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136 Cards in this Set
- Front
- Back
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4 types of opioids
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1. Opiates (straight from opium)
2. Semisynthetics (derived from opiates) 3. Synthetics 4. Endogenous Opioid Peptides |
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Who are the Opiates?
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Morphine
Codeine Thebaine |
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Who are the semisynthetics?
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Hydromorphine
Buphrenorphine Oxycodone others |
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Who are the Synthetics?
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Meperidine
Tramadol Methadone others |
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Who are the Endogenous Opioid Peptides?
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Enkephalins
Endorphins Dynorphins others |
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What is the opioid motif?
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Its the common Tyr-Gly-Gly-Phe backbone of Endogenous Opioids
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What happens when we make synthetic opioids that change the motif?
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they bind to different receptors
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What are all Opioid Receptors?
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G-protein coupled
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Mechanism of these G-protein coupled receptors?
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Inhibit adenylate cyclase
Activate K currents Suppress Ca currents |
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Opioid Receptor subtypes?
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MOP (mu)
DOP (delta) KOP (kappa) NOP (new kid) |
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Roles of the Receptor subtypes
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MOP-analgesia
DOP-analgesia KOP-analgesia or antianalgesia NOP-still workin on it |
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What is unique about NOP binding?
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Unlike the other 3, NOP doesn't bind conventional opioid ligands
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Types of Nociceptive Fibers?
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C-Fibers
A-delta Fibers |
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C vs A-delta
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C: unmyelinated so slow dull pain
A-delta: myelinated, so sharp, prickly pain |
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Things all nociceptive fibers have in common?
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slow conduction velocity
Polymodal (signal lots of noxious stimuli) |
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How do Opioid Receptor Activation affect Neural Transmission?
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PRESYNAPTICALLY by decreasing NT release (Ca suppression)
POSTSYNAPTICALLY by decreasing neuronal activity (K activation-->hyperpolarization) |
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How do Opioid Receptor Activation affect Pain Transmission?
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Stop the Glutamate (NT) release at the Dorsal Horn
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What are the Ascending Pain Pathways?
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Spinothalamic
Spinoreticular Spinomesencephalic |
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Descending Pain Pathways come from where to modulate pain?
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CTX (ant cingulate)
Amygdala Hypothalamus Periaqueductal Gray Rostral Ventromedial Medulla (raphe and reticular) |
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What is the Direct action of Opioids on Pain Transmission?
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They stop the transmission from Nociceptor Fibers to Ascending Pathways
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What is the Indirect action of Opioids on Pain Transmission?
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Normally there is inhibition by GABA of (endogenous?) opioids on pain transmission. The indirect action of opioids is to turn off GABA's inhibition
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What is the difference between Spinal Action and Supraspinal Action?
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Spinal is the direct action which shuts off ascending pain transmission
Supraspinal is the indirect action which shuts off pain modulation coming down the descending pathways |
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Where else does the supraspinal action take place? why?
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In the forebrain knock out the emotional side of the pain
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What are the Opioid Agonist Effects in the CNS?
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Analgesia
Resp Depression** Miosis Euphoria Sedation** Cough N&V** Myocardium Vascular Constipation** Histamine Release |
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What happens to the miosis caused by opioids if asphyxia occurs?
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Pupils will dilate
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Effect of opioids on coughing?
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Depress the cough reflex
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When does N&V normally occur w/ opioids?
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SubCu injection b/c of direct stimulation of medulla
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When does Truncal Rigidity occur with opioids?
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rapid administration of a high dose (think surgery)
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What's up with opioids and the cardiovascular system?
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They help relieve ischemia after an MI.
They can also cause orthostatic hypotension |
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What can happen with the histamine release opioids trigger?
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asthma attack
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What is a good way to slow the build up of tolerance?
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small doses over long intervals
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What is each drugs' rate of tolerance dependent upon?
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Half Life
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Which effects of opioids don't exhibit tolerance?
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Miosis
Convulsions Constipation |
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What the crap is cross tolerance?
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it means if i'm tolerant to one opioid i'll be somewhat tolerant to another one too...but its not complete so you can/should still rotate them
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What is dependence?
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Complex Changes in Homeostasis
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which opioids exhibit tolerance and dependence?
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ALL OF THEM
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How does opioid excess affect our organs?
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Opioids exert NO end organ effects
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Sx's of Opioid withdrawal?
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chills
vomiting hyperthermia muscle aches diarrhea anxiety hostility |
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What are two pharmacokinetic factors that will predict level of withdrawal?
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Half Life
Full or Partial Agonist |
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how does half life change things?
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longer half life = less withdrawal (methadone)
short 1/2 life = more withdrawal (heroin) |
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Which has worse withdrawal, full or partial agonist?
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FULL
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What is the discrepancy between resolution of physcial sx's vs psychological ones?
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Physical Sx's gone in months
Psychological could take years |
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What is Antagonist Precipitated Withdrawal?
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Its a transient (1hr) and explosive (onset 3min) withdrawal thanks to the administration of an opioid antagonist
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Where are opioids metabolized?
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LIVER
except for heroin and remifentanil via tissue/plasma esterases |
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Where are opioids excreted?
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pee or poo
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Which liver enzyme metabolizes opioids?
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CYP2D6
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What must be taken into account with CYP2D6?
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polymorphism alter the metabolism of opioids like codeine, hyrdocodone, and oxycodone
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3 broad categories of Opioids?
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MOP Receptor Agonists
Mixed Receptor Actions Antagonists |
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Types of MOP Receptor Agonists?
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Strong Agonists
Mild-Moderate Agonists |
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Who are the strong MOP Agonists?
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Morphine and its congeners
Meperidine Methadone Fentanyl and its congeners Levorphanol Heroin |
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Who are the mild to moderate MOP agonists?
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Codeine and congeners
Propoxyphene Tramadol Diphenoxylate Loperamide |
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MORPHINE
half life? |
short
2hr |
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MORPHINE
bioavailability after oral? |
bad
25% |
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MORPHINE
SE? |
Histamine Release
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MORPHINE
metabolism? |
Morphine 3 Glucuronide (90%)
Morphine 6 Glucuronide (10%) |
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What's up w/ Morphine 3 and 6?
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3 doesn't do much but get excreted
6 is twice as potent as regular morphine with a longer half life (2.5-5hr) |
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MEPERIDINE (demerol)
half life? |
not much better
3hr |
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MEPERIDINE
oral bioavailability? |
better
52% |
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MEPERIDINE
vs morphine |
equianalgesic and less pee retention and constipation
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MEPERIDINE
metabolites? |
Normeperidine
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What's up with Normeperidine?
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It can cause CNS excitation (tremors, seizures, etc)
Half Life is 15-20hr so it can build up too So not recommended for chronic pain |
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When can Normeperidine really screw you up?
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if pt is on MAO inhibitors too
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METHADONE
half life |
looooong
15-40hr |
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What is one reason it lasts so long?
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90% bound to plasma proteins-->accumulation in tissues-->time release action
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METHADONE
oral efficacy? |
great
92% |
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METHADONE
potency vs morphine? |
same
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METHADONE
used for? |
opiate addicts
chronic pain opioid withdrawal |
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METHADONE
contraindicated for? |
Labor
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FENTANYL and friends
half lives? |
around 3 except for Remifentanil is 8-20hr
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FENTANYL and friends
common administration? |
IV
epidural intrathecally |
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FENTANYL and friends
Lipid Solubility? so what? |
HIGHLY lipid solube
Fast onset b/c they can cross the BBB in a hurry |
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What else besides analgesia is faster with fentanyl than morphine?
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Resp Depression
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Potency of FENTANYL and friends vs morphine
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Sufentanil (1000x) > fentanyl = remifentanil (100x) > alfentanil (3-5x) > morphine (1x)
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Metabolism of FENTANYL and friends
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All in liver except Remifentanil which is via plasma esterases
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What should I remember about Levorphanol?
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that it exists
maybe its half life 12-16hr better oral than parenteral |
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HEROIN
half life |
tiny
3-10 MINUTES |
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HEROIN
vs morphine potency? |
2x as potent as morphine
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HEROIN
metabolism |
Metabolized by tissue esterases to 6MAM which is then metabolized to morphine
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HEROIN
why is it fast acting? |
both heroin and 6MAM are very lipid soluble, so they shoot across the BBB
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CODEINE
half life |
short
2-4 |
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CODEINE
Mech? |
Partial Agonist
Low Affinity for opioid receptors |
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CODEINE
oral efficacy |
good
50% |
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CODEINE
metabolite? |
10% metabolized into morphine
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CODEINE
indications? |
Moderate Pain
Antitussive |
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CODEINE
typically given as a____? |
Combo with aspirin or acetaminophen
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PROPOXYPHENE
vs Codeine? |
Longer Half Life (6-12)
Lower Efficacy |
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PROPOXYPHENE
metabolism? |
Metabolized to Norpropoxyphene
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What's up with norpropoxyphene?
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Cardiotoxic w/ long half life (30hr)
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TRAMADOL
half life |
medium
6hr |
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TRAMADOL
mech? |
weak MOP agonist
Inhibits uptake of serotonin and norepinephrine |
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TRAMADOL
metabolism? |
active metabolite is 2-4x more potent with long half life (7.5hr)
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TRAMADOL
caution? |
Risk of CNS excitatory rxn ESP w/ MAOI
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Opioids w/ active opioid metabolites?
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Morphine (Morph6)
Heroin (morphine and 6MAM) Codeine and friends (morphine) Naltrexone |
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Opioids w/ excitatory/toxic metabolites?
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Morphine (morph3!!!)
Meperidine (normeperidine) Propoxyphene (norpropoxyphene =cardiotoxic) Tramadol (CNS excitatory) |
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Opioids that alter NMDA or monoamine activity?
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Meperidine
Methadone Tramadol* Dextromethorphan |
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Why are there Mixed Receptor Agents?
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b/c of the attemps to produce less resp depress and less addictive potential
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Who are the Mixed Receptor drugs?
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Nalbuphine
Pentazocine Butorphanol Buprenorphine Dezocine |
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NALBUPHINE
Mech |
Strongest Agonist of KOP
Competitive MOP antagonist |
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NALBUPHINE
potency vs morphine |
same at 10mg, but hits a ceiling for analgesia and resp depression at 30mg
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NALBUPHINE
What happens at high doses? |
Psychotomimetic
you hallucinate |
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PENTAZOCINE
mech |
KOP agonist
weak MOP antagonist or partial agonist |
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PENTAZOCINE
why isn't it a big deal? |
ceiling effect
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PENTAZOCINE
high dose effects |
dysphoric
psychotomimetic inc BP, HR, and cardiac work |
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BUTORPHANOL
mech |
KOP agonist
Competitive MOP antagonist or partial agonist |
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BUTORPHANOL
fun fact? |
greater analgesia in women than in men
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BUPRENORPHINE
mech |
Partial MOP agonist w/ high binding affinity, but low activity
KOP and DOP antagonist |
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BUPRENORPHINE
so why is it a big deal? |
High affinity binding means it takes ~166 minutes to dissociate (fentanyl takes 7). This means its hard to reverese it's resp depression, but it can also antagonize other drugs' (fentanyl) resp depression
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Besides Codeine and hyrdocodone, who else is an Antitussive?
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Dextromethorphan
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Dextromethorphan
mech? |
not through opioid receptors
rather its an NMDA receptor antagonists |
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Anti-Diarrheal's
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Loperamide
Diphenoxylate |
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Origin of the Anti-Diarrheals?
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They're Meperidine Derivatives
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What happens at high doses?
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Loperamide: nada
Diphenoxylate: typical opioid activity...but it ain't worth it |
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Who are the straight up Opioid Antagonists?
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Naloxone
Nalmefene Naltrexone |
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What are their mechanisms?
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They all antagonize MOP, KOP, and DOP (but mostly MOP)
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When are they most effective?
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w/ prior opioid agonist administration
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what about tolerance and withdrawal?
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doesn't happen
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What is Naloxone used for?
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to prevent opioid abuse
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Which is the least potent of the three?
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Naloxone
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Who is used to treat boozers?
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Naltrexone
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How long does it take the antagonists to reverse resp depression?
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1-2 minutes with IM or IV
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What about Antagonists vs Buprenorphine?
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Takes the antagonists longer to reverse resp depression
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What about Antagonists vs psychotomimetic effects?
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Takes longer but they still handle em
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What is Acute Opioid Toxicity?
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Triad of Coma, Miosis, and Resp Depression (can kill you)
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Rx for Acute Opioid Toxicity?
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Naloxone
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What is key to Rx?
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B/c antagonists' duration of activity is much shorter than some of the agonists, continuous monitoring and additional antagonist administration is needed
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What happens when you give an Antagonist to a morphine treated patient?
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Agonist effect reversed
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What happens when you give an Antagonist to an acutely depressed pt?
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Pt normalized
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What happens when you give an Antagonist to normal opioid dependent person?
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Transient, Explosive withdrawal
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What happens when you give an Antagonist to normal opioid naive person?
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nada
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Opioid Contraindications?
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Don't mix Full and Partial Agonists
Impaired Resp Fxn Hepatic Disease Renal Disease Asthmatics (morphine and histamine) Pregnant Women (RD in baby) Head Injuries (RD) Elderly (drug interaction and prolonged effect) Other CNS depressants Antipsychotic Tranquilizers MAOI's |
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What is the Opioid Sparing Strategy?
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Recommendation that Opioids should be combined with other analgesic in order to be able to decrease opioid dose and SE's
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What technique do you use for chronic pain?
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Around the Clock
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Special Routes of Administration
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Intraspinal Infusion
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Pros and Cons of Intraspinal infusion?
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PRO's
fast minimizes dose minimizes SE's CON's Epidural SE's: N&V Resp Depression, etc |
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What is rostral spread?
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its when opioids "spread" from injection site in thoracic spine to lungs and cause DELAYED resp depression
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What is up with PCA?
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its a patient controlled (though limited) pump so they can control when they get the meds
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