Buprenorphine

Question 1

MOA?

Answer 1

partial mu receptor agonist but with a very high affinity for the receptor
antagonist at kappa receptors - unknown action as a result

Question 2

Main risk of administration?

Answer 2

displacement of other more potent mu receptor agonists resulting in precipitating acute withdrawal or pain crisis
This will typically occur 1 - 4hrs post administration

Question 3

When to give?

Answer 3

1) opioid effects are waning (6 - 12 hrs post short acting opioids or >24hrs post long acting opioids)
2) when in withdrawal state (reverses opiate withdrawal in doses above 4mg)
3) maintenance therapy

Question 4

Methods of administration?

Answer 4

sublingual and IV

Question 5

What form of buprenorphine is used in MATOD?

Answer 5

1) Subutex (buprenorphine alone)

2) Suboxone (buprenorphine and Naloxone)

Question 6

At what dose does the consumption of other opioids have little or no further effect and why?

Answer 6

16mg
All receptors are saturated - so the duration of buprenorphine effect is increased but the receptor is not available for further stimulation

Question 7

What is the half life?

Answer 7

24 - 32hrs

Question 8

time to peak effect?

Answer 8

1 - 4 hrs post sublingual dose

Question 9

duration of action?

Answer 9

12 - 72hrs depending on the dose (the higher the dose the longer the duration of action)

Question 10

bioavailability?

Answer 10

30 - 40%
Variable between individuals and also dosing between acute versus chronic situations.
Has been shown to improve with practice of self administering sublingual strips due to the bioavailability being directly related to the amount of mucosal contact time that is achieved.

Question 11

Pharmokinetics?

Answer 11

• extensive first pass metabolism when oral with the metabolite having minor opioid activity
• hepatically metabolised by CYP450 3A4 (azoles, calcium channel blockers may increase plasma concentrations)
• cleared in bile then faeces and some urine

Question 12

Overdose concerns?

Answer 12

does not continue to depress respiratory drive like methadone does in a dose dependent manner, however is toxic even at low doses if combined with sedatives like alcohol or benzodiazepines

Question 13

side effects?

Answer 13

headaches (resolve after the first few weeks)
sleep disturbance
sweating
constipation
nausea 
reduced libido

Question 14

Benefits over methadone?

Answer 14

less sedating

However some patients prefer the sedating/anti-anxiolytic properties of methadone for co-morbidities eg PTSD

Question 15

Dosage preparations available?

Answer 15

Suboxone 2mg/0.5mg, 8mg/2mg

Subutex 0.4mg, 2mg, 8mg

Question 16

Why does naloxone work in combination with buprenorphine?

Answer 16

Buprenoprhine is a supra-agonist so has higher affinity for the mu receptor than naloxone.
Some fentanyl derivatives are also able to displace naloxone due to being supra-agonists.

Question 17

Disadvantages over Methdone?

Answer 17

clients tend to cycle in and out of treatment more so are then at risk of overdose

Question 18

what does a short withdrawal program look like?

Answer 18

2 - 3 day induction and then tapering dose to 0 over 3 to 14 days

Question 19

How do you skip days on suboxone?

Answer 19

if alternate days for dosing then the dosing needs to be twice the normal 24hr dose. eg. usually has 4mg daily the on days prior to alternate daily dosing they have 8mg or if going to be 2 days skipped then have 12mg

• be careful - if 4hrs after dose they are having overdose effects then reduce the dose or if they get withdrawals before they are due their next dose then dose needs to be increased
• it does not suit all patients

Question 20

initiating dose on first day?

Answer 20

4mg if mild withdrawal
up to 8mg if moderate to severe withdrawal
2mg if low opioid tolerance or significant co-morbidities

Question 21

Do all patients stabilise with suboxone?

Answer 21

No, 30% will require a transfer to Methadone

Question 22

What rate is appropriate to wean off suboxone?

Answer 22

2mg every 2 - 4 weeks