2018B14 Describe the factors determining transdermal uptake of drugs (50%).
Briefly outline the advantages and disadvantages of this route.

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

Fick’s law of diffusion

↑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 slow if hypovolaemia, hypothermia)

↑Area

↑Patch area

↓Thickness

Flexor skin (e.g. abdomen) cf. extensor skin (back)

(note epidermis 0.5centimetre cf. lung 0.5micrometre)

↑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

Pros

Cons

Painless

Risk of inadvertent removal

Non-invasive

Often hidden

Convenient

Risk of adverse reaction to carrier

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