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34 Cards in this Set
- Front
- Back
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Opioid Receptors
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G Protein Coupled Receptors
Inhibit adenylyl cyclase Activate K currents post-synaptically Inhibit Ca currents pre-synaptically |
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Opioid Receptor Subtypes
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MOP-analgesia & majority of opioid effects
DOP-analgesia KOP- analgesia or antianalgesia (inhibits MOP) NOP- analgesia effects inconclusive |
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Nociceptive C Fibers
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Unmyelinated
Transmit slow, dull pain Nociceptor Thermoreceptor Mechanoreceptor |
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Nociceptive Ad Fibers
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Transmit sharp, prickly pain
Nociceptor Mechanoreceptor |
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Indirect Pathway of Opioid Action
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Opioid receptors (in the PAG, Reticular formation, median raphe, nucleus raphe magnus, gigantocellular reticular nucleus, rostral ventromedial medulla) are activated and cause inhibition of GABA such that the pain control circuits in the descending pathway are modified and more opioid activity occurs in the SC
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Direct Action of Opioid Receptors
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Direct inhibition of ascending transmission of nociceptive information from the SC dorsal horn
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Opioid agonist effects
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Analgesia
Respiratory Despression Miosis Euphoria Sedation Cough Nausea and Vomiting Vascular (Orthostatic Hypotension) Constipation Histamine release |
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Effects of opioids that exhibit little or no tolerance
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Miosis, Convulsions, Constipation
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Opioids affected by CYP2D6 Polymorphisms
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Codeine, Hydrocodone, and Oxycodone
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Morphine
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Half life: 2 hrs
Hydrophilic so doesn't cross BBB as readily 25% Bioavailability Metabolite Morphine-3-Gluc (90%) has excitatory effects Metabolite Morphine-6-Gluc has inhibitory effects more potent than morphine |
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Meperidine
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Half life: 3 hrs
52% Bioavailability Produces same side effects as morphine at equianalgesic doses except it has less urinary retention and constipation Metabolite normeperidine has half life of 15-20hrs and can cause CNS excitation |
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Methadone
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Half life: 15-40hrs
92% bioavailable 90% bound to plasma proteins Equianalgesic effects to morphine as well as side effects Also blocks NMDA receptors and monoaminergic reuptake Treats chronic pain, opioid addicts and opioid abstinence syndrome |
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Fentanyl
Alfentanil Sufentanil Remifentanil |
Synthetic MOP agonists
Highly lipid soluble Faster onset than morphine and more rapid respiratory depression Potency greater than morphine Remifentanil is metabolized by plasma esterases Fentanyl and Sufentanil- surgical pain mgmt Alfentanil and Remifentanil- short painful procedures |
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Levorphanol
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Synthetic opioid
Comparable to morphine for analgesia Less nausea and vomiting than morphine |
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Heroin
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Given IM is 2x more potent than morphine
Metabolized to 6-MAM and morphine All are lipid soluble Excreted as free and conjugated morphine |
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Codeine
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Partial agonist
50% bioavailable 10% is metabolized to morphine Used for mod. pain and as an antitussive Combined with Aspirin or Acetaminophen to increase analgesia Active metabolites |
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Propoxyphene
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1/2-1/3 as effective as codeine
Combined with acetominophen or aspirin Norpropoxyphene is a toxic metabolite |
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Tramadol
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Synthetic Codeine analog
Weak agonist Also inhibits Ser and NE uptake Less constipation than codeine and no effects on respiration or CV Active metabolite lends risk for CNS overexcitation |
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Opioids with active metabolites
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Morphine
Heroin Codeine Naltrexone |
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Opioids with excitatory/toxic metabolites
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Morphine
Meperidine Propoxyphene Tramadol |
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Nalbuphine
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Agonist at KOP and antagonist of MOP
10mg is equianalgesic to 10mg morphine Psychomimetic at high doeses Analgesia and Resp depression at 30mg Precipitates withdrawl in patients on low opioid doses |
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Pentazocine
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Agonist at KOP, MOP agonist/antagonist
Like Nalbuphine (Ceiling effects, resp. depression) but also has effect on cardiac system Precipitates withdrawl in MOP agonist dependent person Doesn't antagonize morphine induced resp. depression Psychomimetic at high doses |
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Buprenorphine
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MOP partial agonist (High binding affinity but low intrinsic activity)
KOP and DOP antagonist Resp depression is preventable with prior opioid antag Antagonizes resp dep of Fentanyl because of binding affinity As effective as methadone in Detox |
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Butorphanol
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KOP agonist, MOP antagonist/partial agonist
Analgesic doses increase pulmonary arterial pressure and cardiac work |
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Dextromethorphan
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Antitussive
Doesn't act through opioid receptor: an NMDA antagonist Fewer SEs than codeine High doses may cause CNS depression |
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Loperimide
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Meperidine derivative for antidiarrhea
Slows GI motility Doesn't cross BBB No pleasurable effects at high doses |
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Diphenoxylate
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Meperidine derivative only used for treating diarrhea
Typical opioid activity at high doses |
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Opioid Antagonists
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Naloxone
Nalmefene Naltrexone Interact at MOP, KOP and DOP but greatest activity at MOP Produce few effects in people not on agonists |
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Naloxone
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Half life of 1 hr. and almost totally metabolized by liver so given IV
Rapid onset and short duration of action |
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Nalmefene
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Half life 8-10 hrs
More potent than naloxone and 40% bioavailable |
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Naltrexone
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More potent than naloxone
Metabolite 6-naltrexol is a weaker antagonist Efficacy is maintained with oral admin. Approved to treat alcoholism |
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Acute Opioid Toxicity
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Triad of coma, miosis, respiratory depression
Naloxone is treatment of choice for acute toxicity (It's duration of action is shorter than most opioids so monitor continuously) |
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Opioid Antagonists effects for different patients
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Morphine treated patient- reverse effect
Acutely depressed patient- normalized Opioid Dependent patient- Abstinence syndrome induced Opioid naiive person- no effects |
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Contraindications
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Impaired respiratory fx, Hepatic disease, Renal disease, Asthmatics (could give fentanyl), pregnant, head injuries (resp depression causes vasodilation), Patients with decreased blood volume, patients on MAO inhibitors
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