Opioids Flashcards
What is meant by opioids?
A natural or synthetic compound that produce morphine like effects
What are opiate analgesics?
Drugs derived from opium, morphine and codeine
What are the three types of opioid?
Agonist - where they bind and stimulate a receptor- morphine - have efficacy and affinity
Low efficacy opioids - codeine, dihydrocodeine
Antagonists- Where they bind but do not stimulate the receptor - have affinity but no efficacy - morphine & naloxone
How may types of receptor & what they mean
5
MU - analgesic properties are primarily mediated by the mu receptors
Kappa - located in the dorsal horn of spinal cord contribute to the analgesic properties
Epsilon - ????
Delta - Endogenous (self made) opioids interact more selectively with delta receptors in the periphery
Sigma - Non-specific, combined to opioid and other drugs as hallucination drugs
What are all type of Opioid receptors?
G-Protein Coupled Receptors
What are the endogenous opioids?
Dynorphins, Endorphins, Enkephalins, Endomorphins & Nociceptin
Where are opioid receptors located?
Nerve cells of the CNS - medulla located in the brainstem - affects the cough centre, vomiting centre, resp centre, vasomotor (balance) centre
Peripheral Nerve cells & endings
GIT
Urinary bladder
Immune cells
Mechanism of action when an opioid receptor is activated
Activation of an opioid receptor decreases activity of adenyl cyclase, decreasing the production of cAMP. This causes the increased efflux of K+ and decreased influx of Ca2+ and lowers the intracellular concentration of calcium. Overall this decreases the neuronal release of neurotransmitters, opioid receptors are coupled negatively to adenyl cyclase by G proteins
MOA of morphine
Works on kappa receptors in lamina 1 & 2 sometimes (2&3) of substantia gelatinosa of the grey matter of the dorsal horn of the spinal cord
Decreases release of substance P.
What is the role of Substance P?
Substance P modulates pain perception in the spinal cord
What are the actions of Morphine?
Analgesia - loss of pain without the loss of consciousness
Euphoria - Stimulation of the ventral tegmentum. Intense release of both serotonin & dopamine, causes addiction
Resp depression - The sensitivity of the resp center decreases and no longer senses CO2 conc - accumulation and lack of exchange with O2 - cellular mechanical failure.
Depression of cough reflex - cancer pt (with cough) on tramadol for pain - doesn’t need anything as tramadol has antitussive properties
Miosis- Pinpoint pupil (enhanced stimulation of the parasympathetic system)
Emesis - vomiting centre is composed of chemoreceptor trigger zone & emetic center, any trigger to these receptors - vomit
GIT - morphine like drugs are used in treatment of diarrhea - they increase tone of intestinal circular smooth muscle and tone of the anal sphincter. Decrease the intestinal motility.
Produces biliary colic- contraction of the gallbladder and constriction of the biliary sphincter.
Cardiovascular System - no major effect but from the CO2 accumulation vessels dilate and therefore increase the pressure of the CSF which is contraindicated during head trauma
Histamine - release - causes histamine release from mast cells in peripheral tissues - in asthmatics can cause bronchoconstriction - naloxone can reverse this.
Hormonal Actions - Decreases plasma conc of luteinizing hormone - menstrual irregularities
Decreases plasma level of testosterone - sexual impotence
Increases ADH & inhibition of urinary bladder voiding reflex - urinary retention - catheter needed.
Prolongs labour
What are the four therapeutic uses of morphine?
Analgesia
Treatment of Diarrhea
Relief of a cough
Treatment of pulmonary edema - vasodilatory effect
What are the three contraindications of morphine?
Prostatic hypertrophy
Head Injury
Asthma
How is morphine administered?
IM, SC & IV injection
Codeine - Oral
Absorption from GIT is slow and erractic, significant first pass metabolism occurs in the liver
How is morphine distributed?
All body tissues, including fetuses (teratogenic) Only small crosses BBB - morphine is the least lipophilic out of all opioids.
What are highly lipophilic opioids?
Fentanyl, Methadone & Heroin.
How is Morphine metabolised?
Conjugated to glucuronic acid in the liver. These are excreted via urine with small amounts in bile.
DOA - 4-6hrs
Explain tolerance with regards to morphine
Neuroadaption occurs through receptor desensitization causing a reduced drug effect. After certain drug doses no more analgesic with occur and it’ll only be side effects
What are the withdrawal symptoms of Morphine?
Vomiting, chills, seizures, anxiety & insomnia
Methadone is substituted for injected opioids. Has equal potency but less euphoria, longer DOA & milder withdrawal
What is Naloxone and its MOA?
Opioid antagonist - used to reverse respiratory depression of opioid overdose. Within 30 seconds of administration.
Competitive antagonist at kappa, MU & sigma receptors - displaces all receptors bound to opioids.
DOA 60 mins
What is naltrexone and explain its MOA
Acts similarly to naloxone. Longer DOA, LASTS UP TO 48 HRS
Why may a mix of both opioid antagonists be given?
As naloxone has a short half life of 60 to 100 mins, its effect can be reversed however with naltrexone - its half life is at least 48hrs
Both hepatotoxic
