Flashcards in Lecture 9 & 10 - Opioids Deck (48):
What are the CNS effects of morphine (2)
Elevates pain threshold, decreases brain awareness of pain
What are some of the side effects or morphine? (6)
Depression of the respiratory centre, constipation, nausea, pupil constriction, euphoria, tolerance, dependence
How many rings does morphine have and what shape are they in?
5 rings and T-shaped structure
Is morphine acidic or basic?
A functionally weak base
What does morphine exist as at physiological pH
What are the four types of opioid receptors?
MOR, KOR, DOR and ORL1 (opioid-like receptors)
Which receptor does morphine bind most strongly to?
MOR instead of DOR and KOR
What type of receptor is the opioid receptor
Where does morphine bind to in the MOR?
A cavity at the extracellular edge of the receptor
What is the difference between opium and morphine?
Opium is an extract obtained form the opium poppy and contained more than 20 alkaloids, morphine is the main active alkaloid in opium.
Why can't morphine poorly absorbed in the gut?
It is polar
Why is octanol used to calculate the partition coefficient?
It has a long hydrocarbon tail so it mimics
the amphiphilic nature of lipid membranes
What logP guarantees oral absorption?
What percentage of morphine is unionised at pH 7.4
What is morphine's pKA
What is the difference between morphine and normorphine
Normorphine has a amine group added instead of the methyl so it has increase ionisation
Which molecule has the highest lipophilicity?
Which molecule has the highest relative analgesic activity?
6-acetylmorphine (an active metabolite of heroin)
Heroin is a prodrug true or false
What groups have been replaced in morphine to make heroin?
The 3-6 hydroxyl groups have been replaced with acetyl groups
What is codeine?
A 3-methylether of morphine
Is codeine a prodrug
Is codeine found in opium
How is codeine metabolised in the liver?
What re the 3 conjugations of morphine in the liver?
Which of the glucuronide conjugations of morphine is active?
Which OH group is important for morphine activity
The 3 hydroxyl
Which confirmation of the target does an agonist stabilise?
The active conformation
What are the three key groups for morphine activity?
1. 3-hydroxyl forms hydrogen bonds
2. Benzene rings have Van der waals interactions
3. The N-methyl group can become charged and form ionic bonds
What is the 'message' responsible for?
Which parts are responsible for the message in morphine?
The charged amine and phenolic group
What is the 'address' responsible for?
Target selectivity (MOR vs KOR)
What is responsible for the address portion of morphine?
The variable hydrophobic portion
How is oxycodone generated?
An an extra OH group at position 14
At which alkyl group does agonistic activity of morphine return?
Pentyl and hexyl
What is one of the most potent N-alkylation substitutions?
Why is naltrexone such an effective antagonist?
It has a cycylpropane group at the N-alkylation
Which is more rapid, naloxone or naltrexone?
Why are fentanyl and sufentanil more potent than morphine?
1. Both are highly lipophilic due to a phenylethyl on N
2. Fentanyl has a phenetyl group attached to the nitrogen ring, sufentanil has a bioisosteric replacement with thiophene
How is etorphine different from morphine and how does this influence potency?
Etorphine is synthesised from thebaine and is conformationall restricted
Which rings have been removed in pethidine and norpethidine?
B, C and D
What is the consequence of removing B, C and D
No 'address' concept, they bind in different manners
What are met and leu enkphalins
Pentapeptides with a preference for MOR and DOR
Dynorphin vs endorphine selectivity for receptors
KOR vs MOR and DOR
Which groups are essential for the activity of met-enkephalin
Tyrosine phenol and amino groups
How do you remove the activity of met-enkephalin (2)
Replace the tyrosine
Inactivate it using peptidase
What provides the message in met-enkephalin?