Opoid Analgesics Flashcards
Why is the class of “Opioids” called this name?
They are an entire class of morphine like substances, specifically they are alkaloid of the opium poppy.
What is the difference between spinal analgesia to supraspinal analgesia?
Spinal analgesia raises the pain threshold at the spinal cord level, but the supraspinal alters the brain’s perception of pain.
What are the 3 endogenous opioid peptides in humans?
Endorphins, enkephalins and dynorphans.
What is the function of the mu receptor subtype? Which opioid peptides hit this type of receptor?
Supraspinal and spinal analgesia: causes sedation, euphoria, inhibition of respiration, slowed GI transit (constipation), and modulation of hormone and neurotransmitter release.
Endorphins > enkephalins > dynorphins, in that order of affinity for the receptor.
What is the function of the delta opioid receptor? What is the receptor affinity to opioid peptides?
Both supraspinal and spinal analgesia, and modulation of hormone and neurotransmitter release. Enkephalins > endorphins and dynorphins.
What is the function of the kappa opioid receptor and what is its receptor affinity?
Also analgesia of supraspinal/spinal levels, psychotomimetic effects (dysphoria, opposite of euphoria) and slowed GI transit. Dynorphins has a high affinity to this receptor, endorphins and enkephalins much less so.
First pass metabolism of opioids? Metabolism and excretion?
Extremely high. Metabolites conjugate with glucoronic acid, gets polarized and renally excreted, (small amounts undergo enterohepatic circulation). Drugs would accumulate with renal problems.
What is a major side effect of patients receiving drugs like morphine and meperidine, which have neuroexcitatory active metabolites?
Seizures.
What is the MOA of morphine like opioid agonists?
2 pronged effect: First, the upon activation of the opioid receptor, it will decrease adenyl cyclase activity and will block the opening of the Ca channels, thus the pain neurotransmitters are not released. Secondly, it will open the K+ channels and thereby induce hyperpolarization in the cell.
What kind of receptors are the opioid receptors?
They are G sub i proteins (inhibitory proteins).
Besides the opioid receptors, what else blocks the release of the pain neurotransmitters?
Alpha 2 receptors.
What is the neurotransmitter of the descending interneuron pathway and what does this receptor do?
Descending interneuron is GABA-nergic, when we do not experience pain this interneuron would inhibit the descending pathway, GABA inhibits the descending pathway.
What is the function of opioids on the descending interneuron pathway?
It will disinhibit the GABA, ergo activate the GABA, and since GABA is an inhibitory neurotransmitter this will inhibit the descending pathway and thus no pain from the CNS.
How do opioids induce tolerance in patients? What effects of opioids do people NOT develop resistance to?
Receptor desensitization, internalization, resensitization and downregulation. However, miosis, constipation and convulsant effects not going to get tolerance.
What are signs/symptoms of physical dependance?
Rhinorrhea, lacrimation, yawning, chills, piloerection, hyperventillation, hyperthermia, mydriasis, muscular aches, vomitting, diarrhea, anxiety and hostility.
What are the CNS effects of morphine like opioids?
Analgesia, euphoria, sedation, respiratory depression, cough suppression, miosis, truncal rigidity, n/v, altered temperature regulation.
What are the neuroendocrine effects of morphine like opioids?
Releases ADH, prolactin and somatotropin. Inhibits the release of LH.
What are the peripheral (non CNS related) effects of morphine like opioids?
Bradycardia and hypotension in susceptable pt’s, constipation, biliary and urinary colic, urinary retention, pruritis and utcaria.
What are the immune system effects of opioids?
Can either mess with or improve the immune system depending on context.
Why do opioids cause pruritis (itching) and urticaria (hives)?
NOT an immune HS reaction (in which the IgE would bind to mast cells). Instead it is the opioid agonists binding to the mast cells which causes mast cell degranulation and release of histamine. Histamine can also induce the hypotension, which is another side effect of Opioid agonists.
What are some Tx uses of opioid agonists?
Tx of severe pain acute or chronic (morphine is always given to terminally ill patients), adjunct to anasthesia, cough suppression, diarrhea (because opioids slow GI motility), M.I. (IV morphine is administered, reduce pain reduce sympathetic tone, etc), Dyspnea (but ONLY with patients with pulmonary edema with LV failure), and post op shivering (Meperidine).
If Opioids cause respiratory depression why is it used to treat patients with pulmonary edema with LVF that is suffering from dyspnea?
Similar to MI, IV morphine will decrease anxiety, decrease venous tone (pre-load), decrease peripheral vascular resistance (afterload), thus decrease work of the heart (decreased O2 consumption) and thus relieve ischemia and reduce pain.
State all the adverse effects of Opioid agonists, regarding CNS, lungs, temperature homeostasis, bladder, uterus, skin, gall bladder, eyes, and constitutional health.
CNS behavior changes such as hyperactivity, restlessness, dysphoria, etc, as well as seizures in high doses, respiratory depression (dose related and worse in pt’s with pulmonary disease), miosis, n/v, increased intracranial pressure, orthostatic hypotension, constipation, biliary colic (constriction of sphincter of oddi leading to increased pressure in bile duct/gallbladder), urinary retention, prolonged labor, itching and hives.
Why are opioids absolutely Contraindicated in patients that already have increased intracranial pressure due to trauma or other causes?
Opioids will increase intracranial pressure as its effect: decreased respiration means increased CO2 –> cerebral vasodilation –> increased cerebral blood flow –> Increased cranial pressure.
Why can’t we give opioids in women that are in labor?
All but one opioid will prolong labor.
What effects do opioids have on the urinary system?
Inhibition of the urinary voiding reflex, increased external sphincter tone and increased bladder volume all leads to urinary retention and urinary colic exacerbation.
When will opioid dosage adjustment be necessary?
In patients with renal or hepatic insufficiency.
What are 3 instances where opioids are absolutely contraindicated?
In cases of head injuries (increased intracranial pressure), patients with pulmonary issues and patients with asthma (because opioid induced mast cell activation may lead to bronchoconstriction which will exacerbate asthma).
Opioid use and preggo?
Opioids crosses the placenta so when the baby is born it will show withdrawal symptoms.
What are some DDI’s with opioids? What’s special about opioids, particularly Meperidine, and MAOIs?
Anything that messes with the CNS such as sedatives-hypnotics, antipsychotics and TCAs, MAOI’s (because they have been shown to have high incidence of hyperpyrexic coma and HTN, relative CI for all opioids, ABSOLUTE CI for Meperedine –> Serotonin syndrome).
Morphine gets glucoronidated into two active metabolites, what are they and what are their effects?
They are M3G and M6G. M3G has no analgesic effects but is neuroexcitatory (GABA/glycine system), so if enough accumulates it can induce seizures particularly in the elderly. M6G has 4-6x the potency of morphine in terms of analagesic activity.
General PK of morphine in terms of bioavailibility and half life?
High first pass metabolism thus low bioavailibility and short half life (less than 2 hrs).
What is the chemistry of Codeine aka methylmorphine?
It is a prodrug of morphine, however only 10% is converted, the rest gets smashed through the high first pass metabolism.
How is codeine metabolized?
Codeine –> CYP 2D6 –> Morphine, and then morphine gets glucuronidated into M3G and M6G.
