BT GS 1.12 Explain and describe the clinical application of concepts related to intravenous and infusion kinetics

Admittedly, this is a rather dry topic.  It is of unequivocal importance to anaesthetists however as our practice revolves around giving drugs that have potent pharmacodynamics effects with rapid onset and offset of action.

Regarding the time to peak effect (TTPE):

Is indicated on a plasma time curve for a bolus dose where the effect site curve crosses the plasma concentration curve TRUE/FALSE

Will be relatively short for any drug that rapidly redistributes TRUE/FALSE

Will be relatively short for drugs with a large keo TRUE/FALSE

Will always be longer than the t ½ keo TRUE/FALSE

Is considered to be a dose insensitive parameter TRUE/FALSE

BT PO 1.91 Outline the pharmacology of glucagon (& other things)

glucagon

Coming in an aesthetically pleasing little orange container, glucagon is a drug anaesthetists administer infrequently. Funnily enough the most common indication that we give glucagon for has nothing to do with hypoglycaemia. Rather it is given to treat suspected spasm of the sphincter of Oddi demonstrated on an intraoperative cholangiogram when performed during a lap chole. The second most common indication in our sphere of influence is probably the management of impacted food boluses. Both of these indications relate to the smooth muscle relaxant action of glucagon.

 

Glucagon is an anabolic hormone TRUE/FALSE

Glucagon is synthesized by the alpha cells of the islets of Langerhans TRUE/FALSE

Glucagon is effective in the management of beta blocker overdose because it  firmly binds to adrenoceptors TRUE/FALSE

Glucagon is an inotrope and chronotrope TRUE/FALSE

Glucagon binds to a G protein coupled receptor and inhibits adenylate cyclase activity and thus reduces cAMP TRUE/FALSE

BT PO 1.90 Describe the pharmacology of insulin preparations

Regarding insulin:CRw26neXIAA8kW7

Insulin preparations are synthesized using recombinant technology TRUE/FALSE

If injected intravenously, long acting insulins will still have a long duration of action TRUE/FALSE

Insulins are metabolized by the liver TRUE/FALSE

Measurement of C-peptide levels can differentiate endogenous from exogenous insulin TRUE/FALSE

Glargine insulin (Lantus) forms microprecipitates when injected subcutaneously* TRUE/FALSE

 

* Lantus commonly stings when injected- my diabetic father will attest to this! This is related to its formulation. Can you hazard a guess at its pH and why it is formulated like that?

Although insulin will degrade at room temperature, it is similar to suxamethonium in that it will be retain adequate activity for well over a month if left out on your anaesthetic trolley.

BT PO 1.85 Explain the control of blood glucose

Mars-reaches-reformulation-limits-and-calls-downsizing-the-only-option_strict_xxl

A standard Mars bar (53g) contains 30g of glucose. They used to be given to pregnant women as a component of the glucose challenge test for gestational diabetes. I don’t know if this is still the case.

The glucose transporter, GLUT-4, is ubiquitous and found in most cells in the body TRUE/FALSE

Hepatic uptake of glucose is dependent on the presence of insulin TRUE/FALSE

Glucokinase phosphorylates glucose and is a pivotal enzyme in the glycolysis pathway TRUE/ FALSE

Alterations in glucose transport occur within seconds of insulin release TRUE/FALSE

Insulin has trophic and mitogenic actions TRUE/FALSE

 

A bonus question- are glucose and dextrose the same thing?

National Anaesthesia Day: Part 2

1016_ether-dome2

That’s the actual Ether Dome pictured above. You can visit it- I haven’t done so yet but it is on my bucket list. The picture on the back wall was commissioned after the 150th celebration of Ether Day. Although possibly not as famous as Robert Hinckley’s painting, ‘The First Operation with Ether’, it is certainly more historically accurate.

To the statements then regarding National Anaesthesia Day:

It has always been celebrated on this date in Australia.  False, it has only been recently that Australia has deigned to celebrate it on the actual date.

Morton tried to patent ether calling his mystery drug ‘Letheon’.  True, he and his mentor, a Professor of Chemistry named Charles Jackson, applied for and got a patent.  This was withdrawn later- Morton was determined to get all the recognition (and profits) for himself. He and Jackson fought a bitter lifelong quarrel to be recognised as the sole true discoverer of anaesthesia.

Morton was running late on the momentous day setting an unfortunate precedent.  True, he was having problems getting his inhaler device ready in time.  Surgeons have been bemoaning ‘equipment issues’ on our part ever since.

Morton was the first person to administer ether successfully for a surgical procedure.  False, we know at least one other person successfully used ether for surgery prior to October 16, 1846. A rural doctor called Crawford Long used ether in 1842. Idiot didn’t tell anyone about it and he didn’t publish his findings until 1849.

Morton killed himself by cutting his femoral artery at the age of 48 while imprisoned. He was incarcerated for throwing acid in a prostitute’s face.  This is false. The details relate to the unfortunate demise of Morton’s partner, Horace Wells. He died at the age of 33, the other details are correct. He never recovered from being booed off ‘stage’ after his failed attempt to demonstrate anaesthesia with nitrous oxide. He was a victim of the pharmacokinetic properties of the agent more than a failing of the agent itself. Morton’s choice of ether, a highly soluble agent with a slower offset of action, was the key to his success. Morton died of a stroke.

National Anaesthesia Day: Part 1

WTG_Morton

Today is a very significant one particularly if you are an anaesthetist.  On this day, 171 years ago, William Thomas Green Morton (pictured above) administered the first successful anaesthetic publically at what is now termed the ‘Ether Dome’ in Massachusetts General Hospital, Boston. I am biased but think this is the most significant medical discovery ever. What is perhaps surprising is that the demonstration didn’t happen many years earlier- ether is not a novel chemical nor is it difficult to synthesize. The analgesic and sedative properties of nitrous oxide had been known about for almost half a century but no one had bothered to apply this knowledge to the more expedient need of surgical anaesthesia. To be fair, Morton’s contemporary, Horace Wells, used nitrous oxide successfully for dental extractions before unfortunately ‘failing’ when he demonstrated it publically on the same stage as Morton would subsequently have success.  I put the ‘failing’ in apostrophes because although Wells’ patient (he was a medical student with a toothache) groaned when under the influence- eliciting the derisory, “Bah humbug!” comment from the surgeon- the patient later stated that he did not recall the procedure and that it had caused him no pain. Surgeons have forever since equated movement or vocalisation from the patient as evidence of inadequate anaesthesia.

Although we commemorate this event with the respect that it deserves, the pioneering anaesthetists of the day were not the most respectable or reputable bunch. For the most part they were greedy, self-serving dentists out to make a quick buck. Nonetheless we are indebted to them.

The following statements relate to October 16, National Anaesthesia Day:

It has always been celebrated on this date in Australia  TRUE/FALSE

Morton tried to patent ether calling his mystery drug ‘Letheon’  TRUE/FALSE

Morton was running late on the momentous day setting an unfortunate precedent  TRUE/FALSE

Morton was the first person to administer ether successfully for a surgical procedure  TRUE/FALSE

Morton killed himself by cutting his femoral artery at the age of 48 while imprisoned. He was incarcerated for throwing acid in a prostitute’s face  TRUE/FALSE

Answers another time. Happy Anaesthesia Day!

 

 

 

 

Evolution of a viva- Part 2

In Part 1 we formulated a viva and I ran through it with my shadow a few times. Now we need to properly ‘test run’ the viva. This entails doing it with trainees, candidates and other people preparing for the exam. I don’t test a viva that will be used in the next exam. But it is important to test a viva because you invariably learn things- eg. what you thought was a straight forward question may turn out to be ambiguous to candidates. You might find that your viva is too long (they are never too short) or too hard (God forbid). A really hard viva does no one any favours. I sometimes find that candidates consistently get a particular question wrong- I need to discern whether it is worth asking that point or not and often end up discarding that question. For example, I asked in a BIS viva what cells in the brain are responsible for producing the EEG waveforms. I wanted people to say ‘cortical pyramidal cells’ but no one did so I canned it. Getting bogged down half way through a viva because of one point is not a productive exercise.

There are other changes that result from testing. I often find I change the wording of my questions or prompts after test running a viva. The ultimate test is using it in the actual exam of course and a viva can even undergo changes during the course of an exam. Believe it or not we want to maximise the chances of the candidate demonstrating to us an understanding of a given viva topic. The challenge for the examiner is to find the best way to extract the desired information. Sometimes the exam experience is very different from that with my local candidates. I have certainly ‘decommissioned’ a viva after an unsatisfactory performance! It is always surprising and enlightening to see what aspects of a particular viva candidates find challenging. It is quite satisfying when candidates consistently do well with a particular viva. This doesn’t necessarily mean it is easy. Indeed the same viva may be done poorly in another sitting of the exam.

That is all I will say for now about writing vivas. But I will give you a little heads up. One of the disturbing  recent trends examiners have noted is that the vivas that were done poorly tended to be on core topics eg. core anaesthetic drugs, PK and PD, cardiac physiology, respiratory mechanics. This tends to reliably distress us examiners (“they should know that etc”) so there is a good chance these topics will be revisited in future exams.

Evolution of a viva- Part 1

Before you get your hopes up I will not be revealing the intimate details of a viva but I will attempt to convey some of the thought processes that are employed in the creation of a viva. I can only speak for myself here but I suspect my colleague examiners do similar things.

It begins with an idea (as do most things) which is often formed during the actual viva exams. I think to myself, “Gee the candidates don’t know much about basic propofol pharmacokinetics.” Often this thought is engendered as I watch a colleague examine on a particular topic. I like to examine on topics that satisfy a few criteria:

  • I think anaesthetists should know this stuff
  • The topic is clinically relevant (hopefully these two aren’t mutually exclusive)
  • I have seen a knowledge deficit about the topic in my trainees (if they already know it then someone else can ask them that!)
  • The ‘answers’ or responses I want need to be in the set texts (this can be quite difficult and has scuppered a few viva ideas along the way)
  • Another person with a FANZCA would at least understand most of what the viva was getting at
  • The nature of the topic lends itself to being asked in a viva format

Once I have the idea I write down what the main points I want candidates to demonstrate an understanding of are. (I also need to make sure there is a learning objective pertaining to the viva!!) Each viva topic is only five minutes long so the path to pass responses needs to be direct and hopefully short. Next I hit the books and confirm that the topic is adequately covered. Occasionally I discover that my understanding of the topic is at odds with what the books say! Not uncommonly I may have to look at six different books and it is frustrating for all of us if they say six slightly different things. Next I need to formulate the questions to get the information I want. Each viva should ideally start with a simple and brief question to allow the candidate to answer the opening question correctly and begin in a good frame of mind. So, for a propofol PK viva I might ask “What is the induction dose of propofol for a healthy unpremedicated 20 year old?” Subsequent questions need to flow on naturally from the opening question. I like a diagram or two in a viva but it needs to be simple and easily drawn. Sometimes it may be better to provide a diagram. It may be deliberately incomplete. Lastly I run through the viva myself a few times to check the timing and make sure the flow of the viva is alright. Then the real hard work starts. Part 2 will elaborate.

BT GS 1.36 Describe the PK of neuromuscular blocking agents

IMG_3494

Regarding rocuronium:

It is a more potent agent than vecuronium   T/F

If you drank it, it would paralyse you eventually         T/F

Its duration of action is dependent on what time of the day you administer it    T/F

It commonly causes stinging when injected*    T/F

It is presented as a racemic mixture                 T/F

 

*Read this paper for a description of what it feels like to have rocuronium and suxamethonium injected when you are wide awake.  Response of the bispectral index to neuromuscular block in awake volunteers. P Schuller et al. British Journal of Anaesthesia 2015; 115(Supp 1): i95-103.

Reading any clinical paper about rocuronium should allow you to answer the third question. Unfortunately, reading any of the recommended texts for the exam won’t be enlightening about this particular property of rocuronium.

BTGS 1.30 and 1.31 Describe and compare the PK/PD of sedative/ induction agents

IMG_3500

Regarding midazolam:

It can sting on administration because it has a high pKa   T/F

It has very poor bioavailability   T/F

It can induce anaesthesia when used as a sole agent    T/F

It tastes nice hence its popularity as a paediatric premed   T/F

It has an active metabolite   T/F

Despite what the practice of many trainees may suggest, the t1/2 keo of midazolam is significantly more than about thirty seconds.