Opioid Pharmacotherapies

Question 1

How do opioids produce reward?

Answer 1

By binding to GABAergic interneurons which release dopamine.

Results in euphoria and analgesia.

Question 2

Why does the IV route have a greater euphoria effect that the oral route?

Answer 2

The faster the influx of drug into the blood, the greater the euphoria.

Question 3

What are the 3 classes of opioids and give examples of each.

Answer 3

Natural opioids: morphine and codeine

Semi-synthetic opioids: heroin and oxycodone

Purely synthetic opioids: fentanyl, methadone and buprenorphine

Question 4

Give examples of drugs that are controlled by the misuse of drugs act, 1971.

Answer 4

• diacetylmorphine (heroin)
• morphine
• fentanyl

Question 5

Which opioid drugs do the BNF list?

Answer 5

• codeine phosphate
• morphine salts
• diamorphine hydrochloride
• dihydrocodeine tartrate
• oxycodone hydrochloride
• pavaveretum
• methadone
• buprenorphine
• fentanyl

Question 6

Name the 7 properties of opioids

PREECAS

Answer 6

• CNS depressant
• pinned pupils
• respiratory depressant
• emesis
• euphoria
• analgesic
• sedation

Question 7

Metabolic pathway for codeine

Answer 7

codeine —> norcodeine —> codeine glucuronide

Question 8

Metabolic pathway for heroin

Answer 8

Diacetylmorphine —> 6-monoacetylmorphine

Question 9

Metabolic pathway for morphine

Answer 9

morphine —> morphine-3-glucoronide + morphine- 6- glucoronide + normorphine —> normorphine glucuronide

Question 10

Metabolic pathway for dihydrocodeine

Answer 10

codeine –> nordihydromorphine + nordihydrocodeine

Question 11

Heroin: diacetylmorphine

Answer 11

• is a prodrug that is metabolised to its active metabolites in vivo- morphine and 6-monoacetylmorphine (6-MAM)
• so heroin itself does not bind to opiate receptors
• used by IV, skin popping, smoking, snorting or chasing
• tolerance and dependence

Question 12

Why does heroin never appear in urine?

Answer 12

The drug has a half life of 3 minutes

Prodrug itself does not bring about its pharmaceutical effect

Question 13

What is the half - life of morphine?

Answer 13

2-4 hours

Low bioavailability when given orally

short acting drug

Question 14

Activity of morphine-3-glucuronide and morphine- 6 glucuronide?

Answer 14

morphine-3- glucuronide has no analgesic activity

morphine-6 glucuronide is able to penetrate the BBB and is pharmacologically active

Question 15

When is morphine clearance decreased and analgesic effects increased ?

Answer 15

in elderly patients who have decreased renal function

Question 16

What is the half life of methadone?

Answer 16

24 hours

orally effective

Question 17

Effects of methadone

Answer 17

• constipation
• sweating
• respiratory depression

Question 18

In what condition is the excretion of methadone much slower?

Answer 18

in chronic severe liver disease/ liver cirrhosis

• not viral hepatitis

Therefore, give lower doses for patients commencing methadone with liver cirrhosis

Question 19

Dose of methadone in acute viral hepatitis?

Answer 19

Dosing as normal

Question 20

When may clearance of methadone slow down?

Answer 20

• in chronic active hepatitis

- obstructive jaundice

Question 21

Buprenorphine

Answer 21

• synthetic opioid
• partial agonsit at the mu receptor
• quick onset of action 30-60 minutes
• peak effects 1-4 hours
• high first pass metabolism so often prescribed sublingually
• available in 0.4, 2 and 8mg sublingual tablets
• standard therapeutic dose: 8mg-24mg per day SUBUTEX
• IV, IM or SC injection: TEMGESIC 0.3mg in 1 ampolues

Question 22

Half- life of buprenorphine?

Answer 22

5 hours

Question 23

Fentanyl

Answer 23

• drug metabolised to norfentanyl within 72 hours after iV dose
• 75% dose is excreted in the urine

Question 24

what is the mean elimination half life or fentanyl IV, transdermal patches and lozenges?

Answer 24

IV: 2 to 4 hours

transdermal patch: 17 hours

lozenge: 7 hours

Question 25

at what levels of fentanyl and norfentanyl in urine indicates use?

Answer 25

fentanyl: >0.2ng/mL
norfentanyl: 1ng/mL

Question 26

What is oxycodone synthesised from?

What is the most commonly found modified release prepa

Answer 26

thebaine- a derivative of opium

oxycontin is the most commonly found MR preparation

Question 27

Effects on the mother of opioid use during pregnancy

may be lifestyle choices rather than opioid use

Answer 27

• poor nourishnment- vitamin deficiencies, iron deficiency anaemia, folic acid deficiency anaemia
• medical complications from IV use- dirty, blunt needles cause abcesses, ulcers, thrombophlebitis, hepatitis, HIV
• sexually irresponsible behaviour- gonorrhoea, syphillis, herpes, HIV infection

smoking illicit drugs is safer

oral consumption is safer

Question 28

Effects of opioid use in pregnancy on the babe?

Answer 28

• low birth weight
• prematurity
• still birth
• neonatal abstinence syndrome
• sudden infant death syndrome

Question 29

what does the magnitiude of the drug’s effect on the foetus depend on?

Answer 29

• stage of gestation
• drug dosage, potency, route
• duration of exposure
• maternal or fetal genotype
• concomitantly taken drugs
• environmental factors