03 - Opioids and Context Sensitive Half Time Flashcards by Helen Wang

Opioid subreceptors and what they do?

Mu - analgesia, resp depression, pruritis, constipation, urinary retention
Kappa - analgesia, sedation
Delta - constipation, urinary retention
Sigma - ??
?? - constipation, urinary retention

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Most opioids bind to which receptor?

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Mechanism of opioids and where their receptors are found

Inhibit release and response of excitatory neurotransmitters in nociceptive neurons
Receptors exist through out CNS and peripheral nerves

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Most rapid and complete route of opioid absorption

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IM morphine and meperidine takes

20-60 min

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Transmucosal absorption of fentanyl takes

10 min

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Transdermal absorption of fentanyl takes

14 to 24 min (reservoir in dermis)

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Benefits of neuraxial opioid absorption

No sympathectomy, motor blockade, or loss of proprioception

Specific visceral > somatic analgesia

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How does neuraxial opioid abs work?

Diffusion to opioid receptors in the spinal cord

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The effects of neuraxial abs are less true with __________ due to

Lipid soluble opioids like fentanyl

More systemic absorption

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Distribution half life of opioids

5-20 min

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First pass uptake of opioids

In the lungs

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Which opioids have active metabolites

Morphine and meperidine (Demerol)

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The template for opioids

Morphine

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Morphine acts on ______ receptors

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Onset and peak of morphine

5 min onset

Peak in 10-40 min

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Morphine can decrease MAC by

65%

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Redistribution of ________ is age dependent

Morphine

7-8 hours in neonates and 4.5 hours for ages 61-80

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Elimination half life of morphine

1.7 - 3.3 hours

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Which opioid should be used with caution in renal failure?

Morphine

Meperidine should not be used at all!!

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Neuro effects of morphine

Sedation, cognitive impairment, euphoria
Decr CMRO2, CBF, ICP if normocarbia maintained
Miosis and pruritis
Muscle rigidity after large doses
Nausea/vomiting - stimulates CTZ in medulla

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Resp effects of morphine

Blunts hypercapnic drive
Hypoventilation
Rousable apnea
Suppresses cough reflex

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GI effects of morphine

Decreased motility (constipation), slower gastric emptying
Increased common bile duct tone
Biliary spasm (sphincter of Oddi)

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GU effects of morphine

Urinary retention

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CV effects of morphine

Hypotension at higher doses | Can cause brady at high doses

5-10x more potent than morphine

Hydromorphone (Dilaudid)

Length of action for hydromorphone

3-4 hours

How is heroin produced?

Acetylation of morphine

Which receptor is responsible for reducing shivering?

Max daily dose of meperidine (Demerol)

600 mg, 1000 mg

Synthetic mu receptor agonist

Fentanyl (sufentanil, alfentanil)

100x more potent than morphine

Fentanyl

Fentanyl reduces MAC by

50-70%

Onset of fentanyl

10 seconds Recovery starts within 5 min Complete recovery in 60 min

1000x more potent than morphine

Sufentanil

__________ has a shorter redistribution half life than fentanyl

Sufentanil (30 min)

Short duration of action even in large doses (opioid)

Alfentanil

Alfentanil can decrease MAC by

Up to 70%

Strong opioid agonists

``` Morphine Hydromorphone Methadone Heroin Meperidine (Demerol) Fentanyl Remifentanil (Ultiva) ```

Ultra short acting opioid

Remifentanil (Ultiva)

Remifentanil can decrease MAC by

Up to 90%

Can cause post operative hyperalgesia

Remifentanil

Partial agonists

``` Codeine Hydrocodone (lortab) Oxycodone and OxyContin (ER) Tramadol Propoxyphene ```

A full agonist + partial agonist, the partial agonist will act as a

Competitive antagonist

What is a competitive antagonist?

Competes with full agonist for receptor occupancy

Ceiling effect

Net decrease in clinical effect compared with full agonist alone

Tylenol 2, 3, 4 is acetaminophen and

Codeine

What is codeine converted to in the body?

Morphine

Vicodin or lorcet is acetaminophen and

Hydrocodone

Roxie's, Percocet, and percodan is acetaminophen and

Oxycodone or OxyContin

Tramadol inhibits

spinal norepinephrine and serotonin uptake

Tramadol has possible interaction with

Coumadin

Darvocet is acetaminophen with

Propoxyphene

This opioid causes arrhythmia and is no longer on the US market

Propoxyphene

IV __ mg meperidine ~ __ mg morphine ~ __ mg hydromorphone ~ __ mcg fentanyl ~ __ mcg sufentanil

``` 100 10 1 100 10 ```

Mixed agonist-antagonist

Nalbuphine (Nubain) Buprenorphine (buprenex) Butorphanol

When a mixed agonist-antagonist is given with a low dose of full agonist, the effect

Is additive up to the max effect of the partial agonist

Why can pretreatment with mixed agonist-antagonist prevent euphoria associated with morphine use?

The mu receptor is competitively antagonized

Nalbuphine (Nubain)

Strong k agonist and mu antagonist

Resp depression with nalbuphine has a ceiling effect similar to

30 mg morphine

Can reverse morphine-induced resp depression without compromise of analgesia

Nalbuphine (Nubain)

Can precipitate withdrawal in opioid dependent patients

Nalbuphine (Nubain)

Elimination half life of nalbuphine

3-6 hours | Similar to morphine

Buprenorphine (buprenex)

Partial mu agonist and k antagonist

Often given sublingually to avoid significant first pass effect

Buprenorphine

Binds more strongly to receptors than other opioids

Buprenorphine | Has 50x greater affinity for mu receptor than morphine

Opioid with slow dissociation from receptors

Seen with buprenorphine | Causes prolonged duration of action

Resistant to antagonism with naloxone

Buprenorphine | Because of slow dissociation

Buprenorphine is used for

Management of chronic pain as well as opioid dependence because it binds more strongly to receptors than other opioids

Which opioid should be used with caution in surgical patients?

Buprenorphine because it causes uncontrolled post op pain

Suboxone is

Buprenorphine + naloxone

Opioid antagonist

Naloxone

Pure antagonist at m, k, and d

How is naloxone administered?

Careful titration to prevent sudden, severe pain (HTN, tachycardia, pulmonary edema)

Dose of naloxone

Dilute one vial (0.4 mg) in 10 mL and titrate 20-40 mcg every 1-2 min

Does naloxone have a long or short duration of action?

Short, repeated dose or infusion may be required

What is context sensitive half time?

Amount of time required for drug conc in central compartment to decrease by 50%

What is context in context sensitive half time?

Duration of the infusion prior to stopping it

Context sensitive half time increases as a function of duration of infusion before it was stopped

Due to movement of drug stored in peripheral compartments back into central compartment