Test 4: Opioids Pharmacodynamics Flashcards

1
Q

What pain fibers do opioids work best on?

A

-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

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2
Q

How do opioids differ from local anesthetics?

A

They block pain, but don’t produce the differential blockade that LA’s produce.
-No effect on touch, temp, etc.

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3
Q

Are opioids anesthetics?

A

NO. They do not reliably produce unresponsiveness.

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4
Q

Opioids are most effective for what kind of pain?

A

Continuous, visceral, dull pain.
-Organ pain
-But, at high doses, can relieve any pain.

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5
Q

What are the CNS effects of opioids?

A

-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.

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6
Q

How do opioids elicit Analgesic effects?

A

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

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7
Q

What is the effect of opioids on neuromonitoring (EEG & EP)?

A

The effect of opioids on electroencephalographic and evoked-potential activity is minimal, therefore neurophysiologic monitoring can be conducted during opioid anesthetic techniques.

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8
Q

What is the effect of opioids on Intracranial Pressure (ICP)?

A

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.

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9
Q

What is Physical dependence?

A

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.

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10
Q

What is Tolerance?

A

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.

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11
Q

What is Cross-Tolerance?

A

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

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12
Q

How does Tolerance develop?

A

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.

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13
Q

How do Opioids effect Awareness?

A

-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

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14
Q

What is Hyperalgesia?

A

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.

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15
Q

What are the Respiratory Effects of opioids?

A

-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).

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16
Q

What are risk factors that increase the risk for respiratory depression with opioids?

A

-High dose opioids
-Advanced age
-CNS depressants
-Renal insufficiency

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17
Q

Which patients are at an increased risk for M&M in the post-operative period due to respiratory depression from opioids?

A

Morbidly obese or OSA patients
Pediatrics < 60 weeks PCA

18
Q

How do opioids produce respiratory depression?

A

Via stimulation of the Mu and Delta Receptors in the Ventilatory control center in the medulla.

19
Q

What do opioids do to the CO2 response curve?

A

RIGHT shift in the CO2 response curve.
-Decrease responsiveness to increased CO2 and decreased O2
-Higher pCO2 is needed to maintain adequate respiration

20
Q

What is the Pupillary Reflex Arc?

A

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

21
Q

T/F: Opioid addicts will develop tolerance to Miosis. (Blue Box)

A

False: Tolerance does NOT develop to miosis. (Blue Box!)

22
Q

When does Miosis occur with opioid administration?

A

-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.

23
Q

How do opioids cause anti-tussive effects?

A

-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”

24
Q

Which opioids are particularly good at cough suppression?

A

Codeine and Heroin

25
Q

How do opioids increase PONV?

A

By stimulating the Chemoreceptor Trigger Zone in the Area Postrema of the Medulla.
-Floor of the 4th Ventricle.
-Increased in ambulatory surgery patients due to possible vestibular nerve involvement. PONV is exacerbated by movement.
-Patient responses vary

26
Q

T/F: Opiate analgesia is safe for people with cardiovascular compromise (Blue Box!)

A

True

27
Q

What are the cardiovascular effects of opioids?

A

-Decrease HR due to increased vagal nerve tone to the Medulla of the brainstem (can be attenuated with anti-muscarinics)
-Bradycardia with little effect on BP
-Dose-dependent vasodilation (both venous & arterial) due to depression of the vasomotor centers of the brain. Decreases PL & AL
-Decrease in BP is mild in healthy patients, but can be pronounced in patients with increased sympathetic tone
-No change in contractility, baroreceptor function, or autonomic response.

28
Q

Which opioids release Histamine?

A

Morphine, Meperidine, and Codeine
-Causes vasodilation (arterial and venous), tachycardia, and hypotension
-Can be blocked/blunted with H1 and H2 antagonists

29
Q

Does fentanyl and its cogeners release histamine?

A

No

30
Q

Do opioids have an effect on nerve conduction?

A

No. Opioids have no major effects on nerve conduction at the neuromuscular junction or at the skeletal muscle membrane.

31
Q

Large IV doses of most opioids can cause what muscular symptoms?

A

Generalized hypertonus of skeletal muscle can be produced by large IV doses of most opioid agonists.
-Muscle rigidity leads to a loss of chest wall compliance and truncal rigidity (“Tight Chest”). Results in difficult mask ventilation.
-Can cause constriction of pharyngeal/laryngeal muscles, leading to vocal cord rigidity and closure
-Mechanism behind this is unknown, but theorized to be related to central Mu receptors interacting with Dopamine and GABA pathways.
-Increased frequency with concurrent administration of N2O
-Can be attenuated with muscle relaxants (if early) or Narcan (if end of case)

32
Q

Which opioid agents are the most likely to cause muscle rigidity?

A

-Fentanyl and Remifentanil most common
-Also seen with Alfentanil and Sufentanil

33
Q

The itchy rash/hive reaction associated with opioids is due to what?

A

Histamine release locally.
-Seen most often with Demerol, Morphine, and Codeine

34
Q

The feeling of warmth in the face, upper chest, and arms (true pruritus) associated with opioids is due to what?

A

Stimulation of Central Mu receptors.
-Most common with neuraxial administration (ex: Duramorph in a spinal)

35
Q

How do you treat pruritus associated with opioids?

A

-Naloxone (reverses activity of Mu receptors)
-Nubain (Agonist/antagonist that reverse itch but not analgesia- blocks Mu and not Kappa)
-Droperidol
-Antihistamines (benadryl)
-Ondansetron (MOA unknown)

36
Q

How do opioids contribute to constipation and post-op ileus?

A

-Decreased gastric motility, prolonging gastric emptying time
-Reduce secretory activity throughout GI system (dec gastric acid secretion)

Inc risk for aspiration, especially with patients having multiple surgeries day after day (ex: trauma patient receiving staged procedures)

37
Q

What drugs are used for the treatment of GI side effects associated with opioids?

A

Peripherally acting Mu Opioid Receptor Antagonists (PAMORAs) that promote peristalsis.
-Alvimopan (Entereg)
-Methylnaltrexone (Relistor)

Work locally in the GI tract, and do not affect centrally produced analgesia.

38
Q

What is the effect of opioids on the biliary duct?

A

-Dose dependent increases in biliary duct pressure
-Increases Sphincter of Odi tone (can give Glucagon to offset this)
-Risk for false-positive cholangiograms

39
Q

What are the opioid effects on the Endocrine System?

A

-Reduction of stress response
-Immunosuppressant effect (bad for cancer patients. Most common with Morphine)
-Release of Vasopressin from post. pituitary
-Inhibition of Anterior Pituitary Hormones: Corticotropin, Gonadotropin, and Thyrotropin
-Potential for decreased BMR and decreased temperature with chronic use of opioids

40
Q

How do opioids decrease temperature?

A

By resetting the equilibrium point of temperature regulation in the hypothalamus.

41
Q

What are the effects of opioids on the Bladder?

A

-Usually produce an anti-diuretic effect
-But, Kappa receptor agonists can cause diuresis.
These two effects are usually balanced out because we don’t have any solely Kappa Agonist drugs.

42
Q

How do opioids produce an anti-diuretic effect?

A

-Decrease tone at the bladder detrusor muscle
-Constrict the urinary sphincter (inc urinary sphincter tone)
These two result in urinary retention
-Especially common SE with intrathecal and epidural opioid administration.