Pain medications Flashcards
Definition of pain
unpleasant sensory and emotional experience associated with actual/potential tissue damage
Analgesia
absence of pain in response to stimulation which would normally be painful
Narcotics
drugs that produce sleep
Opiates
drugs derived from opium
Opioids
drugs that bind to opioid receptors
Mu1 receptor
Morphine
supraspinal analgesia
High density in the brain
Mu2 receptor
morphine
respiratory depression
high density in respiratory centre of the brainstem
Delta receptors
Enkephalins
spinal analgesia
high density in spinal cord - use for epidural
Kappa receptor
Dynorphin A
spinal analgesia
sedation
NOP (ORL1) receptors
non-opioid
opioid-receptor-like
Nociceptin/orphanin FQ binds
action not fully understood
Opioid receptor structures
7 transmembrane segments (G-protein) K+ and Ca2+ channels opioid binding --> conformational change K+ channel opens --> hyperpolarization Ca channel closes in presynaptic membranes --> block conductance
Opioid sites of action
brain
brainstem
spinal cord
primary afferent neurons
medullary respiratory centre –> could lead to death
medullary chemoceptor zone –> activation triggers vomiting
Gut
opioid action in GI
slows down contractile frequency
paralyzes gut
constipation
Opioid MOA
Postsynaptic: hyperpolarization by opening of K+ channels (inhibitory)
Presynaptic: reduction of excitatory transmitter release (glutamate, peptides, tachykinin) by closing of calcium channels (inhibitory)
Activation of inhibitory enkephalin interneurons in dorsal horn of spinal cord
Activation of inhibitory descending pathways: endogenous analgesic mechanism (built in opioids)
Endogenous opioid peptide examples
beta-endorphin
Leu-enkephalin, met-enkephalin
Dynorphin
Endogenous opioid peptide characteristics
Mimic most effects of morphine
Antagonized by naloxene
Produce tolerance and physical dependence
Participate in endogenous control mechanisms
Modulate nociceptive transmission
May be responsible for placebo effect
Phenanthrene examples
Morphine Hydromorphone Diacetylmorphine (heroin) Codeine Oxycodone Nalbuphine Naloxone
Phenylheptylamine example
Methadone
Benzomorphan example
Pentazocine
Phenylpiperidine examples
Fentanyl
Sufentanil
Ramifentanil
Meperidine
Morphinians examples
Levorphanol
Pure opioid agonists
Morphine fentanyl Codeine Hydromorphone Oxycodone Meperidine Methadone
Opioid agonist-antagonists
Nalbuphine
Pentazocine
Opioid partial agonists
Buprenorphine
Dosing of opioids
Most drugs used clinically are pure agonists
Different oral bioavailability
Codeine 12x less potent than morphine parenterally
Fentanyl 100x more potent than morphine parenterally
Agonist-antagonist decrease respiratory depression (agonist at kappa, antagonist at mu)
Absorption of opioids
Most absorbed readily
Absorption of morphine
increased hepatic first-pass, decreased oral bioavailability (25%)
Absorption of codeine
increased oral bioavailability (60%)
Absorption of heroin
increased lipid solubility –> BBB penetration
Metabolism of morphine
hepatically converted to morphine-6-glucuronide (active) and morphine-3-glucuronide (excitatory and toxic at higher concentrations, myoclonic seizures)
Metabolism of meperidine
hepatic conversion to normeperidine (excitatory and toxic)
Heroine/Codeine metabolism
converted to morphine
Remifentanil metabolism
rapidly hydrolyzed by nonspecific esterases
useful for continuous, easily adjustable iv infusion
Morphine excretion
90% as glucuronides (urine), 10% unchanged (bile, feces)
Central effects of morphine
analgesia hyperalgesia (at high doses) cough suppression euphoria (also dysphoria) sedation respiratory depression Nausea and vomiting Pruritis Miosis Truncal rigidity Convulsions
Peripheral effects of morphine
constipation
urinary retention
constriction of sphincter of Oddi (increased biliary colic)
Histamine release (direct mast cell degranulation; particularly morphine)
bradycardia (no other significant direct effects on the heart)
hypotension due to v/d
Indications of morphine
analgesia for acute pain (mod to severe), cancer pain, anesthesia
Cough suppression - codeine, dextromethorphan
Antidiarrheal: loperamide, diphenoxylate
Acute pulmonary edema: iv morphine for pulmonary vasodilation
Opioid tolerance
Begins with first opioid dose
no tolerance to miosis or constipation
cross-tolerance among opioids
Opioid dependence
Occurrence of withdrawal symptoms (physical)
and/or craving (psychological)
Opioid addiction
dependence accompanied by abuse and drug-seeking behaviour
All opioids carry abuse potential
Naloxene/naltrexone MOA
antagonists at mu/delta/kappa receptors
almost no effects when given in the absence of agonists
rapid reversal of agonist effects
no tolerance
potential to precipitate withdrawal symptoms in dependent patients
Opioid OD presentation
clinical triad:
coma
miosis
respiratory depression
Opioid OD tx
general measures - ABCs, 100% O2
Specific: naloxene iv
CI and cautions of opioids
Respiratory disease (COPD, OSA)
Drug interactions: meperidine+ MAOi –> hyperpyrexic coma
Opioids + sedatives/ethanol –> high CNS depression
Pregnancy - physical dependence of fetus
Use of pure agonists with agonist-antagonists: less analgesia, withdrawal
