Test 4: Opioids Pharmacodynamics Flashcards
What pain fibers do opioids work best on?
-Treat “Second pain” sensations: Slowly conducted sensations from unmyelinated C-fibers
-Less effective for “First pain” sensations: quickly conducted sensations from small, myelinated A-Delta Fibers
How do opioids differ from local anesthetics?
They block pain, but don’t produce the differential blockade that LA’s produce.
-No effect on touch, temp, etc.
Are opioids anesthetics?
NO. They do not reliably produce unresponsiveness.
Opioids are most effective for what kind of pain?
Continuous, visceral, dull pain.
-Organ pain
-But, at high doses, can relieve any pain.
What are the CNS effects of opioids?
-Sedation & Euphoria: contribute to the feeling of well-being in awake patients (varies depending on agent and receptor)
-Dysphoria: occurs with strong Kappa agonists or when opioids are taken in the absence of pain.
How do opioids elicit Analgesic effects?
1) Inhibit the ascending transmission of nociceptive stimuli
-From the dorsal horn of the spinal cord
2) Activate pain control pathways that descend from the midbrain
-Via the rostral ventromedial medulla to the spinal cord dorsal horn
What is the effect of opioids on neuromonitoring (EEG & EP)?
The effect of opioids on electroencephalographic and evoked-potential activity is minimal, therefore neurophysiologic monitoring can be conducted during opioid anesthetic techniques.
What is the effect of opioids on Intracranial Pressure (ICP)?
Opiate administration can indirectly cause an increase in intracranial pressure if respiratory depression-induced hypercarbia occurs.
Katzung:
Opioid analgesics affect cerebral circulation minimally except when PCO2 rises as a consequence of respiratory depression. Increased PCO2 leads to cerebral vasodilation associated with a decrease in cerebral vascular resistance, an increase in cerebral blood flow, and an increase in intracranial pressure.
What is Physical dependence?
The need for the drug in order to function properly.
-Physical dependence is defined as a characteristic withdrawal or abstinence syndrome when a drug is stopped or an antagonist is administered.
What is Tolerance?
A gradual loss in effectiveness with repeated doses.
-Decrease in duration comes first, followed by a decrease in effect.
Katzung:
-Tolerance develops most readily when large doses are given at short intervals and is minimized by giving small amounts of drug with longer intervals between doses.
-Tolerance also develops to the antidiuretic, emetic, and hypotensive effects but not to the miotic, convulsant, and constipating actions.
What is Cross-Tolerance?
Patients tolerant to one drug (ex: Morphine) show a reduction in analgesic response to other agonist opioids.
-Particularly occurs with Mu agonists.
-Can be partial or incomplete
How does Tolerance develop?
Both acute and chronic tolerance will develop with opiates.
-The mechanism of tolerance is complex and does not appear to be due to a change in receptor number.
-Receptor internalization, activation of N-methyl-D-aspartate (NMDA) receptors, second messenger changes, and G protein uncoupling (changes in the binding sites) may all play a role.
How do Opioids effect Awareness?
-Opioid agonists are NOT anesthetics
-Mu agonists (even high doses) do not reliably produce unresponsiveness or amnesia.
-High dose opiates do not eliminate the risk of awareness.
-Cannot be considered a complete anesthetic or used alone
What is Hyperalgesia?
Increased sensitivity to pain. Exaggerated response.
-Can be due to damage to nociceptors or peripheral nerves.
Katzung:
-Spinal dynorphin and activation of the bradykinin and NMDA receptors have emerged as important candidates for the mediation of opioid-induced hyperalgesia.
What are the Respiratory Effects of opioids?
-Dose-dependent depression
-Most significant adverse effect (can be life-threatening if airway is not secured)
-Alters the response to hypercarbia and hypocapnia (depresses the hypoxic drive to breathe - important for COPD and OSA patients).
What are risk factors that increase the risk for respiratory depression with opioids?
-High dose opioids
-Advanced age
-CNS depressants
-Renal insufficiency
Which patients are at an increased risk for M&M in the post-operative period due to respiratory depression from opioids?
Morbidly obese or OSA patients
Pediatrics < 60 weeks PCA
How do opioids produce respiratory depression?
Via stimulation of the Mu and Delta Receptors in the Ventilatory control center in the medulla.
What do opioids do to the CO2 response curve?
RIGHT shift in the CO2 response curve.
-Decrease responsiveness to increased CO2 and decreased O2
-Higher pCO2 is needed to maintain adequate respiration
What is the Pupillary Reflex Arc?
1) Opiate depression of GABA interneurons leads to stimulation of the Edinger-Westphal Nucleus
2) E-W Nucleus sends a PNS signal via the Ciliary Ganglion to the Oculomotor nerve
3) Pupil constricts
T/F: Opioid addicts will develop tolerance to Miosis. (Blue Box)
False: Tolerance does NOT develop to miosis. (Blue Box!)
When does Miosis occur with opioid administration?
-Occurs at lower doses than analgesia or respiratory depression
-Qualitative, not quantitative sign
-Reversible with narcan (if patient not breathing)
-Due to Mu receptor agonist (pupillary reflex arc). Mu receptor right on iris itself.
How do opioids cause anti-tussive effects?
-Depresses the cough center in the medulla
-Glottic protective reflexes are intact - not taking away mechanical ability to cough. Still have reflexes intact if needed.
-Therapeutic: helps to decrease stimulation with ETT. Provides “tube tolerance”
Which opioids are particularly good at cough suppression?
Codeine and Heroin
