Block 7 - L1-L4 Flashcards
(137 cards)
1
Q
What are the endogenous opioid peptide families implicated in acupuncture analgesia?
A
- Beta-endorphin
- Enkephalin
- Dynorphin
2
Q
What are the major NT implicated in acupuncture analgesia?
A
- 5-HT
- NE
- Substance P
- GABA
- Dopamine
- ACTH
3
Q
List the various afferent nerve fibers involved in transmitting pain impulses.
A
- C fibers (large unmyelinated)
2. A-delta fibers (small myelinated)
4
Q
Describe transmission of a painful stimulus.
A
- An injury to the skin activates the sensory receptors of small afferent A-delta and C-fibers.
- These synapse onto the STT in the SC.
- The STT projects to the thalamus.
- The thalamus projects to the primary sensory cortex.
5
Q
What does low frequency/high intensity PENS mean? High frequency/low intensity?
A
2 to 15 Hz as strong as the patient can tolerate
30 to 200 Hz just to where the patient can barely feel it
6
Q
Describe the effect of low frequency/high intensity electro-acupuncture stimulation.
A
- Needle activates a Type II or III small afferent nerve from a sensory receptor in the muscle.
- This cell synapses in the SC onto an anterolateral tract (ALT) cell.
- This projects to the SC, midbrain, and pituitary-hypothalamus complex.
- In the SC, the ALT tract causes release of enkephalin or dynorphin pre-synaptically. This inhibits transmission of pain pre-synaptically in the SC.
- In the midbrain, cells in the periaqueductal gray are excited. This causes release of enkephalin, which disinhibits another cell. This activates the raphe nucleus in the medulla, causing it to send impulses down the dorsolateral tract. This releases monoamines (5-HT, NE) onto SC cells. This causes post-synaptic inhibition of pain.
- In the pituitary/hypothalamus, beta-endorphin and ACTH are released.
7
Q
Describe the effect of high frequency/low intensity electro-acupuncture stimulation.
A
This only stimulates the spinal cord and midbrain. Specifically, the SC releases GABA post-synaptically.
8
Q
Why are needles also placed at distal points (away from the painful region)?
A
To activate the midbrain and hypothalamic-pituitary complexes - causes endorphin release
9
Q
Compare low frequency/high intensity to high frequency/low intensity as it relates to the substances released and the locations of this release.
A
LF/HI:
SC: enkephalin, dynorphin B
Midbrain: enkephalin, serotonin, NE
Pituitary/hypothalamus: B-endorphin, ACTH
vs.
HF/LI:
SC/midbrain only: GABA
10
Q
Compare low frequency/high intensity to high frequency/low intensity as it relates to the effect of naloxone.
A
LF/HI: effect blocked by naloxone
vs.
HF/LI: effect not blocked by naloxone
11
Q
Compare low frequency/high intensity to high frequency/low intensity as it relates to the results.
A
LF/HI: slow onset, long duration, cumulative effects
vs.
HF/LI: fast onset, short duration, non-cumulative effects
12
Q
What is the thermocouple effect of Kelvin-Thomas?
A
A gradient along the length of a homogenous conductor with a temperature gradient produced by the ends of the conductor at different temperatures
13
Q
What is the Benedick’s effect?
A
The current along a uniform conductor is reinforced by the electro-magnetic effect between the second (spiraled) metal of the handle in contact with the first metal of the shaft.
14
Q
What are the some of the recommended uses for acupuncture as described by the NIH consensus panel?
A
Adult post-operative and chemotherapy nausea and vomiting and in postoperative dental pain
15
Q
From what plant are exogenous opioids harvested?
A
Poppies (papaver somniferum and papaver album)
16
Q
What is any substance, natural or synthetic, that produces morphine-like effects that are blocked by antagonists such as naloxone?
A
Opioid
17
Q
What are compounds that are found in the opium poppy?
A
Opiate
18
Q
What is a narcotic?
A
Something that induces sleep
19
Q
What are the 6 therapeutic uses of opioids?
A
- Pain management
- Anesthesia, sedation
- Anti-diarrheal
- Antitussive
- Treatment of dyspnea
- Treatment of addiction
20
Q
What are the corresponding pharmacological effects of opioids for each therapeutic use?
A
- Analgesia (pain management)
- Sedation (anesthesia)
- Decreased tone in intestinal muscle and decreased secretions (anti-diarrheal)
- Depression of cough reflex (antitussive)
- Respiratory depression (treatment of dyspnea)
- Addiction, dependence, euphoria (treatment of addiction)
21
Q
What are the risks and AE of opioids?
A
- Addiction, abuse, OD
- Tolerance
- Physical dependence (withdrawal symptoms if stopped)
- Increased pain sensitivity
- GI - constipation, N/V, dry mouth
- CNS - sleepiness, dizziness, depression, confusion
- Sexual - decreased testosterone, decreased sex drive/energy/strength
8 Derm - pruritis, sweating
22
Q
What are the features o the opioid receptors?
A
- 7 transmembrane domains
- Membrane bound
- G-protein coupled
23
Q
How does opioid receptor activation block pain pathways pre-synaptically?
A
Stimulation of mu opioid receptors leads to inhibition of AC, which prevents opening of calcium channels, reducing NT release
24
Q
How does opioid receptor activation block pain pathways post-synaptically?
A
Stimulation of mu opioid receptors increases potassium channel opening, causing hyperpolarization and stimulating the MAPK cascade
25
List the sites where opioids activate opioid receptors to relieve pain.
1. Receptors in the periphery block nociceptor activation
2. Receptors on second-order pain transmission neurons block ascending STT to medulla
3. Receptors at C-fiber terminals in SC blocks release of pain NT
4. Receptors in the midbrain activate descending systems in PAG mediated by NE and 5-HT
26
How do opioids induce respiratory depression?
Opioids alter the response of the body to arterial CO2 levels at the ventilatory control center in the medulla. Normally, minute volume should increase with rising levels. Opioids produce a blunted response of minute volume. This can lead to brain injury and death.
27
What structural feature of morphine and derivative drugs gives it the opioid activity?
Free -OH on a benze ring linked by 2 C atoms to N atom
28
Which opioid receptor agonists are most clinically useful and why?
Those with a high affinity for mu receptors (morphine, fentanyl, levorphanol, methadone, sufentanil, etc.)
29
What are the effects of opioid receptor agonists at mu receptors?
1. Analgesia (supraspinal - mu1, spinal - mu2)
2. Respiratory depression (mu2)
3. Euphoria
4. Miosis
5. Physical dependence
6. Sedation
7. Inhibition of GI motility
30
What are the effects of opioid receptor agonists at delta receptors?
1. Analgesia (spinal)
2. Respiratory depression
3. Inhibition of GI motility
31
What are the effects of opioid receptor agonists at kappa receptors?
1. Analgesia (spinal, peripheral)
2. DYSPHORIA
3. Miosis
4. Sedation
32
How is heroin different than moprhine?
Heroin is more lipid soluble (acetyl groups) than morphine, so it passes the BBB more efficiently.
33
What are the indications for moprhine?
1. Analgesia
2. Dyspnea
3. Anti-diarrheal (in suspension with kaolin)
4. Antitussive
34
How is morphine metabolized?
Conjugation with glucuronic acid
35
What causes the analgesic effect of morphine?
Morphine-6-glucuronide
36
How is morphine-6-glucuronide excreted?
Via the kidney (caution in renal failure, children, elderly)
37
How is codeine different from morphine?
Greater oral efficacy
Lower first-pass metabolism
Metabolized by liver
Low opioid receptor affinity
38
What is the indication for codeine?
Anti-tussive
39
What are the indications of the D-isomer of Levorphanol (destrometorphan)?
Antitussive
Not analgesic, NMDA receptor inhibition
40
The L-isomer of Levorphanol (Levo-Dromoran) binds ___ receptors. It can be administered ___. It is similar to morphine - how is it different?
Receptors: mu, kappa, and delta
Administration: IV, IM, PO
Less N/V, longer half life, repeated administration leads to accumulation in the plasma
41
What are the CNS effects of meperidine on the CNS?
1. Strong analgesic
2. Pupillary constriction, sensitivity of labyrinthine apparatus
3. Decreased secretion of pituitary hormones
4. CNS excitation, tremors, seizures
5. Local anesthetic effects
6. Respiratory depression
42
What are the cardiovascular effects of meperidine?
Increase in HR (after IV due to release of histamine; not for IM)
43
What are the smooth muscle/GI tract effects of meperidine? How does this compare with morphine?
Slows gastric emptying, delays absorption of other drugs
Less constipation and more CNS bioavailability than morphine
44
What are the indications for meperidine?
1. Analgesia
2. Treatment of drug-induced rigors and shaking chills
3. Diarrhea
45
What drugs can induce rigors and shaking chills?
IV amphotericin B, aldesleukin, trastuzumab, alemtuzumab
46
Meperidine congeners are used as a ___ drug.
Anti-diarrheal
47
What synthetic opioids are used in anesthesia?
Fentanyl, sufentanil, remifentanil, and alfentanil
48
What are the benefits to using opioids in anesthesia?
1. Short time to peak analgesic effect
2. Rapid termination of effect after small bolus doses
3. Cardiovascular safety
49
What are fentanyl and derivatives indicated for?
1. Anesthetic adjuvants
| 2. Chronic pain treatment
50
What is tramadol?
Synthetic codeine analog and weak mu agonist
51
What is a significant AE of Tramadol?
Seizures
52
What are the AE of pentazocine, butorphanol, and nalbuphine?
Dysphoria and psychotomimetic effects, increased BP and HR
53
What are the major contraindications of opioids?
1. Increased sensitivity (neonates, compromised BBB, elderly)
2. Hepatic or renal disease
3. Compromised respiratory function
4. Patients with head injury or elevated ICP
5. Patients with reduced blood volume or hypotension
54
What gives morphine derivatives anatagonist activity?
Bulky substituent on the nitrogen atom of moprhine
55
What are the major opioid receptor antagnoists?
Naloxone, Naltrexone, Buprenorphine
56
What are the indications for opioid receptor antagonists?
1. Opioid overdose (reversal by naloxone)
2. Constipation (methylnaltrexone)
3. Management of abuse syndromes
57
What are cautions related to opioids and analgesia?
1. Opioids are not first line therapy for pain
| 2. Establish goals for pain management
58
What are some of the goals of anesthesia?
Unconsciousness, amnesia, immobility, prevent post-operative N/V, retention or improvement of pre-operative organ systemic functions
59
What is the Meyer-Overton hypothesis of inhalational anesthetics?
The higher the lipid solubility of the drug, the more potent it is
60
What might be the MOA of inhalational anesthetics?
GABA chloride channel IPSP (hyperpolarization)
61
True or false - there is no antidote for inhalational anesthetics.
True
62
What are the stages of general anesthesia?
1. Pre-operative anxiolytic +/- analgesic
3. Pre-oxygenation (de-nitrogenation)
3. Induction
4. Maintenance
5. Emergence (turn off the gas, give 100% oxygen, breathe, extubate)
6. Recovery
63
What is the minimum alveolar concentration (MAC)?
The minimum alveolar concentration at 1 ATM that prevents movement during a skin incision in 50% of people
64
What influences MAC?
Temperature, age, and other medications (not influenced by sex, oxygen, pH, BP)
65
What is the relationship between cardiac output and induction of inhalational anesthetics?
As CO increases, induction takes longer (is slower)
66
What is the path of inhalational anesthetics through the body?
Machine - alveoli - arterial blood - brain - venous blood - alveoli - machine
67
How do we measure the amount of inhalational anesthetic going to the brain?
Fa/Fi = end-tidal/inspired = amount returned to alveoli/amount delivered
68
Describe the concept of cascade.
The faster the agent gets from one compartment (airway, alveoli, blood, brain) to the next, the slower it reaches equilibrium
69
How can uptake and distribution of the inhalational anesthetic be increased?
Increase delivery to increase speed of induction, increase [agent], increase MV
70
After delivery to the alveoli, what three factors determine uptake into the blood?
1. Solubility
2. Partial pressure difference
3. Cardiac output
71
Discuss the solubility of NO and halothane.
NO is not soluble in the blood.
Halothane is very soluble in blood. The more soluble agents reach equilibrium slower than less soluble agents. In other words, the blood compartment is larger for a more soluble agent.
72
What determines the solubility of the gas in blood?
Blood/gas partition coefficient (lambda)
A gas with a higher blood gas coefficient will require higher uptake of gas into the blood and induction will be slower.
73
What drives movement of the drug through the body?
Partial pressure
74
Where does the anesthetic go first?
Vessel rich organs - brain, heart, liver, kidney
During maintenance, the skin and muscle start uptake. It goes to the fat latest.
75
What are side effects of inhalational anesthetics?
1. Decreased oxygen consumption
2. Decreased vascular tone (decreases BP)
3. RR becomes regular, rapid, and shallow; status asthmaticus
4. Smooth muscle relaxation
5. Uncoupling in the brain (increased blood flow but decreased O2 consumption)
76
Which inhalational anesthetic is incomplete and has a rapid onset and recovery?
Nitrous oxide
77
Which inhalational anesthetic has a low volatility, poor induction, and rapid recovery?
Desflurane
78
Which inhalational anesthetic has rapid onset and recovery?
Sevoflurane
79
Which inhalational anesthetics have a medium rate of onset and recovery?
Isoflurane, enflurane, halothane
80
What is the main IV anesthetic and what is it used for?
Propofol; induction, maintenance, and sedation
81
What are the effects of propofol?
1. Decreased cerebral metabolic rate of oxygen (CMRO2) and ICP in the brain
2. Veno- and arterio- dilator (preload and afterload reductions, lowers BP)
3. Respiratory depression
82
What is thiopental?
Barbiturate acting on GABA; most-used induction drug until propofol, not available in the US
83
What are the effects of thiopental?
Arterial vasoconstrictor
| Puts brain to sleep (vasoconstriction and decreased CMRO2)
84
How does ketamine work?
NMDA receptor antagonist
85
What are the effects of ketamine and what is it used for?
Dissociative anesthesia
Induction and short procedures, pain
Bronchodilator, increase CMRO2/cerebral blood flow/ICP/BP/HR
86
What are the AE of ketamine?
Bad dreams, salivation, twitchiness
87
Why is etomidate a useful drug?
Few cardiovascular side effects (GABA, vasoconstrictor and decreased CMRO2)
88
What is the AE of etomidate?
Adrenal suppression
89
Broadly, how do local anesthetics work?
Bind to sodium channels in nerves to block nerve transmission
90
What are the 4 types of local anesthetics?
1. Periperhal nerve blocks
2. Neuraxial
3. Subcutaneous
4. Topical
91
What are the indications of local anesthetics?
1. Surgical anesthesia
| 2. Decrease post-op pain
92
How does the nerve anatomy affect local anesthesia?
1. Myelinated vs. non-myelinated: non- are difficult to block, most block ~3 nodes of Ranvier
2. Core vs. mantle fibers - block works proximally first (nerve fibers innervating proximal structures are on the outside), followed by distal
3. Smaller nerves are easier to block
93
Which types of fibers are myelinated? Which are not?
Myelinated: A, B
Unmyelinated: C
94
What are the biggest and slowest fibers? The smallest and fastest?
A > B > C
95
What is the function of A-alpha fibers?
Motor
96
What is the function of A-beta fibers?
Tactile, proprioception
97
What is the function of A-gamma fibers?
Muscle tone
98
What is the function of A-delta fibers?
Pain, cold temperature
99
Where are B fibers located?
Pre-ganglionic sympathetics
100
What is the function of C fibers?
Visceral and slow pain
101
In what order are fibers blocked?
1. B (small and myelinated)
| 2. A delta (smallest of A fibers, myelinated)
102
What are the implications of a differential blockade?
1. Spinal/epidural anesthesia - sympathetics go first, followed by sensory, then motor
2. Peripheral nerve blocks - first sign may be lack of proximal muscle coordination
103
What is the resting membrane potential of nerves?
-70 mV
104
What are the three states of voltage gated sodium channels? Discuss.
1. Resting: m closed, h open
2. Activated/Open: m open, h begins to close
3. Inactivated: h closed, m open
105
Where do local anesthetics bind?
R site, near the h gate
106
Local anesthetics preferentially bind to which states of sodium channels?
Activated/open and inactivated (frequency-dependent)
107
What are the two groups of local anesthetics?
Amides (two "i" in the name) and esters (one "i" in the name)
108
What are the three parts of local anesthetics?
1. Benzene ring
2. Alkyl chain (ester or amide linkage)
3. Tertiary amine group
109
List the 4 esters.
1. Cocaine
2. Procaine (Novocain)
3. Tetracaine (Pontocaine)
4. Benzocaine
110
List the 4 amides.
1. Lidocaine
2. Mepivacaine
3. Bupivacaine
4. Ropivacaine
111
In order to bind to the receptors, what must the anesthetic do?
Traverse the membrane - only the uncharged portion can cross. However, the charged form is the active form.
112
If pH < pKa, what will happen?
Lots of H+ ions - more likely to have charged molecules
113
The more lipophilic a drug is, the more ___ it will be.
Potent
114
Proteins that bind to proteins frequently affect the duration in what way?
Longer duration
115
What are some adjuncts to local anesthetics?
EPI (vasoconstriction, marker for intravascular injection)
Alpha-2 agonists (EPI, dexmedetomidine, clonidine)
116
What are the indications for neuraxial anesthesia?
Anything from the chest down to the lower extremities
117
What are the absolute contraindications for neuraxial anesthesia?
Patient refusal, infection at insertion site, elevated ICP, bleeding diathesis
118
What are the relative contraindications for neuraxial anesthesia?
Bacteremia, pre-existing neurologic disease, abnormal coagulation, cardiac disease
119
Where does the spinal cord terminate in adults and infants?
Adults: L1-2
Infants: L2-3
120
Where does the dural ssac terminate?
S1-2
121
Where are spinal taps usually done?
L4-5
122
Discuss spinal vs. epidural blocks.
Spinal: subarachnoid block, needle inserted at L3-L5 (Tuffier's line), drug deposited around cauda equina
Epidural: any level, volume-dependent segmental blockade, concentration affects quality, site of action is nerve roots
123
What are the respiratory effects of neuraxial anesthesia for a blockade at the thoracic level?
1. Normal tidal volume
2. Minimal reduction in vital capacity with abdominal muscle paralysis
3. Loss of proprioception can be upsetting to patient
124
Discuss a high spinal blockade with respiratory arrest and how to treat it.
Never happens because of paralyzed phrenic nerves - results from hypoperfusion of the respiratory center in the 4th ventricle; treat with vasopressors and supportive ventilation
125
What are the effects of neuraxial anesthesia on the vascular bed?
1. Sympathectomy - arterial dilation and profound venodilation
2. Venodilation - decreased venous return and reduced BP
126
What are the affects of neuraxial anesthesia on the heart?
Bradycardia (due to unopposed vagal stimulation an decreased venous return - Bezold-jarisch reflex)
Cardioaccelerator fibers - T1-4
127
What affects the absorption of local anesthetics?
1. Vascularity (intercostal > caudal > epidural > brachial plexus > sciatic)
2. Drug properties (protein binding, lipid solubility)
3. Patient properties
4. Addition of vasoconstrictors
128
How are esters eliminated?
Plasma cholinesterase
129
How are amides eliminated?
Liver hydrolysis by cytochrome p450
130
Discuss neurotoxicity of local anesthetics.
Happens when inhibition of neurons > excitatory neurons
Signs/symptoms: lightheadedness, peri-oral numbness, tinnitus, seizures
Worsened by acidosis - decreased protein binding, increased cerebral blood flow
131
Discuss cardiovascular toxicity of local anesthetics.
Occur at higher concentrations than neurotoxicity
Cardiac sodium channel bloackade, direct vasodilator effects, inhibition of SNS reflexes, neuro-mediated effects, cocaine-specific
132
What are some EKG findings in cardiovascular toxicity due to LA?
AV conductional blockade (any degree), slurred QRS, Vfib, Vtach
133
How is toxicity of LA addressed with prevention?
Fractionated injection with intermittent aspiration
Use of EPI as intravascular marker
Monitor patient
134
How is toxicity of LA addressed with supportive therapies?
Maintain oxygenation and ventilation
Treat seizures
Treat arrhythmias (DO NOT USE LIDOCAINE)
135
What is the antidote for LA toxicity (just cardiovascular?)?
Intralipid
136
What allergic reactions can happen with LA?
Type I or Type IV hypersensitivity; almost always esters
137
How can you speed the onset time for a block?
Add sodium bicarbonate
