Opioids & Context Sensitive Half-Time Flashcards
What is an opioid?
Any natural, synthetic, or endogenous substances with morphine-
like properties including:
Analgesia without loss of touch, proprioception, or consciousness
Most common opioid receptor?***
Mu (μ) receptors: Analgesia; respiratory depression; miosis, euphoria, physical dependence, constipation; urinary retention?
Opioid mechanism of action
Inhibit release of and response to excitatory neurotransmitters in nociceptive neurons
Opioid receptors are located where?
Throughout the CNS and peripheral nerves
Which opioids have active metabolites?
Morphine, meperidine have active metabolites
Which opioids have inactive metabolites?
Fentanyl, sufentanil, alfentanil have inactive metabolites
How is Remifentanil different than most opioids when it comes to biotransformation?
Its not metabolized in the liver
Its metabolized via ester hydrolysis by blood plasma esterases – NOT pseudocholinesterase which we associate with Sux)
What part of opioid pharmacokinetics has a genetic component?
Biotransformation in the liver. Why? Bc there are genetic differences in the functionality of the enzyme that metabolizes opioids (CYP2D6) in certain populations
- CYP2D6 specifically transforms oxycodone, hydrocodone, tramadol and codeine into their active forms
———–Therefore, any CYP2D6 deficient people may have inadequate analgesia if given these opioid medications
- CYP2D6 also metabolizes meperidine and methadone so any CYP2D6 deficiency can cause prolonged clinical effect if given these opioid medications
How are opioids excreted? Why is this important?
Excretion – mostly in urine
This is specifically significant for the active metabolites of:
1) morphine (morphine-3-glucuronide [M3G] & morphine-6-glucuronide ([M6G])
2) meperidine (normeperidine)
– CAUTION WHEN GIVING MORPHINE or MEPERIDINE TO RENAL PATIENTS bc the accumulation of these active metabolites can lead to substantial side effects for the renal pts
Morphine
Morphine – the template.
o Dose: 0.01 – 0.1 mg/kg OR 2-8 mg every 5-10 minutes.
Acts at the μ receptors
Can decrease MAC to ~65%
Crosses blood-brain barrier slowly – 5 min onset, but peak in 10-40 minutes
35% protein-bound (albumin)
Rapid redistribution; elimination half-life 1.7 – 3.3 hours.
o Age dependent: 7-8 hrs in neonates; 4.5 hrs for ages 61-80
o High hepatic extraction elimination affected by decreased hepatic flow
o Active metabolites (M3G, M6G) as well as morphine urine
Monitor carefully if used in patients with renal failure
Reversed by naloxone (narcan)
Morphine Effects:
Effects:
o Neuro: Sedation, cognitive impairment, euphoria
↓CMRO2
↓ CBF
↓ ICP if normocarbia is maintained
- Pupillary constriction (miosis),
- Pruritis (itching)
- Muscle rigidity after large doses – can even interfere with manual ventilation
- Nausea/vomiting – stimulates CTZ (chemo trigger zone) in medulla
Resp: ↓ response to CO2;
- hypoventilation,
- apnea but arousable on command
- ↓ cough reflex
- Resp. depression can be within minutes or delayed for several hours
GI: decreased motility (constipation),
- slower gastric emptying
- increase common bile duct tone, and can lead to biliary spasm (sphincter of
Oddi)
GU: urinary retention
Endo: histamine release -> leads to hypotension, dilation of cutaneous blood vessels -> leads to flushing or rash
Prevents stress response at high doses
Prevents inflammatory response with cardiopulmonary bypass
CV: **hypotension at higher doses (greater effect in patients with high baseline sympathetic tone);
- Can cause bradycardia at higher doses
Hydromorphone (Dilaudid)
Hydromorphone (Dilaudid) – similar efficacy as morphine (also a strong agonist)
- 5-10x more potent than morphine
- 1.5 mg hydromorphone IV = 10 mg morphine IV
- *** No active metabolites (good choice for renal patients)
- Length of action: 3-4 hours
- Dose: 2-8 mcg/kg or 0.2-0.4 mg IV Q 5-10 minutes
Is Hydromorphone (Dilaudid) a good choice for renal patients?
Yes bc it has NO active metabolites (good choice for renal patients)
Methadone
- ***A strong μ-receptor agonist AND NMDA antagonist (similar to ketamine)
- much longer duration of action than morphine
- ***used for the treatment of opioid withdrawal and chronic pain
The only opioid with local anesthetic properties?
Meperidine (Demerol).
As a result of this anesthetic property, at high doses, it can decrease contractility
Meperidine (Demerol) effects in general
***Euphoria
Similar effects to morphine: sedation, miosis, euphoria, N/V, dizziness; histamine release
What kind of metabolites does Meperidine (Demerol) have?
***Active metabolite (normeperidine) -> excreted in urine
Active metabolite (normeperidine) belongs to which opioid?
- Meperidine experiences high hepatic extraction -> produces active metabolite called normeperidine.
- Meperidine-> Normeperidine active metabolite -> excreted in urine
- Both Meperidine & Normeperidine can cause:
o Can cause CNS excitation, tremors, myoclonus, seizures
o The CNS excitation effect is why we limit the Max daily dose of meperidine to: 600 – 1000 mg per day.
Meperidine + Renal pts
Bc of meperidine’s renal excretion in urine, we should be careful using meperidine in renal patients and consider using lower doses of it.
- High doses are especially dangerous in patients with renal disease
Where is meperidine (demerol) used most commonly?
PACU for reducing shivering
Smaller doses for shivering are probably ok in renal patients
Dose of meperidine (demerol) for analgesia:
0.1 – 1.0 mg/kg
10x that of morphine
Dose of meperidine (demerol) for shivering:
12.5 – 50 mg IV
Smaller doses for shivering are probably ok to use in renal patients
Fentanyl potency compared to morphine:
Fentanyl is ~100x more potent than morphine
Fentanyl solubility compared to morphine
Fentanyl is much more lipid soluble than morphine -> very lipid-soluble -> therefore it rapidly crosses membranes = rapid onset and redistribution to inactive sites
