DD5

Why different pains need different PK?

• Need to have a quicker onset (high Cmax and low Tmax) for Breakthrough Pain

• To have sustained blood levels (controlled or sustained release) over days from chronic pain

• Formation of different metabolites

What other features may affect the RA for pain management?

Avoid 1st pass

Non invasive delivery

What patient’s may affect RA?

Convenience, age, dexterity, support

Describe the characteristics of IR opioids?

for acute pain & breakthrough cancer pain

• Dosed every 2 to 6 hours

• Usually take 30min-1h/2h for onset

Describe SR/CR opioids?

For chronic pain

already been receiving opioids and developed some tolerance

dosed every 12 or 24 hours continuously

Provides more stable blood level PK profile

Must closely follow patient information instructions

Larger doses per unit are more prone to abuse

why is fentanyl dosed in micro grams?

More potent that other opioids

How long is the sustained plasma level in IR formulations?

Steady state plasma level ~ 1 day

How long is the sustained plasma level in SR formulations?

Steady state plasma level within 2-4 days

What PK profile are drug abusers looking for?

large concentration (high Cmax) in the shortest time (low Tmax)

increasing Cmax and decreasing Tmax correlate with the pharmacodynamic property of euphoria

IR formulations offer the easiest dosage form from which to recover the opioid.

Describe physical barrier ADF strategies?

Tablet that includes solids that become gelatinous upon adding water or extraction

May also limit abuse if it deemed too difficult to over come delivery system

Describe aversion ADF strategies?

Utilizes a noxious component added to the powder formulation

Abusers get unwanted adverse effect

Describe Agonist/Antagonist ADF strategies?

morphine sulphate surrounding a central core of sequestered naltrexone hydrochloride in a ratio of 100:4 (morphine/naltrexone)

If tablets are tampered with release naltrexone

Describe pro-drug ADF strategies?

Prodrugs are biologically inactive substances that are metabolized in vivo to their active form

GI biotransformation is the rate-limiting step

Describe the characteristics of fentanyl?

very narrow therapeutic index

1 -2 ng/mL = effective Cp

Mutiple systems on the market

Fluxes on patches 12.5 to 100 μg/hr

Up to 3 days application

most lipophilic of the clinically available IR opioids

Quickly crosses cellular barriers, providing broad tissue distribution and rapid onset of action

What are the newer generics of fentanyl patches formulation?

Matrix systems instead of resivior

Easier to make

Harder to abuse and extract drug

What flux does buprenorphine have?

5-75 μg/hour

How can patches be abused?

• The gel is removed and boiled to extract the opioid.

• The liquid is either injected or drunk.

• Patches are chewed to release 3 days of equivalent dose for mucosal delivery.

• Multiple patches are placed on the skin

Define breakthrough pain?

Transient increases in pain in a cancer patient who has stable, persistent pain treated with opioids

What do patients with high levels of background pain have?

• Background pain

• Peak pain

• Depression

• Anxiety

• Functional impairment

• Negative impact in quality of life

What are the most common drugs used for break through pain?

morphine, oxycodone, hydromorphone and fentanyl

What are the 3 forms of IR fentanyl?

• Sublingual lozenge

• Tablet – either buccal or sublingual

• Nasal spray

Describe the advantages of Buccal/Sublingual administration?

Coinvent/easy to use

• large surface area

• high permeability → NO statum corneum

• high vascularity

• uniform temperature

• High bioavailability, due to avoidance of 1stpass metabolism

What patients must have controlled before starting Intranasal Fentanyl Spray (INFS)?

background persistent pain is controlled by use of chronic opioid therapy

No more than 4 episodes of breakthrough pain in a day

How to work out dose of initial Intranasal Fentanyl Spray (INFS)?

Give one dose and wait 10 minutes to see patients is cured form that and add and taken away doses to control pain