Strong opioid (fentanyl family) - ultra-short-acting - low lipid solubility - -> does not show much increase in the time required for a certain % drop in effector site concentration in prolonged infusion

Partial opioid receptor agonist (mixed agonist / antagonist)[?] Mild opioid analgesic No major side effects except - nausea / vomiting - miosis - constipation - drug interaction with anti-depressants Not a controlled drug

HNNS L16 - Opioid Analgesics Flashcards by Kary Chen

Examples of strong opioid analgesics

Morphine & related compounds, e.g. codeine, heroin

Phenylpeperidines, e.g. pethidine, fentanyl and derivatives

Methadone

*For intense pain

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Examples of mild opioid analgesics

Propoxyphene, e.g. dextropropoxyphene, Doloxene, Dologesic (banned???)

Partial agonists, e.g. Pentazocine, Buprenorphine (Temgesic), Butorphanol, Tramadol[?]

*For mild pain

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Fentanyl

Strong opioid

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Sufentanil

Strong opioid (fentanyl family)

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Alfentanil

Strong opioid (fentanyl family)

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Remifentail

Strong opioid (fentanyl family)

ultra-short-acting
low lipid solubility
-> does not show much increase in the time required for a certain % drop in effector site concentration in prolonged infusion

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Codeine

Morphine related opioid analgesic

Strong opioid

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Heroin

Morphine related opioid analgesic

Strong opioid

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Methadone

(Physeptone)
Strong opioid
Longest acting
Used for getting over opioid addiction
'Complex' analgesic (activity not solely based on opioid receptor)

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Effect when you use strong and mild opioids together

Weaker than using strong opioid alone.
(Mild opioids displacing the strong opioids)
*NO synergistic effect!!!

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Dextroprophoxyphene

Under prophoxyphene

Mild opioid

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Doloxene

Under prophoxyphene

Mild opioid

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Pentazocine

Partial opioid receptor agonist (mixed agonist / antagonist)

Mild opioid analgesic

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Buprenorphine (Temgesic)

Partial opioid receptor agonist (mixed agonist / antagonist)

Mild opioid analgesic

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Butorphanol

Partial opioid receptor agonist (mixed agonist / antagonist)

Mild opioid analgesic

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Tramadol

Partial opioid receptor agonist (mixed agonist / antagonist)[?]
Mild opioid analgesic

No major side effects except

nausea / vomiting
miosis
constipation
drug interaction with anti-depressants

Not a controlled drug

Which opioid analgesic is NOT a controlled drug?

Tramadol
(No major side effects e.g. respiratory depression;
No euphoria –> not likely to abuse)

Drug interaction of tramadol

(Mild opioid analgesic)
Drug interaction with anti-depressants
- decrease serotonin, NA uptake in CNS

Side effects of Tramadol

(Mild opioid analgesic)

nausea / vomiting
miosis
constipation
drug interaction with anti-depressants

What features of opioid analgesics cause higher addictive potential?

Euphoria

Higher lipid solubility + higher non-ionized fraction –> favour crossing of BBB

What parameter to look at when you want an opioid analgesic with faster onset? Is it preferrable to have a faster onset?

Lipid solubility (favour crossing of BBB)
Non-ionized fraction????

Faster onset –> easier to correct the dosage (prevent respiratory depression)

Opioid analgesic: peak effect site concentration determined by… (explain in terms of plasma concentration and effect site concentration)

Peak effect site level = isoconcentration level (level at which plasma concentration = effect site concentration)

Before:

plasma concentration dropping
effect site concentration increasing

After isoconcentration, both drop.

What to take note of if you want to repeat administration of opioid analgesics?

Reduce subsequent doses if repeated administration of opioid analgesics is required.

Longer infusion time of opioid –> longer time required to show a certain % decrease in effector site concentration

Drugs would accumulate in peripheral tissues, e.g. muscles and fat
Slowly diffuse out –> redistribute to CNS

*Over therapeutic window: respiratory depression

Metabolism of morphine

Formation of normorphine, morphine-3-glucuronide and morphine-6-glucuronide in liver

Morphine-6-glucuronide is an ACTIVE metabolite (30% morphine activity)
- Do NOT miss it when considering the dose.

Excretion by kidneys
- dysfunction –> accumulation of active metabolites

Giving morphine to patients with 1. Liver failure 2. Renal failure

1. Liver responsible for metabolising morphine into normorphine, morphine-3-glucuronide and morphine-6-glucuronide (active metabolite) - -> accumulation of morphine 2. Kidney for excretion of metabolites of morphine - -> accumulation of ACTIVE metabolites

Giving pethidine to patients with renal failure?

Pethidine: renal excretion of metabolite *norpethidine (from minor pathway) *major pathway: esterification, conjugation - -> Norpethidine may accumulate in kidney dysfunction - -> convulsion

Route of administration for opioid analgesics

1. IV 2. Indwelling subcutaneous patch 3. Transmucosal (lollipop-like) 4. Epidural / Subarachnoid 5. Transdermal *Patient-controlled Analgesia Oral administration not preferred - Many side effects (vomit the drugs out!) - Decreased absorption with first pass effect

Advantage of epidural / subarachnoid administration of opioid analgesic

Bypass BBB --> more effective

Acute side effects of opioid analgesics

1. Sedation 2. Nausea / vomiting 3. Respiratory depression 4. Euphoria 5. Miosis

Side effects of prolonged use of opioid analgesics

1. Constipation 2. Tolerance / dependence 3. Acute side effects: - Sedation - Nausea / vomiting - Respiratory depression - Euphoria - Miosis

For opioid analgesics, instead of reading ED50 and LD50 for the therapeutic window, what should we read?

ED95 and LD05 | - LD05 already very dangerous!

Which of the following causes the most severe euphoria? | Morphine, Methadone, pethidine

Pethidine > morphine > methadone

What defines physical dependence of morphine?

It is the physiological adaptation of the body to the presence of an opioid, an is defined by the development of withdrawal symptoms when - opioids are discontinued, - dose is reduced abruptly, or - an antagonist (e.g. naloxone) or a partial agonist (e.g. pentazocine) is administered

What to take note of when administering opioid analgesics?

According to the Dangerous Drugs Regulations, medical practitioners are required to maintain proper records of ALL dangerous drugs, whether supplied, dispensed or administered. *Lock it up as well

Antagonist of opioid analgesic

Naloxone (Narcan) - For PCA overdose for exmaple - IV - Half-life shorter than most opioid analgesics --> keep the patient for observation after one dose

Naloxone (Narcan)

Antagonist of opioid analgesics - e.g. for PCA overdose - IV - Half-life shorter than most opioid analgesics --> keep the patient for observation after one dose

Which opioid analgesic would interact with anti-depressants?

Tramadol | - increase serotonin and NA uptake in CNS

Can you release a patient with opioid overdose after giving one dose of naloxone (opioid antagonist)?

No. Half life of naloxone is shorter than most opioid analgesics. Keep the patient under observation after one dose of naloxone.

What to take note of when choosing an opioid analgesic?

1. Efficacy 2. Side effects 3. Onset and duration 4. Route of administration and availability 5. Safety 6. Addictive potential