6th lecture - opioids Flashcards
In high doses, narcotic analgesics can cause
general central nervous system depression
another couple terms for narcotic analgesics
Opioids or
opioid receptor agonists
If they are used repeatedly, they cause medicine dependence or drug addiction.
narcotic analgesics can be classified as follows: (2)
Natural opium alkaloids
&
Synthetic analgesic drugs
(not chemically related to opium, but act as opiate receptor agonists)
Nociceptive receptors are
free nerve endings distributed throughout the body, which detect a nociceptive stimulus.
nociceptive = relating to pain
Opiate =
Opioid =
Opiate = a drug derived from opium
Opioid = a drug that is not derived from opium but interacts at the opioid receptor.
Both terms used for both narcotic analgesic subgroups interchangably despite definition difference.
Opioid receptors are located in the
brain,
autonomic nervous system,
gastrointestinal tract,
heart, kidneys, pancreas,
fat cells, lymphocytes,
adrenal glands, other tissues.
Endogenous ligands to opioid receptors (2)
enkephalins and endorphins,
they have a morphine-like effect. They are released as a reaction to pain and stress.
Opioid receptors are denoted with the greek letter..?
“mu”
μ-opioid receptor
Opioid receptor subtypes (2)
There are two subtypes: μ1 and μ2.
In addition, there are delta (δ), kappa (κ), sigma (σ) receptors (significance of sigma recptor is not understood).
non-μ-opioid receptors (3)
delta (δ),
kappa (κ),
sigma (σ) receptors
(significance of sigma recptor is not understood)
Full agonists produce?
Partial agonists produce?
Full agonists produce a dose-dependent increase in effect until maximum stimulation of the receptor is achieved.
Partial agonists produce a dose-dpendent increase in effect, but less than the maximum effect of full agonist.
An antagonist binds to a receptor and
inhibits the binding of agonists and displace previously bound agonists due to the greater receptor affinity of the antagonist.
Which has a greater affinity for opioid receptors - agonists or antagonists?
antagonists
Natural opium alkaloids are categorised into two chemical groups.
Derivatives of phenanthrene (morphine, codeine etc.) that have an analgesic effect.
&
Derivatives of isoquinoline (e.g. papaverine) that have a spasmolytic effect.
Opium is obtained from
poppy.
give examples of Semi-synthetic opioids (min. 4)
Hydromorphone
Buprenorphine
Butorphanol
Apomorphine
Oxymorphone
Ethylmorphine
Nalorphine
(Heroin)
give examples of Completely synthetic analgesic drugs (min. 3)
Fentanyl
Methadone
Trimeperidine, also known as Promedol
(the earliest and mostly studied opioid analgesic)
Piritramide
Estocin
Pentazocine
Completely synthetic analgesic drugs are Not substantially different from
morphine.
They are absorbed poorly if administered orally, do not cause vomiting, do not cause miosis.
The suppressant effects are equally strong,
the euphoric effect is weaker.
Pharmacokinetics of opioids
Lipophilic compounds, are capable of diffusing throughout the body.
are absorbed enterally & parenterally however absorption from the GI tract is slower and less complete.
penetrate the placenta well (unsuitable for pain relief in labour)
P-glycoprotein efflux pump can efflux absorbed drug from CNS back into the vasculature, in part, limiting central effects.
The primary site of effect for opioids?
What type of effects?
the CNS
for analgesia,
antitussive effects
and sedation.
what type of drug is loperamide
μ agonist,
antidiarrheal drug (immodium)
the P-glycoprotein efflux pump transports it back into the vasculature from CNS, limiting its central effects in most animals.
What is the P-g pump?
also known as multidrug resistance protein 1 (MDR1)
the P-glycoprotein efflux pump is a transmembrane unidirectional efflux pump that uses ATP to actively transport xenobiotics out of the cell against their concentration gradients
likely evolved as a defense mechanism against harmful substances.
Name the situation in which deficiency of functional P-g pump is relevant to small animal medicine.
P-g pump is also known as multidrug resistance protein 1 (MDR1)
Certain herding breed dogs (collies, aussies, shelties!) with homozygous mutations in the gene (MDRI) expressing P-g pump have a deficiency of these P-g efflux pumps.
"”ivermectin sensitive“ Collies”
These dogs show significant CNS effects of e.g. loperamide (among others) including heavy sedation.
opioids are metabolised in the liver into
into glucuronides.
Glucuronidation is often involved in drug metabolism.
glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond.
what is glucuronyl transferase?
Glucuronyl transferase is a drug-metabolizing enzyme that is produced and used in the liver.
What species lacks glucuronyl transferase?
Cats lack glucuronyl transferase, but they still rapidly and efficiently eliminate morphine by sulfate conjugation.
nonetheless, lower opioid doses should be used in cats.
Codeine (cough supressant) and synthetic analgesic drugs go through what process in the liver?
they go through demethylation in the liver and the byproduct is morphine (in humans).
in the case of opioids, potency refers to
the capability of attaching to receptors (and not the strength of the analgesic effect)
main therapeutic effect of opioids
Analgesia
name up to 6 Full μ agonists
morphine,
hydromorphone,
fentanyl,
remifentany,
alfentanyl,
methadone