Pain and Opioids Flashcards
what is pain
an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage
what is nociception
neural process of encoding noxious stimuli
how can pain be measured
pain threshold or pain tolerance level
which fibres are involved in nociception of skin, fascia, bone (sharp, localized pain)
A fibers. C are the muscle and viscera ones
which fibres are involved in nociception of muscle, viscera pain (dull, diffuse)
C fibers (A fibres are skin, fascia, and bone pain)
at is the primary excitatory NT involved in nociception
glutamate
_________ is increased sensitivity to noxious stimuli, while _______ is when normally non-noxious stimuli become capable of eliciting a pain response
hyperalgesia, allodynia
inflammatory mediators such as prostaglandins and leukotrienes perform what 2 functions
activate silent nociceptors and nociceptor sensitization
what is spinal facilitation of pain or wind up
high frequency APs train second order neurons to respond more vigorously to subsequent stimulation (increase glutamate and other NTs, activate inactive NMDA receptors, influx of Ca, up regulate post-synaptic membrane)
what is pre-emptive analgesia
- Pain leads to increased sensitivity (increased nociceptor sensitivity, activation of “silent” nociceptors, wind‐up/spinal facilitation of pain, neuroplasticity): therefore we use PRE‐ EMPTIVE ANALGESIA - easier to control pain before nociceptive stimulus happens
are general anesthetics generally analgesics
generally not. need to provide both
_____ has a conscious component, while ______ does not
pain, nociception
what do descending inhibitory pathways do
Decrease neurotransmitter release from primary afferents and reduce excitability of secondary neurons
give 3 physiological pain inhibition mechanisms
endogenous opioid agonists, up regulation of peripheral opioid receptors at site of injury, migration of opioid-producing leukocytes to site of injury
give 4 sites of analgesia
block nociception at peripheral nociceptors prevent transmission to sp cord, prevent transmission to brain, enhance descending inhibitory pathways
most effective way to prevent and treat pain is to _____, this is referred to as balanced pain management
affect all of the different levels
three types of opioid receptors are
mu, kappa, delta
opioid receptors are GPCRs. how can they lead to reduced NT release?
inhibition of calcium channels in presyn neurons
opioid receptors are GPCRs. how can they lead to hyper polarization?
increased potassium outflow in postmen neurons
how do opioid receptors inhibit calcium inflow in primary afferent neurons
Inhibits calcium inflow into presynaptic neuron through direct binding to calcium channels, and through cAMP‐ modulated mechanisms, reducing NT release
opioid receptors enhance K+ outflow from postsynaptic neurons in spinal cord. enhanced K+ outflow leads to what
hyperbole of postmen neurons
give 6 effects of mu receptor
analgesia, respiratory depression, sedation/excitement (dose and species dependent), decrease in GI motility and secretions, euphoria, and nausea/vomiting
give 3 effects of kappa receptor
analgesia, sedation, decreased GI motility (the mu receptor does these as well)
I’ve effect of delta receptor
analgesia (kappa and mu do this too)
drugs that interact with opioid receptors can be thought of in 4 ways, give em to me
full agonists (maximal effect), partial agonists (same effect as full agonists, but effects plateau), agonist-antagonists (vary effects depending on receptor and dose), antagonists (competitive antagonists)
all of the opioid drugs act on which receptor
mu receptor. some on kappa and delta as well
when given in combination with sedatives or anesthetics, what effect do opioids have
additive/synergistic sedative and analgesia effects
give at least 3 clinically important adverse effects of opioids
respiratory depression (centrally mediated decrease in response to increased PCO2)
vomiting (chemoreceptor trigger zone and dopamine effects)
constipation/ileus
severe pruritus
histamine release
hyperthermia in cats
CNS excitation/dysphoria/seizures
why is morphine not recommended for animals with CHF
variable effects on coronary blood flow
PK of opioids: tell. me about half-life and duration of action
short half life, 0.5-2 hours, and duration of action also short and depends on dose/pain, 2-4 hours
local use of opioids: opioid receptor expression is upregulated locally by what
inflammatory cytokines
this gold standard opioid is a mu agonist, kappa partial agonist, is safe effective and cheap, less effective in cats than dogs, and not routinely used in horses due to CNS effects
morphine
this opioid is a morphine derivative, mu agonist, emetic, less histamine response than morphine, oral bioavailability probably very low, short half-life
hydromorphone
this opioid is a mu agonist, NMDA antagonist, NE and serotonin reuptake inhibitor, may be more effective for chronic pain than other mu agonists, causes fewer CNS effects and less vomiting than other mu agonists, especially in cats
methadone
this synthetic mu agonist is more lipophilic than morphine and more potent, given IV or transdermally, wide safety margin in dogs, generally fewer adverse effects that with other opioids, common drug of abuse
fentanyl
this is a partial mu agonist and a kappa agonist opioid, has a ceiling on analgesic and respiratory effects, transmucosal absorption, less CNS effects in cats, high affinity for mu receptor (potency) but lower efficacy
buprenorphine
drug is a kappa agonist, mu antagonist or partial agonist, effective analgesic for mild/moderate pain, may reduce effects of mu agonists, prominent sedative effects, antiemetic and antitussive, occasionally used to reverse mu agonists but not in cats, commonly used in combination with sedatives
butorphanol
centrally acting multimodal analgesic; active metabolite is a mu agonist, current recommendation is do not use as sole analgesic in dogs, but many be useful as adjunctive analgesic but be mindful of potential for treatment failure
tramadol
reversal of opioids is performed by what kind of agonist or antagonist
competitive opioid receptor antagonist
this competitive antagonist of all opioid receptors, especially mu, is also a GABA antagonist and can indue seizures. generally given at small doses to reverse respiratory depression
naloxone
of fentanyl, buprenorphine, and heroin, which can induce total apnea at lowest dose
fentanyl
what 3 things to base opioid decision making on in small animals
severity of pain, route of admin, and ok in cats
what kind of drugs are drugs of abuse
opioids
sedative effects of alpha 2 agonists are caused by decreased what release
norepinephrine release from brainstem neurons via negative feedback mechanisms
how do descending inhibitory pathways work
decrease NT release form primary afferents and reduce excitability of secondary neurons
all the alpha 2 receptors agonists currently used in vet med also have
alpha 1 activation. usually causes excitation and increased motor activity
this drug is a short-acting general anaesthetic, common for flied procedures, and is an analgesic due to NMDA receptor antagonist and analgesic at subanesthetic doses, is useful in geriatric patients due to excellent safety profile
ketamine
ketamine antagonizes ____ receptors and acts as a ____ analgesic
NMDA; central
lidocaine, bupivacaine, and mepivacaine are all
local anesthetics, they block Na channels and stop AP conduction in nerve fibres
By decreasing or abolishing the transient increase in permeability of excited cell membranes to sodium ions, local anesthetics basically stop what
nerve conduction
adverse effects of local anesthetics are related to what
Na channel blockade
