Analgesics and Anti-inflammatories - Opiates (1) Flashcards
What is the main difference between opiates and opioids?
Opiates are naturally-occurring.
Opioids are synthetic.
What type of receptor are the opioid receptors?
G-protein linked.
What is remifentanyl?
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.
Name the three different types of opioid receptors.
Mu, Kappa, Delta.
How many different subtypes does each type of opioid receptor have?
Mu: 2
Delta: 2
Kappa: 3
Mu receptor agonist action causes… ?
Analgesia, Myosis, Euphoria, Respiratory Depression, Anti-tussive, Bradycardia, Itch and urticaria (due to histamine release) Inhibition of GIT motility, Physical Dependence.
Delta receptor activation causes…?
Analgesia (at spinal level), Respiratory depression.
Kappa receptor activation causes…?
Sedation, Miosis, Slowed GIT transit, inhibition of ADH release, Analgesia (at spinal level).
To a lesser degree: Physical dependence, Respiratory depression.
What happens at a molecular level when Mu receptors are activated?
- 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.
What happens at a molecular level when Delta and Kappa receptors are activated?
Only the closure of voltage-gated calcium channels in the pre-synaptic nerve terminal, preventing neurotransmitter release.
What are the symptoms of physical dependence when opioids are withdrawn?
Rhinorrhoea, Lacrimation, Yawning, Chills, Piloerection, Mydriasis, Restlessness, Irritability, Muscle Cramps, Sweating, Vomiting, Diarrhoea.
How is the distribution of fentanyl different to that of morphine?
Fentanyl is highly lipid-soluble, which means that it crosses the BBB faster, and therefore has a more rapid onset of action.
How is morphine metabolised and excreted?
Metabolised in the liver (and some metabolites are active). Excreted in the urine (caution with renal impairment)
Name three full agonists at the Mu receptor, and one partial agonist.
Full: Morphine, Pethidine, Fentanyl.
Partial: Codeine.
Name two partial agonists at the Delta receptor.
Morphine, Codeine.
Name one partial agonist of the Kappa receptor.
Morphine.
How is the distribution of codeine different from that of morphine?
Codeine crosses the BBB more readily.
Describe the metabolism of codeine.
Codeine is metabolized in the liver, and some of the metabolites are active, with higher potency than codeine itself. 10% is metabolized into morphine.
Describe the metabolism of fentanyl.
Metabolized in the liver, with NO active metabolites.
Describe the basic pharmacodynamics and pharmacokinetics of naloxone.
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.
Describe the active metabolites of morphine.
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.
Which opioids are metabolized by the P450 system?
Codeine, oxycodone and hydrocodone are metabolized by the P450 system into more active metabolites.
