Slides 2 Flashcards by Sarah Assaf

What is the prototypical opioid (1803)?

Morphine

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What is morphine derived from?

The opium poppy, Papaver
somniferum and P. album, after incision of the seed pod = white substance that turns brown gum, which contains 10% morphine.

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What are the 3 families of endogenous opioid peptides?

1) The endorphins.
2) The pentapeptides enkephalins: methionineenkephalin (met-enkephalin) and leucineenkephalin (leu-enkephalin).
3) The dynorphins.

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Why are there 3 families of endogenous opioid peptides?

Because they are derived from three different precursor proteins.

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When are endogenous opioid peptides released?

During stressful conditions such as pain or the anticipation of pain to
diminish the sensation of noxious stimuli.

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Endogenous opioid peptides act through 3 types of opioid receptors:

1) Mu (μ)
2) Delta (δ)
3) Kappa (κ)

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Which receptors function as supraspinal and spinal analgesics?

1) Mu (μ)
2) Delta (δ)
3) Kappa (κ)

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What are the other functions of the Mu (μ) receptors?

1) Sedation
2) Inhibition of respiration
3) Slowed GI transit
4) Modulation of hormone & neurotransmission release

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List the affinity of the Mu (μ) receptors toward the endogenous opioid peptides (from highest to lowest).

Endorphins > Enkephalins > Dynorphins

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List the affinity of the Delta (δ) receptors toward the endogenous opioid peptides (from highest to lowest).

Enkephalins > Endorphins > Dynorphins

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List the affinity of the Kappa (κ) receptors toward the endogenous opioid peptides (from highest to lowest).

Dynorphins > Enkephalins & Endorphins

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What are the other functions of the Delta (δ) receptors?

Modulation of hormone & neurotransmission release

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What are the other functions of the Kappa (κ) receptors?

1) Slowed GI transit

2) Psychotomimetic effects

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What is the approximate equivalent dosage of morphine (in mg)?

10mg (Higher doses = respiratory depression and death)

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What is the approximate equivalent dosage of Hydromorphone (in mg)?

1.5mg

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What is the approximate equivalent dosage of Meperidine/Pethidine (in mg)?

60-100mg

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What is the approximate equivalent dosage of Fentanyl (in mg)?

0.1mg

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What is the approximate equivalent dosage of Sufentanyl (in mg)?

0.02mg

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What is the approximate equivalent dosage of Codeine (in mg)?

30-60^4

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What is the Oral:Parenteral potency ratio for Morphine?

Low

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What is the Oral:Parenteral potency ratio for Hydromorphone?

Low

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What is the Oral:Parenteral potency ratio for Meperidine/Pethidine?

Medium

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What is the Oral:Parenteral potency ratio for Fentanyl?

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Low

What is the Oral:Parenteral potency ratio for Sufentanyl?

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Parenteral only

What is the Oral:Parenteral potency ratio for Codeine?

High

Which drugs are VERY potent and used during anesthesia?

1) Fentanyl | 2) Sufentanyl

Most opioid analgesics are well absorbed when given by which routes?

1) Subcutaneous 2) Intramuscular 3) Oral

Which opioid undergoes extensive first-pass metabolism?

Morphine

Which opioid has reduced first-pass metabolism?

Codeine

Where do opioids concentrate?

In highly perfused tissues, like: 1) Brain 2) Lung 3) Liver 4) Kidneys 5) Spleen

Where are opioids low in concentration?

Skeletal muscle (But it serves as a reservoir because of its large size)

What can frequent high dose administration or continuous infusion of highly lipophilic opioids (fentanyl) lead to?

Accumulation in body fat

Morphine is converted into:

Glucuronide metabolites

Morphine-3-glucuronide (M3G) has which kind of properties and through which receptor?

Neuroexcitatory properties; GABA/glycinergic system (NOT through μ receptors)

Which has more analgesic potency: Morphine-6-glucuronide (M6G) (10%) or Morphine?

Morphine-6-glucuronide (M6G) (10%) is 4-6 times more potent.

Can opioids cross the BBB?

They are polar and have limited ability to cross it.

What causes opioids to accumulate? What are the results?

Renal dysfunction; May result in adverse effects (seizures with M3G, and prolonged opioid action with M6G).

What can enhance uptake of M3G (and M6G)

Probenecid or inhibitors of P-glycoprotein

Hydromorphone is converted into:

3-glucuronide (H3G)

What properties does 3-glucuronide (H3G) have?

CNS excitatory properties.

Esters (heroin, remifentanil) are rapidly hydrolyzed by __ into:

Tissue esterases; Heroin | (diacetylmorphine) is hydrolyzed to morphine.

How are meperidine (pethidine), fentanyl, alfentanil, and sufentanil metabolized?

Hepatic oxidative metabolism

Accumulation of the demethylated metabolite of meperidine, normeperidine, may occur in:

Patients with renal dysfunction = seizures.

Fentanyl N-dealkylation is catalyzed by:

CYP3A4

Codeine is metabolized by __ to __.

CYP2D6; morphine. | PMs vs EMs

What is the mechanism of opioid agonists?

Binding to 3 specific G protein-coupled receptors, located in the brain and the spinal cord regions involved in transmission and modulation of pain. These receptors are μ, δ, and κ, which may have subtypes.

Opioid analgesics have 2 direct G protein coupled actions:

1) They close voltage-gated Ca2+ channels on presynaptic nerve terminals = reduce transmitter release (large number of neurotransmitters - glutamate, acetycholine, norepinephrine, serotonin and substance P). 2) They hyperpolarize and thus inhibit postsynaptic neurons by opening K+ channels.

The majority of the clinically available opioid analgesics act primarily at which receptor?

μ opioid receptor

What properties of morphine does the μ opioid receptor mediate?

1) Analgesic 2) Euphoriant 3) Respiratory depressant 4) Physiologic dependence

Which compounds show preference for κ receptors?

1) Butorphanol | 2) Nalbuphine

What are the effects of Butorphanol and Nalbuphine (κ receptors)?

1) Analgesia 2) Dysphoria 3) Reduced respiratory depression and propensity for addiction and dependence

What are the sites of action of opioid analgesics on the afferent pain transmission pathway?

1) Direct action of opioids on inflamed or damaged peripheral tissues. 2) Inhibition in the spinal cord. 3) Possible sites of action in the thalamus.

Opioids exert a powerful analgesic effect directly on:

The spinal cord = spinal action.

What are the results of direct application of opioid agonists to the spinal cord?

1) Provides regional analgesia 2) Reduces the undesired respiratory depressant effect, nausea, vomiting, and sedation that may occur from the supraspinal action of systemic opioids.

Sites of action of opioids on pain-modulating neurons in the midbrain and medulla include:

1) The midbrain periaqueductal gray area 2) Rostral ventral medulla 3) The locus caeruleus

Slides 2 Flashcards

(55 cards)