Pharmacology of opiod analgesics.txt

  1. Pharmacology of opiod analgesics
    • Nociceptive pain: results from injury to tissues - somatic and visceral pain
    • Neuropathic pain: results from injury to peripheral nerves
    • both types respond differently to analgesic drugs
  2. Nociceptive pain
    • Somatic: from injury to tissues - bones, joints, muscles; localized and sharp in quality
    • Visceral: Results from injury to visceral organs - e.g. small intestine; vaguely localized with a diffuse aching quality
  3. Opium alkaloids
    • Morphine: chiefly responsible for pharmacological actions of opium
    • Codeine: methylmorphine, has similar but weaker actions
    • Thebaine: practically devoid of analgesic activity; no medicinal use, but it provides a synthetic route for hydroxylated opioids
  4. Structural relationships among some opiates
    • heroin is converted to morphine - on its own has no activity
    • Codeine - has increased bioavailability but decreased action
    • Naloxone: perfect antagonist blocks pharmacological action of heroin
    • Oxycodone: have methyl group at 3 position increases bioavailability but decreased action
  5. Opiods: absorption, distribution, metabolism, excretion
    • absorption: absorbed well IM, SC, and oral and nasal mucosa
    • rapidly distributed: from blood into highly perfused tissues (lung, liver, kidney, spleen) - brain < other tissues, due to BBB
    • First pass metabolism: in the liver inactivates many opiods (e.g. morphine)
    • Polar metabolites are excreted: in urine
  6. Glucoronidation of opioids
    promotes renal excretion of drugs
  7. Pharmacological Actions of Morphine: CNS
    • analgesia
    • euphoria
    • miosis
    • respiratory depression
    • cough suppression
    • nausea/vomiting
    • mood altering / rewarding properties
  8. Analgesic properties
    • Relief of moderate to severe acute pain
    • renal colic
    • biliary colic
    • acute MI
    • dyspnea associated with LVF and pulmonary edema
    • extensive surgical procedures and post-operative pain
    • severe burns*
    • serious wounding*
    • severe chronic pain (e.g., associated with malignancy)
  9. Continuous dull pain***
    • is relieved more effectively than sharp intermittent pain: Adelta fibers; sharp pain is more memorable, and dull pain tends to be forgotten
    • In patients suffering from pain, morphine induces a feeling of well being and tranquility (euphoria)
    • In pain-free individuals, the response to morphine is not always present!!: general malaise; sensations of anxiety or fear (dysphoria); also nausea and vomiting
  10. Miosis
    due to excitation of the parasympathetic nerve innervating the pupil
  11. Respiration
    • Morphine depresses respiration, even at normal therapeutic doses: due to decreased sensitivity of brain stem to increases in Pco2 and H+
    • The main stimulus to breathing at this point: becomes hypoxia
    • This effect is increased by the concurrent use of other CNS active drugs: alcohol, barbiturates, benzodiazepines
    • Caution: pregnancy (neonate)**** b/c fetal respiratory drive will also be affected
  12. Respiration effects
    • Suppression of respiratory drive contributes to usefulness of morphine in relieving difficult or labored breathing in certain conditions such as
    • Left ventricular failure - very difficult to breathe, decreased respiration, lower "depth" of respiration
    • Pulmonary edema
  13. Morphine increases intracranial pressure
    • Mechanism: indirect
    • Decreased respiration, increased pCO2 -> causes arteriolar dilatation -> CSF pressure
    • But, if respiration is maintained at a normal rate, ICP will remain normal: especially if ask the patient to breathe consciously more
  14. Antitussive action
    • Morphine suppresses the cough reflex that originates in the medulla oblongata: unrelated to its analgesic action, unrelated to its respiratory depressant action
    • Can modify the morphine molecule to select this single property: dextromethorphan
    • Dextromethorphan: cough suppressant - binds possibly at glutamate receptors, not morphine receptors
  15. Emesis
    Morphine stimulates the CTZ in the medulla to cause nausea and vomiting: a vestibular component? possibly because people laying down have less than those with an orthostatic change
  16. Cardiovascular system
    • Blunts the baroreceptor reflex
    • Causes peripheral arteriolar and venous dilatation: results, in part, from morphine-induced release of histamine
    • Orthostatic hypotension and fainting: in recumbent individuals, effect is mild; in standing individuals, the effect is profound
  17. GI Tract
    • Morphine decreases propulsive peristalsis through GI tract: leads to constipation
    • Morphine suppresses awareness of bowel stimuli
  18. Propulsive peristalsis through GI tract is decreased
    • Passage of GI contents is delude
    • This leads to enhanced absorption of water: dehydration of feces
    • Tone of anal sphincter is increased: the constipation action of morphine
  19. Urinary retention
    • Morphine causes urinary hesitancy and urinary urgency: increased tone of bladder smooth muscle; increased tone of sphincter muscle
    • Morphine suppresses awareness of bladder stimuli!!: ***
  20. Biliary colic
    • Morphine can cause spasm of the lower end of the common bile duct (the sphincter of oddi)
    • increases pressure within the biliary tract
    • in patients with pre-existing biliary colic, morphine can intensify the pain
  21. Chronic Actions of Morphine
    • Tolerance: tolerance develops to - analgesia; respiratory depression
    • Tolerance does not develop to: constipation; pupillary mitosis
    • Depencence: too
  22. Opioid poisoning
    • Triad of 3 signs strongly suggests opioid poisoning:
    • Coma
    • Pinpoint pupils
    • Depressed respiration
  23. Treatment of opioid poisoning
    • Maintain patent airway and ventilate the patient
    • Treat with antagonists to reverse CNS effects - Naloxone is drug of choice
  24. Mechanism of action - the morphine receptor
    • Morphine binds to a specific receptor:
    • binding is stereospecific: only the L-isomer is active; implies that binding involves at least three binding sites
    • Regional distribution: the regions of highest binding are associated with the limbic system
    • Three principal receptors: mu, kappa, delta
  25. Opiate binding sites
    Morphine binds to opiate receptors concentrated within the reward pathway and the pain pathway
  26. Mu Morphine receptor
    • Spinal and supra-spinal analgesia
    • Miosis
    • Respiratory depression
    • Euphoria
    • Physical dependence
    • decreased GI motility
  27. Kappa Morphine Receptor
    • Spinal analgesia
    • Miosis- less intense than Mu
    • Respiratory depression - less intense than Mu
    • Sedation
    • Durphoria
  28. Endogenous opioids
    • Opioid drugs produce analgesia by activating the same receptors that are acted on by the endogenous pain suppressing system:
    • enkephalins
    • endorphins
    • dynorphins
  29. Enkephalins:
    have similar structures and produce the same psychic effects
  30. Mechanisms of Action
    • Opioid receptors respond to opioids and to endogenous peptides (suppress painful simuli)
    • Opioids work both presynaptically and post-synaptically:
    • In general, opioid receptors are G-protein-coupled receptors
    • Activation reduces Ca++ influx during the action potential, leading to less neurotransmitter release
  31. Spinal sites of opioid action
    • Mu, Kappa, delta agonists reduce transmitter release from presynaptic terminals of nociceptive primary afferents
    • Mu agonists also hyperpolarize second-order neurons: by increasing K+ conductance -> imps
Card Set
Pharmacology of opiod analgesics.txt