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

Reference
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.

IMG_0248

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

Tapentadol

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.

BT_PM 1.16 Opioid dose conversion

Ok this is a bit of a weird one for the primary syllabus in my books. It could be asked in an MCQ but I don’t think it would be asked in a viva, because we all know it is virtually impossible to do mental arithmetic under pressure!

It is of practical consideration for us though and is something we do all the time, when managing patients in the post operative period.

There are various opioid conversion tables out there, including an app produced by the FPM. If you look the app, I would suggest that you look at the “practical considerations” in the information section (it is a bit hidden at the bottom of the Opioid Dose Equivalence  page)

I think this poor patient needs more of whichever opioid he has received…. Taken at the Legend of Hong Kong Toys exhibition. I hate to think what happens when you turn that toy on…..

OLYMPUS DIGITAL CAMERA

BT_PM 1.16 Outline the dose conversion between commonly used opioids

No change in tramadol dose is required when switching from oral to s/c dosing  TRUE/FALSE

Twice as much oral compared with intravenous morphine is required to produce the same analgesic effect   TRUE/FALSE

It is easy to calculate an equipotent dose of morphine for a patient taking methadone  TRUE/FALSE

When switching a patient between one opioid and another, equipotent doses of the two drugs tend to underestimate the amount of the new opioid that will be required  TRUE/FALSE

A buprenophine patch 20mcg/hr is equipotent to a 12.5mcg/hr fentanyl patch  TRUE/FALSE

2017.1 : SAQ 3

Propofol and remifentanil target controlled infusions are often given together as a total intravenous anaesthesia technique. Discuss pharmacological reasons why this is a useful combination.

BT_GS 1.59    BT_GS 1.53    BT_GS 1.41

A practical pharmacology question on a common drug combination. Before setting out to write a model answer try asking yourself first what are the clinical reasons you use this combination.

There are significant pharmacokinetic interactions between these drugs  TRUE/FALSE

There are significant pharmacodynamic interactions between these drugs  TRUE/FALSE

Both drugs have a rapid offset  TRUE/FALSE

Adding remifentanil to propofol can lead to more stable haemodynamics  TRUE/FALSE

Can be used in patients susceptible to malignant hyperthermia  TRUE/FALSE

 

 

BT_PM1.18

Sticking with neuraxial opioids…

Intrathecal fentanyl has fewer adverse effects than intrathecal morphine TRUE/FALSE

Intrathecal morphine produces better postoperative analgesia than intrathecal fentanyl after LSCS   TRUE/FALSE

Doses of intrathecal morphine greater than 50mcg have no greater benefits in terms of analgesia but carry a higher incidence of respiratory depression    TRUE/FALSE

100 mcg of morphine is 0.1ml of morphine 10mg/ml    TRUE/FALSE

extended-release epidural morphine is associated with less respiratory depression than IVPCA morphine    TRUE/FALSE

BT_PM1.18 : neuraxial opioids

This has been a popular topic in vivas (and the occasional SAQ) for ages. It’s an important and relevant topic that is not always well-covered in the basic texts.

BT_PM 1.18 Describe the pharmacology of opioids deposited in the epidural space or cerebrospinal fluid

With regard to epidural fentanyl (1 mcg.kg-1)

plasma concentrations of fentanyl are similar to the same dose given intramuscularly TRUE/FALSE

the duration of analgesia is 1 hour TRUE/FALSE

the CSF concentrations of fentanyl are maximal at 50 minutes  TRUE/FALSE

the incidence of pruritis is greater than following an equi-analgesic dose of epidural morphine  TRUE/FALSE

the onset of analgesia is around 2-5 minutes because fentanyl is highly lipid soluble  TRUE/FALSE