Opiods! Flashcards
what is chronic pain
longer than 6 m
nociceptor vs neuropathic pain
nociceptor- pain from tissue injury may cause somatic pain/ visceral pain (generalized/dull)
Neuropathic- Pain that is usually described as burning/shooting/tingling/pins/needles
What are the mediators to fever
Lipopolysaccharides
What is released in the imflammatory process (5)
Protaglandins 5-HT Leukotriens Histamines Bradykinin
What plant is the opiote derived from
Papaver Somniferum
What are the phenanthrene alkaloids (3) and effects
Morpine, codeine, thebaine
Algesic, euphoric, central nervous system depressent
What is the benzylisoquinoline alkaloid and effects
Papaverine
-smooth mm relaxant causing dilation of peripheral arterioles
What are the 3 major receptoes for opiods
Mu
Kappa (more hallucinagens than mu)
Delta
What type of channel are the opiod receptors
G pro coupled
-activates pottasium currents or decreased voltage gated calcium current or inhibition of adenyly cyclase
Where are the opiod receptors mainly found
spinal cord and brain in association w neurons that modulate pain perceptopn
What does the mu receptor do compared to the delta and kappa
Mu- most of the algesia
Delta/Kappa- Contribute to analgesia at the spinal level
3 main effects on the cell of opiotes
Hyperpolarize cell to decrease firing ( open K channels)
Close Ca channels (decreased nt release)
Endorphone autoreceptors decrease release of cells nts
Main major effects of opiots
Analgesia- better pain tolerance Sedation Miosis (constricted pupils) Respiratory depresion (decreasing sensitivity of the respiratory center in medulla to CO2) Antitissive (anti cough) \+ neusa/vommiting
How does opiotes affect the GIT
- billiary and bladder sphinchters contract
- depressed peristalsis–> constipation
What does opiotes do to histamine
causes release
–causes peripheral vessels to dialate, decrease blood pressure causing hypotennsion
What is poikilothermia and what is it associated w
opiote use
- inhibit thermoregulatory mechanism in the hypothalamus ( unable to maintain a constant body temp)
- -excessive heat loss
What does widthdawl from opiotes cause
restlessness anxiety vomiting diarrhea pupil dialation chills
What % of orla dose of opiods reach systemic circulation and how much larger should it be than an iv dose
15-30%
morphine oral dose should be 5-6x higher
What opiotes are less susseptible to first pass metabolism
Codeine and oxycodone
At plasma PH what happens to opiotes and how does it affect distribution
is ionized therefore limiting CNS distribution and absorption in GIT
How quick is teh onset of opiods after IM injection
10-20 mins
How is mophine metabolized in liver, half life and metabolism
Highly metabolized in the liver via hydroxylation + glucurondation (phase I + II)
-half life is 1.5-4 hrs
90% is excreted in urine, 10% in bile
What is the metabolite of opium and characteristics
morphine 6b glucuronide- longer half life and is more potent
What receptor does morphine work on
full mu antagonist ( produces both supraspinal and spinal level analgesia)
What happens when codeine enters teh bodu
10-15% of codeine is converted to morphine by CYP2D6 (5-10% of ppl don’t have this and wont work)
Heroine compared to morphine
Prodrug for mophine
*very lipid solube due to rapid mvmt acrss BBB
Oxycodone bioavailability/potency vs morphine
better bioavailability (no first pass effect) twice as potent as morphine
Meperidine vs mophine
less potent than morphine and shorter half life
What is the toxic metabolite of meperidine and who should it not be given to
Has toxic metabolite normeperidine which is excreted renally (should not be given to those with renal probs or are taking monoamine oxidase inhibitors)
How much more potent is fetanyl compared to morphone
80x
Mathadone compared to morphine
similar potency to morphone but has higher bioavailability and longer half life- used for withdrawal tx
What is hydromorphone and action timeline
semi synthetic derivative of morphine
-onset of action of about 15 mins duration 5 hrs
What is tramadol a analogue of and what does it do at the synaptic cleft level
synthetic analoauge of codeine
produces an increased level of serotonin and noradrenaline in synaptic clefs and decreases excitability of spinal pathways
what do combonation therapies overcome
ceiling effect
