Opioids

Question 1

Morphine

Answer 1

-strong agonist to moo receptors with complete activation and minimal for delta and kappa
Absorption 
-oral morphine used generally but people that are more severe you give IV since their gut mobility may be bad
-significant first pass effect with 40% oral bioavailability
Distribution
-rapidly enters all tissues including foetal
-struggles to cros blood-brain barrier
Metabolism
-happens in liver
-morphine + glucuronic acid
Elimination
-renal 
Action
-analgesia and euphoria 
Side effects
-resp depression 
-emer is
-GI tract
-CVS
-miosis
-histamine release: caution in asthmatics

Question 2

Fentanyl

Answer 2

-strong agonist
-100x more potent to morphine and higher affinity to moo receptors
-less histamine release, sedation and constipation than morphine
Absorption
-IV, epidural
-80-100% bioavailability
Distribution
-highly lipophilic, highly protein bound
-high level of CNS crossing so greater CNS effect
Metabolism
-hepatic via CYP3A4
Elimination
-half life 6 minutes
-really excreted
Actions
-analgesia
-anaesthetic (usually given with other drugs for surgery)
Side effects
-resp depression
-constipation
-vomiting

Question 3

Codeine

Answer 3

-moderate agonist
-less potent than morphine
Absorption
-oral or subcutaneous
Metabolism
-broken down into morphine via CYP2D6
-CYP2D6 inhibited by Fluoxetine and other SSRIs
-variable expression: some people have high levels of CYP2D6 while others have low
Elimination
-glucoronidation of morphine and renal excretion
Action
-mild-moderate analgesia
-cough depressant
Side effects
-constipation so give laxatives to combat this
-resp depression which is worse in kids

Question 4

Burprenorphine

Answer 4

-mixed agonist/antagonist
-compared to morphine: higher affinity for moo receptor, low Kd, long duration of action, partial agonist so lower efficacy, antagonist at K receptors
Absorption
-transdermal, Buccal, sublingual
Distribution
-very lipophilic
Metabolism
-hepatic via CYP3A4
-then gluoronidation before biliary excretion
Elimination
-biliary>renal
-safe in renal impairment
-half life 37 hours
Actions
-moderate to severe pain
-opioid addiction treatment
Side effects
-resp depression
-low BP
-nausea
-dizziness

Question 5

Naloxone

Answer 5

-main antagonist
-compared to morphine: affinity moo>delta>K, greater affinity than morphine but less than buprenorphine
Absorption
-IV because very low oral bioavailability due to most gone in first pass
-rapid onset of action
Distribution
-rapid distribution because lipophilic
Metabolism
-hepatic metabolism
-renally excreted
Elimination
-duration of action is 30-60min
Action
-competitive antagonism of opioid
-used as a reverse agent for overdose
Side effects
-short half life
-slow infusion
-will act quickly and wear off, leaving patient still in overdose so must give drug slowly and gradually

Question 6

What are the considerations and contraindications of opioids?

Answer 6

Considerations

• manual labourers/drivers
• elderly
• bedbound
• asthmatics
• biliary tract obstruction
• resp diseases
• renal impairment
• pregnancy

Contraindications

• hepatic failure
• acute resp distress
• comatose
• head injuries
• raised ICP
• will cloud the underlying cause of problem, because with or without drug patient is drowsy