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 12th 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". 

Factors which Influence Drug Absorption
Route of administration Unique site-specific factors which influence absorption

All routes

Oral (gastrointestinal)

  • Rate of tablet dissolution
  • Destructive effect of gastric acid
  • Gastric emptying, intestinal transit
  • Characteristics of the gut content (eg. food)
  • Metabolism by gut organisms

Mucosal (eg. sublingual, rectal, vaginal)

  • Irritant effects

Transdermal

  • Integrity of the dermis
  • Characteristics of the subcutaneous tissue

Inhalational

  • Volatility of the drug
  • Size of droplets / particles

Injection (eg. intramuscular)

  • Blood flow to the site
  • Solubility of the drug in the interstitial fluid

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:

Influence of Shock States on Drug Absorption
Route Cardiogenic /obstructive / haemorrhagic / septic Anaphylaxis

Oral 

  • Decreased gut perfusion and therefore decreased intestinal absoprtion
  • Delayed gastric emptying due to poor perfusion
  • Intestinal wall oedema
  • Altered gut microbiome (different metabolism of the drug and excipients)

Mucosal

  • Decreased mucosal perfusion
  • Increased mucosal permeability (loss of barrier function)
  • Increased mucosal perfusion and drug absorption

Transdermal

  • Decreased skin perfusion, and therefore decreased absorption 
  • Increased skin absorption, aprticularly from urticaria

Inhalational

  • Decreased absorption due to impaired pulmonary perfusion, increased shunt due to consolidation, or poor diffusion due to oedema 
  • Increased absorption due to increased cardiac output
  • Decreased penetration of drug to the absorption site due to bronchospasm

Intramuscular /subcutaneous

  • Decreased absorption due to decreased perfusion of peripheral vascular beds.
  • Increased IM / SC absorption because of systemic vasodilation
       

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).

References

Kedziora, Andrew, and Johan Duflou. "Attempted Suicide by Intravenous Injection of Mercury: A Rare Cause of Cardiac Granulomas; A Case Report." The American journal of forensic medicine and pathology 16.2 (1995): 172-176.

Shargel, L., and A. B. C. Yu. "Physiologic factors related to drug absorption." Shargel, L. & Yu, AB. C., eds. Applied biopharmaceutics & pharmacokinetics. 4th ed. Stamford, Conn: Appleton & Lange (1999): 99-121.

Hogben, C. Adrian M., et al. "Absorption of drugs from the stomach. II. The human." Journal of Pharmacology and Experimental Therapeutics 120.4 (1957): 540-545.

Schou, Jens. "Absorption of drugs from subcutaneous connective tissue.Pharmacological reviews 13.3 (1961): 441-464.

Wester, Ronald C., and Howard I. Maibach. "Percutaneous absorption of drugs." Clinical pharmacokinetics 23.4 (1992): 253-266.

Rathbone, Michael J., and Jonathan Hadgraft. "Absorption of drugs from the human oral cavity." International journal of pharmaceutics 74.1 (1991): 9-24.

Prescott, L. F. "Pathological and physiological factors affecting drug absorption, distribution, elimination, and response in man." Concepts in Biochemical Pharmacology. Springer Berlin Heidelberg, 1975. 234-257.

Martinez, Marilyn N., and Gordon L. Amidon. "A mechanistic approach to understanding the factors affecting drug absorption: a review of fundamentals." The Journal of Clinical Pharmacology 42.6 (2002): 620-643.

Chillistone, Shruti, and Jonathan G. Hardman. "Factors affecting drug absorption and distribution." Anaesthesia & Intensive Care Medicine 18.7 (2017): 335-339.