18)Opioid analgesics

Question 1

Opioids

Answer 1

Natural or semi-synthetic compounds

• Produce morphine-like effects
• Opiates is reserved for drugs such as morphine + codeine
• These are obtained from juice of opium poppy

Question 2

Classification

Answer 2

Strong agonists

• Morphine, pethidine, hydromorphone
• Mechanism of morphine ⇢ Full activation of mu receptor site

Partial agonists

• Codeine, oxycodone, hydrocodone
• They combine agonist + antagonist activity on different receptors

Mixed agonist-antagonists

• Buprenorphine, Nalbuphine + Pentazocine

Question 3

Mechanism of Action

Answer 3

They bind to 3 main types of receptor ⇢ mu, kappa, delta

• They’re all G-protein receptors ⇢ inhibit adenylyl cyclase ⇢ ⇣ Intracellular cAMP
• Binding of opioids to receptors ⇢ inhibits opening of Ca²⁺ channels + promotes opening of K⁺ channels

Question 4

Pharmacokinetics

Answer 4

• Well absorbed from mucosal + intramuscular surfaces
• Widely distributed to body tissues

Metabolism:

• Morphine undergoes conjugation w/glucuronic acid ⇢ forms active metabolite Morphine-6-Glucoronide
• Excreted in urine + bile
• Morphine + pethidine ⇢ subject to 1st pass metabolism

Question 5

Pharmacological effects

Answer 5

Analgesia

• Opioids are used to relieve pain of trauma (except head injury), pain of myocardial infarction, pain associated w/cancer

Euphoria

Sedation

Cough suppression

Histamine release

• Morphine causes mast cell degranulation + vasodilation

Question 6

Clinical use

Answer 6

• Pain relief ⇢ morphine, pethidine, fentanyl
• Suppress coughing ⇢ codeine
• Management of opioid addiction
• Neuroleptanalgesia ⇢ mix of Droperidol + Fentanyl ⇢ GA providing analgesia whilst patient is conscious

Question 7

Contrainidications

Answer 7

• Head injury ⇢ morphine can ⇡ intracranial tension
• During pregnancy ⇢ due to crossing placental barrier

Question 8

Side effects

Answer 8

Sedation

Nausea + vomiting

Skin rashes

Respiratory depression

Constipation