Opioids Part II (Morphine/Pharmacological Effects)

Question 1

Morphine Analgesia Pharmacological Effects

Answer 1

• Prototype of the opioids
• Analgesia achieved by raising pain threshold at spinal cord level and altering CNS perception
• May cause hyperalgesia with persistent administration

Question 2

Morphine Antitussive Pharmacological Effects

Answer 2

• Antitussive effects occur at subanalgesic doses

- Do not correlate with analgesic/respiratory depression effects

Question 3

Morphine Euphoria Pharmacological Effects

Answer 3

• Sense of contentment and well being
• Especially apparent when relief of pain occur with administration
• Mu agonists enhance DA release from nucleus accumbens and induces euphoria, tolerance developed
• Separate mechanism from analgesia

Question 4

Morphine Mental Clouding Pharmacological Effects

Answer 4

• Drowsy, lethargic, apathetic, trouble thinking, tendency to sleep
• Normal response to opioids and could be reported as dysphoric

Question 5

Respiratory Depression

Answer 5

• Can occur at therapeutic doses
• Common cause of death though some of tolerance development
• Morphine decreases response of brain stem to respiratory neurons causes a hypoxic response
• Chemoreceptors are only affected at HIGH doses of opioids, but if this occurs oxygen, giving oxygen may decrease breathing further
• Bronchoconstriction can also occur from morphine’s release of histamine when given parenterally

Question 6

Respiratory Depression + Impaired Pulmonary Fxn

Answer 6

• Caution in administering opioids in these cases

- Includes COPD, chronic bronchial asthma, and other medications that cause respiratory depression

Question 7

Respiratory Depression causes…

Answer 7

Along with increased pCO2:

• Cerebrovascular casodilation
• Secondary elevation of cerebral spinal fluid pressure
• *TREAT WITH NALOXONE**
• Don’t use if CSF increase isn’t secondary

Question 8

Risk Factors for Respiratory Depression

Answer 8

1. CNS depressant medications: alcohol, benzos, hypnotics
2. Sleep/Sleep apnea (possibly fatal)
3. Age: newborns have permeable BBB
4. Elderly patients
5. Relief of pain
6. Organ dysfunction: renal or hepatic dysfunction

Question 9

Miosis

Answer 9

• Stimulation of u and kappa receptors in Edinger-Westphal nucleus of oculomotor nerve
• Causes parasympathetic outflow and pupil constriction
• High doses of opioids => pinpoint pupils
• Miosis doesn’t develop with meperidine so it tends to be a narcotic of choice for abuse by health care professionals
• Blocked/reversed by atropine or opioid antagonist
• *Marked mydriasis with asphyxia onset**

Question 10

N/V

Answer 10

• Opioids stimulate CTZ to cause N/V
• Inhibited by antipsychotics, naloxone, and 5HT3 antagonists
• Relatively uncommon in recumbent patients given therapeutic doses of morphine, suggests a vestibular component may be in effect
• All clinically useful agonists produce some degree of N/V

Question 11

Drugs + Antiemetic Effect

Answer 11

• D2 receptor antagonist: Chlorpromazine
• ACH receptor Antagonist: Scopolamine
• Histamine Receptor Antagonist: hydroxyzine, promethazine
• 5HT3 Antagonist: Ondansetron and Granisetron

Question 12

GI Effects

Answer 12

• Affects smooth muscle to relieve diarrhea by decreasing peristaltic gut motility and increase tone of contraction
• Acts by peripheral opioid receptors (loperamide)
• Constipation is resistant to tolerance and will delay passage of GI contents and drug absorption

Question 13

Naloxegol

Answer 13

• Movantik
• Pegylated derivative of naloxone
• Doesn’t cross BBB and can reverse constipation

Question 14

Relistor

Answer 14

• Methylnaltrexone
• Selective mu-opioid receptor antagonist
• Quaternary amine, doesn’t cross BBB
• Treat OIC in those receiving palliative care when laxative therapy response isn’t sufficient

Question 15

Eluxadoline

Answer 15

• Viberzi
• Used for IBS with diarrhea
• Mu-opioid receptor agonist, delta antagonist, kappa agonist
• Modestly effective
• Warnings: spasms in muscle of digestive system (can worsen pain) and pancreatitis (is >3 drinks a day)
• CIV substance

Question 16

Urinary Retention

Answer 16

• Inhibits urinary voiding reflex and increases tone of external sphincter
• Water retention from increased ADH release and decreases blood pressure from reduced glomerular filtration
• Catheterization may be required after spinal drug administration
• Effect is through peripheral opioid receptors and tolerance will develop to this effect

Question 17

Histamine Release

Answer 17

Mirphine causes mast cell degranulation with release of histamine

• Causes itching, diaphoresis, vasodilation commonly at the site of injection
• Asthmatics may have bronchospasms from this
• Reversed from antihistamines, NOT naloxone
• Itching seen less with oxymorphone, methadone, fentanyl and sufentanil
• Itching seen more with morphine and meperidine

Question 18

Hormonal Actions

Answer 18

• Follows chronic therapy or abuse
• Inhibits gonadotropin hormone release
• Decrease LH/FSH release, decreases testosterone and estrogen
• Switch to non-opioid or used buprenorphine (less endocrine problems)

Question 19

CV Effects

Answer 19

• High doses of morphine produces hypotension
• From histamine release causes vasodilation and from CNS depression of vasomotor and adrenergic tone
• May cause postural hypotension
• Dramatically relieves the dyspnea associated with pulmonary edema due to LV failure by reducing peload and afterload