Opioid Drugs: General Properties and Mechanisms of Action Flashcards
Regarding endogenous opioids (true or false):
The endogenous opioids are steroids
False. They are peptides derived from precursor proteins.
Regarding endogenous opioids (true or false):
B-endorphin and ACTH are both derived from the same precursor, pro-opiomelanocortin
True
Regarding endogenous opioids (true or false):
The enkephalins are predominantly kappa receptor agonists
False. Enkephalins bind primarily to the mu and delta receptor. The dynorphins bind primarily to the kappa receptor.
Regarding endogenous opioids (true or false):
The dynorphins are involved in appetite regulation and control of the circadian rhythm
True
Regarding endogenous opioids (true or false):
Endorphins are present at high concentrations in the pituitary and hypothalamus
True
What type of receptors are all opioid receptors?
The G proteins linked to the opioid receptors are of the Gi/o type:
-There is inhibition of adenylyl cyclase activity reducing cyclic adenosine monophosphate (cAMP) formation
-There is reduced opening of voltage-gated calcium channels reducing presynaptic neurotransmitter release
-There is increased potassium efflux resulting in hyperpolarisation of the cell
Regarding opioid receptors (true or false):
Opioid receptors are ligand-gated ion channels
False. They are G protein coupled receptors (GPCRs).
Regarding opioid receptors (true or false):
Activation of opioid receptors leads to closure of voltage-gated calcium channels
True
Regarding opioid receptors (true or false):
Activation of opioid receptors results in potassium efflux and hyperpolarisation
True. The Ga subunit inhibits adenylyl cyclase; the By dimer is responsible for increasing potassium conductance and closing voltage-gated calcium channels.
Regarding opioid receptors (true or false):
There is increased production of cyclic adenosine monophosphate (cAMP) production due to activation of adenylyl cyclase
False. Opioids receptors are Gi/o GPCRs.
Regarding opioid receptors (true or false):
Naloxone is an antagonist at all mu, delta and kappa receptors
True
Are opioids weak acids or bases?
Weak bases
Why does alfentanil have a more rapid onset of action compared to fentanyl, despite being less potent?
The pKa of alfentanil is one pH unit below plasma pH, so it is 90% unionised; fentanyl has a pKa of one pH unit above plasma pH, so only 9% is unionised. This is a 10-fold difference and, since alfentanil is less potent, a higher dose of drug is needed. This creates a very large concentration gradient for the unionised drug to cross the blood-brain barrier.
What are the pKas of morphine, fentanyl, alfentanil and remifentanil?
Morphine 8.0
Fentanyl 8.4
Alfentanil 6.5
Remifentanil 7.1
What percentage of morphine, fentanyl, alfentanil and remifentanil is unionised at biological pH?
Morphine 23%
Fentanyl 9%
Alfentanil 90%
Remifentanil 68%
What percentage of morphine, fentanyl, alfentanil and remifentanil is bound to proteins in the plasma?
Morphine 30%
Fentanyl 84%
Alfentanil 90%
Remifentanil 70%
What are the terminal half lives of morphine, fentanyl, alfentanil and remifentanil?
Morphine 3 hours
Fentanyl 3.5 hours
Alfentanil 1.6 hours
Remifentanil 3.5 minutes!
What are the clearance rates of morphine, fentanyl, alfentanil and remifentanil?
Morphine 15-30 ml/min/kg
Fentanyl 0.8-1.0 ml/min/kg
Alfentanil 409 ml/min/kg
Remifentanil 30-40ml/min/kg
What is the volume of distribution of morphine, fentanyl, alfentanil and remifentanil?
Morphine 3-5 L/kg
Fentanyl 3-5 L/kg
Alfentanil 0.4-1.0 L/kg (so much lower than fentanyl due to its lower lipid solubility)
Remifentanil 0.2-0.3 L/kg
What is the relative lipid solubility of fentanyl compared with morphine?
Fentanyl is 580 times more soluble than morphine
What determines the clinical onset time of most drugs used in anaesthetics including opioids?
Ability of the drug to cross the BBB. Therefore, the amount of unbound drug that is unionised at biological pH (dictated by pKa) and the drugs lipid solubility.
What is the oral bioavailability of morphine?
About 25%
Which of the following can be considered as opiates:
A. Fentanyl
B. Codeine
C. Remifentanil
D. Oxycodone
E. Morphine
Morphine, Codeine and Thebaine are examples of opiates. The term opiate refers to all naturally occurring drugs derived from opium.
Regarding opioids (true or false):
They act via G protein-coupled receptors to open voltage-gated calcium channels, increase potassium efflux and reduce production of cAMP
False. Opioids do act through G protein-coupled receptors to close voltage-gated calcium channels, increase potassium efflux and reduce production of cAMP.
