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72 Cards in this Set
- Front
- Back
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What are the two major metabolites of Morphine? |
Morphine-3-glucuronide (90%)- excitatory; Morphine-6-6 Glucuronide- longer t1/2, active metabolite
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What is the standard of comparison for analgesic strength?
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Morphine
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What are the side effects of Meperidine (Demerol)?
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~produces as much sedation, respiratory depression, and euphoria as morphine ~Causes less urinary retention and constipation, no miosis ~IV can increase HR |
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What is the toxic metabolite of Meperidine?
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Normeperidine- cause CNS excitation; eliminated by kidney and liver; It can accumulate in renal
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What happens if a person on MAOIs is given meperidine?
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Severe excitatory rxn (convulsion, coma, rigidity) b/c it blocks serotonin reuptake
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Describe the duration and bioavailability of Methadone?
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It is a long lasting Mu agonist with an extended duration of action; It has high oral efficacy (90% bioavailability)
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What is Methadone used to treat?
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Opioid addicts, chronic pain, opioid abstinence syndromes
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Which scenario would you NOT want to use Methadone?
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DON’T use in labor- increase risk of neonatal depression
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How are Fentanyl, sufentanil & alfentanil metabolized?
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Liver
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How is Remifentanil metabolized?
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Plasma esterases
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Arrange from most potent to least potent: Morphine, alfentanil, sulfentanil, remifentanil, fentanyl
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Sufentanil>fentanyl=remifentanil>alfentanil>morphine
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Why do you see respiratory depression faster with Fentanyl & congeners than with morphine?
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They are highly lipid soluble (get to CNS fast) and thus have a fast onset
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How does Levorphanol compare to morphine in terms of side effects (N&V)
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produces less N&V than morphine
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Describe the metabolism of Heroin (diacetylmorphine)
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Rapidly hydrolyzed by tissue esterase -> 6-MAM -> hydrolyzed -> morphine; ~also, heroin & 6-MAM are lipid soluble -> cross BBB more rapidly than morphine
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Name some Strong MOR agonists
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Morphine, hydromorphone, oxymorphone, Meperidine, Methadone, Fentanyl, sufentanil, alfentanil, remifentanil, Levophanol, Heroin
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Name some mild-Moderate MOR agonists
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Codein, oxycodone, dihydrocodeine, hydrocodone, Tramadol, Diphenoxylate, loperamide
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Briefly describe Codeine's metabolism
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10% converted to morphine by CYP450 2D6 (10% pt don’t have this enzyme)
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What is Codeine used for and what is it often combined with?
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Used for Moderate pain, and as an antitussive; combined with aspirin or acetomenophen to increase analgesia
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What are the most common opiods used to treat cough?
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Codeine,Hydrocodone
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What is OxyContin?
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controlled released formula of Oxycodone; used to treat moderate to severe pain for extended time
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What is the most popular prescription drug in the US and what is it used for?
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Vicodin= hydrocodone with acetominophen; for chronic pain
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What kind of toxicity can Propoxyphene (Darvon) induce?
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Toxic metabolite (norpropoxyphene) has a long t1/2; it produces cardiotoxicity, pulmonary edema, and convulsions
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What is the MOA of Tramadol (Ultraam)?
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It is a weak opioid receptor agonist (Mu & delta); it inhibits uptake of NE & serotonin; it is also an Alpha2-adrenergic receptor agonist
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How does Tramadol compare to morphine in terms of Side effects?
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Risk of CNS excitatory rxn; less respiratory depression, constipation, urinary retention
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What is Diphenoxylate (Lomotil) used for?
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Treat diarrhea
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How does Loperamide work?
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It's a Meperidine derivative that acts on intestinal muscle to slow GI motility
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Which Opioids have active opioid metabolites?
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Morphine, Heroin, Codeine & congeners
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Which Opioids have "excitatory/toxic" metabolites?
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Morphine, Meperidine, Propoxyphene, Tramadol
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Which Opioids/metabolites alter NMDA/monoamine activity?
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Meperidine, Methadone, Tramadol |
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What is the triad of Acute Opioid Toxicity?
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Sutuporous/coma, Pupillar Miosis, Depressed respiration (also see decr body temp & convulsions)
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What drug class is Nalbuphine? |
Mixed Agonist-antagonist (strong KOR agonist, competitive MOR antagonist)
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What drug class is Pentazocine (Talwin)?
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Mixed Agonist-antagonist (KOR Agonist, weak MOR antag or partial MOR agonist)
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What happens as you give higher and higher doses of Pentazocine or Nalbuphine?
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Ceiling effect- higher doses have progressively smaller effect
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What drug class is Butorphanol (Stadol)?
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Mixed Agonist-Antagonist (KOR agonist, competitive MOR antagonist or partial agonist)
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Where is Butorphanol metabolized?
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Extensive first pass metabolism in liver
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What is Butorphanol used for?
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For acute pain relief (greater analgesia in women than men)
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What drug class is Buprenorphine (Buprenex)?
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Mixed Agonist-Antagonist (partial MOR agonist, KOR & DOR antagonist)
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Describe special characteristics of Buprenorphine that make it more potent than morphine?
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High affinity binding to Mu receptor & slow dissociation from Mu receptor; highly lipophilic so cross BBB easily
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What is a major contraindication for Buprenorphine? |
Shouldn’t be use in LABOR
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What do naloxone, Nalmefene and Naltrexne interact with? What does it have the most affinity to?
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MOR, DOR, KOR; highest affnity for MOR
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What drug class are Naloxone, Nalmefene, and Naltrexone?
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Pure Opioid Antagonists
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Does tolerance develop with Opioid Antagonists? |
No; & no recognizable withdrawal syndrom after prolonged admin
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Who would you give an Opioid Antagonist to?
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Morphine treated pt (reverse agonist effect); Acutely depressed/OD pt (normalized), Normal opioid dependent person (induce transient explosive abstinence syndrome) Normal opioid naiive person
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Where are Naloxone, Nalmefene metabolized?
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Almost completely metabolized by liver
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What is the bioavailability of Naltrexone and what is it used for?
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100% bioavailability; used to treat dependence (alcoholism)
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What is Naloxone used for?
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It is the treatment of choice for acute opioid toxicity
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What are some contraindications for giving Opioids?
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Pt w/impaired resp functl hepatic disease, renal disease, asthmatics (histamine release), pregnant women, head injuries, elderly (risk for dru-drug interaction)
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What is the "opioid sparing strategy'?
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opioids should be combined with other analgesic agents (NSAIDS, acetominophen) to minimize opioid dose and SE
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Which Opioid Receptors are responsible for analgesics?
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MOR, DOR, KOR
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How does MOR compare to the rest?
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Responsible for most of analgesic effects, and also for major side effects
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What ligands bind to MOR?
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B-endorphin, endomorphin
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What ligands bind to KOR?
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Dynorphins
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What lignds bind to DOR?
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Enkephalins, dynorphins
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Which Ligands bind to NOR?
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Nociceptin, orphanin FQ2, nocistatin
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What is the general structure of Opioid Receptors?
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Seven transmembrane GPCRs; couple to Gi/G0
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How to Opioid Analgesics work?
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Gi/G0= inhibit cAMP (adenylate cyclase); inhibit Ca currents -> decr NT release; activate K current-> hyperpolarize neuron
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Name the two components of pain. Do opioid analgesics alleviate them?
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Sensory & affective (emotional) components; yes they alleviate both aspect
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How do Opioid Analgesics affect Spinal action?
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Inhibit transmission of nociceptive infor from dorsal horn of spinl cord
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How do Opioid Analgesics affect Supraspinal action? |
Reduce GABA release-> indirectly activating descending inhbitory pathways from midbrain |
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Does tolerance develop in regards to Miosis and Convulsions?
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No tolerance doesn’t develop
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When is Truncal Rigidity most apparent?
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When there is rapid administration of high does of lipid soluble opioids (fentanyl & congeners)
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Describe Normal dose vs chronic dose effects of body temperature.
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Normal dose temp falls (hypothermia); chronic high dose, temp may rise
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What are some effects that Opiods may have on the Circulatory system?
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Peripheral vasodilation-> reduced peripheral resistance -> orthostatic hypotension
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How do opioids cause constipation?
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All MOR analgesics inhibit GI motility; increase water absorption; do not develop significant tolerance
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How do Opioids affect the Bladder?
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Increased contration -> inhibits voiding reflex-> urinary rentention
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How do Opioids affect the Uterus?
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Reduce tone & contractions -> prolong labor
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What do you see in marked tolerance?
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Analgesia, sedation, respiratory depression
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What do you see in little or no tolerance to Opioids?
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miosis, convulsions, constipation
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What is cross tolerance?
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Tolerance to opioid also have tolerance to opioid targeting same receptor
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Physical dependence vs Addiction
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Physical dependence (changes in homeostasis); Addiction (behavioral pattern where you seek drugs)
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What is abstinence syndrome and what do you see?
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Withdrawal from opioids; effects are opposite (vomiting, diarrhea, anxiety, hyperthermia)
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What is an antagonist precipitate withdrawal? |
explosive abstinence syndrome when you give an opioid antagonist to an opioid dependent person |
