LINDA WUNDER,MSN,CRNA

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OPIOIDS
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• LINDA WUNDER,MSN,CRNA
• NURSE ANESTHESIOLOGY
• FLORIDA INTERNATIONAL UNIVERSITY

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OPIOIDS
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• First, morphine in 1803 with active component
  opium
• Narcotic is greek for stupor and is referred to
  morphine-like analgesics with potential to
  produce physical dependence.

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OPIOIDS-OBJECTIVES

• Explain the mechanisms for pain relief provided
  by opioid agonist and opioid agonist-antagonist.
• Describe the Pharmacodynamics and
  pharmacokinetics for the opioid agonist, opioid
  agonist-antagonist, and opioid antagonist.
• Identify the most common adverse effects of
  various opioids by mode of delivery.
• Discuss the mechanisms of metabolism and
  elimination of opioid agonists, opioid
  agonist-antagonists, and opioid antagonist.
• Summarize the effects of opioids on the stress
  response.

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OPIODS
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• Opioids act at stereospecific opioid receptors at
  presynaptic and postsynaptic sites in the central
  nervous system brain(periaqueductal gray,
  amygdala, corpus striatum, and hypothalmus) and
  spinal cord (substantia geltinosa) and in the
  peripheral tissues.
• Endogenous ligands for the opioid receptors are
  collectively known as endorphins.
• The term endorphin comes from endo, meaning
  inside, and m-orphine, indicating opioid agonist.
  

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OPIOIDS
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• The endorphins are peptides that are released
  upon a painful stimuli
• They bind to opioid receptors to decrease the
  individuals perception of pain
• Endorphines include enkephlins, endorphines and
  dynorphins
• The opioid agonist mimic the endogenous
  endorphins and bind to the opioid receptors hence
  inhibiting pain transmission

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OPIOIDS
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• Ionized state is necessary for strong bonding at
  the anionic receptor site
• Only the levorotatory forms of the opioid exhibit
  agonist activity
• The affinity of most opioid agonists for
  receptors correlates well with their analgesic
  potency

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OPIOIDS

• Opioids receptor activation decreases
  neurotransmission
• Mostly decreasing presynaptic release of
  acetylcholine,dopamine,norepinephrine ,substance
  P(postsynaptic can occur)
• Substance P is an excitatory neurotransmitter
  presumed to be released by terminals of pain
  fibers that synapse in the substantia gelatinosa
  of the spinal cord

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OPIOIDS

• Opioid receptors are classified as mu, delta,
  kappa
• An ideal opioid agonist would have have high
  specificity for receptors, producing desirable
  responses (analgesia) and little or no
  specificity for receptors associated with side
  effects ( hypoventilation, nausea, physical
  dependence)

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OPIOIDS
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OPIOIDS

• EFFECTS
• Cv not a negative inotrope
• Respiratory- decrease respiratory rate and
  increase tidal volume.
• Decrease the CO2 response in the medulla
• Chest wall rigidity-rapid administration of
  opioids increases airway pressure
• Spasm of biliary smooth muscle-sphincter of Oddi
• GI-constipation, N/V(stimulation of the
  chemotrigger zone floor of fouth ventricle)
• Placenta-opioid cross and produce fetal
  respiratory depression
• Miosis-excitatory action of edingerwestphal
  nucleus of the occularmottor nerve
• Awareness-not a hypnotic
• Decreases MAC requirements for inhalational
  anesthetics
• Tolerance occurs 2-3 weeks, dependence 25 days
• Opioids block the normal stress release of
  catecholamines, anidiuretic hormone and corisol
  to surgical stimulation
• Opioids block the hemodynamic response to
  intubation

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OPIOIDS

• Onset 15-30min,1/2 time 1.7-3.3 hr
• 75-85 metab to morphine-3-glucuronide inactive
• 5-10 metab to morphine 6-glucuronide, produces
  analgesia and resp depression via mu activation
• Metab conjugationwtih glucuronic acid
• Releases histamine

• MORPHINE

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OPIOIDS

• MEPERIDINE
• 1/10 as potent as morphine
• Duration 2-4 hours
• Mu and kappa receptor agonist
• Structurally similar to atropine, derived from
  phenylepiperidine
• 90 metabolized to normeperidine,1/2 as active as
  a analgesic
• Normeperidine toxicity causes myoclonus and
  seizures
• No miosis, causes mydriasis, large doses causes
  decrease in myocardial contractility
• Do not administer if patient is taking moa
  inhibitors,cns excitation hypotension
• Treatment for postop shivering

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OPIOIDS

• Hydromorphone- derivative of morphine that is 5
  times as morphine with a slightly shorter ½ life.
• Produces more sedation that morphine with less
  euphoria.
• Rapid elimination and redistribution.
• Great alternative to morphine when moderate to
  severe pain is opioid responsive.
• IV 1-2 mg, ½ life 1-3 hours, onset 15-30 mins

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OPIOIDS

• FENTANYL

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OPIOIDS

• FENTANYL-phenylpiperidine derivative
• 75-125 more potent than morphine
• Rapid onset, highly lipid soluble
• First pass-75 initial dose to lungs
• Duration of action is by redistribution rather
  than elimination, slowly released and elimination
  by the liver-N-demethylation and excreted by the
  urine

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OPIOIDS

• FENTANYL
• Elimination half time is longer than morphine
  because Vd is larger and is more lipid soluble
• Stable hemodynamicno cardiac depressant effects,
  absence of histamine release, suppression of
  stress response during surgery

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OPIOIDS

• 12 times more potent than fentanyl
• 60 first pass pulmonary uptake
• Smaller Vd than fentanyl
• Metabolized N dealkylation ,O demethylation

• SUFENTANIL

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OPIOIDS

• ALFENTAto fentanyl but 1/5-1/10 as potent with
  1/3 duration
• Rapid onset 1.4 minslow PK
• 90 nonionized, Vd 4-6 times smaller than
  fentanyl, lower lipid solubility
• Bound to alpha1 acid glycoprotein
• Metabolized piperidine N-dealkylation to
  noralfentanil and amide N-dealkylation to
  N-phenylpropionamide
• Interindividual variability inhibit metabolism
  especially alteration in P-450 for those taking
  erythromycin

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REMIFENTANIL

• Potency similar to fentanyl
• Metabnonspecific plasma esterases inactive
  metabolites
• Small Vd
• Context-sensitive half-time is independent of its
  infusion about 4 min (this is unlike fent,
  sufent, and alfent in which it is dependent on
  duration of infusion)
• Not used for neuraxial placement

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OPIOIDS

• MORPHINE .1-1mg/kg intaop
• FENTANYL 2-150ug/kg intraop
• SUFENANIL-- .25-30ug/kg intraop
• ALFENTANIL 8-100ug/kg intraop
• REMIFENTANIL loading dose-1ug/kg,
  maintenance.5-20ug/kg/min intraop

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Pk nonionize ph7.4 Pro-bind Vd ½-time hr Blood brain min
mso4 7.9 23 35 224 1.7-3.3
mepe 8.5 7 70 305 3-5
fent 8.4 8.5 84 335 3.1-6.6 6.8
sufe 8.0 20 93 123 2.2-4.6 6.2
alfen 6.5 89 92 27 1.4-1.5 1.4
remif 7.3 58 66-93 30 .17-.33 1.1
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OPIOIDS

• AGONIST/ANTAGONIST
• NALBUPHINE-NUBAIN
• Chemically related to oxymorphine and naloxone-as
  potent as morphine and ¼ as an antagonist
• Metabolized in liver with half time of 3 to 6
  hours
• 10-20 mg IV
• Reverses postop ventilatory depression effects of
  fentanyl maintaining the analgesia
• Relieves itching produced by peripheral opioid
  mu receptors and maintains analgesia

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OPIOIDS

• Butorphanol (Stadol)
• Agonist-antagonist opioid
• Agonist effects 20 times gtthan pentazocine
• Antagonist effects 20-30 times gtthe pentazocine
• Low affinity for mu receptors to produce
  antagonism
• Moderate affinity for kappa receptors to produce
  analgesia
• IM 2-3mg, ½ life 2.5-3.5 hours, (similar
  analgesic effects to 10mg of morphine)
• Metabolites inactive via bile and urine.

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OPIOIDS

• Opioid induced respiratory depression
• Metabolized conjugation-glucuronic acid to form
  naloxone 3-glucuronide
• Half time 60-90 minutes
• 1-4uq/kg IV
• Side effects tachycardia,hypertention,pulmonary
  edema,cardiac dysrhythmias,vfib
• Crosses placenta
• Pure opioid antagonist

• NALOXONE (Narcan)

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OPIOIDS

• NEURAXIAL
• Epidural or subarachnoid placement of opioids are
  based on mu receptors in the substancia
  gelatinosa of the spinal cord
• Epidural placement of opioids reflect diffusion
  of the drug across the dura to gain access to the
  mu opioid receptors on the spinal cord as well as
  systemic absorption to produce effects similar to
  those that would follow IV administration

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OPIOIDS

• Side effects
• Pruritus
• N/V
• Urinary retention
• Depression of ventilation
• Sedation
• Central nervous system excitation
• Neonatal morbidity
• Viral reactivation
• Ocular dysfunction
• Sexual dysfunction
• GI dysfunction
• Thermoregulatory dysfunction
• Water retention

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OPIOIDS

• Factors that increase risk of respiratory
  depression
• High opioid dose
• Low lipid solubility
• Concomitant administration of parental opiods or
  other sedatives
• Lack of opioid tolerance
• Advance age

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ENTEREG

• ANTAGONIZES the peripheral effects of opioids on
  the GI tract u-opioid receptors.
• Does not reverse opioid analgesia

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KETOROLAC

• NSAIDs possess analgesic, antiinflamatory,
  antipyretic,and platelet inhibitory effects
• NSAIDs inhibition of cyclooxygenase activity and
  the resulting decrease in peripheral synthesis of
  prostaglandins

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KETOROLAC

• NSAID potent analgesic, moderate antiinflammatory
• 30mg IM,produces analgesia that is equivalent to
  10 mg of morphine
• Has no ventilatory depression or biliary spasm
• Metabolized by glucuronic acid conjugation
• Clearance is decreased in elderly and dosed less
  in younger patients

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KETOROLAC

• SIDE EFFECTS
• Bleeding
• Life threatening bronchospasm may follow if
  administered to patients with
• Nasal polyposis, asthma, and aspirin sensitivity