BT_PM 1.11 Describe the different modes of administration of analgesic agents and evaluate their clinical application

I though I would stick with the same artistic subject matter today, to further strengthen the link between today and yesterday’s LO. From Ben Quilty’s exhibition currently showing at the Art Gallery of SA

I thought that we could probably make this poor neglected LO fit with yesterday’s post. How effective various routes of administration are, often depends on pharmacokinetic properties of the drug – ta da – link made!

BT_PM 1.11 Describe the different modes of administration of analgesic agents and evaluate their clinical application

I think all of these statements would be within the realm of expected knowledge. The latter ones are trickier and the last a bit controversial

The relatively high potency of buprenorphine and fentanyl is an important factor in their ability to be delivered transdermally T/F

Transdermal admistinistration of fentanyl by patch enables the drug to be given in a rapidly titratable form T/F

Placing a patient with a fentanyl patch on their posterior body on an electronic underbody warmer will not change the rate of drug delivery T/F

Oral oycodone with naloxone, reduces the risk of respiratory depression compared with oxcodone alone T/F

Patients may experience fewer side effects with oral compared with intravenous opioids because of a slower rise in plasma concentration T/F

No dose adjustment is required when giving oral tramadol, compared with a parenteral route, because there is no first pass metabolism T/F

Fentanyl given epidurally solely acts at level the dorsal horn level T/F

BT_GS 1.42 and BT_PM 1.17 Describe the pharmacokinetics of intravenous opioids

I visited the Escher X Nendo exhibition at the NGV on Friday. The work was amazing, but my phone died almost as I walked in the door Here is the one image I managed to capture – a lino cut produced as a 19yr old.

I find it hard to believe that this has not already been covered elsewhere, but it is still in the list of “left over” LOs, so just in case I’ll cover it today.

I think there is very little point memorising a huge list of pharmacokinetic numbers for drugs. The only reason to know these numbers is to enable you to predict how the body will handle the drug, influencing a drug’s behaviour both in states of normal, and abnormal, physiology. As most traditional opioids have very similar pharmacodynamic effects, pharmacokinetic factors usually influence drug selection.

Some standout numbers may be worthwhile committing to memory, but only to help illustrate the clinical implication. Otherwise, you just need to know ball park figures.

There are plenty of tables where you can find the pharmacokinetic numbers. It takes a little bit more thought to work out how they affect drug’s clinical behaviour

Most of the answers to today’s post can be found in the new edition of the Hemmings and Egan book (which I would have to say I am quite partial too…)

BT_GS 1.42 Describe the pharmacokinetics of intravenous opioids

BT_PM1.17 Pharmacokinetics of intravenous opioids and clinical relevance (I knew that this important topic couldn’t have been neglected – it wasn’t and here is my previous post under a duplicate LO)

All opioids are weak bases, so will be more ionised at a pH lower than their pKa T/F

The rapid onset of effect of alfentanil, can be largely attributed to its low pKa T/F

Fentanyl’s relatively rapid onset of effect is also due to a low pKa T/F

Both morphine and tramadol have metabolites active at the mu opioid receptor, with longer half lives than the parent drug T/F

For those opioids which are metabolised in the liver, hepatic blood flow is the main factor which limits the rate of metabolism T/F *

Morphine has a prolonged action when given intrathecally due to its low lipid solubility T/F

Fentanyl’s high lipid solubility helps account for a relatively rapid offset of effect after an single bolus T/F

* this one is actually a bit trickier than it may seem ( and not the same for all patients – hint, hint)

BT_PM 1.21 Describe the pharmacology of opioid antagonists

T/F  naloxone is a competitive opioid antagonist, which binds covalently to opioid receptors

T/F  in the presence of an agonist, a competitive antagonist has the effect of making the agonist less potent

T/F  the structure of naloxone is almost identical to morphine

T/F  naloxone has zero efficacy, and low receptor affinity

T/F  using small titrated doses of naloxone, it is possible to reverse respiratory depression without reversing analgesia

T/F  especially at high doses, the partial agonist buprenorphine can act as an antagonist to other opioids

T/F  Suboxone™ contains a mixture of buprenorphine and naloxone, and is used in the management of opioid abuse (can you explain why the naloxone is added?)


  • any decent pharmacology book will contain the answers to the above
  • general information about agonists and antagonists would be found in the chapter(s) on pharmacodynamics


BT_PM 1.22

You have probably read the recent discussion of the role of slow release opioids for postoperative analgaesia. Tapentadol is now available as an immediate release tablet, and I think you will be seeing this drug used more and more more commonly.

T/F changing an opioid tolerant patient to tapentadol may cause opioid withdrawal

T/F tapentadol has a similar rate of nausea to hydromorphone

T/F tapentadol has a similar risk of death from overdosage to conventional opioids.

T/F tapentadol is primarily excreted unchanged in the urine

T/F tapentadol predominately acts at the NMDA receptor

Answers to the questions can be found in Acute Pain Scientific Evidence 2015 Chapters 4 & 10.

2018.2 SAQ 7 – dose response curves for opioids

Using opioids as examples, describe and illustrate with graphs, what you understand by the terms “potency”, “efficacy”, “partial agonist”, “competitive antagonist” and “therapeutic index”

The above terms are staples of pharmacodynamics and enable us to describe the effects of drugs on the body. This question asks you to apply your knowledge of these terms to a group of drugs we use on a daily basis.

To answer this question well you would need to have a good working knowledge of both graded and quantal dose response curves.

There are some previous posts on dose response curves here,  here and here. They might help get you in the mood…

BT_GS 1.3 Define and explain dose-effect relationships of drugs with reference to:

· Graded and quantal response

· Therapeutic index

· Potency and efficacy

· Competitive and non-competitive antagonists

· Partial agonists, mixed agonist-antagonists and inverse agonists

· Additive and synergistic effects of drug combinations

BT_PM 1.22 Describe the pharmacodynamics of individual opioids and evaluate their clinical applications

The analgesic potency of fentanyl is about 10 times more than morphine T/F

Therapeutic index is defined as ED50/TD50 T/F

Both naloxone and naltrexone are competitive antagonists at mu opioid receptors T/F

The dose response curve for an antagonist always shows the effect of the antagonist in the presence of an agonist, as the antagonist itself has no intrinsic activity T/F

Buprenorphine is a partial agonist at the mu opioid receptor but is still a potent analgesic. T/F

The relative analgesic potency of fentanyl and alfentanil could be determined on both a graded and quantal dose response curve. T/F

The therapeutic index for morphine with respect to itch is likely to be smaller than the therapeutic index for respiratory depression T/F

Morphine, alfentanil and fentanyl have equal analgesic efficacy T/F

IT_PM 1.3 Outline the basic concepts of multimodal analgesia and pre-emptive analgesia

T/F  multimodal analgesia involves the use of a combination of analgesic drugs which each have a different mode or site of action

T/F  multimodal analgesia can: (i) improve the quality of analgesia, and (ii) reduce opioid use, thereby limiting opioid induced side effects

T/F  an opioid is always needed for multimodal analgesia to be effective

T/F  The concept of pre-emptive analgesia involves giving analgesic drugs prior to skin incision. This emerged from animal studies which showed that this technique minimised dorsal horn changes associated with central sensitisation. However, in clinical studies, there are conflicting outcomes when comparing “pre-incisional” and “post-incisional” interventions.

T/F  epidural analgesia is one intervention which has a clear pre-emptive analgeic effect

T/F  The concept of pre-emptive analgesia has largely been replaced by the concept of preventive analgesia. This refers to interventions which can reduce peripheral and central sensitisation, and thereby reduce the intensity and duration of post-operative pain (compared with other interventions, or no intervention). Preventive analgesia is not defined by the timing of the intervention.

T/F  preventive analgesic effects can be produced by – local anaesthetics (regional and neuraxial), ketamine, and gabapentin

APM-SE (2015), Chapter 1, Chapter 8

2018.1 SAQ 5

BT_PM 1.12 (Opioid receptors)

List the desired and adverse effects of opioids and the corresponding anatomical location of the receptors being activated

Opioids have multiple sites of action and many of their effects are undesirable. These should be considered in your patients, and other analgesic techniques used if harms potentially outweigh benefits.

Opioids can mediate analgesia through presynaptic primary sensory afferents T/F

Opioids can mediate analgesia in the dorsal horn of the spinal cord T/F

Opioids have no supra-spinal mediation of analgesia  T/F

Immunosuppression is an adverse effect of opioids T/F

Biliary spasm is an adverse effect of opioids T/F

Bonus question, definitely not core material in answering this question but interesting. First paragraph of the pethidine entry on wikipedia leads you to the answer but it’s worth considering why the Germans were trying to develop drugs of this class in 1939.

Pethidine can cause mydriasis T/F

BT_PM 1.17 Pharmacokinetics of intravenous opioids and clinical relevance

I am not a massive fan on memorising a whole lot of numbers for the sake of it – boring!!

However, sometimes these pesky numbers can actually help us guide clinical practice and, in that situation, they take on a whole new level of relevance. The pharmacokinetics of opioids are a case in point.


Hopefully no opioids in this handbag (although to be honest, I couldn’t be sure) Cottesloe, WA

BT_PM 1.17 Describe the pharmacokinetics of intravenous opioids and their clinical applications

The high lipid solubility of fentanyl confers a long duration of action when given intrathecally  TRUE/FALSE

The rapid speed on onset of alfentanil is primarily due to its low pKa  TRUE/FALSE

Duration of action of remifentanil is determined by its elimination half life   TRUE/FALSE

The terminal elimination half life of morphine and fentanyl is similar   TRUE/FALSE

Active metabolites of both morphine and pethidine contribute to the duration of analgesic effect   TRUE/FALSE


BT_PM 1.22

Tapentadol (Palexia) is relatively new, but has some major advantages over conventional mu agonists. Several surgeons I work with now use it for their routine postop pain control rather than oxycodone.

T/F Tapentadol is a combined µ agonist and SSRI

T/F Tapentadol causes less constipation compared to oxycodone

T/F Tapentadol has a similar rate of abuse and diversion as oxycodone

T/F Tapentadol is ineffective in neuropathic pain

T/F Tapentadol is safe to use in a breast feeding mother

BT_GS 1.53 Describe the synergism between anaesthetic agents, opioids and regional blockade and how this is used clinically

TRUE/FALSE  Moderate doses of opioids can reduce MAC of volatile agents by as much as 75%.

TRUE/FALSE  50% reduction in doses is expected when propofol and midazolam are used together for hypnosis.

TRUE/FALSE  The exact degree of drug synergism can be calculated from pharmacokinetic data of individual agents.

TRUE/FALSE  The bispectral index is additive when propofol and remifentanil are used in total intravenous anaesthesia.

TRUE/FALSE  Midazolam has no effect on the ketamine dose required to suppress movement to a noxious stimulus.