Midterm 1 (without 0.4 + 0.5 readings) Flashcards
Bupivacaine is markedly toxic if inadvertently given intravenously, causing what possible effects in the body?
- excitation,
- nervousness
- tingling around the mouth
- tinnitus
- tremor
- dizziness
- blurred vision
- seizures
^^ these are followed by a depression:
- drowsiness
- loss of consciousness
- respiratory depression
- apnea
When has bupivacaine caused death?
Bupivacaine has caused several deaths by cardiac arrest when epidural anesthetic has been accidentally inserted into a vein instead of the epidural space.
What are the known risks about acute exposure to fentanyl through epidurals with the fetus?
- Prolonged labor (opioid and local anesthetic epidural may reduce uterine activity)
- Increased need for forceps and C-section
- Fetal and maternal respiratory depression
(*most serious risk) - Problems with breast feeding (may be due to disrupted oxytocin release in labor)
- Maternal hypotension (low blood pressure)
If administered improperly, the epidural may puncture
the dura and cause _____________?
a prolonged headache
When was morphine first introduced into the epidural space? What year was it first officially used in child birth?
It was first introduced in 1979, and was used for the first time in an epidural infusion for pain relief during labour in 1980
What is an opiod?
any substance that acts on the opioid pain receptors in the body, that bind to 1 or more of the different types of opioid receptors in the body
**can be naturally occurring or synthetic
When was cocaine clinically used for the first time? For what purpose?
In 1884 by Sigmund Freud, who used it on a patient with a morphine addiction
What was the first synthetic version of cocaine?
PROCAINE, developed in 1904
LINDOCANE was influenced by this as another synthetic version of cocaine in 1943 that was heavily used in WW2
What do raw coca leaves cause when injested?
a mild stimulant that suppresses hunger, thirst, pain and fatigue
When was cocaine first used in an epidural?
In 1885 in New York
What is the most common local anesthetics found in epidurals?
BUPIVACAINE
What is the most common opiod found in epidurals?
FENTANYL
What are the 2 common ways of local anesthetic administration?
- topical anesthesia (applied externally and has a rapid onset with high concentration) –> ex. over the counter tooth gel
- Infiltration anesthesia (applied through injection) –> used for minor surgical procedures
What are the 5 ways opiods can be delivered?
- orally
- trandfermally (through skin, ex. patch)
- Intravenously (into blood)
- subcutaneously (into lower layer of skin)
- injected into the epidural or subarachnoid space
Where is epidural anesthesia injected?
in the space immediately outside the DURA MATTER (why it’s called an epiDURAl)
**most widely used in childbirth
What is spinal anesthesia?
involves injecting medication into the subarchnoid space (CSF)
*Synonyms: a spinal block, subarachnoid anesthesia, intrathecal anesthesia
What does Neuraxial blockade mean?
it refers to local anesthetics being delivered around the nerves of the CNS (includes both spinal and epidural anesthesia)
**does not having both forms of epidurals at the same time, just Neuraxial blockade is an umbrella term that includes both
When drugs are in the epidural space, what can they do?
- diffuse across spinal cord meninges
- exit invertible foramina to reach muscle space
- diffuse into epidural fat
- diffuse into ligaments
What determines how drugs diffuse in the body?
Fat solubility –> whether the substances mixes better with fat or water
Is epidural morphine better or worse than systemically (ex. IV) administered morphine?
Epidural morphine > systemical morphine
What is a more effective epidural than just morphine alone?
An epidural with morphine and bupivacaine is more effective than morphine alone
What are local anesthetics? How do they work?
medication that causes absence of pain sensation
**must cross the spinal cord in order to work
They work by reversibly BINDING TO THE SODIUM CHANNELS ON MEMBRANES OF THE NEARBY NEURONS
(this prevents the sodium ions from entering inside the neuron, resulting in the action potentials of those neurons to be inhibited, aka no longer able to send pain signals)
What type of neural fibers do local anesthetics have a better effect on?
On neural fibers that are ACTIVELY TRANSMITTING than those not. Meaning…
**neural fibers with faster firing rates are more susceptible to local anesthetics
What is the order of how nuerons are effected by local anesthetics?
- autonomic
- temperature
- pain
- touch
- pressure
- vibration
- proriveption
- motor
**local anesthetics reduce sensory functions more than motor functions, but all of them are effected
How do opiods work?
by binding to different types of opiod receptors (e.g. mu, kappa, delta opiod receptors) found in the brain, spinal cord, and nervous tissue
What are the main potential risks of epidurals?
- respiratory depression
- low blood pressure
Describe the characteristics of fentanyl
- highly FAT-soluble
- acts primarly through supraspinal/systemic effects (aka. quick effects on brain way faster than effects on spinal cord)
- quickly absorbed by blood
*blood levels of fentanyl after epidural can reach the SAME levels of IV administered fentanyl
Describe the characteristics of morphine
- highly WATER-soluble
- acts primarily through direct spinal effects
*more likely than fentynal to be absorbed into the epidural space
What does bupivacaine have a higher potential of compared to other agents?
higher risk for DIRECT CARDIAC TOXICITY than other agents
When local anesthetics are absorbed in injection, the PNS and CNS are depressed in a _______________ manner
DOSE DEPENDENT MANNER
(can lead to CNS respiratory depression or cardiac arrest)
What type of blood is fentanyl diffused into when delivered epidurally?
MATERNAL BLOOD
*repeated administration of fentanyl runs an increased risk of the drug being taken up by fetal tissues
What is the concentration of fentanyl in the blood during respiratory depression?
greater than 2ng/mL concentration in the blood
*the concentration it takes for respiratory depression is assumed to be lower for babies, but no direct evidence
What is fentanyl likely to cause based on it’s solubility? What about for morphine?
As fentanyl is fat-soluble, it is more likely to cause early-onset respiratory depression
As morphine is water-soluble, it is more likely to cause BOTH early + late onset respiratory distress
What are some of the different factors that are a possible reason for congenital insensitivity/congenital analgesia?
- excessively high levels of endorphins
- problems with their nociceptive sensory fibers and the corresponding peripheral nociceptors.
In what ways is pain influenced by cultural factors?
People who are raised in cultures where they are taught to show pain stoically (without showing one’s feelings or complaining about pain) will show LESS discomfort than those who are taught to focus directly on the pain
In what ways is pain influenced by cognitive or psychological factors?
Stress and depression can increase feelings of pain while while other factors such as a calm attitude can reduce the negative experience of pain.
**Distress and anxiety are two of the cognitive factors
that most often amplify pain.
How much attention is being focused on the pain by the individual or those close to them can effect pain levels also: (ex. in experiments where men were interviewed about their sensations of pain, those men who knew
that their sympathetic wives were listening behind a two-way mirror evaluated their pain as more intense than those men who did not have this sympathetic ear.)
Pain becomes less active when _________ are played?
SOUNDS
studies have shown that simply listening to sounds when receiving a painful stimulus reduces the perception of pain.
There are various types of _______ whose free endings form _________.
nerve fibers (axons)
nociceptors
What does the thickness of the myelin sheath and the diameter of the fiber on the axon effect?
They both affect the speed at which these axons conduct nerve impulses.
*the greater the diameter of the fiber and the thicker its myelin sheath, the FASTER A FIBER WILL CONDUCT NERVE IMPULSES
What pain occurs from A delta fibers?
FAST PAIN (goes away pretty quick, comes from the stimulation and transmission of nerve impulses of these A delta fibers)
**A fibers are mylienatied –> why the pain is fast, because of faster nerve impulses
(A delta fibers carry messages at the speed of a messenger on a bicycle)
What pain occurs from C fibers?
SLOW PAIN (persists longer, comes from stimulation and transmission over non-myelinated C-fibers)
(C fibers carry messages at the speed of a messenger on foot)
C fibers are estimated to account for about _____% of all nociceptive fibers.
70%
Which fibers carry the signals that trigger your withdrawal reflex?
A DELTA FIBERS (The fast-pain pathways)
can happen in milliseconds, like when you step on a nail.
What are the types of neural pathways that DECEND from the CNS?
they DIMINISH THE PAIN signals travelling up the ascending pathways from the body to the brain.
*can sometimes even completely eliminate certain forms of pain
What theory is now recognized as best describing the mechanisms involved in the descending control of pain?
GATE-CONTROL THEORY OF PAIN:
theory where at each of the main points along the ascending pain pathways, there are “gates” that can be closed to make it harder for nociceptive impulses to get through (depending on how open the gates are at each of these relay points, a nociceptor will not always create the same level of pain intensity even with the same stimulus)
What are the 3 different levels of the CNS where
neural mechanisms can act as a gate/filter to reduce the transmission of pain impulses?
- SPINAL CORD
- BRAIN STEM **including the midbrain and medulla oblongata
- THE BRAIN (including the prefrontal cortex)
What is visceral pain caused by?
caused by activation of nociceptors of the internal organs (internal organs are largely innervated by C fibers)
What are some characteristics/way to describe visceral pain?
- highly sensitive to distension, ischemia and inflammation (yet visceral organs are LESS sensitive to other stimuli that would normally evoke pain in other organs such as burning or cutting)
- the pain tends to be vague and is usually described as deep or dragging.
- can be associated with nausea and changes in heart rate and can evoke emotional responses.
**These qualities of visceral pain are due to the low
density of sensory innervation of viscera & the extensive divergence of visceral input onto the central nervous system (CNS).
What do all cognitive, emotional and sensory processes that affect pain perception arise from?
they arise from THE CONTEXT SURROUNDING THE PAINFUL EXPERIENCE (different contextual factors play an important role in the perception of pain)
EXAMPLES:
- physical properties of the medication (colour, shape, taste and smell)
- characteristics of the hospital room
- the sight of health professionals and medical instruments
- the interaction between patient and doctor.
What do both contextinduced positive expectation and
contextinduced conditioning produce?
BRAIN CHANGES that are associated with the activation of at least two neurochemical systems:
- endogenous opioid system
- endocannabinoid systems.
What has Cholecystokinin (CCK) been found to reduce?
been found to reduce PLACEBO ANALGESIA (perceived reduction of pain from placebo) with its anti-opioid action
There is agreement that administration of ___________ along with _________ activates a descending pain modulating network
A placebo
Positive verbal suggestions
Which main 3 brain regions are activated with a positive therapeutic context?
- DLPFC (dorsolateral prefrontal cortex)
- PAG (periaqueductal grey)
- rACC (rostral anterior cingulate cortex)
These functions are activated and deactivated by the placebo response
What is the nocebo response phenomenon?
Opposite to the placebo response, the nocebo response is induced by negative expectations.
Ex. if a placebo is given within a negative context along with a negative verbal suggestion of pain, a nocebo response can occur.
What are some real examples of how someone might experience a nocebo response?
- can also occur when patients distrust medical personnel or the prescribed therapy
- negative diagnoses and prognoses can lead to
an amplification of pain intensity, and can have effects on the emotional state of patients
What can the nocebo hyperalgesic effect be mediated by?
CCK!
this suggests that anticipatory anxiety has an important role in nocebo hyperalgesia as CCK is linked with anxiety/panic attacks.
What are nocebo effects associated with?
its associated with decrease in dopamine and opioid activity in the nucleus accumbens.
What is the nocebo hyperalgesic effect?
an increase in pain after implementation of a non-hyperalgesic procedure or substance, i.e. placebo. or WHEN NEGATIVE EXPECTATIONS INCREASE PAIN
What’s the difference between analgesia vs. hyperanalgesia vs algesia
Analgesia = the inability to feel pain (in practice, often partial)
Hyperanalgesia = An increased sensitivity to feeling pain and an EXTREME RESPONSE to pain
Algesia = sensitivity to pain
What is anxiety-induced hyperalgesia?
attention is focused on the IMPENDING PAIN, and the biochemical link between this anticipatory anxiety and the pain increase involves CCK.
What is stress-induced analgesia?
a general state of arousal that stems from the focus of attention on an environmental stressor.
**some evidence shows that stress-induced analgesia results from activation of endogenous opioid systems.
How do CCK, HPA and NAcc respond to a negative context/negative expectations?
CCK: ACTIVATES to have facilitating effect on pain transmission
HPA: ACTIVATES (related to anticipatory anxiety)
NAcc: DEACTIVATION, reduce μ‑opioid receptor and dopamine receptor signalling in the NAcc.