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OPIOIDS. First, morphine in 1803 with active component opiumNarcotic is greek for stupor and is referred to morphine-like analgesics with potential to produce physical dependence. . 0. OPIOIDS-OBJECTIVES. Explain the mechanisms for pain relief provided by opioid agonist and opioid agonist-antag
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1. LINDA WUNDER,MSN,CRNA
NURSE ANESTHESIOLOGY
FLORIDA INTERNATIONAL UNIVERSITY OPIOIDS
2. OPIOIDS 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.
3. 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.
4. OPIODS 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.
5. OPIOIDS 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
6. OPIOIDS 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
7. 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
8. 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)
11. OPIOIDS
12. 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
13. 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
14. 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
15. 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
16. OPIOIDS FENTANYL
17. 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
18. OPIOIDS FENTANYL
Elimination half time is longer than morphine because Vd is larger and is more lipid soluble
Stable hemodynamic—no cardiac depressant effects, absence of histamine release, suppression of stress response during surgery
19. OPIOIDS 12 times more potent than fentanyl
60% first pass pulmonary uptake
Smaller Vd than fentanyl
Metabolized N dealkylation ,O demethylation SUFENTANIL
20. OPIOIDS ALFENTA—to fentanyl but 1/5-1/10 as potent with 1/3 duration
Rapid onset 1.4 mins—low 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
21. REMIFENTANIL Potency similar to fentanyl
Metab—nonspecific 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
22. 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
24. 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
25. OPIOIDS Butorphanol (Stadol)
Agonist-antagonist opioid
Agonist effects 20 times >than pentazocine
Antagonist effects 20-30 times >the 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.
26. 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)
27. 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
28. 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
29. 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
30. ENTEREG ANTAGONIZES the peripheral effects of opioids on the GI tract u-opioid receptors.
Does not reverse opioid analgesia
31. KETOROLAC NSAIDs possess analgesic, antiinflamatory, antipyretic,and platelet inhibitory effects
NSAIDs inhibition of cyclooxygenase activity and the resulting decrease in peripheral synthesis of prostaglandins
32. 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
33. KETOROLAC SIDE EFFECTS
Bleeding
Life –threatening bronchospasm may follow if administered to patients with
Nasal polyposis, asthma, and aspirin sensitivity