Pharm exam 4 - Opioids

Endogenous opioid peptides:

found in the central nervous system (CNS) and in peripheral tissues
• serve as neurotransmitters, neurohormones, and neuromodulators

Opioids:

drugs that have actions similar to endogenous opioid peptides, based on morphine

What are the opioid receptors?

• Mu

• Kappa

• Delta

Mu receptor

activation causes analgesia (pain relief), respiratory depression, euphoria, sedation, decreased GI motility, and eventual physical dependence

Kappa receptor

activation causes analgesia, sedation, and decreased GI motility

Delta receptor

no significant effects

Pure Agonists

• agonists for Mu and Kappa receptors (divide into strong & mod-strong)
• morphine, fentanyl, codeine, meperidine (Demerol), etc

Agonist-Antagonists

• antagonist for Mu, agonist for Kappa receptors
• Pentazocine (Talwin), nalbuphine (Nubain)

Pure Antagonists

• antagonists for Mu and Kappa
• Naloxone (Narcan), naltrexone

Strong Opioid Agonists drugs:

include morphine, hydromorphone, fentanyl, meperidine (Demerol), heroin, methadone

Strong Opioid Agonists prototype:

Morphine

Morphine MOA:

mimics endogenous opioids, activating mu and kappa receptors

Morphine clinical use:

relief of moderate to severe pain (postoperative, cancer-related, labor/delivery, MIs)

Morphine absorption/distribution:

 can be given practically any route, onset and duration differ
 small amount crosses BBB
 scheduled is usually best, amount depends on pain severity

Morphine metabolism:

 affected by first-pass effect
 liver inactivation

Morphine adverse effects:

 Respiratory depression: onset varies with route, most serious
 Constipation (common)
 Orthostatic hypotension
 Urinary retention
 Nausea/vomiting
 Cough suppression

Morphine toxicity:

coma, respiratory depression, pinpoint pupils

Morphine drug interactions:

 other CNS depressants
 anticholinergics
 antihypertensives
 agonist- antagonists
 antagonists

Morphine physical dependence:

 Intensity and duration of withdrawal syndrome depend on T ½ and degree of dependence on drug
 Morphine has a short half-life: withdrawal is intense (7-10 days)
Initial reactions include yawning, rhinorrhea, and sweating
 Anorexia, irritability, tremor, gooseflesh
 Violent sneezing, N/V/D, abd cramping, bone & muscle pain, kicking movts

What is fentanyl?

Strong Opioid Agonists

What differs for fentanyl compared to morphine?

about 100x more potent than morphine

Fentanyl administration:

 Parenteral administration: for induction and maintenance of anesthesia
 Transdermal administration: postoperative pain, chronic pain
- usually reserved for persistent severe pain in patients who are opioid tolerant

Fentanyl metabolism / adverse:

 Metabolism is hepatic, by CYP3A4
 Adverse effects same as morphine

Moderate-Strong Opioid Agonists examples:

codeine, oxycodone, hydrocodone

Moderate-Strong Opioid Agonists MOA:

same as strong opioid agonists

Difference between moderate strong and strong opioid agonists:

Less analgesia and respiratory depression
 Less abuse potential than strong agonists but tolerance and abuse can occur

What is codeine?

Moderate-Strong Agonist

Codeine uses:

 relief of mild to moderate pain, often co-formulated with acetaminophen
 Cough suppressant

Codeine pharmacokinetics:

Administration/Absorption
 PO most common method

Metabolism
 liver (CYP2D6) metabolizes about 10% of codeine to morphine; this is likely how it produces analgesia
 genetic differences in this enzyme affect analgesia from codeine

Codeine adverse effects:

 Similar to morphine
 Increase with higher dosages
 High dosages required for significant pain relief = dangerous side effects

Agonist- Antagonist Opioids do what?

 Activate kappa receptors and block mu receptors
 Provide analgesia without as many side effects as pure agonists

Can Agonist- Antagonist Opioids cause withdrawal?

Yes if used to replace a long-term opioid agonist

BUT less potential for abuse

What is Pentazocine?

Agonist-Antagonist

Pentazocine MOA:

Activates kappa receptors causing analgesia, sedation, and limited respiratory depression

Pentazocine pharmacokinetics:

Absorption
 PO administration
Metabolism
 short T ½ ; frequent dosing

Pentazocine adverse effects:

 Many similar to morphine, but less respiratory depression
 Increases cardiac workload; not a good choice for pain related to myocardial infarction
 Physical dependence can develop but withdrawal is mild compared to pure opioid agonists

Opioid Antagonists MOA:

block the opioid receptors

Opioid Antagonists uses:

reversal of opioid overdose, relief of opioid-related constipation,
and treatment of opioid addiction

Do Opioid Antagonists have an effect on their own?

No, only used in combination with an opioid agonist

What is Naloxone (Narcan)?

Opioid Antagonist

Naloxone pharmacokinetics:

 Absorption
highly affected by first- pass effect given parenterally or intranasally, longer effects when given IM/SC

 Metabolism
hepatic, T1/2 about 2 hours

Naloxone adverse effects:

 None on its own
 If given to a person physically dependent on opioids, will cause immediate/severe withdrawal problems

The Opioid Epidemic- Nursing Considerations

Nursing goals to minimize physical dependence and abuse of opioids
Assess pain and dosage sufficient to relieve pain
Administer lowest effective dose for shortest time need
As pain diminishes, opioid dosages should be reduced
Switch patient to nonopioid analgesic as soon as possible