BT_PM 1.20 Describe the potential adverse drug interactions between opioids and other agents

T/F  benzodiazepines and opioids act synergistically to cause sedation and respiratory depression (1)

T/F  metoclopramide can reduce the analgesic efficacy of tramadol

T/F  tramadol may cause serotonin syndrome if given together with a tricyclic antidepressant, or a SSRI

T/F  in a patient taking methadone, droperidol would increase the risk of prolonged QT (2)

T/F  some anti-HIV medications can impair methadone metabolism via inhibition of CYP3A

T/F  A patient is taking long term buprenorphine, and now needs a knee replacement. The buprenorphine can reduce the efficacy of other opioids like morphine or fentanyl. (3)

Notes
(1)  what do you think about giving both midazolam and fentanyl in the anaesthetic bay?
(2)  can you list 6 (common) drugs that can prolong the QT interval?
(3)  does it depend on whether the patient is taking high or low dose buprenorphine? Why / why not?

BT_PM 1.19 Describe the adverse effects of opioids … and their prevention and management

T/F  morphine causes more nausea and vomiting, compared with other opioids

T/F  3-5% of Caucasians are ultrarapid metabolisers of codeine, which results in very little analgesia in these people

T/F  methadone can cause prolongation of the QT interval, and arrhythmias

T/F  naloxone is added to slow-release oxycodone (Targin) to reduce the risk of respiratory depression

T/F  sleep disordered breathing is NOT an independent risk factor for developing opioid induced ventilatory impairment

T/F  tolerance to some opioid effects can develop over time (e.g. analgesia, sedation, respiratory depression), but tolerance is not seen with respect to constipation

Reference – APMSE 4th edition

BT_RT 1.6 Describe the physiological basis of anaphylactic and anaphylactoid reactions

Agasgal has previously posted on these topics.

BT_RT 1.6 Describe the physiological basis of anaphylactic and anaphylactoid reactions

BT_PO 1.128 Describe the immunological basis and pathophysiological effects of hypersensitivity

She also mentioned NAP6 https://www.nationalauditprojects.org.uk/NAP6home

The UK National Audit Projects have provided us with some invaluable information courtesy of their size and widespread buy in by the UK anaesthetic community. This is particularly helpful when you look at important adverse outcomes which are quite uncommon. NAP6 looked at perioperative anaphylaxis and the results came out earlier this year. If you don’t look at anything else look at the one page infographic summary. NAP7 will look at perioperative cardiac arrest. Our College’s ANZAAG have developed an online module which can be done to complete the anaphylaxis activity for the emergency CPD module.

Although NAP6 is undoubtedly important it hasn’t made its way to any of the textbooks yet- but it will. I am going to be proactive and ask a few questions relating to its findings as well as the content of the ANZAAG module.

T/F anaphylaxis is the leading cause of death directly related to anaesthesia

T/F the incidence of anaphylaxis in NAP6 was 1 in 10,000 anaesthetics

T/F the single worst offender for causing anaphylaxis in the UK was teicoplanin

T/F IM adrenaline should be administered as first line therapy for low grade anaphylaxis responses

T/F tryptases should be taken at 1, 2 and 4 hours post event.

T/F Noradrenaline, vasopressin and glucagon are recommended for use in refractory anaphylaxis

The top three causes of anaphylaxis in Australasia are antibiotics, muscle relaxants and what?

 

BT_GS 1.19 Describe the mechanisms of drug interaction

Mechanisms of drug interaction can be classified as: pharmacodynamic, pharmacokinetic, and pharmaceutic.

T/F  the interaction between nitrous oxide and sevoflurane is an example of synergism because the combined effect is greater than would be predicted by simple addition

T/F  the interaction between propofol and remifentanil can be represented by a linear isobologram

T/F  in a patient using buprenorphine patches, morphine can have a reduced effect because buprenorphine is a partial antagonist

T/F  in a patient who has been reversed with neostigmine, but then needs to be urgently reintubated, suxamethonium would have a significantly reduced effect

T/F  cigarette smoking inhibits many of the cytochrome P450 enzymes, thereby slowing the metabolism of many drugs

T/F  competition for plasma protein binding sites between drugs, is a common reason for adverse drug effects in anaesthesia

T/F  if suxamethonium is injected into an IV port immediately after thiopentone, a precipitate will form in the line

Reference

Hemmings & Hopkins, Chapter 9 (Anesthetic drug interactions)

 

BT_PO 1.128 Describe the immunological basis and pathophysiological effects of hypersensitivity

Hedgerow by Angela Singer currently exhibited at Te Papa, Wellington

With the recent publication of the findings of the NAP6 audit, hypersensitivity (HS) is in the spotlight.

I have previously posted on anaphylaxis here but today we will stay a bit broader.

It may not be essential to know the exact Gell and Coombs classification of HS reactions, but it is not too complicated ( although I see that there have been some more recent amendements to it) and I think it does help with understanding of this reasonably common group of conditions

Power and Kam do this topic by far the best of the recommended texts in their chapter on the immune system. It would be reasonable for you to know the answer to the top 3.

BT_PO 1.128  Describe the immunological basis and pathophysiological effects of hypersensitivity

A single allergen may only produce a single type of HS reaction T/F

Type II hypersensitivity reactions, caused by antibodies binding to cell based antigens, include ABO incompatibility reactions T/F

A type I HS reaction can only occur after a prior exposure to the antigen T/F

I wouldn’t expect you to know the answer to these, but have a look if you are interested

Extrinsic allergic alveolitis is an example of Type III hypersensitivity caused by small immune complex deposition in tissues T/F
(as an aside the names of the causes of extrinsic allergic alveolitis are so descriptive . There is a list of some of them here – Hot Tub lung 😳)

Stevens-Johnson syndrome is a type of type IV hypersensitivity T/F

And one last thing. Blood is potentially a very immunogenic product. Have a think about the hypersensitivity reactions that can be caused by homologous blood. Then, have a think of what other immune mediated problems blood can cause.

SS_OB 1.15 Outline the potential effects on the neonate of drug administration in association with lactation

T / F  drug transfer into breast milk occurs by passive diffusion (therefore, influenced by Fick’s law)

T / F  for weak bases, a high pKa would slow the rate of transfer into breast milk, compared with a low pKa *

T / F  neuromuscular blocking drugs are not transferred into breast milk

T / F  neonatal deaths have occurred with mothers taking codeine while breast feeding – this risk is increased in mothers who are ultrarapid metabolisers (see also reference 3)

T / F  propofol is transferred into breast milk – however, studies have not shown any clinically detectable effect on the infant **

T / F  generally speaking, there is no need for interrupting breast feeding and/or discarding milk in the postoperative period

 

References:
1. Evers & Maze 2nd edition, p 950-951
2. Priti etal, Safety of the breast feeding infant after maternal anesthesia. Pediatric Anesth, 2014, 24: 359-371
3. SPANZA advisory on the use of Tramadol during breastfeeding, click here

Discussion Points
* what other PK properties of weak bases would determine drug transfer?
** are you surprised by this? can you explain why?

SS_OB 1.14 Outline the potential effects on the foetus and neonate of drugs administered during pregnancy

T / F  warfarin is potentailly teratogenic – but heparin and LMWH are safe during pregnancy

T / F  pregnancy induced hypertension may be managed with ACE inhibitors

T / F  phenytoin can cause foetal abnormalities – but levetiracetam is safe during pregnancy

T / F  morphine has a “category C” rating for use in pregnancy – this means that it is contraindicated

T / F  if propofol, suxamethonium, sevoflurane and vecuronium are given to a woman for an emergency GA Caesarian – the neonate would be born anaesthetised, but not paralysed

T / F  general anaesthetic agents may potentially be neurotoxic to a developing foetus

BT_GS 1.6 Describe the mechanisms of adverse drug effects

T/F Pharmcogenetic variation in acetylator status is important for several anaesthetic drugs

T/F Anaphylaxis to neuromuscular blocking drugs is more common in females

T/F Chlorhexidine may be associated with severe hypersensitivity reactions

T/F Both sevoflurane and desflurane may trigger immune-mediated hepatic failure

T/F Nitrous oxide directly inhibits the conversion of homocysterine to methionine

Serotonin Syndrome

BT_PO 1.102 Discuss the clinical features and management of serotonin syndrome

 

T / F   all serotonin receptors are ligand gated ion channels

T / F   tramadol, pethidine, fluoxetine, amphetamines and amitriptyline are all potentially serotonergic

T / F   monoamine oxidase inhibitors are not serotonergic

T / F   features of serotonin syndrome include: CNS excitation; hyperthermia; and hyper-reflexia

T / F   treatment is usually supportive, although cyproheptadine is a potential antidote