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Flashcards in Leffler 1a Deck (18)
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1

Opioids:ADME

  • Absorption
    • subject to first pass effect
      • much higher oral dose is needed than parenteral dose
      • codeine and oxycodone has reduced first-pass effect
    • Buccal (Lozenges)
    • Transdermal patches (fentanyl patch)
    • nasal spray
    • IV
  • Distribution
    • leave blood rapidly
    • concentrate in highly perfused tissues
  • Metabolism
    • Most are glucuroniated (Phase II metabolism)
      • to M3G(neuroexcitatory) and M6G (analgesia)
  • Excretion:
    • Renal

2

Opioid Drug Classification:

  • Pure Opioid Agonists
  • Agonist-Antagonist Opioids (mixed)
  • Pure Opioid Antagonists

3

Morphine

  • Pure opioid agonist prototype
  • General MOA:
    • ​agonist at MU receptors
    • less at KAPPA
  • Therapeutic use: Mainly analgesic

4

Morpine: ADME

  • Absorption:
    • PCA Pump
    • IV
    • IM
    • Oral
    • subcutaneous
    • epidural 
    • intrathecal
  • Metabolism:
    • 1st pass metabolis m
    • Glucuronidatd to M6G(analgesia) and M3G(neuroexcitatory)
  • Excretion:
    • Renal (mostly)

5

Morphine: Tolerance and Dependence

  • Tolerance:
    • prolonged Tx=tolerance to analgesia, Euphoria, sedation, respiratory depression
    • little tolerance to miosis and constipation
    • cross tolerance to other opioid agonists
  • Physical Dependence
    • minimize withdrawal by tapering dose overe 3 days 
      • or 7-10 days in addict

6

Morphine: Specific Clinical Uses

  • Analgesia
    • pre and post operative analgesia (regional analgesia via epidural or intrathecal)
    • Pain of terminal illness
    • Visceral pain of trauma (Burns, cancer, acute MI, renal/biliary colic)
    • Continued dull pain is relieved more effectivley than sharp intermittent pain (but can be achieved with higher doses)
    • Controlled pain in patient
  • Acute pulmonary edema
    • relieves dyspnea
  • Pre-anesthetic
    • supplement to anesthesia

7

Morphine: Specific Adverse Effects

  • Respiratory Depression:
    • direct inhibition of respiratory center in brainstem
    • decreased respiratory rate
  • Constipation
    • decreased GI motility
  • Sedation
  • Emesis-Nausea and Vomiting
    • direct stimulation of the CTZ in the medulla
  • Elevation of ICP
  • Urinary Retention
  • Orthostatic hypotension
  • Miosis (pin poin pupil)
  • Pruritus
  • Loss of recent memory
  • decreased abilty to concentrate

8

Morphine: Contraindications

  • Pregnant
    • physical dependence of infant
  • Labor and Delivery
    • can suppress uterine contractions and prolong labor
    • respiratory depression in neonate
  • Emphysema and COPD
    • Decreased respiratory reserve, can reduce resipration in patient with impaired pulmonary function 
  • Head injury
    • can increase respiratory depression and increase ICP
  • IBD
    • Toxic Megacolon
  • Drug Interactions:
    • Other CNS depressants:
      • antipsychotic
      • antidepressents 
      • antiepileptics
    • MAOIs (monoaminno oxidase inhibitors)
      • hyperthermia
      • seizures
      • coma

9

Other Pure opioid agonists?

  • Hydromorphone 
  • Oxymorphone
  • Levorphanol
  • Meperidine
    • short term use only
    • toxic metablite that could accumulate and cause CNS excitation
    • serotonin syndrome when given with MAOIs
  • Fentanyl 
  • Methadone
  • Codeine 
    • prodrug
  • Oxycodone, Hydrocodone
  • Diphenoxylate/Atropine,Difenoxin,Loperamide
    • treat diarrhea
    • minimal dependency liability 

10

Codeine

  • Pure Opioid agonist
  • Prodrug
    • metabolized by CYP2D6-->Morphine (active component)

11

Mixed Action Opioids

AKA Agonist-Antagonist Opioids

  • Partial Antagonist/Agonist at Mu receptor and Agonist at Kappa receptor
  • Drugs:
    • Pentazocine
    • Butorphanol
    • Nalbuphine

12

Mixed Action opioids used for:

  • Moderate pain
  • Not much:
    • respiratory depression
    • euphoria
    • potential for abuse
  • Less dependence than morphine
  • Given alone=Analgesia 
    • less analgesia than morphine
  • If given to a patient already taking a pure opioid, it will inhibit the analgesia 
  • Increase workload of the heart
    • avoid in MI patients
  • Can precipitate withdrawal in patients who are physically dependent on pure opioid agonists

13

Buprenophrine

  • Mixed action opioid
  • Buprenorphine + Nalozone=Suboxone 
  • MOA:
    • partial Mu agonist
    • Full antagonist at Kappa
  • Used to maintain abstinence from addiction (heroin)

14

Methadone HCl

  • More effective orally than morphine
  • Abstinence:
    • slower in onset
    • longer in duration
    • less intense
  • Detoxification and maintenance of heroin addicts
  • used as an analgesic in chronic pain

15

Opioid Antagonists:

  • MOA:
    • antagonist at MU and Kappa receptor
  • used to treat opioid OD, but also post operative opiod depressoin
  • Drugs:
    • Naloxone (narcan)
      • prototype
      • block or reverse the effects of morphine
        • respiratory depression
        • coma
        • analgesia
      • Nasal spray
    • Naltrexone
      • similar to naloxone but oral
    • Nalmefene
      • Long-acting analog of naltrexone

16

Opioid antagonist usd to treat opioid-induced constipation with advanced illness or pain:

  • Methylnaltrexone
    • injectable
    • long term use
  • Alvimopam
    • short term
    • post operative

17

Spinal Cord Transection: Immediate vs Long Term results

  • Immediate Results:
    • Areflexia-loss of all reflexes
    • Flaccid paralysis
    • loss of autonomic function
    • lasts 3-4 weeks in humans
  • Long Term:
    • Slow return of reflex actions
    • Hyperreflexia-Reflexes strengthen:
    • Spastic paralysis
    • Pathological reflex:
      • babinski sign
      • Clonus
      • Clasp-Knife response

18

Myotatic (Stretch Reflex)

  • Role=posture
  • Myotatic-extended muscle
  • Graded resistance to change in muscle length 
  • Muscle spindle=sensory receptor
  • Length detector:
    • muscle spindle attached parallel to extrafusal fibers