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52 Cards in this Set
- Front
- Back
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Opiods:
Derived from the ... plant as raw opium ... is the “gold standard” against which all other analgesics are compared |
poppy
Morphine |
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Endogenous receptors:
Opioids act on 3 physiologic receptor sub-types: -...: most commonly found receptor throughout the body. most opioid analgesics have at least some effect at this receptor. It is responsible for analgesia, euphoria, respiratory depression and physical dependence -...: have analgesic potential, without respiratory depression. -...: limited analgesic properties. Associated with dysphoric reactions and neuroexcitation (ie, seizures) * It’s important to remember that most opioids have the ability to act at one, two or all three receptor sub-types |
μ: (mu)
δ: (delta) κ: (kappa) |
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The μ, δ, κ receptors are present in high concentrations in the ... of the spinal cord
There are ... receptors located on smooth muscle in GI tract They are also located on pain transmission neurons and the primary afferents that relay signals to them |
dorsal horn
μ |
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Three families of endogenous opioid
peptides have been described: -... (runner’s high) -Enkephalins -... (thought to be related to hyperalgesia-pain becomes worse) Each opioid peptide has activity at the opioid receptor sub-types |
Endorphins
Dynorphins |
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Opioids can act at a receptor to:
completely activate it (...) partially activate it (...) -Provide analgesia with less respiratory depression or dysphoria -Potential for inducing ... in patients on long term opioid regimens completely block the effect of a receptor (... – ie, naloxone) |
agonist
partial agonist withdrawal antagonist |
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Absorption:
Most opioids are well absorbed when given by subcutaneous, intramuscular or oral routes Of course, absorption is not an issue when given by ... route Because of high first pass effect, ... doses of opioids must be given in larger doses than by parenteral routes (typically, 3:1 ratio oral to IV) |
intravenous
oral |
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Distribution:
-Once administered and absorbed into the bloodstream, opioids rapidly leave the blood compartment and penetrate the central nervous system and organs with high ... perfusion -In spite of low vascular perfusion, ... tissue can be a site of high concentrations of opioids due to high ... of these compounds -Re-distribution can sometimes be problematic, especially with ... |
vascular
adipose lipophilicity fentanyl |
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Metabolism:
Generally, the opioids are converted in the liver to ... (ie, water soluble) molecules This process is called ... Morphine is converted to two primary glucuronide metabolites, known as -Morphine-3-glucuronide (M3G) -Morphine-6-glucuronide (M6G) |
polar
conjugation |
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M3G:M6G 9:1 (approximate)
... has little to no analgesic activity ... is 4-6 times more potent than morphine Neither M3G or M6G penetrates the ..., therefore, have little to no pharmacologic effect at ... doses. |
M3G
M6G blood brain barrier normal |
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When given at high doses for a prolonged period of time, or in patients with ... failure, both M3G and M6G can accumulate
... can cause seizures, agitation, hyperactivity ... prolongs the narcotic effect at μ receptors, potentially resulting in narcosis, respiratory depression, etc |
renal
M3G M6G |
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-An exception to conjugation is ... metabolism - the primary route of degradation for certain opioids (ie, meperidine, fentanyl)
-Meperidine is metabolized to ... -In patients with renal dysfunction, normeperidine can accumulate and cause ... -Normeperidine may also ... the μ receptor, resulting in a lack of efficacy for meperidine -Don’t develop the habit of prescribing ...! |
hepatic oxidative
normeperidine seizures antagonize meperidine |
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-Fentanyl is metabolized by ... to inactive metabolites
-High concentrations of CYP3A4 in the small intestine contribute to high ... of fentanyl when it is taken orally (most of it is obliterated before reaching the systemic circulation when taken orally) -... is responsible for metabolizing codeine, oxycodone and hydrocodone, producing opioids of greater potency (each of the resulting drugs end up being pore potent than the parent drug) |
CYP3A4
first pass effect CYP2D6 |
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-Codeine is metabolized by ... to morphine.
-Codeine itself is a very ... agonist at the μ receptor -There is wide genetic variability in concentrations of CYP2D6 -Approximately 10% of Caucasians are CYP2D6 deficient -Depending on the source, as many as 25% of Asians are CYP2D6 deficient -An Asian patient who is CYP2D6 deficient would not metabolize codeine to morphine and therefore would have ... pharmacologic benefit (ie, relief of pain) -... metabolism (due to an overexpression of CYP2D6) can also occur |
CYP2D6
weak little to no Ultrarapid |
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Hydrocodone is metabolized to ...
Oxycodone is metabolized to ... HOWEVER – both hydrocodone and oxycodone are ... at the μ receptor, thus have a pharmacologic benefit (don’t have to worry about polymorphic responses) |
hydromorphone
oxymorphone agonists |
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Excretion:
-Glucuronide metabolites of opioids are excreted in the ... -Small amounts of glucuronides are found in ... -Small amounts of ... drug may be found in the urine as well |
urine
bile unchanged |
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Effects of opiods by organ system:
Central Nervous System: ... (main effect) Euphoria, with or without dysphoria Sedation, without amnesia (unintended effect) ..., with little or no tolerance -Valuable in diagnosis of opioid ... -Can be blocked by ... |
Analgesia
Miosis overdose atropine |
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CNS effects:
All opiods can cause ... (what kills the patient with overdose) Dose related, but .../... insufficiency can play a role Respiratory depression can be overcome by ... If the patient is not sedated, then respiratory depression ... a concern |
respiratory depression
hepatic/renal noxious or painful stimuli isn’t |
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CNS effects:
... suppression (intended effect) ...: -Intensification of muscle tone in large trunk muscles -Can interfere with ventilation -Most commonly observed when high doses of highly lipophilic opioids are used (ie, fentanyl) -Can be reversed by opioid ... (which will of course reverse the ... effect also) -Frequently requires use of a neuromuscular blocking agent to overcome this affect |
Cough
Truncal rigidity antagonist analgesic |
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CNS effects:
... and ... – related to activation of the chemoreceptor trigger zone in the brain. Often worsened by ambulation, suggesting a vestibular component (unintended affect) ... changes – rarely seen clinically. In experiments where opioids were administered directly to the anterior hypothalmus, -μ receptors produce hyperthermia -κ receptors produce hypothermia |
Nausea and vomiting
Temperature |
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Peripheral effects:
Cardiovascular system: -... (most common) -Meperidine can cause ... -... – usually caused by release of histamine, resulting in arterial and venous dilation *Use caution when administering opioids to hypovolemic patients |
Bradycardia
tachycardia Hypotension |
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Peripheral effects:
GI –... is frequent, often requiring laxatives/stool softeners to relieve GU/RENAL -... renal function -Opioids can have an ... effect -Ureteral and bladder tone is increased -... sphincter tone results in urinary retention |
constipation
Decreased anti-diuretic Increased |
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Peripheral effects:
Uterus – prolonged ... Neuroendocrine -Stimulate release of ..., prolactin and somatotropin -Inhibit release of luteinizing hormone -Role of endogenous opioid peptides suggested -Clinical significance unknown |
labor
ADH (anti-diuretic hormone) |
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Peripheral effects:
Derm – pruritis with or without urticaria – related to ... release. (rash with or without itching) Commonly misinterpreted as allergy Misc – non-specific immune system modulation |
histamine
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clinical uses of opiods:
... – relief of pain Acute ... edema associated with left ventricular failure -Decreased O2 demand -Reduced preload -Anxiolytic effect Cough Diarrhea Shivering Anesthesia |
Analgesia
pulmonary |
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... - A gradual loss of effectiveness following repeated doses of opioids, requiring larger subsequent doses to provide the same initial benefit
-Manifests after 2-3 weeks of frequent exposure -Results in ... dosing of opioids -Tolerance dissipates about 2-3 days after discontinuation of an opioid regimen ... can occur -... cross-tolerance can be present and must be considered when changing a patient from one opioid to another (eg, morphine to oxycodone) – start with a decreased dose |
Tolerance
higher Cross-tolerance Incomplete |
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Physical dependence:
-A characteristic ... syndrome that results shortly after an opioid is stopped or if an opioid antagonist is administered -Accompanies tolerance -Symptoms include rhinorrhea, lacrimation, yawning, chills, piloerection, hyperventilation, hyperthermia, mydriasis, pain, vomiting, diarrhea, anxiety and ... -Can be triggered by administration of an opioid ... or by ... opioid agonists |
withdrawal
hostility antagonist partial |
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Psychologic dependence - ...
Euphoria, indifference to environment and sedation promote ... by compulsive persons Rarely occurs when opioids are used for ... Should not be a consideration for patients with severe, pathologic pain (ie, cancer) |
Addiction
addiction acute pain |
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Cations (Do not use in these situations):
-Use of pure agonists with ... agonists -Use in ... injury patients -Use in... – can cause withdrawal syndrome in the infant -Impaired pulmonary function -Impaired hepatic or renal function |
partial
head pregnancy |
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“allergy”
-Allergies to morphine, codeine etc are frequently reported by patients -... of the allergy is critical! (ask what happened) -Most reported “allergies” are not ... mediated; instead, adverse reactions (nausea, rash) are commonly interpreted by patients (and unfortunately medical personnel) as allergies |
History
immune |
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If the patient has experienced an adverse effect, can safely administer another opioid (eg, rash from morphine – can try hydromorphone)
If patient truly experienced an immune mediated reaction (ie, ...), then select an opioid from a different ... (eg, anaphylaxis from meperidine – try morphine and closely observe the patient) |
anaphylaxis
class |
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... – gold standard
Astramorph®, Duramorph® (IV/IM) MS Contin®, Avinza®, Kadian® Strong, pure ... agonist Can be given IV, IM, PO, SL/buccal, or rectally Onset (IV) 5-10 minutes Duration ...-... hours |
Morphine
μ 3-4 |
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...:
Dilaudid ® Can be given IV, IM or PO Onset 5-15 minutes Duration ...-... hours A bit more potent than morphine -10 mg of morphine = ... mg of Dilaudid |
HYDROMORPHONE
4-5 1.5 |
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...:
-Also known as diacetylmorphine -Schedule I – no approved clinical use in the US or Canada -Faster onset and way more potent than morphine |
HEROIN
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...:
-Weak μ agonist – does not give a great amount of analgesia. Must be converted physiologically and metabolically to morphine -Can be prescribed alone or in combination with acetaminophen (Tylenol® #2, #3 or #4) – the higher the number, the more ... it has -Frequently used as an anti-tussive (Robitussin AC® and many others) |
Codeine
codeine |
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...:
-Moderate μ agonist -Prescribed as a single entity (OxyContin®, Oxy-IR®) or in combination with acetaminophen (Percocet®, Tylox®) and aspirin (Percodan®) -Abuse of OxyContin® began in this region -“Redneck Heroin” |
OXYCODONE
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...:
-Mild-moderate μ agonist -Prescribed in combination with acetaminophen (Vicodin®) or ibuprofen (Vicoprofen®) -Used as an ... in combination with the expectorant guaifenesin (Codiclear®) |
Hydrocodone
antitussive |
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...:
-Nubain® -Mixed activity –it is an ... at κ receptors and an ... at μ receptors -Can induce withdrawal syndrome in patients currently receiving μ agonists -Used in detox programs |
Nalbuphine
agonist antagonist |
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...:
-Buprenex®, Suboxone®, Subutex® -Partial μ agonist -Potent and long acting -Approved by the FDA in 2002 for management of opioid addiction -In high doses, can become a μ ... (limits abuse potential) -Often combined with a pure μ antagonist to prevent diversion -Used in detox programs and as part of outpatient detox regimens |
Buprenorphine
antagonist |
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...:
-Potent μ agonist -Also blocks NMDA receptors and monoaminergic reuptake transports -This may explain the efficacy of methadone in difficult to treat neuropathic pain or some types of cancer pain -Used in narcotic detoxification programs -Dosing highly individualized; expert consultation suggested -Sometimes causes QT prolongation (QTC prolongation) – makes patients prone to arrhythmias. Life-threatening emergency! |
methadone
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...:
-***Very weak μ agonist -Can be prescribed alone (Darvon) or in combination with acetaminophen (Darvocet) -Analgesic effect of this said to be no greater than a regular strength aspirin -Avoid in elderly and patients with renal dysfunction |
Propoxyphene
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...:
-is 80 times more potent than morphine -Frequently used to induce anesthesia or for short term diagnostic procedures -Also used as a analgesic -Prescribed as a transdermal patch (Duragesic®,) as a lozenge (Actiq®) and several others -Don’t use this in opioid naïve patients – at risk for respiratory depression and sedation |
Fentanyl
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...:
-Alfentanil, sufentanil and remifentanil -Only used for induction of anesthesia -These drugs provide quick onset of sedation and analgesia and can facilitate intubation -Quick onset = short duration of action |
Fentanyl derivatives
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... - don’t prescribe often. There are better options
-Demerol® -Potent μ agonist (not as potent as morphine) 50 mg of Demerol = 10 mg of morphine -Has a neurotoxic metabolite (normeperidine) - can cause seizures -Onset 5-10 minutes -Duration ...-... hours |
MEPERIDINE
2-3 |
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... is an active metabolite of diphenoxylate
Used for abdominal cramping and diarrhea Diphenoxylate is combined with atropine in Lomotil® and is a Schedule V substance Atropine decreases abuse potential of diphenoxylate |
Difenoxin
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...:
Imodium AD® Used for abdominal pain, cramping and diarrhea Sold over-the-counter (negligible abuse potential) |
Loperamide
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Morphinans:
-... (Stadol®) – commonly used in OB wards and EM rooms -Given IV/IM or intranasally -Primarily a κ agonist and a partial agonist-antagonist at the μ receptor1 -Frequently used in labor and delivery due to low potential to cause sedation -Nasal spray used for migraine headaches -Onset 1-2 minutes -Duration 3-4 hours |
Butorphanol
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Morphinans:
-... is a popular antitussive -Found in over the counter products such as Robitussin DM® -Sometimes abused by teenagers who will drink an entire 8 ounce bottle -“Robo” |
Dextromethorphan
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... (Ultram®)
-Weak μ agonist, primarily acts to block reuptake of serotonin and norepinephrine1 -Can cause seizures; do not use in patients with epilepsy or with drugs that lower the seizure threshold1 ... (Apokyn®) -Used historically as an emetic -Recently approved by the FDA for Parkinson’s Disease (reverses “on/off” phenomenon) |
Tramadol
Apomorphine |
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Opiod antagonists:
-Used to ... opioid overdose or to maintain abstinence -Often given empirically to an unresponsive patient when ... is suspected -Naloxone, naltrexone and nalmefene |
reverse
overdose |
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... – most common antagonist used today
-Narcan® -Usually given IV -Almost instantaneously reverses opioid agonists -Can precipitate withdrawal if given to opioid tolerant patients -Has short duration of action (about ...-... hours) -This becomes extremely important in the opioid overdosed patient, as the opioid agonist typically lasts longer than the antagonist. Thus, patients may appear to have recovered, only to relapse into coma later |
Naloxone
1-1.5 |
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...:
-Revia -Oral tablet -Used to maintain abstinence in heroin dependent patients enrolled in detox programs -Blocks effect of IV heroin for up to 48 hours -Also approved for use in alcohol detox programs |
Naltrexone
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...:
Revex® Longer acting IV antagonist (half life 8-10 hours) |
Nalmefene
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