Analgesics and Anti-inflammatories - Opiates (1)

Question 1

What is the main difference between opiates and opioids?

Answer 1

Opiates are naturally-occurring.

Opioids are synthetic.

Question 2

What type of receptor are the opioid receptors?

Answer 2

G-protein linked.

Question 3

What is remifentanyl?

Answer 3

A pure Mu-agonist, with a very rapid onset and offset, used in general anaesthesia. It is rapidly hydrolyzed by plasma esterases, into a metabolite that has almost zero activity, which is excreted in the urine.

Question 4

Name the three different types of opioid receptors.

Answer 4

Mu, Kappa, Delta.

Question 5

How many different subtypes does each type of opioid receptor have?

Answer 5

Mu: 2
Delta: 2
Kappa: 3

Question 6

Mu receptor agonist action causes… ?

Answer 6

Analgesia, Myosis, Euphoria, Respiratory Depression, Anti-tussive, Bradycardia, Itch and urticaria (due to histamine release) Inhibition of GIT motility, Physical Dependence.

Question 7

Delta receptor activation causes…?

Answer 7

Analgesia (at spinal level), Respiratory depression.

Question 8

Kappa receptor activation causes…?

Answer 8

Sedation, Miosis, Slowed GIT transit, inhibition of ADH release, Analgesia (at spinal level).
To a lesser degree: Physical dependence, Respiratory depression.

Question 9

What happens at a molecular level when Mu receptors are activated?

Answer 9

• Closure of voltage-gated calcium channels in the pre-synaptic nerve terminal, preventing neurotransmitter release
• Opening of potassium channels on post-synaptic membranes, causing hyperpolarisation.

Question 10

What happens at a molecular level when Delta and Kappa receptors are activated?

Answer 10

Only the closure of voltage-gated calcium channels in the pre-synaptic nerve terminal, preventing neurotransmitter release.

Question 11

What are the symptoms of physical dependence when opioids are withdrawn?

Answer 11

Rhinorrhoea, Lacrimation, Yawning, Chills, Piloerection, Mydriasis, Restlessness, Irritability, Muscle Cramps, Sweating, Vomiting, Diarrhoea.

Question 12

How is the distribution of fentanyl different to that of morphine?

Answer 12

Fentanyl is highly lipid-soluble, which means that it crosses the BBB faster, and therefore has a more rapid onset of action.

Question 13

How is morphine metabolised and excreted?

Answer 13

Metabolised in the liver (and some metabolites are active). Excreted in the urine (caution with renal impairment)

Question 14

Name three full agonists at the Mu receptor, and one partial agonist.

Answer 14

Full: Morphine, Pethidine, Fentanyl.
Partial: Codeine.

Question 15

Name two partial agonists at the Delta receptor.

Answer 15

Morphine, Codeine.

Question 16

Name one partial agonist of the Kappa receptor.

Answer 16

Morphine.

Question 17

How is the distribution of codeine different from that of morphine?

Answer 17

Codeine crosses the BBB more readily.

Question 18

Describe the metabolism of codeine.

Answer 18

Codeine is metabolized in the liver, and some of the metabolites are active, with higher potency than codeine itself. 10% is metabolized into morphine.

Question 19

Describe the metabolism of fentanyl.

Answer 19

Metabolized in the liver, with NO active metabolites.

Question 20

Describe the basic pharmacodynamics and pharmacokinetics of naloxone.

Answer 20

Naloxone is an antagonist at opioid receptors, particularly at Mu receptors. It can be given IV. It results in reversal of opioid-induced effects within 1-3 minutes. Its duration of action is only about 20 minutes.

Question 21

Describe the active metabolites of morphine.

Answer 21

10% of morphine is metabolised into Morphine-6-glucuronide, which has 6 times the potency of morphine itself. Another active metabolite of morphine is hydromorphone.

Question 22

Which opioids are metabolized by the P450 system?

Answer 22

Codeine, oxycodone and hydrocodone are metabolized by the P450 system into more active metabolites.