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?

 

 

 

 

 

Patient of the week – 2

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Another piece for the V&A, this made entirely from cutlery (I am drawing a long bow for today’s post)

Here is another case in this sporadic series

Some months ago I looked after a young patient who had been retrieved following a machete injury near the shoulder, resulting in almost total amputation of the arm. The injury had occurred some hours previously, with the patient left at the side of the road.

He had been intubated by the retrieval team at the scene.

On arrival to the Emergency Department his potassium level was 6.5 mmol/L

BT_GS 1.38

Normal serum potassium rise following an intubating dose of suxamethonium is 1.5mmol/L TRUE/FALSE

BT_PO 1.72

ECG changes associated with hyperkalaemia include tall peaked T waves and a shortened PR interval. TRUE/FALSE

He was taken to theatre to reattach the arm. He was hypovolaemic and anuric.

I set about trying to lower his serum potassium and restore his blood volume.

BT_PO 1.40

Salbutamol may be detected as halothane when nebulised within the circle circuit TRUE/FALSE

BT_PO 1.72

Calcium gluconate is used in the  management of hyperkalaemia as it lowers serum potassium TRUE/FALSE

BT_RT 1.9

Hyperkalaemia and hypercalcaemia are potential metabolic consequences of massive transfusion    TRUE/FALSE

To be honest, nothing I tired (and I tried a lot of everything I could think of, short of starting dialysis) lowered his potassium at all. But at least it didn’t increase any further. He survived the reimplantation  and was transferred to ICU for further management, including some much needed haemodialysis.

BT_RT 1.17 and 1.18 Adrenaline in shock and resuscitation

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Not sure that these fit the topic, but they were beautiful and I am a sucker for a rainbow (viewed at the V&A). I think these would give you a surge of dopamine rather that adrenaline, but we will save that for another day…

The current ARC guidelines (see 11.5) provide a very minimalist approach to drug therapy in cardiopulmonary resuscitation, emphasising the importance of high quality and minimally interrupted CPR. However of the couple of drugs left, adrenaline in front and centre.

BT_RT 1.17 With reference to the management of shock, describe the pharmacology of vasopressors and inotropes, including:

adrenaline,

and lots of other drugs (click on the link to view them)

BT_RT 1.18 With reference to cardiopulmonary resuscitation, describe the pharmacology of

adrenaline,

vasopressin,

amiodarone and

lignocaine

 

During cardiac arrest, adrenaline has a role in the treatment of both shockable and non shockable rhythms     TRUE/FALSE

Adrenaline has been shown to improve the chances of return of spontaneous circulation in arrest situations   TRUE/FALSE

Adrenaline is useful in the treatment of anaphylactic shock, in part, because it prevents further mast cell degranulation  via a beta mediated response TRUE/FALSE

Adrenaline may improve myocardial blood flow in low flow states as it causes aortic diastolic pressure to rise   TRUE/FALSE

If giving adrenaline via the endotracheal tube, the dose should be increased by 10 fold TRUE/FALSE

 

SS_OB 1.12 Labetolol

At least where I work we have to fill out the Special Access Scheme form to use IV labetolol, but worldwide it is a commonly drug for blood pressure control in pre-eclampsia, and it has many advantages over hydralazine.

SS_OB 1.12 Describe the pharmacology of agents used for the treatment of pre-eclampsia including magnesium, hydralazine and labetolol

 

T/F Labetolol is a non specific alpha antagonist

T/F Labetolol is a non specific beta antagonist

T/F A beta blocker with Intrinsic Sympathomimetic Activity is particularly useful for prevention of myocardial infarction

T/F Labetolol may cause profound foetal bradycardia

T/F Cardiac output rises after intravenous but not oral Labetolol

 

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 1.122 Classify and describe the pharmacology of anti-platelet drugs

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Vallecula suggested that the photo from the other day (quite similar to this one) could have been the wall of the operating theatre due to platelet dysfunction. I liked that description and thought it apt for today’s topic….

Here is a link to the BJA education article on antiplatelet agents. The link above will take you to the post with an article on the physiology. Again these agents will be widely covered in the textbooks…

BT_PO 1.122 Classify and describe the pharmacology of anti-platelet drugs

Both clopidogrel and prasugrel are prodrugs and subject to inter-individual differences in activity due to genetic polymorphism of their metabolic pathways       TRUE/FALSE

Both clopidogrel and prasugrel block the ADP receptor and are hence associated with the same risk of bleeding as each other       TRUE/FALSE

Platelet function returns to normal approximately 7 days after ceasing abciximab  TRUE/FALSE

All GP IIb-IIIa receptor antagonists can produce thrombocytopenia TRUE/FALSE

Low dose aspirin (75 100mg/day) is the only drug which selectively inhibits the COX-1 isoenzyme    TRUE/FALSE

 

BT_PO 1.112 Describe the physiology of haemostasis, including the role of platelets


This photo is from the Yayoi Kusama exhibition I went to in Washington earlier this year. Each visitor was given a sheet of stickers to place in the room. Aggregated platelets???

This topic will be covered in any physiology textbook, but also a nice overview in BJA Education here.

It seems to be quite a popular in the vivas as it lends itself to integtation of physiology and pharmacology (which I will cover on Thursday)

BT_PO 1.112 Describe the physiology of haemostasis, including:

• Coagulation

• The role of platelets

• Fibrinolysis

von Willebrand’s factor is essential for platelet activation  TRUE/FALSE

Fibrinogen and collagen are both ligands for platelet glycoprotein receptors  TRUE/FALSE

Thrombopoeitin is produced by the liver and kidneys in response to thrombocytopenia  TRUE/FALSE

Glycoprotein IIb -IIIa is important for platelet aggregation. TRUE/FALSE

Platelet activation results in release of light and dense granule contents TRUE/FALSE
I noticed that the link in yesterday’s post was broken – it’s fixed now

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