Opoids Flashcards
What is an opiate?
An ALKALOID derived from the popy, Papaver somniferum. (E.g opiaTES are from natural sources)
What is the tertiary nitrogen needed for? What is the significance of the side chain?
To anchor the opoid onto the receptor. Otherwise will have no analgesic effect. The longer the side chain, the more likely to be antagonistice.g. naloxone.
What is the significance of the hydroxyl group at position 3?
Required for actual binding. Codein has a methylated hyrdorxyol group here so is actually a prodrug for morphine.
What is the significance of the hydroxyl group at position 6?
Affect liphophilicty. Heroin has acetylated hydroxyl groups at both 3 and 6- 10x lipophiliity than morphine.
What are the exceptions to the rule in terms of opiod structure? What are they used?
Methadone- no hydroxyl groups at 3 and 6. Fenatnyl- has a tertiary carbon, not a quaternary one. Most potent.
Fentanyl is very potent and has rapid metabolism- rarely used clinically. Methadone has a slower metabolism= longer half life= useful to wean patients off morphine.
Describe two aspects of opiod pharmacokinetics
1) They are alkaline (pKa>8) so are ionised in the stomach. Some absorption in the SI but generally poorly absorbed via enteral route (+ extensive 1st pass metab) 2) More lipid soluble= more potentent so Meth/Fent>Heroin> Morphine.
Describe the metabolism of morphine
10% (extensive 1st pass) converted to an ACTIVE metabolite morphine-6-glucuronide.
Describe the metabolism of codeine (a prodrug) and morphine (exception)
Codeine: SLOW activation by O-dealkylation by CYP2D6. 5-10%. FAST deactivation by CYP3A4.
Morphine metabolized by uridine 5 diphosphate glucoronosyltransferase.
What type of receptors do endorphins act on and where are they found?
Mu and delta. Mu found in the amygdala, NA, thalamus and PAG . Influence pain, mood and CVS
What type of receptors do enkephalins act on and where are they found?
Delta recpetors. Found in the amygdala and NA and cortex. Influence pain, mood and CVS.
What do dynorphins act on and where are they found?
Kappa receptors, found in the hypothalamus.
Describe the 3 ways in which opiods act as depressants cellularly.
Hyperpolarisation (increase K efflux), inhibits Ca influx (common with alcohol) , decrease adenylate cyclase.
Describe effects of opoids
Euphoria, anti-tussive, analgesia. depression of respiration, N+V, miosis and GI effects.
Describe pain perception (green)
Pain detected in PERIPHARY, trsnamitted to DORSAL HORN (mu, kappa), to THALAMUS (mu) to CORTEX (mu, delta). Inputs from hyopthalamus (kappa) and locus coerulus (sympa, inhibitory)
Describe pain tolerance (PINK)
Side chain from dorsal horn to the NUCLEUS RETICULARIS PARAGIGANTOCEULLARIS (NRPG) (mu, delta). Side chain from thalamus to PERIAQUADECTAL GREY (mu, kappa). Both of these feed to the NUCLEUS RAPHE MANGNUS (delta) which has a an inhibitory effect on pain felt in the dorsal horn (also influcned by substantia gelatinosa)
