Forensic pharmacokinetics

Have a look at this document – Trial of Conrad Murray  – a most fascinating read which illustrates some interesting pharmacokinetics. There are two expert witness reports in this document – read the brief letter from Paul White to Mr Flanagan first, ponder the below questions, then read the prolix submission from Steven Schafer where you’ll find a lot more detail and most of the answers.

 

A range of propofol concentrations (2.6-4.1 mcg/ml)  was given for the circulatory system – why would there be differing propofol concentrations in different sampling sites?

The propofol concentration in the stomach at autopsy was 1.9 mcg/ml. Why? Do you think he ingested the drug with fruit juice as Dr White speculates?

The lignocaine concentration in the femoral vein was 0.84 mcg/ml and in the stomach 23 mcg/ml. Can you explain this?

 

 

 

 

 

BT_PO 1.79 : Acid-base chemistry

BT_PO 1.79 : Describe acid-base chemistry using the Henderson-Hasselbach equation and strong ion difference

 

The SID in NaCl is 0 mmol/L        TRUE/FALSE

Normal Se Cl is approximately 100 mmol/L        TRUE/FALSE

The normal SID in plasma is approximately 40 mmol/L        TRUE/FALSE

Large volumes of NaCl as a replacement fluid can take the Se Cl to around 120 mmol/L (not that I would know as this is not routinely reported in my hospital)…

Administering large volumes of NaCl causes a metabolic acidosis by decreasing the SID    TRUE/FALSE

Administering large volumes of NaCl causes a metabolic acidosis by impairing renal bicarbonate absorption with the chloride load        TRUE/FALSE

Hypoalbuminaemia will give a metabolic acidosis        TRUE/FALSE

 

BT_PO 1.79 : Acid-base chemistry

Third in my series on acid base physiology, see last week’s post for the suggested reading material…

BT_PO 1.79 : Describe acid-base chemistry using the Henderson-Hasselbach equation and strong ion difference (SID)

So Stewart would look at this LO and say, yes, those 2 factors are important, but you also have to consider the dissociation of water, and the amount and dissociation of the non-volatile weak acids in the system. 

The independent variables in his model are SID, and volatile (pCO2) and non-volatile acids.

pCO2 is controlled by the lungs        TRUE/FALSE

SID is controlled by the liver        TRUE/FALSE

Albumin levels are controlled by the kidney        TRUE/FALSE

Acid-base differences across a membrane are predominantly from CO2 as it crosses membranes so easily        TRUE/FALSE

Acid-base differences across a membrane are predominantly from proteins as they cross membranes so poorly        TRUE/FALSE

Study tip : revision tactics

 

IMG_20171206_110918

Inspired by PLOOTD we’ve started the creation of a local bank of TRUE/FALSE statements for revision purposes. At the end of each tutorial, each trainee writes 2 statements that they thought were important and/or interesting from the session, and we’re keeping them in a spreadsheet. Every couple of months we run a little quiz with 50 random statements and give the trainees the answers to mark themselves.

 

BT_PO 1.79 : Acid-base chemistry

BT_PO 1.79 : Describe acid-base chemistry using the Henderson-Hasselbach equation and strong ion difference

Strong ion difference (SID) refers to the Stewart approach to acid-base analysis. Stewart’s underlying tenet is that hydrogen ions are the dependent variable in a complex system of physico-chemical interactions, not simply an entity that is shuttled across membranes. He makes the point that water is a practically inexhaustible source of hydrogen ions as it is usually so minimally dissociated. As we saw yesterday, just raising the temperature of an aqueous solution will increase the dissociation of water leading to a higher [H+] – though it’s important to realise that it will remain at a neutral pH as the [OH-] increases equally. 

Peter Stewart’s book is available free on the internet but for the majority of you I would recommend Kerry Brandis’ work on the topic – Quantitative acid-base analysis.

Strong ions in solution are fully dissociated        TRUE/FALSE

Sodium, chloride and lactate are strong ions        TRUE/FALSE

pCO2 determines [H+]        TRUE/FALSE

The SID determines [H+]        TRUE/FALSE

If the SID is non-zero then electro-neutrality requires the presence of weak electrolytes    TRUE/FALSE

These weak electrolytes are predominantly weak acids        TRUE/FALSE

Albumin is the predominant weak acid in the body        TRUE/FALSE

There will be more on this topic after a brief foray into respiratory physiology 🙂

 

 

BT_PO 1.78 : Acid Base Regulation

BT_PO 1.78 : Describe the regulation of acid/base balance

Looking at the effect of temperature…

Decreasing temperature will decrease the solubility of carbon dioxide in blood     TRUE/FALSE

Arterial pCO2 will decrease as temperature drops for a given content of carbon dioxide     TRUE/FALSE

As temperature increases the dissociation of water increases      TRUE/FALSE

The pH of neutrality of water at 37 degrees C is 6.8       TRUE/FALSE

Blood at a pH of 7.4 is at a neutral pH       TRUE/FALSE

 

 

 

 

BT_PO 1.50 CVS and obesity

BT_PO 1.50   Describe the cardiovascular changes that occur with morbid
obesity

An increased extracellular volume may be a causative factor in hypertension in the obese  TRUE/FALSE

Blood volume per kg body weight is less in the obese than in the lean      TRUE/FALSE

Hyperinsulinaemia may be a causative factor in hypertension in the obese      TRUE/FALSE

A cuff that is too small will over-read the blood pressure in the obese      TRUE/FALSE

Fat blood flow is approximately 10 ml/min/100g      TRUE/FALSE

I have taken this from Hemmings and Hopkins Chapter 71 but the material is scattered throughout the recommended texts and can also be deduced if you have a good grasp of the topic

 

 

 

SAQ perusal

Many candidates write unstructured text that doesn’t answer the question. It’s a known problem generally with the SAQ format that in the heat of the moment candidates will write down everything they think they know about the topic regardless of relevance.  It’s hard though when you’ve only got 10 minutes to answer a question to spend some of that time planning, not actually writing. And it’s hard, once you’ve (mis)interpreted the question, to get back on track.

So perusal time is changing! It’s longer at 15 minutes – 1 minute per question! And you can now write stuff! Not in the answer books, it’s not a default exam extension. But you can write notes on the question paper.

We strongly recommend you spend this time underlining all the key points and jotting down rough outlines of your answer.

Simplicity beyond complexity

Last week I advised a rather algorithmic SAQ approach of thinking of and writing relevant facts. Excellent candidates however are already writing and succinctly explaining relevant facts because they understand the material well enough to distil out what is important. Oliver Wendell Holmes coined the term ‘simplicity beyond complexity’ which is where you want to aim for – to understand the material well enough to know what’s important, sum it up and explain it. If you’ve not heard of Oliver Wendell Holmes before then read Letter to Dr Morton.