Opiods Flashcards
Hyperalgesia
High intensity stimuli are perceived as more painful than usual
Major known peripheral sensitizing effectors: inflammatory mediators bradykinin, protons, histamine, prostaglandins E2 & nerve growth factor
Prostaglandins E2 act on EP receptors (g-protein) phosphorylating voltage gated Na+ channels- decrease in its activation threshold & increase in current when open
Allodynia
Normally innocuous stimuli are perceived as painful
Strong opioids
Fentanyl
Morphine
Meperidine
Methadone
Weak opioids
Codeine
Mixed agonist/antagonist opioids
Pentazocine
Opioid antagonist
Naloxone
Opioids MOA
Analgesics- decrease release of nociceptive peptides & inhibit post synaptic activation- alter emotional perceptions of pain in the cerebrocortex by decreasing pain perception, increasing euphoria and sleep
Act on g-protein coupled receptors mu, delta & kappa present in nervous system
Opioid receptor effect:
-Reduce presynaptic calcium conductance impeding presynaptic neurotransmitter release
-Opens post synaptic potassium channels causing potassium efflux/hyper polarization with resulting decreased conductance of neuronal responses
-Reduce adenylyl Cyclases activity effect unknown
Opioid effects (brain, brainstem & spine)
Brain- alter mood, produce sedation, reduce emotional reaction to pain
Brainstem- can produce nausea, vomiting & respiratory depression//increase activity of cells that provide descending inhibitory innervation to the spinal cord//antitussive- reduce cough reflex at cough center in medulla
Spinal cord- inhibit synaptic vesicle release from primary afferents, hyper polarize post synaptic neurons, and reduce primary efferent activation
Opioid adverse effects
Medullary effects- tolerance develops- decreased respiration through stimulation of mu2 receptors decreasing response to CO2 levels in blood//vomiting by stimulating the chemoreceptor trigger zone (CTZ)
Miosis (pinpoint pupils)- tolerance does not develop- disinhibition of Edinger-Westphal nucleus increasing parasympathetic discharge causing pupil constriction (diagnostic for opioid abuse)
Constipation- tolerance does not develop- increased sphincter tone, decreased gastric motility
Biliary colic- cause biliary spasm- the sphincter of Oddi constricts and the pressure in the common bile duct increases; fluid pressure may increase in gallbladder- symptoms may vary from epigastric distress to typically biliary colic
Histamine release- pruritis, hypotension, bronchoconstriction (especially in asthmatics)
Physical dependence- develops only after several weeks of chronic treatment
Opioid withdrawal symptoms
Chills, fever, sweating, yawning, diarrhea, nausea, vomiting, dizziness, hypertension
Timeline: 6-12hrs. after last dose
Duration: 3-5 days after last dose, craving and anxiety may last 6-12 months
Opioid contraindications
Hepatic disease- can cause increased bioavailability of drug
Renal disease- can cause accumulation of metabolites
Pulmonary disease- histamine release for drug can exacerbate causing bronchoconstriction in asthmatics
Head trauma- can increase intracranial pressure//miotic effect of opioids will block pupillary reflex necessary to diagnose concussion
Opioid drug interactions
Other sedatives (alcohol, barbiturates)- can increase sedation and decrease respiration
Fentanyl
Available for transdermal administration via a patch
Greater intensity of morphine (80-100x) but shorter duration of action
Particularly contraindicated for cardiac patients due to drug-induced bradycardia & hypotension
Morphine
Prototypical opioid and the one all others are compared
Morphine administration & elimination
Parenterally, orally, rectally
Metabolized in liver (undergoes extensive first pass metabolism upon oral administration)
Methadone
Longer duration and better oral bioavailability than morphine
Meperidine
Less antitussive and constipating effects than morphine- good for pulmonary disease
Metabolized to normeperidine which has proconvulsant and hallucinogenic effects (particularly contraindicated for patients w/ seizures or with renal or liver disease)
Pentazocine
Mixed agonist (kappa)/ antagonist (mu)
Potent opioid effect in naive patients but precipitates withdrawal
Administered orally with naloxone to prevent abuse (naloxone inactivated orally but will block effects of drug when administered IV)
Pentazocine adverse effects
Psychotomimetic (hallucinations)
Hypertension & bradycardia
Naloxone
Opioid receptor antagonist blocking all receptors and their effects
Precipitates withdrawal (no effect in non addicted users)
Used for overdose- fast onset IV but fast offset as well- administer until opioid is eliminated
Used to reverse respiratory depression in neonates of mothers who used opioids
Naloxone administration
Small doses (0.4 to 0.8mg) given IM or IV- promptly reversing the effects of mu receptor agonists Duration of action is short and often must be given repeatedly or by continuous infusion
Codeine
Metabolized to morphine
Used with nonopioids
Decrease pain by two different mechanisms
Used for antitussive effects
