Pharmacology Of Opioids Flashcards
What are the 3 types of opioid receptors and what do they do?
Mu Rs - analgesia, respiratory depression, dependence, bradycardia
Delta Rs - analgesia and reducing gastric motility
Kappa Rs - analgesia and dysphoria
Define desensitization, tolerance, dependence and addiction
D - receptor gets phosphorylated and the G-protein uncouples from the opioid receptor. Internalisation of the OR receptors.
T - decrease in effectiveness of opioid agonist with repeated administration. Effectiveness returns after a few weeks of stopping
D - Physiological state of adaptation which is shown by state of withdrawal. Withdrawal is seen at organ level: agitation, diarrhoea, pupilliary dilation
A - Behavioural pattern resulting in compulsive use of agonist
What is the analgesic effect of opioids?
Pain intensity is reduced or totally absent. Clinically therapeutic doses are needed to reduce both affective and somatomotor/autonomic repsonses
What are the respiratory effects of opioids?
Mu Rs depress breathing rate, tidal exchange, rhythm generation. Depression of excitability of brainstem chemosensory neurons.
What are sedation and neuroendocrine effects?
S - causes drowsiness and cognitive impairment. Tolerance develops
N - Decrease release of many hormones OR agonist, may also cause stimulation of HPA axis. LH and FSH in females.
What about miotic, seizure and cough suppressant?
Miotic - contraction of the pupil. Causes pinprick pupils.
Seizure - occur because the inhibution of inhibitory interneurons by OR agonists
Cough suppressants - morphine, codeine and related opioids depress the cough reflex
What are the effects on the cardiovascular system?
Decreases blood pressure and decrease heart rate
What about GIT effects?
It can cause constipation, increase epigastric distress and increase gastric emptying time
Effects on the skin and the immune system and the ureter?
Skin - may cause flushing and dilation of cutaneous blood vessels. May also cause pruritus because of release of histamine
Immune system - moderately immunosuppressive and increased infections have been seen
Ureter - inhibit the urine voiding reflex
What is morphine metabolised to?
Morphine-6-glucuronide
What must be considered when the eGFR is less than 10-50ml/min?
Give 75% of the dose if the eGFR is less than 10-50ml/min
What is the dose of tramadol?
50-100mg 4-6 hourly
What is special about tramadol?
Acts centrally and is used to inhibit re-uptake of noradrenaline and serotonin. Also used combination
What are some adverse effects of tramadol?
Seizures - can precipitate seizures
Avoid in patients who are on SSRIs, MAOIs and drugs that lowers the seizure threshold
What is the central analgesic MOA of opioids?
GABA release is reduced from PAG regions, 5-HT and enkephalin neurons are stimulated. They connect with the dorsal horn, reducing excitability and thus reduce nociceptive transmission from the the periphery to the thalamus.
