Lecture 10 - Nov 25 Flashcards
Pain:
-an unpleasant sensory and emotional experience associated with or resembling that associated with, actual or potential tissue damage
-six key notes and etymology:
-pain is always a personal experiences that is influenced to varying degrees by biological, psychological and social factors
-pain and nociception are different phenomena. Pain cannot be inferred solely from activity in sensory neurons
-through their life experiences individuals learn the concept of pain
-a persons report of an experience as pain should be reposted
-although pain usually serves an adaptive role, it may have adverse effects on function and social and psychological well being
-verbal description is only one of several behaviours to express pain; inability to communicate does not negate the possibility that a human or a nonhuman animal experiences pain
4 major steps in pain reaction:
Transduction - conversion of a stimulus into a action potential
Transmission - of the action potential along nervous to the dorsal horn of the spinal cord, signal is processed and various neurotransmitters are released which either facilitate and/or inhibit further transmission, further transmission to the cerebral cortex
Perception - an amalgamation of the autonomic response to the stimulus, localization and characterization of the pain, addition of emotional and behavioural components
Modulation - inhibition or facilitation spain via descending fibres or pathways (ex neurotransmitters, endogenous opioids)
-management of pain can be non-pharmacological or pharmacologic, acting at any of these 4 steps
Pain during the perinatal period:
Antenatal - common complaints of pregnancy/physical adaptations
Intrapartum
Postpartum - afterpains (uterine involution), perineal or vaginal lacerations, post operative pain, breast engorgement (normally, these pains will rescind to mild analgesic or nonpharmacologic interventions)
Glucocorticoids
-produced and released in adrenal cortex
-main glucocorticoid in humans is cortisol - released in response to stress
-glucocorticoids stimulate gluconeogenesis (from protein and fat catabolism), hepatic glucose secretion, immunosuppression and increase in systemic blood pressure
-glucocorticoids inhibit the effect of insulin, the growth of muscles and tissue repair, from a pharmacological perspective, the autoimmune activities of glucocorticoids are a useful feature
Inflammation, pain and glucocorticoids
-inflammation is the body’s response to injury and infection
-inflammatory mediators such as prostaglandins, proinflammatory cytokines and chemokines induce pain via direct activation of nociceptors
-synthetic glucocorticoids have potent anti-inflammatory and immunosuppressive actions
-main immunosuppressive effect results from the inhibition of neutrophils - an important part of the innate immune response
-anti inflammatory effects are also mediated by the inhibition of phospholipase A2 - therefore prostaglandins can be made
Glucocorticoids:
-used in a wide variety of conditions that require suppression of inframammary symptoms - to alleviate pain due to inflammation
-relevant to midwifery care:
-treatment of inflammatory dermatoses
-ex OTC low concentration (0.5%) hydrocortisone cream for eczema or polymorphic eruption of pregnancy (pruritic urticarial papules and plaques of pregnancy - PUPPs)
-itchy, bumpy rash that starts in the stretch marks of the add some in the last 3 months of pregnancy then clears with delivery
-treatment of hemorrhoids
-treatment of nipple pain - betamethasone valerate is a component of APNO
Glucocorticoid Classes:
Glucocorticoid Classes:
Class 1
-very potent, 600x as potent as hydrocortisone
-ex betamethasone dipropionate
Class 2
-potent, 100-150 x hydrocortisone
-betamethasone valerate (search long term effect of high potent ct GC cream)
Class 3
-moderate, 2-25x hydrocortisone
Class 4
-mild
-ex hydrocortisone 0.5-2% solution
NSAIDS for pain relief
-ibuprofen, naproxen and diclofenac
-inactivate cyclooxygenase (COX)
-cox 1 is constitutively active and not associated with inflammation
-cox 2 is produced in response to inflammatory stimuli
-preferred to inhibit this enzyme when it comes to pain control
Naproxen
-an NSAID used for its anti-inflammatory/analgesic properties postpartum
-available in 225 mg dose over the counter (aleve)
-not as specific for cox2 as diclofenac
Metabolism:
-mainly by the liver, metabolites excreted in urine
-t1/2 is about 14h (administered PO q12h)
Adverse effects:
-when used acutely for postoperative pain there are a few side effects
-naproxen is excreted in the breast milk however the doses given post-operatively should yield tiny doses to the newborn (RID is 3.3%, MP = 0.01)
-contraindicated in pregnancy, teratogenic, associated with oligohydramnios, premature closure of DA, bleeding problems, avoid if hypersensitivity
-there has been controversy whether NSAIDs should be avoided in clients with hypertension
-current evidence
-drug interactions:
-because there is an antiplatelet effect of naproxen, other anticoagulants and antiplatelet drugs should be avoided - do not combine with other NSAIDs such as ibuprofen or ASA
-drugs in the midwifery legislation will not have significant interaction with naproxen particularly in the modest doses given to control postpartum pain
-difference between naproxen and ibuprofen for postpartum pain: half life of ibuprofen is only 2h compared to 14h for naproxen
Diclofenac
-oral formulation = reaction only analgesic in canada (voltaren) - voltaren ointment available OTC
-diclofenac is more specific for cox2 than cox1 but still acts upon both to some degree
-because cox2 is more targeted, there is less of an effect on platelet aggregation compared to ibuprofen and ASA (important consideration for postpartum bleeding)
-metabolism and excretion of diclofenac:
-mainly metabolized by liver
-t1/2 is about 3h, given every 8h
-clinical use:
-post surgical pain relief and inflammation
-good for reducing perineal pain and swelling from operate delivery and episiotomy
-adverse effects:
-used acutely for postoperative pain there are few side effects
-diclofenac is excreted in breast milk however the doses given post operatively should yield tiny doses ti newborn (RID unknown)
-don’t give to someone with cardiovascular disease (although <100mg is likely fine)
-contraindicated in pregnancy, teratogenic, associated with oligohydramnios, premature closure of DA, bleeding problems, avoid if hyperactivity
-there has been controversy whether NSAIDs should be avoided in clients with hypertension
-drug interactions:
-because there may be antiplatelet effect of diclofenac other anticoagulants and antiplatelet drugs should be avoided - do not combine with other NSAIDs such as ibuprofen or ASA
Pain in labour:
-a physiological response to a natural process - rather than a sign of pathology
-pain may occur because of:
-myometrial ischemia, cervical, vaginal and perineal stretching, distention of other perineal structure
-the perception of pain in labour is highly individualised
-experience of the physical stimulus is affected by myriad social, cultural and psychosocial factors
-pain in first phase of labour:
-visceral pain predominates, myometrial ischemia during contractions initiates the release of mediators that activate chemoreceptors and signal pain (transmitted by sympathetic fibres to posterior root ganglia t10-L1), predominantly referred pain is slowly transmitted, difficult to define and localise (may be described as abdominal, rectal, lower back, thighs)
-pain in 2nd stage of labour: pain from distension of cervical, vaginal, perineal and other structures, transmitted by the pudendal nerves, through the sacral plexus to ganglie in s2-s4, pain is characterized as intense, sharp, and easy to localise (mainly by perineum, anus and lower part of sacrum)
slide 19
Summary pain pathways:
1.Specific pain nerve fibres in tissues stimulated by inflammatory mediators (histamine, PGs) release when tissues are damaged - NSAIDS block PG synthesis
2.passage of pain impulses spend on action potentials - blocked by LAs
3.Integration of pain and touch fibers and descending messages in dorsal horn of spinal cord - ‘pain gate’ opiods act here with other gate control theories such as sterile water injections
3.pain pathways in brainstem activate SNS and increase resp., HR, BP, emesis, persperation - anesthetic gases and opiods act in brainstem
5. pain pathways in cerebal cortex activated - opiods act in cerebral cortex
Nonpharmacologic methods of pain relief:
-can positively impact subjective experiences of pregnancy and childbirth
Relaxation techniques - breathing, yoga, music, hypnosis, mindfulness
-manual technique - massage, reflexology, shiatsu, warm/cold packs
-acupuncture, birth ball, position changes, tens, sterile water injections, aromatherapy
Synthetic anesthesia - use of inhaled nitrous oxide (N2O)
-used worldwide for labour analgesia for several decades
-stimulates neuronal release of endogenous opioid peptides (dynorphins) and activation of postsynaptic opioid receptors
-efficacy in alagaesia is unclear - show improved satisfaction with the birthing experience, potentially as use allows for more autonomy
Inhaled nitrous oxide N2O entonox
-50% nitrous oxide, 50% oxygen compressed in a gas cylinder
-very lipid soluble
-client needs to self administer - so they know when they’ve had enough and can take it before contraction starts
-timing of inhalation is critical: effects start 25-30 seconds after administration and persist for about 60 seconds after inhalation stops
-counsel client to breath normally, slowly and deeply but do not hyperventilate
-increased ventilation increases delivery of gas to blood, they will also exhale too much CO2 which can lead to: maternal hyperventilation and vasoconstriction of placental arteries which can lead to hypoxia in fetus, cerebral vasoconstriction - dizzy
-when used 1:1 with oxygen N2O has a good safety profile
-adverse effects in clients:
-use has been associated with nausea, dizziness and drowsiness
-use caution if client has a pre existing respiratory disease (like pulmonary hypertension) this could make it worse
-can exacerbate any existing placental insufficiency
-if fetal heart rate is abnormal, do not use
-N2O is a greenhouse gas and is considered an environmental pollutant
Local anesthesia
-definition - the loss of sensation in an area of the body without the loss of consciousness
-local anaesthetics work by blocking open sodium channels
-several different forms:
-topical - at a mucous membrane
-infiltration - skin, superficial tissues and organs - not targeting a specific nerve
-field block - beneath the cutaneous layers to target specific nerves
-nerve block - larger region of anaesthesia than a field bicol, injections of LA near specific peripheral nerves, ex pudendal block
-regional - a type of nerve block but is higher than individual nerves, ex epidural, spinal
Slide 26, 27, 28, 29 action potential
Axon sensitivity to LAs
-LAs will first block:
Visceral and deep somatic pain: c fibers, thin and unmyelinated
Sympathetic nerves: b fibres are thin and myelinated
Superficial somatic pain: a-delta fibers are thinner and have less myelin than a-alpha
Somatic motor nerves: a-alpha fibers are thick and myelinated - can maintain motor control after pain is blocked
-ex epidural will block deep somatic and visceral pain first, then sympathetic nerves of blood vessels, maintains motor control
Local anesthetics for perineal repair:
lidocaine xylocaine
-amide local anaesthetic
-by far the most common
-rapidly metabolized by the liver - biotransformation includes oxidative n-dealkylation, ring hydroxylation, cleavage of the amide linkage and conjugation, only 2% of lidocaine is excreted unchanged, provides anaesthesia for 30-60 min
Bupivacaine marcaine
-amide local anaesthetic
-slightly slower acting, longer lasting
-meteoblue by the liver
-CYP3A4, conjugation with glucuronic acid
-only 6% of bupivacaine is excreted unchanged
-provides anaesthesia for 2-4 hours
-commonly used epidural and spinal anaesthesia
LA adverse effects and overdose
LA potential adverse effects:
-contraindications = history of known hypersensitivity to amid LAs or their components - hypersensitivity reactions to lidocaine and bupivacaine are extremely rare
Overdose:
-toxicity symptoms include cardiac arrest and ventricular arrhythmia refractory to treatment
-the onsets of a toxic reaction is often preceded by tongue/circumoral paresthesia and light-headeness, tinnitus
-visual disturbance and nuclear tremors are more serious and precede onset of convulsion
-unconsciousness and grand mal convulsions may follow
-linked to hypoxia and hypercarbia d/t increased muscular activity and interference with normal respiration
-most of the serious side effects will only occur secondary to direct intravascular injection because the absorption into systemic circulation is very slow when given subcutaneously
Regional anaesthesia in labour:
-regional anaesthesia refers to the use of local anaesthetics solutions to produce circumscribed areas of loss of sensation - regional anaesthesia is a generic term including conduction, nerve block, spinal, epidural, field block, infliction and topical anaesthesia
-approx 64% of women in notation hospitals will ha some form of regional anaesthesia in labour
-injection of LA into epidrual or intrathecal space
-regional anesthesia at lumbar spind level affects sympathetic nervous system because part of SNS emerges from under lumbar spine
Lumbar spine anatomy
-spinal cord ends L1
-below L1 the spine countries to case equina (nerves spread out so if needle/epidural is put in, nerves move out of way) at cauda equina
Regional anesthia
Epidural anestheisa
-injection of drug into the fat-filled epiral space (ex bupvianine HCL anasthetizes whatever peripheral nerves in contact with drug; in combination with an opiate, often fentanyl)
-some of the anesthic diffuses into the arachnodid space but of the injection is small enough and caudally applied then aneasthia is motley on the nerve roots passing though the epidural space - the somatic sensory fibres
-can be patchy or incomplete in anestheitcs do not reach all nerves
-the subarachnoid injection is often called a spinal or intrathecal injection - the injection of a local anasethc into the space below L2 (spinal cord ends and cauda equine beings and less liekoy to damage nerves)
-advantages:
-clear end point - withdraw synrege and see if CSF leaves little doubt in intrathecal space
-unliey to falu to rpvide anestheis because drugs into CSF which bathes the nerves so less drug reuqired
-relable for ceaseran deilvery
-less morbidity and mortality than general anestheisa
-works within a few minutes vs 10-15 min with epidural
Epidural vs spinal slide
Adverse effects of neuraxial anestheisa (epidural)
-inadequate anesheisa - incomplete or pathy epidural -20%, block failure -5%
-milkd headache due to symathc blockade - vasoldaialtion
-spinal headache - caused by leaked of CSF, very severe psotional headache, occurs in 1-5% of users, treated with blood patch
-backache reposted in 20% - phsycail nature of the injection (brusinging)
-less than 1% possibility of infection
opioids for pain managment
-ontario midwives have 4 opiod analgesics in pharmacopeia
-can be adminstered by own authority by injection, in public hospital, with skill to do so
-primary indication = managment of prodromal early labour
-fentanyl citrate
-meperidine
-morphine sulfate
-nalbuphine
endogenous opiods
-regulate most physilogic functions (nociception in brain and spinal cord)
-upregulated during stress, pain, tissue injury and infllamamtion to maintain homeostasis
-bind to opiod receptors
-g coupled protein receptors are 55-58% homolohus to eachother - when opiod binds to its receptors, the g protein and 2nd messenger systems alter cellular membrane condutance for K+ and Ca2+
slide 39 receptor type and subtype chart
slide 39
how opiods work for pain managemtn
-opiates work in number locations in cps and pns
-administered exogenous opioids bind to opioid receptors and activate descending inhibitory pathways that project to the dorsal horn of the spinal cord
-opiates bound to opiate receptors leads to hyperpolarization of nerve endings (more negatively charged)
-hyperpolariation decreases firing (pain messages)
-inhibits nociceptive processing
opiate action on spinal cord
2 mecanishms
- bind to presynaptic recpetors in dorsal horn of spinal cord
-results in inhibition of the release of stimulatory neurotransmitters (ex glutamate which binds to its receptorNMDA and opens sodium channels which would propagate the pain message) - bind to postsynaptic receptors causing hyperpolarization
-opiates bind to receptors and open potassium channels (K+ leaves the cell) causing increased negative charge and decreased neuronal excitability
slide 43 chart
exogenous opioid ligands
-classified as full or partial agonists according to their ability to initiate GCPR signaling
-bind to receptors reversibly
-full agonists (ex fentanyl) have very high potency and recquire little receptor occupancy for a full response
adverse effects with opioid use -respiratory depression
-drive to breathe located in resp centres of brainstem
-opiods reduce responsiveness to CO2 and attenuate the hypoxic ventilator response to decreased PO2
-reduction in breathing rate, delay expiratory time, promote irregular breathing rhythm
adverse effects with opioid use - cardiovascular
-inhibit sympathetic tone and enhance parasympathetic tone - can cause hypotension, bradycardia, circulatory arrest
-modulate the stress response through the hpa axis
-opiod receptors are also present on the endothelial cells of arterial vessels (activation results in NO mediated vasodilation)
adverse effects with opioids - GI
-inhibitory effect on neurons in myenteric plexus (controls tone of gi wall) and submucosal plexus (control secretory and absorptive activities)
-reduce GI motility, increase circular contractions
-decrease GI motility, increase circular contractions
-decrease gi mucous secretion
-increase fluid absoprtion (results in constipation)
-causes nausea and vomiting due to activation of neurons in area of postrema of medulla
adverse effects with opioid use - pruritus
-cns mediated mechanism
-pain processing spinal neurons antagonize the sensation of itch (by inhibiting pruriceptive neurons)
-analgesic effects of opiods prevent inhibition so you can feel the itch
adverse effects with opioid use
desnsitization, tolerance and physical dependance
-long term use can result in pharm tolerance, decreased effect with a contant dosage, increasing doses are required to maintain same effect
-the result of cellular adaptations to chronic receptor activation
-early mechanisms (seconds to minutes), receptor desensitization to d/t phosphorylation and diminshed g-protein signaling
-subsequent mechanisms (minutes to an hour) receptor internalization - translocation from the cell membrane to a vesicular compartment
-late mechanisms (minutes to several hours) downregulation with receptor degradation within lysosomes
-even later mechanisms - modulation of receptor gene expression
slide 49
opioids in spinals and epidurals
benefits
-allow less LA to be used, results in less motor blockade = better mobility and better proprioception, touch maintained to a greater extent to allow for better position changes in labour and more effective 2nd stage (pushing)
limitations
-less effective at preventing somatic pain associated with 2nd stage
-do not provide surgical anesthesia (LA must be added for cesarean section)
opioids for prodromal early labour management
-parenteral opioid administeration for pain managment in labour is a long standing practice (not much evidence)
-no longer given during active labour d/t impacts on the newborn (resp depression, lethargy, poor feeding)
-should not be given if delivery is expected within 4 hours
-various protocols for theraputic rest in latent pjhase of labour if other methods do not aid client in coping
-common = IM morphine (10-15mg) with dimenhydrinate/gravol 50-100mg, works within 20-30 min, pain relief lasts up to 4 hours
opioids for therapeutic rest - early labour management
-supportive reccomendations to not admit people to hospital if not in active labour (associated with more oxytocin use, IUPC, epidural and client dissatisfaction)
-provide some pain relief, aid in reducing fatigue, anxiety, fear
-associated with drowseiness, nausea and vommitning (effects on newborn unclear)
-depending on fetal wellbeing and hospital protocol, may be done outpatient
-clients are potentially more likely to return to hospital in active labour, less likely to go on to induction
-no difference in labour and birth outcomes
