Opioid 4-14

Question 1

What are all clinical effects of opioids?

Answer 1

CNS (sedation, sleep, agitation, dysphoria, convulsant, cerebral vasodilation)
Ventilatory depressive effect
Cough suppression
N/V
Miosis
Skeletal muscle rigidity
Bradycardia
Vasodilation
Cardiovascular
Histamine release effect
Smooth muscle spasm
Drug tolerance

Question 2

CNS effects of opioids?

Answer 2

Sedation and sleep often accompany pain relief.
Opioids are poor hypnotics.
High doses may cause convulsions.
Can also cause agitation and dysphoria.

Question 3

Increased Intracranial Pressure (ICP)

Answer 3

Caused by opioid-induced hypercarbia. Modest direct cerebral vasodilation.

Question 4

What opioids have caused Recurrent Postoperative Respiratory Depression?

Answer 4

Seen with fentanyl, sufentanil, alfentanil. The recurrent postop respiratory depression is dangerous because: it occurs even after patient appears recovered/ previously seemed to be breathing well.

Question 5

Ventilatory Depression of opioids and the principles of ventilatory depressive effects?

Answer 5

Dose-dependent depression of response to hypercapnia and hypoxia.
Pattern: when dose is increased, respiratory rate↓initally + tidal volume ↑ , → gradually↓ tidal volume overtime → apnea.
Equianalgesic doses = similar ventilatory effects.
Reversal of depression also reverses analgesia.
Tolerance develops to both effects equally.

Question 6

Why opioids cause Cough Suppression?

Answer 6

Acts on medullary cough centers.
Agents: codeine, heroin, dextromethorphan.

Question 7

Why opioids cause Nausea and Vomiting?

Answer 7

Direct stimulation of chemoreceptor trigger zone area postrema). Worsened by motion (labyrinth input).

Question 8

Why causes miosis (Pupil Constriction)?

Answer 8

Direct effect on autonomic nucleus of CN III. Little to no tolerance develops. Meperidine may cause mydriasis (atropine-like effect).

Question 9

Skeletal Muscle Rigidity

Answer 9

“Truncal or chest wall ridigity” is actually Generalized hypertonus of striated muscles throughout the body with most pronounced with potent opioids (fentanyl) given rapidly.
Mechanism: GABA inhibition + dopamine enhancement. Occurs mainly during induction, rarely during emergence.
Can impair ventilation due to pharyngeal/laryngeal hypertonus (not necessarily chest wall compliance)
Treat with muscle relaxants or naloxone.

Question 10

Effect of opioids -Bradycardia?
What drugs do we give to prevent bradycardia?
Which drug in opioid is less likely to cause bradycardia and why?

Answer 10

Due to direct vagal stimulation.
Preventable with atropine, pancuronium, or other vagolytics.
Meperidine less likely to cause bradycardia due to weak anticholinergic properties.

Question 11

Vasodilation and Blood Pressure Effects of opioids?

Answer 11

Due to medullary vasomotor depression and decreased sympathetic tone.
Causes mild orthostatic hypotension, but responds to fluids and recumbency.

Question 12

Cardiovascular Profile of Opioids - good stuff?

Answer 12

Opioid based anesthesia is good choice for critically ill patients with low cardiac reserve. Due to:
- No myocardial depression
–Does not pre-dispose to arrhythmias
–Does not blunt baroreceptor reflexes
–Preserves cardiac response to circulating catecholamines

Question 13

Histamine Release effect of opioids - What are the symptoms like? What opioids don’t release histamine? How to preveny? What are notorious cause of itching?

Answer 13

• True allergy to opioids is extremely rare.
• Hives and itching usually from mast cell histamine release.
• Fentanyl and congeners do not cause histamine release.
• Histamine → ↓ SVR, hypotension, tachycardia.
• Prevent with H1 or H2 blockers.
• Epidural opioids are the notorious cause of generalized itching.

Question 14

Smooth Muscle Spasm effect of opioids: sites affected? MOA? What drug reverses peripheral effects?

Answer 14

Sites affected: enteric plexus, sacral plexus, biliary tree, ureters, bladder.
Decreased peristalsis → constipation (chronic opioid use always need bowel regimen, because little if any tolerance develops to this effect).
Delayed gastric emptying.
Postoperative ileus.
Methylnaltrexone reverses peripheral effects without entering CNS (since permanently ionically charged).
Biliary effects: contraction of gallbladder & sphincter of Oddi leads to increased intrabiliary pressure and biliary colic or false positive cholangiograms —> Reversible with naloxone, atropine, or nitroglycerin.

Question 15

Urinary Retention - effect of opioid: MOA? Urinary effects are most likely happens in what situation?

Answer 15

•Urinary retention secondary to decreased tone of bladder detrusor muscle and increased tone of urinary spinchter.
•Decreased awareness of bladder distension
•Inhibition of urge to void
•Urinary effects are most likely in epidural or intrathecal administration

Question 16

Tolerance to Opioids

Answer 16

•Acute (tachyphylaxis): Occurs within hours usually after single high dose or rapid infusion.
•Chronic:
–Decrease in duration of effect
–Decrease in intensity of effect
–Tolerance most rapid to analgesic and ventilatory depression; slower to constipation and miosis.
–Unknown mechanism, but may involve NMDA activation and production of nitric oxide

Question 17

Physical Dependence and Withdrawal

Answer 17

–Opiate withdrawal syndrome
»Restlessness
»Mydriasis
»Goose flesh
»Runny nose
»Diarrhea
»Shaking chills
»Drug seeking behavior

–Onset of symptoms related to elimination of opioid
–Opioid antagonist or mixed agonist/antagonist can cause immediate severe withdrawal
–Methadone tape
»Slow dosage reduction with protracted withdrawal syndrome
–Separation of physical and psychological dependence (addiction)

Question 18

What are Opioid Agonists?

Answer 18

Morphine, Meperidine, Sufentanil, Fentanyl, Alfentanil, Remifentanil, Codeine, Dextromethorphan, Hydromorphone, Oxymorphone, Methadone, Heroin

Question 19

What are Opioid Agonist/Antagonists?

Answer 19

Pentazocine, Butorphanol, Nalbuphine, Buprenorphine, Nalorphine, Bremazocine, Dezocine

Question 20

What are Opioid Antagonists?

Answer 20

Naloxone, Naltrexone, Nalmefene, Methylnaltrexone

Question 21

Name 2 distinct chemical classes of alkaloids of opium?

Answer 21

Phenanthrenes
Benzylisoquinolines

Question 22

What are the characteristics of Phenanthrene, an Alkaloid of Opium?

Answer 22

3-ring structure, 14 carbon atoms, tertiary amine (highly ionized and water-soluble at physiologic pH), levorotatory isomers most active.
Examples: Morphine, Codeine, Thebaine (inactive but precursor to etorphine, >1000x potency of morphine)

Question 23

What are Benzylisoquinoline - another Alkaloids of opium?

Answer 23

Lack opioid activity.
Examples: Papaverine, Noscapine

Question 24

What are Synthetic Opioids?

Answer 24

Levorphanol,
Methadone derivatives,
Benzomorphan derivatives (e.g., Pentazocine),
Phenylpiperidine derivatives (Meperidine, Fentanyl)

Question 25

What are the side effects of neuraxial opioids?

Answer 25

Pruritis N/V Urinary retention Ventilatory depression Sedation CNS excitation Viral reactivation Neonatal morbidity

Question 26

Neuraxial Opioids on Pruritis: where you see it most pronounced at? And what population? What is it mechanism of action? How to treat it?

Answer 26

•Generalized; but most pronounced in face, neck, and upper thorax •More pronounced in obstetrical patients due to interaction of estrogen with opioid receptors. •Not histamine mediated; most likely mechanism is opioid receptors in trigeminal nucleus. •Naloxone is effective in treating pruritis; effect of antihistamines on pruritis is secondary to sedative effects.

Question 27

What causes Nausea/Vomiting from Neuraxial Opioids?

Answer 27

•Activation of chemoreceptor trigger zone; depression of vomiting center. •Dopaminergic process that responds well to anti-dopamine agents (metoclopramide/promethazine)

Question 28

What is the cause of Urinary Retention with Neuraxial Opioids?

Answer 28

Related to activation of opioid receptors in sacral spinal cord; reduced parasympathtetic outflow with detrusor muscle relaxation and increase in maximum bladder capacity

Question 29

What factors increase the risk of Ventilatory Depression with Neuraxial Opioids? There is one opioid that cause delayed ventilatory depression - what drug is that and how long? What population has lower risk and why? What can even develop even with normal breathing rate - How to monitor this and how to treat this? What is the best indicator of impending ventilatory depression?

Answer 29

•Risk factors: high opioid dose, low lipid solubility, concomitant parenteral opioids or other sedatives, lack of opioid tolerance, advanced age, patient position, increased intrathoracic pressure •Delayed depression can occur 6-12 hours after morphine, but has never been described more than 24 hours after neuraxial administration. •Obstetric patients have lowered risk for depression secondary to ventilatory stimulation by progesterone. •Arterial hypoxemia and hypercarbia may develop despite normal breathing rate; monitor with pulse oximetry and treat with supplemental oxygen. •Decreased level of consciousness may be best indicator of impending ventilatory depression.

Question 30

What is the relationship between Neuraxial Opioids and Sedation?

Answer 30

Dose-dependent, most common with sufentanil. When there is ↓ LOC = always think ventilatory depression first.

Question 31

What can cause CNS Excitation (Seizures) with Neuraxial Opioids?

Answer 31

From large IV doses, rare in neuraxial use. Caused by cephalad spread with GABA/glycine blockade.

Question 32

What is the effect of Neuraxial Opioids on Viral Reactivation?

Answer 32

Herpes reactivation seen especially in obstetric patients. Caused by cephalad spread + trigeminal nucleus interaction.

Question 33

What is the impact of Neuraxial Opioids on Neonatal Morbidity?

Answer 33

•Clinically important ventilatory depression in the newborn has been observed as placenta has no real barrier to transfer of opioids •Effects of morphine are much more pronounced when compared with meperidine.