2018B Question 14
Describe the factors determining transdermal uptake of drugs (50%). Briefly outline the advantages and disadvantages of this route.
33% of candidates achieved a pass in this question.
To pass, candidates had had to define Fick’s equation correctly AND have further examples or specifics, and to outline the advantages and disadvantages of using this as a route of administration.
Poorly performing candidates often wrote the Fick’s equation and then did not expand on the components of this equation. It is not enough to write, for example, that increased solubility increases the uptake, as the equation has already mentioned this.
Better performing candidates would explain the type of solubility that was important and why, and use examples to make their point. This example could be applied to all the components of the Fick’s equation.
High scoring candidates often mentioned factors outside the Fick’s equation, or indirectly related to this equation and often used clinical examples as to hose these factors could occur. Overall there was a lack of detail in the answers, a lack of clinical application and a lack of examples of medications used transdermally.
- Factors increasing rate of uptake
- Logistics: Pros and cons
- Kinetics: Pros and cons
|Definition||Absorbed through the skin|
|Path of Drug||
Patch → Epidermis → Dermis → Blood vessel
Multiple lipid membranes
|Locally Acting||Lignocaine/prilocaine, amethocaine|
|Systemically Acting||Fentanyl, buprenorphine, GTN, nicotine|
Factors Increasing Rate of Uptake
e.g. Lignocaine 2% cf. 1%
e.g. EMLA eutectic mix 1:1 → Mutual liquid dissolution → Allows high concentration (2.5% ea)
↑ Tissue blood flow rate
(Note slower in hypovolaemia, hypothermia)
|↑ Area||↑ Patch area|
Flexor skin (e.g. Abdomen) cf. extensor skin (back)
(Note epidermis 0.5cm compared with lung 0.5μm)
|↑ Lipid solubility||e.g. Fentanyl 600x morphine 1x|
|↓ Molecular weight||
The ‘500 Dalton rule’
e.g. Amethocaine 264 Da
e.g. Amethocaine: 40%, highest of all local anaesthetics
e.g. EMLA: Added OH → ↑ PH → ↑ %Unionised lignocaine and prilocaine
|Painless||Risk of inadvertent removal|
|Convenient||Risk of adverse reaction to carrier|
|Not reliant on gut absorption||
Slow and variable onset, long time to peak effect
Risk of dose stacking and toxicity
e.g. >24 hours for fentanyl
|No first pass hepatic metabolism||
Slow offset → Long duration of toxicity
(e.g. >24h for fentanyl)
e.g. GTN near 100% cf. oral near 0%
Constant plasma concentration once at steady state
Quasi IV infusion
Slow offset → Infrequent dosing
e.g. Buprenorphine 7 days