Routes of administration

This chapter is theoretically relevant to something in Section B of the 2023 CICM Primary Syllabus, which describes the sort of stuff an ICU early training exam candidate should be confidently able to discuss. Given that the syllabus-builders have neither infinite time nor infinite paper, some things naturally end up being omitted and routes of administration were one of those things. However it is probably still important to know the various advantages and disadvantages of the different routes. One day in the future it might come up. In view of this, a short tabulated summary is offered here as a reference. It originated from the Katzung textbook.

Routes of Drug Administration
Route Advantages  Disadvantages
  • Most convenient
  • Cheapest, safest
  • Requires cooperation
  • Some drugs may be inactivated by the gut environment, eg stomach acid
Enteric coated
  • Gastric irritant drugs cannot irritate the gastric mucosa if they don’t come in contact with it
  • Drugs which are inactivated by gastric pH will remain active
  • Cannot be crushed and pushed down the NGT
Controlled release
  • At the best of times, a good way to have a sustained serum level
  • Effect is maintained overnight
  • Avoid non-therapeutic troughs
  • Anything which slows intestinal transit will result in “dose dumping”: tables will accumulate in the intestine, and all be digested at once when motility returns to normal
  • Variability of systemic concentration will be more variable than with immediate-release preparations, because dissolution of the tablet depends more on the chemical properties of the gut content (which fluctuates)
  • Bypass the first pass metabolism:  tongue venous blood drains to the superior vena cava
  • Convenient in nil-by mouth population
  • Only useful for drugs when a very small amount produces the desired therapeutic effect (eg. nitroglycerine, olanzapine, LSD) – don’t be expecting to absorb several grams of something via your oral mucosa.
  • Only useful for drugs which are highly lipid-soluble
  • Drugs taste gross
  • Bypass the first pass metabolism
  • Convenient
  • Absorption depends on area of the patch, and on the lipid solubility of the drug.
  • The epidermis is a lipid solubility barrier; the dermis is not! Burnt or abraded skin will absorb much faster. However, many drugs will not penetrate intact skin.
  • Only useful for highly lipid-soluble drugs
  • Absorption is highly dependent on skin integrity, skin hydration, and skin perfusion.  The mottled shocked patient will not benefit from the nitroglycerine patch. Hydrated skin is more absorbent than dry skin
  • 50% will bypass the first pass metabolism
  • Convenient?...
  • Absorption is unreliable
  • Smaller surface area is open for absorption
  • Irritation of the mucosa may occur.  
  • Bypass the first pass metabolism
  • Immediate
  • Delivery is controllable
  • You need intravenous access
  • One must guard to not give drugs which hemolyse, thrombose, or precipitate when give together
  • For the most, absorption of the drug is predictable
  • You can slow absorption intentionally by giving a vasoconstrictor (eg. lignocaine and adrenaline)
  • You can adjust the rate by changing  drug particle size, protein complex formation tendency and the pH of the injected fluid (this is the way insulin is made into long and short acting variants)
  • You can't give irritating drugs this way
  • Absorption is poor in poorly perfused shocked patients- The mottled shocked patient will not benefit from the subcut morphine
  • Theoretically any volume could be used, but practically only small volumes are usually injected
  • Water soluble drugs are absorbed rapidly
  • Vasodilated muscles absorbs very well – eg. IM is the route of choice for giving adrenaline in anaphylaxis
  • If the intention is slow release (eg. as a depot injection)
  • Rate of absorption depends on blood flow to the muscle-  exercise or a  hot bath or can accelerate absorption
  • Drugs injected into the vastus lateralis or deltoid will absorb faster;
  • Drugs in the gluteus maximus will absorb more slowly.
  • Drugs in a female gluteus maximus, or in an obese person, will absorb even more slowly
  • The drug arrives at the target tissue, rather than systemically
  • The artery itself is frequently the target tissue (eg. verapamil, papaverine)
  • Access issues
  • You can really do some damage to somebody’s artery
  • Bypasses the blood-CSF barrier, gets straight to the meninges
  • Tiny amount of drug is required
  • Little of it reaches the systemic circulation
  • Access issues: requires spinal or EVD
  • Bypasses the blood-CSF barrier, gets straight to the meninges
  • Without a skilled operator, you are not getting into that space.
  • Significant amounts of drug can be systemically absorbed
  • Onset depends on how much of the drug is ionized at a physiological pH;  thus, your lignocaine (with its lower pKa ) will work faster than your bupivacaine
  • Rapid access to the circulation, owing to the vast 70m2 surface area
  • First pass metabolism is avoided
  • Most drugs are irritating when given in this way
  • Requires the drug to be finely atomized; only droplets less than 1 micron in diameter will get to the alveolus
  • If your target site is the bronchus, that’s great; but the drug will also be systemically absorbed.
  • If your site is the whole body, you will have untoward effects on the bronchus.
Nasal mucosa
  • Rapid absorption
  • Bypasses first-pass metabolism
  • Most drugs are irritating when given in this way
  • Absorption is perhaps TOO good. Some drugs with intended local effect (eg. lignocaine, phenylephrine) may become systemically active with ahem, overzealous administration.
Topical in the eye
  • If its an eye effect you want, then that’s what you will get
  • Systemic absorption is usually very limited
  • Corneal infection or trauma increases systemic absorption,  but this shouldn’t ever matter because the dose is typically laughably small
Topical, eluted from a stent
  • Effect is purely local: one would not want to be systemically effected by sirolimus or paclitaxel.
  • Less restenosis than bare metal stent, but more thrombosis: dual platelet therapy is recommended for at least 1 year
  • Stent gets rethrombosed in 1% in the first year, despite dual antiplatelets. Oh well. 



For this sort of really basic stuff, no matter where you look you will find essentially the same information.

I used chapters from "Goodman & Gilman's The Pharmacological Basis of Therapeutics" 11th ed by Brunton et al, and "Basic & Clinical Pharmacology" 11th ed. By Katzung et al.

I also perused Peck and Hill "Pharmacology for Anaesthesia and Intensive care" as well as the notoriously error-prone "Handbook of Pharmacology and Physiology in Anaesthetic Practice" by Stoelting and Hillier. Neither covered this subject in a depth I found satisfying.

Goodman and Gilman's remains a canonical text.