Lecture 21 - Pharmacology Of Opioids

Question 1

Opioids - morhine like drugs

Answer 1

• endogenous substances: endorphins, enkephalines
• morphine, oxygocone, methadone, codeine, buprenorphine
• all work through GPCR

Question 2

Prescribing opiates: considerations

Answer 2

• tolerance: increased doce/concentration required for a given effect with chronic administration. This works through progressive internalisation of GPCR receptors
• withdrawal: physical : tachycardia, treamor, sweats
• dependence: psychological: craving, drug seeking behavior

Question 3

Action of opiates

Answer 3

• Analgesia for acute and chronic pain, not very effective for neuropathic pain
• euphoria: sense of contentment, well being
• sedation
• respiratory depression: decreased sensitivity to raised PaCO2
• dyspnoea; very effective

Question 4

Aciton of opioates continued

Answer 4

• GI tract: increase sphincter tone: treat diarrhoea. Can cause constipation as a side effect
• Pupillary constriction because of receptors in oculomotor nucleus

Question 5

Morphine kinetics

Answer 5

• bioavilibility 20-30%
• T1/2 short: 2-3 hours
• sustained release form

Question 6

Morphine metabolism

Answer 6

Conjugated in phase II with glucuronic acid

• M6G and M3G
• M6G has twixe the potenxy of morphine when given systematically but less effective at crossing blood brain barrier
• M3G is possibly responsible for adverse CNS effect such as dysphoris

Question 7

Excretion of morphine metabolites

Answer 7

• M6G and M3G are excreted renally
• dose reduction required if impaired renal function
• magnitude of contributin of M6G to analgesia not established in ptients when morphine is given

Question 8

Morphine route of administration

Answer 8

• oral
• subcutaneous: repeated injections/ infusions/ osmotic mini-pump
• intrathecal or epidural: tendency for rostral spread in CSF, may affect C4/5 roots

Question 9

Codeine

Answer 9

• 3-methyl morphine
• higher oral bioavailablility
• inactive until converted to morphine
• less potent than morphine
• less euphoria
• constipation
• cough suppression
  Converted to morphone with CYP2D6 (only 8% of it)
• caucasians have a higher proportion of poor metabolisers

Question 10

Oxycodone

Answer 10

• not a prodrug
• binds directly to opiate recpetors
• good oral bioavailability (80%, comapred to 30% for morphine)
• nearly full agonist
• use orally
• short acting: endone (4-5 houris)
• sustained release preparation: Oxycontine -> 12 hours duration

Question 11

Oxycodone: how to release constipation

Answer 11

• oral administration + naloxone
• oxycodone is absorbed and has the systemic analgesic effects
• oxycodone in bowel causes constipation
• naloxone prevents abuse
• systemic effects of naloxone unlikely

Question 12

Fentanyl

Answer 12

• synthetic opioid
• mainly u agonist
• 60-80% more potent than morphoine
• high lipid solubility
• rapid transit of blood brain barrier
• short half life: used in anesthesia
• patient controlled analgesia
• transdermal patches

Question 13

Buprenorphine

Answer 13

• strong analgesis for short term use
• less effect han morhine on respiratory depression and CNS Depression
• partial agonist
• long half life
• available as injection or sublingual
• long half life

Question 14

Suboxone

Answer 14

• buprenorphine + naloxone
• sublingual film or tablet
• used for treating opiate dependence
• buprenorphine dissociates slowly from u receptors in CNS
• if taken IV (illegal): naloxone blocks opiate receptors, causes unpleasant symptoms of opiate withdrawal: deters IV use
• naloxone very low bioavailability if taken sublingual

Question 15

Tramadol

Answer 15

• analgesia due to u agonist and inhibition of neuronal noradrenaline and serotonin uptake
• side effects: less constipation, less respiratory depression less addiction potential
• less analgesia

Question 16

MEthadone

Answer 16

• super analgesis
• cimilar actions to morphine
• little euphoria (less potential for abuse)
• once daily dosing
• commonest agent used in oral maintenance program for addicts

Question 17

Tolerance and pain management

Answer 17

• patient on metadone daily for previous addiction
• acute pain
• methadone long half life so not optimal for acute pain management
• better to use short acting opioids in higher dose

Question 18

Opiate overdose

Answer 18

• on target: respiratory depression

- off target; propoxyphene, pethidine, tramadol

Question 19

Problems with nalozone

Answer 19

• acute opioid withdrawal: hypertension, cardiac arrythmias, sudden death
• confusion, violence, self discharge
• does not reverse some drug effect: seizures and cardiotoxity
• short duration of effect