Drug absorption in brief summary

This chapter answers parts from Section B(ii) of the 2017 CICM Primary Syllabus, which expects the exam candidate to "Describe absorption and factors that will influence it". Basically, absorption is the process by which the drug gets from its site of administration to the central compartment, the bloodstream if you will. This is obviously going to be influenced by numerous properties of the drug itself, the site where it has been administered, the patient's disease state and the various crude physical and chemical factors which govern the movement of substances from one place to another. 

This has appeared several times in the written and oral primary exams. Most often the college will ask about oral absorption, as if that was the only sort. For instance, Question 20 from the first paper of 2014 asked what the college had described as "a very broad and open question" about the factors which might affect gastrointestinal absorption. The college answer to it is somewhat unsatisfactory, inviting the exam candidates to "think on the fly" or some such.  Question 5(p.2) from the first paper of 2010 was somewhat clearer and more clinically relevant, requiring a discussion of factors which influence bioavailability and how they are influenced by shock. Additionally the topic of how critical illness in general affects pharmacokinetics had come up in Question 5 from the first Fellowship paper of 2011, and is discussed extensively elsewhere.

As far as literature goes, this topic is well-supplied. The candidate instead ruins the risk of having too much reading material. The college answer to Question 5(p.2) gives Rang and Dale (Ch. 7) and Goodman and Gilman (Ch.1, and Ch.2 in the current 12^th edition). These sources were used extensively for this summary and cannot be considered optional for pre-exam reading. For the hardcore freegan unwilling to buy or pirate these textbooks, Martinez and Amidon (2002) do an excellent overview of the factors which affect intestinal drug absorption.

In summary:

• Absorption is the movement of drugs from the site of administration into the central compartment
• Absorption may be oral, through the mucosa, transdermal, inhalational, intramuscular or subcutaneous
• Multiple factors influence absorption which can be broadly classified into drug factors (eg. molecular properties, solubility, etc) and site properties (surface area, porosity, acidity, perfusion with blood etc).
• In critical illness and particularly in shock states, absorption is almost always delayed and decreased (except in anaphylaxis, where the muscle absorbs more IM drug)

Definition of drug absorption

Goodman and Gilman define absorption reasonably clearly:

"Absorption is the movement of a drug from its site of administration into the central compartment ...and the extent to which this occurs"

Rang and Dale, with even greater brevity:

"Absorption is defined as the passage of a drug from its site of administration into the plasma"

Either would be satisfactory if one ever had to memorise any of these definitions for some sort of oral viva exam. Little additional benefit is to be gained by adding that the concept of absorption does not apply to intravenously administered drugs, as these are administered directly into the central compartment. One can also imagine creative scenarios which confront this definition with absurdity, including settings where the bulk of centrally injected drug remains somehow apart from the circulating plasma and absorbs slowly into it across some sort of blood/drug interface (eg. in the context of a gas embolus or intravenously injected mercury). However these probably fall into the realm of hilarious apocrypha and should not be mentioned during any sort of exam situation.

To add to the list of apocryphal or irrelevant material, one might consider that outside of pharmacokinetics absorption has a specific definition in chemistry:

"Absorption is the physical phenomenon of one substance's atoms, molecules or ions entering a bulk phase, be it solid liquid or gaseous".

The characteristic feature of absorption is that the substance is taken up by a volume, in contrast to adsorption where the substance is deposited on a surface. The usual analogy given to medical students is that absorption is like eating a cake, and adsorption is like having it smooshed into your face.

Factors which influence drug absorption from various routes

The major routine sites of administration and the factors which influence drug absorption from these sites are listed here as a convenient table, in case this ever comes up in the SAQs. In addition to pedestrian categorieslike "oral" and "rectal", one needs to have an encompassing "all" category to reflect the fact that all drug absorption is ultimately influenced by the molecular properties of drugs, the characteristics of the environments they are traversing, and the indifferent laws of physics. These factors are described in greater detail in the chapter on the transfer of drugs, and will be summarised here as "physicochemical properties of drugs and biological membranes". 

Drug absorption from the gastrointestinal tract is sufficiently interesting (and, having been the topic of  Question 20 from the first paper of 2014, relevant) to merit a chapter dedicated all to itself. 

The influence of disease states on drug absorption

Question 5(p.2) from the first paper of 2010 specifically asked how shock states influence drug absorption. In fact some forms of shock will have different effects on absorption to other forms. A brief brainstorm of how best to present this information has again yielded a tabular format:

In essence, all the shock states are rather alike in their effect on drug absorption, with the exception of anaphylaxis. In anaphylaxis, systemic vasodilation and an increased cardiac output results in an actual improvement of  drug absorption from various vasodilated vascular beds, such as muscle and skin. Hence the advice to give IM adrenaline (its absorption will be significantly enhanced by anaphylaxis).