2018B Question 14

Describe the factors determining transdermal uptake of drugs (50%). Briefly outline the advantages and disadvantages of this route.

Examiner Report

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.

Model Answer

Structure:

  • Introduction
  • Factors increasing rate of uptake
  • Logistics: Pros and cons
  • Kinetics: Pros and cons

Introduction

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

Factor Detail
Fick’s Law
↑ C1

e.g. Lignocaine 2% cf. 1%

e.g. EMLA eutectic mix 1:1 → Mutual liquid dissolution → Allows high concentration (2.5% ea)

↓ C2

↑ Tissue blood flow rate

(Note slower in hypovolaemia, hypothermia)

↑ Area ↑ Patch area
↓ Thickness

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

↑ %Unionised

e.g. Amethocaine: 40%, highest of all local anaesthetics

e.g. EMLA: Added OH → ↑ PH → ↑ %Unionised lignocaine and prilocaine

Logistics

Pros Cons
Painless Risk of inadvertent removal
Non-Invasive Often hidden
Convenient Risk of adverse reaction to carrier

Pharmacokinetics

Pros Cons
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)

High bioavailability

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


Last updated 2021-08-23

results matching ""

    No results matching ""