opioids Flashcards
opium
-drugs derived from poppy juice
opiod drugs
-mainly synthetic drugs, act as opioid receptors, produce analgesia and other effects used for perioperative and acute pain in vet med
opiates
-naturally occuring from opium
narcosis
analgesia and stupor bordering on anesthesia
neuroleptanalgesia
- analgesia and amnesiac state produced by administration of neuroleptic and narcotic
- deep sedation, possible unconciousness
effects of opiods on nociception
-perception, modulation, transduction
opioid receptors
- mu, kappa, delta
- G-coupled protein, inhibition of signal transmission
- location- brain, spinal cord, endogenous ligand
- mu: beta endorphins, endomorphins, main effect is analgesia, sedation, respiratory and GI depression
- kappa- dynorphin main effects are analgesia and sedation
mu 1 and mu 2 receptors
- most common, most affected by opioids
- supraspinal analgesia- mu 1
- spinal analgesia- mu 2
- respiratory depression
- euphoria
- sedation
- GI motility
- physical dependence
- brain, spinal cord, joint capsule
kappa receptor
- weakly affected by opioids
- brain and spinal cord
- spinal/supraspinal sedation
- analgesia/antinociception
- dysphoria
- GI motility
delta receptor
- spinal/supraspinal antinociception
- CV depression
- mild analgesia
- minimally affected by opiod drugs
full mu agonist (affinity and activity)
- morphine
- oxymorphine
- hydromorphine
- methadone
- fentanyl
- remifentanil
partial mu agonist (affinity, partial activity)
-buprenorphine
mixed agonist-antagonist- affinity but no activity
-K agonist and mu antagonists
full mu agonist
naloxone
schedule I drugs
-most addictive- heroin
schedule II drugs
-full mu agonists, oral drugs in human med
schedule III drugs
-buprenorphine, codone with NSAID, hydrocodone
schedule IV drugs
butorphanol, tramadol
schedule V drugs
-cough suppressants
MOA of opioids
- activation of mu opioid receptor- inhibits excitatory NT release and substance P
- opioid coupling with membrane-associated Gi/o proteins- hyperpolarization of neurons, block of substance P, decrease in NT activity, decrease of calcium influx
- inhibit neurotransmission
- opioid tolerance and resistance of Ca+ channels open in presence of opioid
opioid pharmacokinetics
- absorption- readily absorbed from all tissues
- IV/IM most common routes of administration, commonly given as CRI (fentanyl)
- SQ/TM (buprenorphine)
- transdermal (fentanyl patch)
- epidural (morphine)
- distribution- widely dist., depends on lipid solubility (morphine one of least lipid soluble), cross specialized barriers (BBB, placenta)
- metabolism and elimination- mainly conjugation to glucuronic acid (what cats are deficient in so they metabolize slower), metabolites are renally excreted
full opioid mu receptor agoinists
- morphine
- hydromorphone
- oxymorphone
- fentanyl
- cerfantanil/etorphine
morphine
- prototypical analgesic, onset 5-15 minutes, lasts several hours, used in epidurals
- may have histamine release
hydromorphone
-less histamine released, used in IV instead of morphine, similar onset and duration to morphine
oxymorphone
- similar to hydromorphone, may be less emetogenic
- may have smoother sedation in cats and peds
fentanyl
-potent onset ~1 min, lasts ~30 minutes so suitable for CRI administration, available as transdermal patch
cerfantanil/etorphine (M99)
- very potent
- wild life tranquilizer
partial opioid mu receptor agonist
-Buprenorphine
Buprenorphine
- semisynthetic partial mu agonist
- 30-50% more potent than morphine
- strongly binds to opioid receptors, not at every site
- ceiling effect- at certain point dose increases won’t have effect
- slower onset (about 45 mins), longer duration- up to 8 hrs in cats
- less apparent adverse side effects
- IV, IM, SC, TM
mixed opioid receptor agonist-antagonist
-Butorphanol
Butorphanol
- synthetic K agonist and mu antagonist
- analgesic in dogs, cats, horses, antitussive in dogs
- lower ceiling effect, visceral pain, less apparent negative effects
- commonly used in equines
- IV, IM, SC, PO
- antitussive effect is greater than pure mu agonist
- anxiolytic effects in upper airway crisis
- recovery from anesthesia
opiod agonists main effects
- CNS- behavioral changes -depression (dogs), stimulation (cats, horses, ruminants, pigs), interacts with dopamine and NE pathway in brain
- motor activity- decrease motor area in dogs, increase locomotor in horses
- thermoregulation- hypothermia in dogs, hyperthermia in cats
- pupil size- miosis in dogs, mydriasis in cats and horses
- antitussive
- dyspnea/excitement
opioid agonists- respiratory system
- dose dependent respiratory depression
- reduced sensitivity to increased CO2
- decreased respiratory drive, hypoventilation
- panting in dogs sometimes
- risk factors for more severe resp effects- ill patients, upper airway obstruction, severe acidemia, use with respiratory depressants
CV effects of opioid agonists
- less CV effect than other sedatives
- dogs:may have bradycardia and hypotension
- coronary artery vasoconstriciton in dogs
- cerebral vasodilation and increased intracranial pressure
- opioids may cause hypotension IV because of histamine release
GI effects of opioid agonists
- nausea, vomiting, regurgitation
- apomorphine–> emetic in dogs, toxic in cats
- salivation
- hydromorphone= nausea
- methadone= less emetogenic
- ileus and constipation- increase intestinal wall tone, sphincter tone, and non-propulsive rhythmic contractions, decrease propulsive motility
- delayed gastric emptying, constipation, and ileus
urinary tract effects of opioid agonists
-urinary retention and increased sphincter tone
immunological effects of opioid agonists
- histamine release
- uticaria
- WBC funciton and immunity
addiction and abuse potential
-schedule II-IV
opioid agonist clinical uses
- analgesia
- sedation
- preanesthetic/ premedication
- antitussive
- emetic
- antidiarrheal
full opioid mu agonists
- competitively antagonize opioid agonist effects
- indications: overdose, toxicity, opioid induced respiratory depression, prolonged anesthetic recovery, imminent cardiac arrest, cardiorespiratory arrest
Naloxone
- full opioid mu agonist
- competitive receptor agonist, reversal of opioid induced adverse effects
- rapid onset (minutes), short duration (1-2 hrs), repeat dose until gone
- reverse analgesics as well
other opioid antagonists
- naltrexone, diprenorphine
- methylnatrexone- doesn’t cross BBB
other opioids
- tramadol
- hydrocodone
- apomorphine
- loperamide
tramadol
- weak opioid mu agonist, inhibits serotonin and NE reuptake
- risk of serotonin syndrome if with MAOIs or SSRIs
- oral/post op, sometimes IV
- schedule IV
- may lower seizure threshold
hydrocodone
- antitussive
- schedule II
apomorphine
emetic in dogs, toxic to cats
Loperamide
-anti-diarrheal
precautions for opioid use
- pre-existing ileus
- conditions with increased intracranial pressure
- severe cardiac/hypoventilation
- renal injury/failure
- may recover special training
- history of opioid intolerance/hypersensitivity
- always address underlying cause of pain
- full mu agonists may be fully reversed
- cats can get hyperthermia
