Leffler 1a Flashcards Preview

• 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

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

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

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

• 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

• 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

• 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

• 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

• 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 

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

AKA Agonist-Antagonist Opioids

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

• 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

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

• 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

• 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

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