulated the more time it is in the open or resting state.
18
Q
Where are the Na channel binding sites for LA’s located?
A
internal opening
19
Q
Is the ionized or nonionized portion of a LA more likely to bind to Na channels?
A
ionized
The nonionized portion crosses the cell membrane, but the ionized portion actually binds the Na channels
20
Q
Which LA can penetrate the lipid bilayer and can directly inhibit the Na channel without entering the axoplasm first?
A
Benzocaine (secondary amine)
21
Q
What is the order of differential block?
A
autonomic function - first superficial pain perception temperature motor function proprioception
22
Q
What are characteristics and function of A-alpha fibers?
A
largest diameter (12-20)
heavily myelinated
fast conduction
motor function and proprioception
23
Q
What are characteristics and function of A-beta fibers?
A
diameter 5-12
myelinated
motor function, touch and pressure
24
Q
What are characteristics and function of A-gamma fibers?
A
diameter 3-6
myelinated
muscle spindles and reflexes
25
What are characteristics and function of A-delta fibers?
diameter 1-5
myelinated
slowest conduction of the A fibers
pain and temperature sensation
26
What are characteristics and function of B fibers?
smaller diameter and less myelin than A fibers.
| preganglionic autonomic nerves
27
What are characteristics and function of C fibers?
smallest diameter 0.3-1.3
slowest conduction
pain and temperature
28
What is the ratio between the magnitude of the action potential and the magnitude of the critical membrane potential?
safety factor or conduction safety
29
What are the two type of LA's used in clinical practice?
aminoesters
| aminoamides
30
What are the three characteristic segments of LAs?
intermediate ester or amide carbon group
unsaturated aromatic ring
amine end
31
What parts of LA structure are hydrophilic and lipophilic?
lipophilic benzene ring
| hydrophilic amine
32
Name the LA.
33
How are ester LAs metabolized?
plasma and tissue cholinesterase via hydrolysis
34
How are amide LAs metabolized?
liver by CYP1A2 and CYP3A4
35
Which class of LA is more likely to cause an allergic reaction?
ester
36
Which class of LAs tend to be shorter acting?
esters due to metabolism. Tetracaine is the exception
37
What is the mechanism for amide LAs being longer acting?
more lipophilic and protein bound and require transport to the liver for metabolism
38
What determines offset and termination of LAs effect?
systemic absorption
39
What factors have a significant impact on LA duration of action?
vascularity and blood flow of injection area, lipid and protein binding, and vasoconstrictors
40
What determines local anesthetic potency?
lipid solubility
41
What does increased lipid solubility correlate to?
increased protein binding, increased potency, longer DOA, higher tendency for cardiac toxicity
42
The addition of a butyl group to the amide end of mepivicaine yields what LA?
bupivicaine
43
The addition of a butyl group to the aromatic end of procaine yields what LA?
tetracaine
44
What determines a LAs duration of action?
protein binding and lipid solubility
45
What proteins do LAs mainly bind?
alpha1-acid glycoprotein. They are weak bases
46
What is the most important determinant of LAs onset of action?
ionization.
47
Do LAs with a pKa closer to physiologic pH have a slower or faster onset?
Faster, the nonionized fraction will be a higher.
48
Despite its high pKA which LA has a rapid onset of action? Why is this?
Chloroprocaine, due to high concentrations injected
49
Which two LAs have low potency and short DOA?
procaine and chloroprocaine
50
Which two LAs have intermediate potency and DOA?
mepivicaine and lidocaine
51
Which 3 LAs have high potency and long DOA?
tetracaine, bupivicaine, and ropivicaine
52
Which LAs do not produce relaxation of vascular smooth muscle? 3
cocaine, ropivicaine, and lidocaine
53
What are the consequences of LAs causing vasodilation?
increased absorption, limits DOA, increase potential for toxicity
54
What is the mechanism of cocaine causing vasoconstriction?
it blocks reuptake of NE
55
What is the order of tissue absorption from greatest to least?
interpleural > intercostal > caudal > epidural > brachial plexus > sciatic femoral > subcutaneous
56
What determines the peak plasma concentration of a LA?
total dose
57
The addition of epinephrine to what two LAs for epidural does not decrease peak plasma levels?
prilocaine and bupivicaine
58
What is the concentration of epi added to LAs?
1:200,000 or 5mcg/mL
59
How does the addition of sodium bicarbonate affect LA?
speeds onset of sensory and motor block
60
How does the addition of hyaluronidase affect LAs?
facilitates diffusion of LA in the tissues
61
What are the undesirable effects of adding hyaluronidase to LAs?
allergic reactions, shortened DOA, increased risk of toxicity
62
What tissue group receives the greatest amount of LA from redistribution?
muscle
63
How are ester LAs metabolized?
plasma cholinesterase
64
How are amide LAs metabolized?
in the liver by P450 enzymes mainly 1A2 and 3A4
65
What is the primary factor that determines the elimination of amide LAs?
hepatic blood flow
66
What are the most common causes of LAST?
IV injection or absorption from large volumes injected into vascular tissues
67
Are inhibitory or excitatory neurons blocked first in LAST?
inhibitory - mechanism of seizure (lack of inhibition of excitatory neurons)
68
What is the first observed arrhythmia of LAST and the most serious?
Bradycardia
| V-fib
69
Most reported deaths from LAST are involve which LA?
Bupivicaine
70
What is the progression of symptoms in last?
agitation, tinnitus, circumoral numbness, blurred vision, metallic taste, muscle twitching, coma and seizures, cardiac and respiratory arrest
71
What are the preferred medications for seizure suppression in LAST?
benzos
72
What is the treatment of LAST?
20% lipid emulsion 1.5mL/kg over 1 minute
| infusion 0.25mL/kg
73
What medications are avoided in treating LAST?
vasopressin, CCBs, B-blockers
74
What are essential first steps in managing LAST?
avoid hypoxia and acidosis
75
Which class of LAs has the higher incidence of allergic reactions? Why?
```
Esters
Metabolite PABA (para-aminobenzoic acids)
```
76
What preservatives of LAs can cause allergic reactions?
methylparaben, paraben, metabisulfite
77
What is methemoglobin?
oxidized form of hemoglobin with reduced O2 carrying capacity. Causes Left shift of oxygen-Hgb response curve
78
What is the formula for methemoglobin?
HbFe3OH
79
What are clinical symptoms of methemoglobinemia?
hypoxia unresponsive to increased O2
abnormal colored blood
Normal PaO2, with low SpO2
Cyanosis
80
Which local anesthetics are most likely to cause MetHgb?
benzocaine and prilocaine
81
What is the mechanism of Prilocaine causing MetHgb?
metabolite o-toulidine oxidizes Hgb to MetHgb
82
What is the treatment for MetHgb?
Methylene Blue 1-2mg/kg over 3-10 minutes
83
What complication of LA's presents as bowel and bladder dysfunction, bilateral LE weakness and sensory impairment?
Cauda equina syndrome
84
What is the only naturally occurring LA?
cocaine
85
What is the maximum dose of cocaine?
5mL of 4% or 200mg
86
What is the onset and duration of EMLA cream?
1 hour onset
| 2-3 hour duration
87
What are the concentrations of Tetracaine, Epinephrine and Cocaine used for traumatic lacerations?
Tetracaine: 1%
Epi: 1:200,000
Cocaine: 4%
88
What is the maximum dose of exparel?
266mg
89
What makes up tumescent local anesthesia?
lidocaine, sodium bicarb and epinephrine
90
What is the maximum dose of lido for tumescent anesthesia?
35-55mg/kg
91
Where are supraspinal opioid receptors primarily located?
midbrain and medulla
92
Spinal anesthesia occurs by activation of what receptors?
presynaptic opioid receptors
93
What are the cellular mechanisms of opioids?
activation of G-proteins, decrease adenylate cyclase, decrease cAMP, decease pre- and postsynaptic Ca conduction, increase K conduction
94
What are the effects of Mu receptors?
supraspinal analgesia, euphoria, decreased ventilation
95
What are the effects of kappa receptor stimulation?
spinal anesthesia, sedation and miosis
96
What are the effects of delta receptor stimulation?
spinal analgesia, response to enkephalins, and modulate mu receptors
97
How does dose of opioids effect their termination?
small doses- effect is terminated by redistribution
| large doses- effect is terminated by metabolism
98
Which opioid metabolite is neurotoxic and may accumulate in the elderly or those with decreased liver or kidney function?
meperidine - normeperidine
99
How are opioids excreted?
primarily by the kidney
| secondarily by the billiard system and GI tract
100
What type of pain are opioids most effective for?
visceral continuous dull pain
101
Where do the analgesic properties of opioids come from? 2
1. directly inhibit ascending transmission of pain signals from the dorsal horn
2. activate pain control pathways descending from the midbrain to the dorsal horn
102
How do opioids increase ICP?
from respiratory depression induced hypercarbia
103
Rank the potency of opioids used in anesthesia?
Sufent > fent = remi > alfent
104
Which opioid receptor is most likely to cause dysphoria?
kappa receptors
105
opioid agonists at what receptors are more likely to cause respiratory depression>
Mu and kappa
106
How do opioids effect the CO2 response curve?
right shift. Require a higher CO2 to stimulate repirations
107
How do opioids stimulate N/V?
stimulate the chemoreceptor trigger zone, and vestibular system.
108
What are the cardiac effects of opioids?
bradycardia from vagal stimulation
| vasodilation
109
Which opioids cause histamine release leading to HoTN?
morphine, meperidine, and codeine
110
What are the GU effects of opioids?
detrusor muscle relaxation, urinary spincter contraction -> urinary retention.
Kappa receptor agonist cause diuresis.
111
Skeletal muscle rigidity is most often caused by what opioids?
Fentanyl and its derivatives
| especially Remi infusions
112
opioid induced muscle rigidity is mediated by what receptors?
central mu
113
Stimulation of what opioid receptors cause pruritis?
Mu
114
What medication is considered first line treatment of opioid induced pruritis?
nalbuphine
115
What are the endocrine effects of opioids?
release of vasopressin
| inhibition of corticotropin, gonadotropin, and thyrotropin
116
What are the most common side effects of spinal administration of opioids?
pruritis and urinary retention
117
What is the most common serious complication of intrathecally administered opioids?
respiratory depression
118
Which intrathecally administered opioid has the longest duration of action?
morphine`
119
What are the uses of methadone?
chronic pain, opioid abstinence syndromes, heroin addiction
120
What receptors is meperidine an agonist at?
mu
121
What is the metabolite of meperidine and its effects?
normeperidine - decreases the seizure threshold
122
Which opioid can induce serotonin syndrome if combined with MAOIs?
meperidine
123
Which opioid reduces shivering? What receptor does it act on?
Meperidine. Kappa
124
How is alfentanil metabolized?
N-dealkylation and O-demethylation by P450
125
Which medication can prolong the metabolism of alfentanil leading to respiratory depression and sedation?
erythromycin
126
How is fentanyl cleared and metabolized?
cleared by hepatic blood flow
| metabolized by N-dealkylation and hydroxylation
127
Which phenylpiperidine opioid is the most potent?
sufentanil
128
Which receptors is sufentanil an agonist at?
Mu
129
How is sufentanil metabolized?
O-demethylation and N-dealkylation
130
Sufentanil causes the most respiratory depression in which age group? Why?
elderly. smaller Vd
131
How does tramadol exert its effects?
mu agonist
inhibits NE and serotonin
stimulates 5-hydroxytryptamine release
132
What are the three opioid agonist/antagonists (partial agonists)?
Buprenorphine, Nalbuphine, Butorphanol
133
What do you need to know about buprenorphine?
mu agonist
long DOA = 8 hours
naloxone not effective
significant respiratory depression
134
What do you need to know about Butorphanol?
Kappa agonist, mu antagonist
more potent than morphine
can be given intranasal
treats shivering
135
What do you need to know about Nalbuphine?
Kappa agonist, Mu antagonist
reverse respiratory depression but maintain analgesia
Naloxone ineffective
antagonist pruritis
136
What are the three opioid antagonists?
naltrexone, naloxone, nalmefene
137
What is the MOA of naloxone?
blocks the opioid receptors and reverses respiratory depression and opioid analgesia
138
What are the potential side effects of naloxone?
pulmonary edema and increased catecholamine release leading to V-Fib
139
What do you need to know about nalmefene?
half life 10 hours
DOA 8 hours
dose is 0.1-0.5 mcg/kg
not for opioid dependent patients
140
What do you need to know about naltrexone?
longest DOA - 24 hours
used in alcohol withdrawal programs
prevents euphoric effects of opioids
active metabolite half life exceeds that of the parent compound
141
What enzymes do NSAIDs and acetaminophen inhibit?
cyclooxygenase
142
What are the beneficial effects of NSAIDs and acetaminophen?
NSAIDs: analgesic, antipyretic, anti-inflammatory
Acetaminophen: analgesic, antipyretic
143
In which patients is toradol avoided?
asthma, elderly, renal or GI dysfunction, bleeding disorders
144
What is the dose of acetaminophen in children?
15mg/kg
145
What is the preferred method to determine neuromuscular blockade?
quantitative method with a numerical value
| MMG, AMG, KMG, EMG
146
What is the preferred site for determining the level of neuromuscular blockade?
adductor muscle of the thumb via the ulnar nerve
147
What brach of the facial nerve is stimulated to assess NMB's? What are the muscles stimulated?
```
temporal.
Corrugator supercilii (eyebrow)
Orbicularis oculi (around the eye)
```
148
What is the order of NMB onset and recovery?
Eye muscles, then extremities, neck and chest trunk muscles, abdominal muscles, diaphragm.
Recovery is opposite
149
Which muscle of the eye is more resistant to NMB?
corrugated supercilii
150
Describe single twitch monitor.
0.1-1Hz for 0.1-0.2 milliseconds.
muscle movement = not 100% paralyzed
no movement = 100% paralyzed
151
Describe TOF monitor.
4 stimuli every 0.5 seconds at 2 Hz for 2 seconds
152
How much paralysis occurs with each amount of twitches?
0/4: 100%
1/4: 90-95%
2/4: 80-85%
3/4: 75-80%
153
What is the ideal degree of paralysis for surgery?
1 or 2 twitches (85-90% block)
154
Describe Double burst stimulation
two short bursts of 50 Hz tetanus separated by 0.75 seconds.
155
Describe tetanus?
continuous stimulation for 5 seconds at 50 or 100Hz
156
Describe post-titanic count.
50 Hz for 5 seconds, wait 3 seconds, then a series of single 1 Hz twitch stimulations
157
What is the ED95 of succinylcholine?
0.3 mg/kg
158
How does NMB potency affect speed of onset?
Lower the potency the faster the speed of onset
159
How do patients with atypical pseudocholinesterase respond to succinylcholine?
prolonged response
160
For Succinylcholine what is the:
half life:
DOA:
full recovery:
half life: 2-4 min
DOA: 5-10 min
full recovery: 12-15 min
161
How is succ metabolized?
By pseudocholinesterase into succinylmonocholine and choline
162
How does succ affect ICP?
increases by 10-15 for 5-8 minutes.
| Prevented with a nondepolarizer
163
What medications should be given before a second dose of succ?
Atropine or Glyco
164
A second dose of succ is most likely to cause bradycardia in which patient population?
peds
165
Which of the following are "nonspecific esterases"?
paraoxonase and albumin esterase
166
What are all the names for AchE?
```
"The 1 and True Specific Genie"
Type 1
True
Specific
Genuine
```
167
What are all the names for pseudocholinesterase?
"The 2nd But False Plasma Princess"
Type 2, Butylcholinesterase, False, Plasma, Pseudocholinesterase
Serum, benzoyl, nonspecific
168
What populations is PChe decreased in?
Pregnant, newborns, infections, PE, muscular dystrophy, MI
169
What type of PChE does dibucaine inhibit?
typical or usual PChE
| Not atypical
170
What drugs may inhibit Cholinesterase?
Donepezil, Rivastigmine, Galantamine
171
What is the dose of Succ for obese patients?
1mg/kg based on TBW
172
How does succ affect IOP?
increases by 5-15 mmHg for 10 minutes.
| Airway is the priority, seeing is overrated
173
What situations cause an up regulation of AChR's?
upper/lower motor neuron denervation, infection, muscle trauma, muscle tumor, muscle inflammation, burns, immobilization, chemical denervation
174
Succ is safe within what time period after a burn?
48 hours
175
Where are succ induced myalgias most likely to occur?
subcostal region, trunk, neck, upper abs, shoulders
176
What does of nondepolarizers reduce the incidence of myalgias and fasciculations?
10-30% of ED95
177
How can we prevent fasciculations?
Lidocaine, NSAIDS, higher dose of Succ
178
Who is most prone to fasciculations?
young, physically inactive women
179
What populations have the lowest incidence of myalgias?
extremes of age, pregnant
180
What are the doses of vec, roc, and Atracurium to prevent fasciculations?
0.04mg/kg Roc, 1.5mg Atracurium, 0.3mg Vec
181
What dose of Succ causes a phase 2 block?
6-8mg/kg
182
What is the preferred nondepolarizer for RSI?
Roc
183
What is the relationship between NDNMB potency and onset?
inverse.
| The lower the potency the faster the onset
184
Giving 10% of the intubating dose of a NDNMB prior to induction is referred to as what?
priming. It speeds the onset but produces respiratory depression in some patients
185
What is the dose, onset, DOA, and elimination of Roc?
Dose: 0.6-1.2mg/kg
Onset: 45-90 seconds
DOA: 30-60 minutes
Elimination: biliary excretion unchanged
186
What is the dose, onset, DOA, and elimination of Vec?
Dose: 0.1mg/kg
Onset: 3 minutes
DOA: 30-45 minutes
Elimination: Liver and kidney
187
What is the dose, onset, DOA, and elimination of Pancuronium?
Dose: ED95 0.14mg
Onset: 4 minutes
DOA: 60-90 minutes
elimination: kidneys,
188
What is the dose, onset, DOA, elimination, and metabolite of Atracurium?
```
Dose: 0.1-0.25mg/kg
Onset: 1-3 minutes
DOA: 30-60 minutes
elimination: Hoffman
Metabolite: laudanosine
Histamine release
```
189
What is the dose, onset, DOA, elimination, and metabolite of Cisacurium?
```
Dose: 0.1mg/kg
Onset: 2-4 minutes
DOA: 30-60 minutes
elimination: Hoffman
Metabolite: laudanosine
```
190
What is the dose, onset, DOA, elimination, and metabolite of Mivacurium?
Dose: 0.08mg/kg
Onset: 2-4 minutes
DOA: 15-20 minutes
elimination: plasma cholinesterase
191
What are the CV effects of Atracurium and mivacurium? What causes this?
increased HR and decreased BP
| Histamine release
192
Which NMB has vagolytic properties?
Pancuronium
193
What NMB's are preferred for patients with liver and kidney disease?
Atracurium and Cisatracurium
194
How should you dose NMB's for obese?
Ideal body weight
195
How does core temperature affect DOA of NMB's?
hypothermia prolongs DOA
196
What two categories of drugs are most likely to cause allergic reactions/
Antibiotics and NMB's
197
What are the main components of the allergic sites on NMB's?
quaternary and tertiary ammonium ions
198
Which of the cholinesterase inhibitors is used to treat myasthenia gravis, and rarely used in anesthesia?
Pyridostigmine
199
What is the gold standard type of monitoring to determine residual paralysis?
Quantitative
200
What is the most rapid acting cholinesterase inhibitor?
edrophonium. 30-60 seconds, DOA 5-10 minutes. Renal elimination
201
Neostigmine
Onset 4-8 minutes
DOA 30-120 minutes
Liver and Kidney metabolism
202
What are the vagal effects seen if you only give a cholinesterase inhibitor?
Diarrhea, Urination, Miosis, Bradycardia, Bronchoconstriction, Emesis, Lacrimation, Laxation, Salivation
203
Which anticholinergics are tertiary amines?
Atropine and scopolamine
204
What are adverse reactions to sugammadex?
N/V, allergy, HTN, bradycardia
205
What increases potency of LAs?
increasing lipid solubility, increased carbon atoms, adding a halide to the aromatic ring, an ester linkage, or the presence of large alkyl groups on the tertiary amide nitrogen.
