Narcotic Analgesics (opioids)

Question 1

Describe the classification of opioids based on pharmacodynamics and the receptors they act on
Give some examples

Answer 1

Agonists: high affinity for MOP(e.g. Morphine, codeine, methadone)

Partial agonists: dont produce full response at rceptors (MOP) e.g. Buprenorphine)

Agonist/antagonists: e.g. Nalbuphile - antagonist at MOP, partial agonost at KOP, agonist at DOP = analgesia without euphoric effect

Antagonist: e.g. Naloxone - binds mainly to MOP and can reverse effects of antagonists (i.e. Treat overdose)

Question 2

Describe the pharmacokinetics of morphine

Answer 2

Not very lipid soluble : low oral bavailibility

Metabolism involved glucuronidation (bypass phase 1)

Any hepatic or renal failure increases t1/2

Question 3

Describe the pharmacokinetics of diamorphine

Answer 3

Very lipid soluble so readily crosses BBB and diffuses into tossues

A prodrug: activated by converting to morphine

So administered IV and can allow large amounts to act on CNS

Question 4

Describe the pharmacokinetics of methadone

Answer 4

High bioavailibility but also highly protein bound

Longer t1/2 so better for treatment of chronic pain

Question 5

Describe the pharmacokinetics of codeine

Answer 5

A prodrug: metabolised (de-methylated) to morphine to become activated

Some caucasians have a polymorphism of the demethylating CYP enzyme, making the drug less effective

Question 6

What are the ADRs of opioids

Answer 6

Respiratory depression: MOP-mediated action on CO2 sensitivity

Euphoria

Constipation (MOP receptors also in gut plexus)

Hypotension and bronchoconstriction (smooth musc relaxation)

Vomiting and diarrhoea (stimulatory effect in medulla)

Confusin, miosis (pupil constriction), psychosis, coma

Antitussive

Requires monitoring

Question 7

What is naloxone used for

Describe a relevant element of its pharmacokinetics

Answer 7

An opioid antagonist
Used to treat opioid toxicity, reverse respiratory depression and treat opioid dependence

Has a shorter t1/2 than morphine so may need repeated doses: needs monitoring

Question 8

Describe the pain pathway and where opioids can act/how

Answer 8

Nociceptor
Afferent pain fibres 
Dorsal root of spinal cord
Interneurones of SG
thalamus and primary sensory cortex

Opioids can act on many aspects of the pathway to limits transmission of pain responses (inhibit release of substance P from nerve terminals)
Can act peripherally, centrally and on limbic system