Dr. David Lyness
Synthetic phenylpyperidine opioid - strong μ-receptor agonist
100x more potent than morphine and 500x more lipid soluble.
ANALGESIC IV 1-2 mcg/kg will work within 2-3 minutes and last about 30 mins.
Analgesic in acute and chronic pain, attenuates laryngeal reflex, pre-medication for theatre
Can be used to augment epidural (25-100mcg) and spinal (10-25mcg) anaesthesia.
IV, PO, SL, BUCCAL, IM, SC, TRANSDERMAL, LOLLIPOP
Used extensively in cardiac anaesthesia due to CVS stability (50-100mcg/kg)
In high doses, attenuates laryngeal & metabolic stress response
- Lipid solubility = rapidly and extensively distributed in the body (Vd of 4 L/kg).
- Small doses (1-2 microgram/kg), plasma and CNS concentration fall below an effective level during rapid distribution phase.
- Following prolonged administration or with high doses, its duration of action is significantly prolonged.
- With longer admin, the distribution phase is complete while the plasma concentration is still high.
- Recovery then depends on its slow elimination from the body (terminal half life 3.5 hours).
- Fentanyl is predominantly metabolised in the liver to norfentanyl which is inactive.
- The metabolite is excreted in the urine over few days.
CONTEXT SENSITIVE HALF-LIFE
- TD route avoids first pass metabolism and large variations in plasma drug concentrations.
- Stratum corneum is the greatest barrier to transdermal transport.
- Drugs suitable for TD patches have a low molecular weight and high lipid solubility.
- Two types available: reservoir and matrix systems (most moving to matrix if possible...)
- Opioid patches are frequently utilized in chronic malignant and non-malignant pain management.
- Four constant rates: 25, 50, 75, and 100 mcg/h for a period of 72 h.
- A depot of fentanyl forms in the upper skin layers and serum fentanyl conc increase gradually, generally levelling off between 12 and 24h.
- Steady-state in serum is reached after 24 h and maintained as long as the patch is renewed.
- Concs tend to be higher in the first 24 h and decrease on the 2nd and 3rd day (decreasing conc gradient between patch and skin).
- Delivery is not affected by local blood supply, but an increase in body temperature up to 40c can increase absorption rate by about 30%
- Fentanyl is metabolized by the P450 cytochrome enzyme system - cimetidine and isoniazid will affect this.
- The elimination half-life after patch removal is 13–22 h, this is probably due to slow release of fentanyl from the skin depot.
- Due to gradual onset, another analgesic is likely to be necessary in the first 12 h.
NEW: The fentanyl patient-controlled transdermal system (PCTS) is approximately the size of a credit card and is worn on the upper arm or chest. Iontophoresis is utilized to deliver fixed drug boluses.
The lollipop comes in 200 micrograms, 400 micrograms, 600 micrograms, 800 micrograms,
1.2 mg and 1.6 mg with a bioavailability of ~50%
It produces respiratory depression in dose-dependent manner.
Large dose = sedation is profound and unconsciousness may occur, muscular rigidity of the chest wall may affect ventilation.