Deranged Physiology

This chapter answers parts from Section B(c) of the Primary Syllabus; "Describe isomerism and provide examples". At the time of writing, this chapter represents the only pharmaceutics question ever asked in the Primary written paper, this being Question 20 from the second paper of 2012.  "Explain the clinical relevance of enantiomerism"and "give a clinically relevant example" seems to be the entire expectations from the college regarding this topic. 

These are atrioventricular blocks, arising from some abnormality of conduction between the atria and the ventricle. The PR interval describes this conduction.  The PR interval is not just the conduction through the atria- it is also the AV node, the bundle of His and the Purkinje fibers. But, most of the time when this is prolonged, it's the AV node ( in most cases with a PR of 200-300 msec). First degree and Mobitz type 1 are usually AV nodal processes; Mobitz type 2 and third degree heart block are typically due to disease below the AV node.Previous SAQs involving these phemomena include Question 30.3 from the first paper of 2015 (2nd degree heart block, Mobitz type I) and Question 30.4 from the second paper of 2012 (complete heart block).

Half-life (t½) is the time required to change the amount of a drug in the body by one-half during elimination. The two main factors which affect drug half-life are volume of distribution and clearance; the formula for half-life is (t½ = 0.693 × Vd /CL). The 0.693 factor is in fact the logarithm of 2, which represents the fact that drug clearance typically occurs at an exponential rate. It takes about 5 half-lives for a drug to be roughly 97% eliminated. (50%, then 75% then 87.5% then 93.75% then 96.875%). For drugs eliminated by first-order kinetics, half life is constant regardless of concentration. With zero-order kinetics the term becomes meaningless, and one refers instead to a dose or concentration removed over time.

Question 23 from the second paper of 2008  and Question 25 from the first paper of 2006 asked the candidates to define "study power". In short,  it is the percentage chance of detecting a treatment effect if there actually is one. This is something you decide upon before commencing the trial; the higher the power value, the more patients you will need. Typically, beta is 0.8, so there is a 20% chance (1-beta) of commiting a Type 2 error , or a "false negative".

 This biomarker is an enzyme involved in the excitation-contraction coupling of the myocardium. Troponin T serves to attach the troponin complex to actin and tropomyosin. There is a cytosolic pool (which is released early in the infarct) and a structural pool (which is slowly released over days as the damaged myocardium decomposes).

Exposure to extreme cold results in a series of predictable changes in human physiology, which can be broadly described as "everything stops working". From the coagulation cascade to the the nephron to the interactions of haemoglobin with oxygen, all things become slower and more disorganised. Ultimately, the borders of survival can be found somewhere around 13.7°C, which was the temperature of the coldest survivor (unreliable accounts suggest it may be as low as 9°C for children). Beyond this point, the defrosted organism tends to be permanently damaged by their experience.

ECMO is briefly covered in a short summary elsewhere on this site. One of these days, a more detailed exploration of this fascinating modality will become available. In the meantime, an excellent troubleshooting guide is offered by LITFL, and brilliant videos accompany a practical guide based at the venerable merylandccproject.org.

The college wanted their candidates to "critically evaluate the role" of SSEPs in  Question 2 from the first paper of 2005. Another question on SSEP results was Question 11 from the second paper of 2014 ("Describe how SSEPs can be used for prognostication in patients with hypoxic-ischaemic brain injury"); by a totally arbitrary decision that question was left in the Cardiac Arrest and Resuscitation revision section.

Interactions between drugs can be classified as pharmacokinetic and pharmacodynamic. Pharmacodynamic drug-drug interactions are briefly described in another chapter. Here, the focus is on the mechanisms by which drugs interfere with each other's absorption, distribution, metabolism and elimination.

The key statement to define pharmacokinetics in critical illness is "everything is slow and broken". Nothing is absorbed properly, nothing is metabolised properly, clearance is impaired, half-lives are increased and drugs end up distributed randomly into wasteful third spaces where they sit pointlessly, unavailable to either their target tissue nor organs of clearance. In short, critical illness is terrible for pharmacokinetics.