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_AM 1.3 Describe the effect of anaesthetic agents and other drugs on airway reflexes

Hello again my friends! It feels like ages since I have posted on the blog, but I am happy to be back…

Today, a fairly core bit of business for us.

Part of my absence involved a holiday. We visited the Science Museum in London (not my favourite to be honest) where I came across this delightful contraption.

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We all know what nicotine does to the airways when inhaled, but how about when given rectally as this device was designed for ?!? It was used in patients who had drowned in the hopes of reviving them….

BT_AM 1.3 Describe the effect of anaesthetic agents and other drugs on airway reflexes

This article looks at the problem of laryngospasm, but does discuss the impact of anaesthetic agent on airway reflexes.

All iv induction agents EXCEPT ketamine depress laryngeal reflexes equally  TRUE/FALSE

Hypercapnoea protects against laryngospasm   TRUE/FALSE

Of the modern volatiles, sevoflurane causes the greatest depression of airway reflexes  TRUE/FALSE

A surgical depth of anaesthesia is in itself a protection against laryngospasm TRUE/FALSE

In addition to its irritant effect on the airways, nicotine stimulates the respiratory centre   TRUE/FALSE

 

2017.2 SAQ 14

Describe the pharmacodynamic properties of propofol EXCLUDING its effect on the central nervous system. Describe how these influence clinical use.

Propofol is a drug which anaesthetists use every day. Candidates should not be surprised to find that the primary exam requires an in depth and intimate knowledge of this drug. Many candidates did not address the second part of this SAQ at all.

T / F  propofol does not inhibit hypoxic pulmonary vasoconstriction, and is a slight bronchodilator so it is suitable to use in patients with COAD

T / F  propofol reduces uterine tone, so it can increase the risk of PPH

T / F  a dangerous fall in blood pressure can result from a propofol induction if the patient is hypovolaemic, because propofol is a direct vasodilator and inhibits the baroreceptor reflex

T / F  propofol blunts upper airway reflexes – it was serendipitous that propofol came into clinical use at the same time as Dr Archie Brain delevloped the LMA

T / F  propofol increases intraocular pressure, so it should not be used in cases of eye trauma

T / F  a propofol infusion alone can reliably prevent movement during surgery in an unparalysed patient

 

BT GS 1.29 Describe the physical properties of sedative/ hypnotic agents

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Regarding a propofol ampoule:

It contains egg products so shouldn’t be given to patients with an egg allergy   T/F

The contents are white because it contains soya bean oil$       T/F

It costs more than an ampoule of thiopentone               T/F

It contains antimicrobial preservative                            T/F

If you drank a 100ml ampoule it would make you quite sleepy*     T/F

$ Ask yourself what colour most oils are and what colour mayonnaise is and why they aren’t the same…

*In the trial of Michael Jackson’s cardiologist come ‘anesthesiologist’, Conrad Murray, an expert witness for the defence suggested that Jackson swigged a whole lot of propofol. This hypothesis was strongly refuted by the expert witness for the prosecution who happened to be none other than Steve Shafer. Who was correct?

BT_GS 1.59 Describe the pharmacological principles and sources of error with TCI

kindle cover2504Many of us use TCI on a daily basis. Indeed some people use it almost exclusively. Fewer appreciate the remarkably small data set that the algorithms were created from. Even fewer understand the limitations of the algorithms. If you want to find the answers to the statements below can I suggest you look at the chapter “Everything you should know about Propofol TCI” in the book The First Year. It can be freely downloaded from the College Library: click on Library Guides> Medical Education> Featured Resources and scroll to the bottom. The pdf is waiting for you. The cover is reproduced above. The TCI pump algorithms are poorly treated in the texts.

Q. A TCI using the Marsh algorithm will give the same dose of propofol to an eighty year old and a twenty year old patient of the same weight.  TRUE/ FALSE

Q. TCI can be used for morbidly obese patients.  TRUE/ FALSE

Q. The Minto algorithm for Remifentanil was devised by an Australian anaesthetist.  TRUE/ FALSE

Q. Plasma or effect site TCI can be used effectively for the Schnider algorithm.

Q. The James equations are used to calculate LBM in the Minto and Schnider algorithms.  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_GS 1.59 TCI

BT_GS 1.59 Describe the pharmacological principles of and sources of error with target controlled infusion

I am sure you have all looked at this screen. Here are some questions to test your knowledge of these models.

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TRUE/FALSE Inaccurate drug delivery from the infusion pump contributes to 55% of the overall inaccuracy of a TCI infusion

TRUE/FALSE With most modern TCI algorithms actual plasma concentrations are within 20-30% of predicted concentrations 95% of the time

TRUE/FALSE The Marsh model uses age and weight to calculate the compartment size

TRUE/FALSE The Schnider model may calculate a negative lean body mass in very obese patients

TRUE/FALSE The most clinically reliable method is to target the effect site concentration observed at loss of consciousness.