Morphine and Other Opioids Flashcards
True or false:
Opioids are naturally-occurring compounds
False. The term ‘opioids’ encompasses all ligands that act at opioid receptors. These include endogenous substances, e.g. enkephalins, endorphins and dynorphins; naturally occurring exogenous substances (opiates) e.g. morphine, and synthetic drugs, e.g. fentanyl.
True or false:
Opioids act at G-protein coupled receptors
True
True or false:
Equi-analgesic doses of µ agonists cause a similar degree of respiratory depression
True. At equi-analgesic doses all opioids acting through the μ receptor will demonstrate similar μ receptor-related side-effects.
True or false:
All opioid side-effects are mediated by opioid receptors
False. Pruritis is a common side-effect, particularly with subarachnoid or epidural administration, and is mediated by histamine release.
True or false:
Speed of onset of analgesia after IV administration depends primarily on lipid solubility
True. Fentanyl and structurally related opioids have high lipid solubilities and rapid onset after an IV dose. Morphine is much less lipid soluble and the onset of analgesia is significantly slower.
Regarding morphine and structurally related drugs (true or false):
Morphine is a naturally occurring opium alkaloid
True
Regarding morphine and structurally related drugs (true or false):
The typical duration of action of a bolus dose of morphine is 2-3 h
True. This correlates with its elimination half-life, but is subject to great interindividual variability.
Regarding morphine and structurally related drugs (true or false):
The principal metabolite of morphine is the 6-glucuronide
False. The principal metabolite is M3G, which is inactive, but M6G is of concern as it is a μ agonist.
Regarding morphine and structurally related drugs (true or false):
Diamorphine is a pro-drug
True. It has no activity, but is metabolised to 6MAM and morphine.
Regarding morphine and structurally related drugs (true or false):
When used clinically, diamorphine has twice the potency of morphine
True
Is the following true or false concerning morphine?
Increases the production of antidiuretic hormone (ADH).
True
Is the following true or false concerning morphine?
May cause bronchospasm.
True. Due to possible histamine release associated with morphine.
Is the following true or false concerning morphine?
Has a higher affinity for the opioid receptor than diamorphine.
True. Diamorphine has almost no affinity for the opioid receptor and is a prodrug of morphine.
Is the following true or false concerning morphine?
Causes direct myocardial depression.
False. Morphine does not cause direct myocardial depression, although it may cause a bradycardia. The hypotension associated with its use is because of a decrease in the systemic vascular resistance (SVR) which is due, in part, to histamine release.
Is the following true or false concerning morphine?
Is a phenylpiperidine.
False. Phenylpiperidines include pethidine and fentanyl, whereas morphine is a phenanthrene.
What is the relative potency of pethidine compared with morphine?
Pethidine has one tenth of the potency of morphine
What is oral bioavailability of pethidine?
50%
True or false:
Pethidine is more lipid soluble than morphine
True. Pethidine is much more lipid soluble than morphine, and crosses the blood-brain barrier faster, giving it a more rapid onset of action. It has a shorter duration of action than morphine.
What is the important metabolite of pethidine?
Norpethidine. It is epileptogenic.
What is the elimination half-life of pethidine and what is the elimination half-life of norpethidine?
The elimination half-life of pethidine is about four hours but that of norpethidine is much longer (14–21 h). The elimination of norpethidine is dependent on renal function so it may accumulate in patients with renal dysfunction: it is epileptogenic.
What is the significant group of drugs to be aware of with pethidine due to a potential serious drug interaction?
There is a serious drug interaction between pethidine and monoamine oxidase inhibitors (MAOIs), which causes cardiovascular instability, convulsions and coma.
What is the active metabolite of fentanyl?
Fentanyl has no active metabolites. It is dealkylated to norfentanyl, which is inactive.
What is the relative potency of fentanyl compared with morphine?
Fentanyl is 100 times more potent than morphine
Why does alfentanil have a more rapid onset of action than fentanyl despite being less lipid soluble?
Because nearly 90% of unbound drug is non-ionized (compared with 9% for fentanyl), creating a large concentration gradient across the blood-brain barrier. This is due to it’s pKa being 6.5.
What is the elimination half-life of alfentanil?
Its elimination half-life is 1.6 h, mainly because its relatively low lipid solubility results in a much smaller volume of distribution than fentanyl. Alfentanil has a very short duration of action: its redistribution half-life is 11 min.
Name three phenylpiperidines.
Pethidine
Fentanyl
Alfentanil
Tramadol
What is the principle breakdown product of remifentanil?
The main breakdown product is a carboxylic acid derivative, which has only 0.1% of the potency of the parent compound, and thus has clinically insignificant pharmacological effects.
Regarding phenylpiperidines and esters (true or false):
Pethidine (meperidine) is a less potent analgesic than morphine
True. Pethidine has one tenth the potency of morphine but, like morphine, is a μ agonist and has the same efficacy.
Regarding phenylpiperidines and esters (true or false):
Fentanyl always has a short duration of action
False. The duration of action of fentanyl is dose-dependent, and varies significantly between individuals.
Regarding phenylpiperidines and esters (true or false):
Alfentanil given IV has the most rapid onset of all opioids licensed in the UK
True
Regarding phenylpiperidines and esters (true or false):
Fentanyl and remifentanil are approximately equipotent
True
Regarding phenylpiperidines and esters (true or false):
Remifentanil is metabolised by plasma cholinesterase
False. Remifentanil is metabolised by non-specific plasma and tissue esterases. There are no abnormal variants of these enzymes, and there are insignificant interindividual differences in its pharmacokinetics.
How is overdose of tramadol different to other opioids?
Seizures occur in up to 15% of cases; this is more common than with other opioids. In severe poisoning coma, seizures and hypotension can occur. Overdose can also cause serotonin syndrome which is potentially fatal.
Tramadol overdose does also result in drowsiness, constricted pupils, agitation, tachycardia (as opposed to bradycardia with morphine), hypertension and nausea, vomiting and sweating.
Regarding opioid pharmacodynamics (true or false):
Anti-nociception and major side-effects of opioid drugs are mediated by the μ receptor
True. The drugs covered in this session are selective μ agonists. However, anti-nociception is also mediated by κ and δ receptors.
Regarding opioid pharmacodynamics (true or false):
Opioids exhibit stereo-specificity
Most opioids are used as single stereoisomers: their enantiomers do not conform to the opioid receptor and have little or no activity.
Regarding opioid pharmacodynamics (true or false):
In equi-analgesic doses all opioids cause serious side-effects to a similar degree
True. Respiratory depression, nausea, constipation, euphoria and dependence are all mediated by the μ receptor.
Regarding opioid pharmacodynamics (true or false):
Tramadol has a different mode of action from other μ agonists
True. Tramadol has weak μ affinity and also acts by inhibition of 5-HT and noradrenaline uptake.
Regarding opioid pharmacodynamics (true or false):
Some of the side-effects of morphine and pethidine are caused by histamine release
True
Regarding opioid pharmacokinetics (true or false):
Opioids generally have low oral bioavailability
True. Opioids are subject to first-pass metabolism. Bioavailability of some opioids is so low that they cannot effectively be administered orally. Codeine derivatives (codeine, oxycodone, tramadol) have the highest bioavailability; approximately 70%.
Regarding opioid pharmacokinetics (true or false):
The elimination half-life of morphine is approximately three hours
True. However, there is a very large interindividual variation in t1/2β among normal subjects.
Regarding opioid pharmacokinetics (true or false):
The elimination half-life of fentanyl is shorter than that of morphine
False. t1/2β is typically 3-4 h.
Regarding opioid pharmacokinetics (true or false):
Fentanyl and alfentanil have clinically active metabolites
False. Fentanyl and alfentanil have inactive metabolites.
Regarding opioid pharmacokinetics (true or false):
The plasma half-life of remifentanil is unaffected by hepatic or renal function or duration of infusion
True. Remifentanil is metabolised by plasma esterases, and its plasma half-life is predictable (about 5 min).
Regarding the use of opioids (true or false):
Opioids produce better quality of analgesia when given as part of a multi-modal analgesic regimen
True. NSAIDS and paracetamol decrease opioid requirements (morphine sparing effect) and improve the quality of analgesia.
Regarding the use of opioids (true or false):
Dosage requirements for morphine decrease with increasing age
True. This is partly due to volume of distribution of morphine decreasing with increasing age.
Regarding the use of opioids (true or false):
The dosage of opioids required to produce analgesia is predictable
False. Both pharmacodynamics and pharmacokinetics exhibit great interindividual variation.
Regarding the use of opioids (true or false):
Fentanyl PCA is a good option for postoperative analgesia in patients with renal dysfunction
True. Accumulation of active metabolites may cause problems with other opioids; fentanyl has no active metabolites.
Regarding the use of opioids (true or false):
Tramadol may be a better option than other opioids for patients in whom respiratory depression is of particular concern
True. Tramadol has a different mode of action, as well as weak μ agonism and, as a result, a different side-effect profile; in particular, it causes less respiratory depression.
