BT_PM 1.10 Describe the effect of physiological change and pathological disturbance on the pharmacology of analgesics with special reference to the elderly

ANZCA’s Acute Pain Management Scientific Evidence is the obvious resource to use for all these vile (my bias is revealed) pain LO’s. At over 700 pages it must surely be the driest tome on the recommended reading list for the Primary exam. Section 10.2 relates to the ‘Older Patient’. Seems it is not PC to use the term ‘elderly’- Miller doesn’t use it but Stoelting does.

Click to access fpm-apmse4-final-20160426-v1-0.pdf

When I am doing the pain round I can never remember whether this particular opioid or adjuvant agent needs dose adjustment in renal impairment or not. So, in an attempt to ask some clinically relevant and useful questions for when you are next on the pain round, have a crack at the following:

T/F A healthy eighty year old will have a normal serum creatinine despite loss of half of their nephrons.

T/F A healthy eighty year old will have a normal eGFR despite loss of half their nephrons.

T/F Opioid dose alterations in the elderly are primarily for pharmacodynamic rather than pharmacokinetic reasons.

T/F In general, the opioid dosing requirements for an eighty year old are half those of a forty year old.

T/F Elderly patients are more likely to develop PONV with opioids than younger patients

T/F The opioids of choice for the patient with renal impairment are alfentanil, fentanyl and buprenorphine

T/F morphine can be used safely in patients with hepatic impairment

T/F pregabalin shouldn’t be used in patients with renal impairment

T/F tramadol and tapentadol have active metabolites

BT PM 1.27 Ketamine

The pic above is of an inhaler that delivers S-ketamine intranasally. It is licensed for use in the USA for the treatment of depression. It is not licensed for use in Australia and probably won’t be. There was a small trial of racemic intranasal ketamine* for the treatment of depression in Australia but it was abandoned because of a high incidence of adverse effects. Adverse effects have been the bane of ketamine throughout its use in clinical anaesthesia and pain medicine.

Pity the Aussie researchers couldn’t use the S+ pure enantiomer form of ketamine in their trial. They could reasonably expect a more favourable adverse effect profile than that associated with racemic ketamine. Despite this ketamine is enjoying a resurgence of use in the treatment of psychiatric illness through its use in ECT. When I was a trainee I was told not to give ketamine to ‘mad’ patients because it would make them ‘madder’. Seems this is not true. I was also told not to give it to patients with a head injury. Seems this also is not necessarily true.

The following statements relate to the ketamine enantiomers: S+ and R-

S+ has greater analgesic potency than racemic ketamine  T/F

S+ has less emergence delirium reactions than racemic ketamine  T/F

S+ causes less salivation than racemic ketamine  T/F

S+ has a more rapid offset of action than racemic ketamine  T/F

S+ ketamine rotates polarised light in an anti-clockwise direction  T/F

Really is a pity we don’t have it.

I used Stoelting  for this one.

*the dose was 100mg- how much would have reached the systemic circulation?

 

2019.1 SAQ 14 – tramadol metabolism and excretion

Describe the metabolism and excretion of tramadol, including the implications for clinical practice

When I sat the Final ANZCA exam back in the very early 2000s (2001 to be precise), tramadol was a new drug and quite topical. So much so that I was asked about it in 3 of the 9 anaesthetic viva stations. It is now a drug with an established role in clinical practice. Its metabolism and subsequent elimination of metabolites is of interest to us, largely due to the role of Cyp2D6, which is subject to significant genetic polymorphism.

Hemmings and Egan again has the best section on this of the standard texts. The information on Cyp2D6 polymorphism can be found fairly widely and is important because it effects many drugs we commonly use.

BT_PM 1.9 &1.10 Pharmacology of analgesic agents

BT_GS 1.20 Describe and give examples of the clinical importance of pharmacogenetic variation

All the statements below relate to care material in this area.

The overwhelming majority of tramadol’s opioid activity comes from the parent drug T/F

About 20% of tramadol is excited unchanged in the urine T/F

Tramadol has a potent active metabolite O-desmethyl tramadol produced through the action of Cyp2D6 T/F

People with a normal level of activity at the Cyp2D6 enzyme have 1 or 2 fully functional alleles and are known as extensive metabolisers T/F

Poor metabolisers at the cyp2D6 enzyme have reduced opioid effectfrom tramadol T/F

Active metabolites of tramadol are renally cleared T/F

Those with poor renal function, are at risk of accumulation of the active metabolite T/F