Viva B(ii)b

This viva is relevant to Section B(ii) of the 2017 CICM Primary Syllabus, which expects the exam candidate to "Describe absorption and factors that will influence it".

Define drug absorption. 

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

- Goodman and Gilman

What is the difference between absorption and adsorption?

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. 

How do drugs cross biological membranes?

In summary, there are only a few ways for a drug to make its way through a living organism:

  • Paracellular diffusion (aqueous)
  • Intracellular diffusion (lipid)
  • Membrane diffusion (usually, aqueous)
  • Active transport / facilitated diffusion
Define Fick's First Law of Diffusion

 "The molar flux due to diffusion is proportional to the concentration gradient".

Fick's Law


  • J is "diffusive flux", the magnitude and direction of the flow of a substance from one compartment to another
  • dφ is the concentration difference 
  • dx is the distance for diffusion (or the thickness of the membrane)
  • D is a diffusion coefficient which is influenced by solution temperature, viscosity of the fluid, and the size of the molecules.
What factors influence drug diffusion?
  • Drug molecule size (and molecule shape)
  • Concentration gradient
  • Membrane thickness
  • Surface area of the membrane
  • pKa of the drug
  • pH of the solution
What factors determine the lipid solubility of a drug?

The pKa of a drug and the pH of the solution.

A substance will become more lipid soluble in a solution with a pH similar to its own pH.

Define pKa

The pKa of a molecule is a pH at which there is a 50:50 equilibrium of dissociated and non-dissociated molecules in solution, i.e. 50% of the drug is ionised and 50% is non-ionised.

 What is the pH-partition theory?
  • pH-partition theory describes the influences on the rate of diffusion of drugs across lipid membranes. 
  • Drugs are absorbed from the biological membranes by passive diffusion depending on the fraction of un-ionized form of the drug at the pH of that biological membrane.
What are the limitations of this theory?

pH-partition theory does not explain all cases:

  • zwitterions (hermaphroditic neutral molecules with both positive and negative polar groups) penetrate lipid bilayers by presenting themselves "side-on" to the hydrophobic membrane, thus appearing as neutral non-polar molecules while they pass. It is thought that fluoroquinolones gain intracellular access in this manner (Cramariuc et al, 2012).
  • Some ionised substances are present in such high concentrations that they are able to cross the lipid bilayer purely by the brute force of their concentration gradient (the classic example of this is water: the concentration of water in pure water is 55.5 mol/L).
What properties, generally, can be expected of drugs with a low pKa? Give an example
  • Drugs with a pKa under 7 (i.e. weak acids) will usually be water-soluble (ionised).
  • Acidic drugs tend to...
    • have higher oral bioavailability
    • have poorer hepatic clearance
    • have higher protein binding
    • have smaller volumes of distribution
  • Examples include
    • Levodopa (2.3)
    • Amoxycillin (2.4)
    • Aspirin (3.5)
    • Cephalexin (3.6)
    • Frusemide (3.9)
    • Warfarin (5.0)
    • Acetazolamide (7.2)
    • Phenytoin (8.4)
    • Theophylline (8.8)
What properties, generally, can be expected of drugs with a high pKa? Give an example.
  • Weakly basic drugs with a pKa closer to 8 will usually be lipid-soluble.
  • Basic drugs tend to...
    • have poorer protein binding
    • have larger volumes of distribution
    • have better CNS penetration
    • have "receptor promiscuity", i.e. a decreased selectivity
    • get sequestered in acidic organelles, including mitochondria
    • get absorbed better in the stomach
  • Examples include
    • Diazepam (3.0)
    • Lignocaine (7.9)
    • Codeine (8.2)
    • Cocaine (8.5)
    • Adrenaline (8.7)
    • Atropine (9.7)
    • Amphetamine (9.8)
    • Metoprolol (9.8)
    • Methyldopa (10.6)
Explain "ion trapping". Give an example.
  • Trapping effects take place when drugs cross a lipid membrane and enter an area with a significantly different pH to the one they previously occupied.
  • The change in pH may suddenly render the drug more ionised and therefore less lipophilic.
  • Unable to cross the membrane in the opposite direction, ionised drug molecules will become concentrated in this ionising solution
  • One example is the effect of using sodium bicarbonate to alkalinise the urine and promote the ion trapping of salicylate molecules, thereby enhancing their clearance.  
Apart from these physicochemical properties of drugs and biological membranes, what other factors influence drug absorption?
Factors which Influence Drug Absorption
Route of administration Unique site-specific factors which influence absorption

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


  • Integrity of the dermis
  • Characteristics of the subcutaneous tissue


  • Volatility of the drug
  • Size of droplets / particles

Injection (eg. intramuscular)

  • Blood flow to the site
  • Solubility of the drug in the interstitial fluid
How does drug absorption change in shock states?
Influence of Shock States on Drug Absorption
Route Cardiogenic /obstructive / haemorrhagic / septic Anaphylaxis


  • 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)


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


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


  • 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


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