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MSII Pharmacology > Unit 3 - Narcotic Analgesics > Flashcards

Unit 3 - Narcotic Analgesics Flashcards

1
Q

what is the general structure of opioids?

A

5 ring structure with substitutions at 3, 6, and 17 that create the profile

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2
Q

what are endogenous opioid peptides? their function?

A

endorphins

  • share protein sequences “Opioid motif”
  • precursor has commonality with ACTH, MSH, b-LPH
  • -ACTH may account for stress analgesia
  • inhibit responses to painful stimuli
  • modulate GI, endocrine, autonomic function
  • rewarding (addicting) properties
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3
Q

where are opioid receptors found?

A

in the brain, spinal cord, and peripheral receptors

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4
Q

what do agonists to opioid receptors do?

A
  • inhibit release of substance P and inhibit ascending transmission from dorsal horn
  • activates pain control circuits descending from midbrain
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5
Q

what is the structure of opioid receptors and how they’re activated?

A

GPCR

  • ligand recognition on extracellular domain
  • transmembrane and intracellular domains
  • G proteins bind to cytoplasmic aspect of receptor
  • activates/binds GTP to G-protein
  • activates effector protein, inhibits AC, activates receptor-operated K currents, and suppresses voltage-gated Ca currents (inhibits substance P)
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6
Q

what are the opioid receptor subtypes? most important?

A
  1. Mu opioid receptor (MOR) - most important for analgesia, most prescribed opioids
  2. Delta opioid receptor (DOR) - analgesia but not across BBB
  3. Kappa opioid peptide receptor (KOR)
  4. Nociceptin opioid receptor (N/OFQ or NOR) - orphanin FQ
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7
Q

what do opioid side effects depend on?

A

receptor subtypes

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8
Q

explain the mechanism of tolerance for opioids?

A

modification of opioid receptors

  • decreased effectiveness with repeated administration
  • short term desensitization: phosphorylation or receptor internalization
  • long term tolerance: additional mechanisms

can also get tolerant of side effects EXCEPT constipation

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9
Q

what are side effects of opioids?

A
  • analgesia
  • mood alteration/reward
  • neuroendocrine
  • miosis
  • convulsions (lowers seizure threshold)
  • depressed respiration (most fatal)
  • antitussive
  • nausea/emesis
  • GIT issues
  • GU issues
  • skin (vasodilation, urticaria)
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10
Q

what is the max serum concentration reached for the different methods of administration? the half life?

A

oral: 1 hour
sub-cutaneous or intra-muscular: 30 minutes
IV: 6 minutes

half life at steady state is the same for all methods = 3-4 hours

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11
Q

what is the duration of effect of “immediate-release” formulations (except methadone)?

A

3-5 hours (shorter with parenteral bolus)

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12
Q

what is the bolus effect?

A

swings in plasma concentration

  • drowsiness 1/2 to 1 hour after ingestion
  • pain before next dose due
  • must move to ER preparation, continuous SC, or IV infusion
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13
Q

morphine

A

2 major metabolites: morphine-6-glucuronide and morphine-3-glucuronide

  • M6G: active metabolite and higher potency
  • M3G: little receptor affinity
  • for severe pain
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14
Q

codeine

A

low recceptor affinity, but analgesia is due to conversion to morphine

  • only 10% is demethylated to morphine, and for mild-moderate pain
  • conversion is effected by CYP2D6
  • -10% of Caucasians cannot convert, and experience side effects without analgesia
  • antitussive action may involve other receptors that bind codeine itself
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15
Q

tramadol

A

synthetic codeine analog, but weak Mu agonist

  • demethylated metabolite is more potent analgesic
  • part of analgesia from inhibition of NE and serotonin uptake
  • for mild to moderate pain, and as effective as morphine or meperidine
  • less effective for severe pain
  • less constipating
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16
Q

fentanyl

A

very potent, very long half life, and many forms

  • much more lipid soluble than morphine
  • delayed effect and toxicity are common
  • transdermal patch useful for long term Rx
  • -ensure adherence to skin (must shave hair)
  • -may not be as effective if patient is very thin, as there is no adipose tissue
  • wait a week between dose changes, or else trouble with iatrogenic overdose
  • for severe pain
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17
Q

methadone

A

extended duration of action

  • 90% bound to plasma proteins and gradual accumulation in tissues
  • used in treatment of chronic pain, and treatment of heroin users
  • affordable, but must be careful with dosage
  • for severe pain
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18
Q

oxycodone

A

very effective, potent oral analgesic for severe pain

  • short and long-acting
  • long acting form oxycontin has seen widespread abuse and overdoses
19
Q

what is Percocet?

A

oxycodone + acetaminophen

20
Q

meperidine

A

no longer recommended b/c of metabolite toxicity (normeperidine)

  • congeners for treatment of diarrhea:
  • -diphenoxylate (Lomotil)
  • -loperamide (Immodium)
  • -mech: slow peristalsis via opioid receptors in intestine, and possibly decreased GI secretion
21
Q

naloxone

A

opioid antagonist used in treatment of opioid toxicity (IV bolus and continuous infusion)

  • administered parenterally (oral almost completely metabolized by liver)
  • -effective immediately, but only lasts 15 minutes so require IV drip
22
Q

naltrexone

A

opioid antagonist used in treatment of alcoholism

23
Q

what is the caution of using opioids and acetaminophen?

A

many commonly prescribed opioids come in this combo form, which can be other the counter
-easy to inadvertantly take too much acetaminophen (max dose is 3000 mg/24 hours)

24
Q

what is routine oral dosing for immediate-release preparations?

A

codeine, hydrocodone, morphine, hydromorphone, oxycodone

  • dose q 4 h, and adjust daily
  • -mild/moderate pain increase by 25-50%
  • -severe/uncontrolled pain by 50-100%
25
Q

what is routine oral dosing for extended-release preparations?

A

improve compliance, adherence

  • dose q 8, 12, or 24 h (product specific)
  • don’t crush or chew tablets
  • may flush time-release granules via feeding tube
  • adjust dose q 2-4 days (steady state reached)
  • -adjust methadone dose q 4-7 days (longer half-life and risk of overdose)
26
Q

what is breakthrough dosing?

A

if currently on opioids, but then PT makes the pain worse

  • use immediate-release opioids, NOT ER release
  • -5-15% of a 24-hour dose
  • -offer after Cmax reached
  • –po/pr: q 1 hr
  • –SC, IM: q 30 min
  • –IV: q 10-15 min
27
Q

what are clearance concerns with opioids?

A

conjugated by liver

  • 90-95% excreted in urine
  • dehydration, renal failure, severe hepatic failure
  • -decreased dosing interval and size if oliguria or anuria
  • –STOP routine dosing of morphine, and use ONLY as needed
28
Q

what are mixed agonist-antagonist opioids?

A

not recommended

  • pentazocine, butorphanol, nalbuphine, dezocine
  • -compete with agonists –> withdrawal
  • -analgesic ceiling effect
  • -high risk of psychotomimetic adverse effects with pentazocine, butorphanol
29
Q

what must be considered before labeling patient as “opioid addict”?

A
  1. substance use = true addiction
  2. pseudoaddiction = undertreatment of pain
  3. behavioral/family/psychological disorder
  4. drug diversion
30
Q

what is physical dependence?

A

not tolerance, but a process of neuroadaptation

  • abrupt withdrawal may cause abstinence syndrome
  • -agitation, abdominal pain, N/V, diarrhea, yawning, piloerection
  • to avoid, reduce dose by 50% every 2-3 days (taper dose out)
  • antagonists will cause abrupt withdrawal symptoms
31
Q

how do you manage pain in substance abusers?

A

management is more complex, with protocols and contracting

-consultation with pain or addiction specialists is important

32
Q

what happens if pain is poorly responsive to opioids?

A

dose escalation may cause adverse effects

  • try alternate route or rotate opioid
  • try coanalgesic
  • use nonpharmacologic approach
33
Q

what is equianalgesic dosing?

A

necessary to convert to alternative routes of delivery (transitions in/out of hospital, severeity of pain)

  • must convert between opioids while maintaining analgesia (insurance change, intolerable ASE, etc.)
  • use a table to find initial dose selection
  • significant first pass metabolism
34
Q

what are common and uncommon ASE of opioids?

A

common: constipation, dry mouth, N/V, sedation, sweats
uncommon: bad dreams/hallucinations, dysphoria/delirium, myoclonus/seizures, puriritus/urticaria, respiratory depression, urinary retention

35
Q

when does sedation from opioids start and what do you do?

A

onset with start of opioids

  • must distinguish from exhaustion due to pain
  • tolerance develops within days
  • if persistent, change opioid or route
  • psychostimulants may be useful (methylphenidate)
36
Q

what is the presentation of opioid delirium? how to minimize risk?

A

presentation:

  • confusion, ad dreams, hallucinations
  • restlessness, agitation
  • myoclonic jerks, seizures
  • depressed level of consciousness
  • respiratory depression

minimize risk by following dosing guidelines
-check liver/kidney function and ensure well hydrated

37
Q

explain respiratory depression with opioids?

A

loss of consciousness precedes respiratory depression (major cause of death0

  • tolerance is rapid
  • manage by identifying and treating contributing causes
  • -reduce opioid dose and observe
  • if unstable vital signs, O2 sat, or CO2 retention, use naloxone
38
Q

what is opioid allergy?

A

rare, but be sure to separate from ASE

-urticaria and bronchospasm can be allergies, and need careful assessment

39
Q

what is urticaria from opioids?

A

much more common than allergy

  • mast cell destabilization by morphine, hydromorphone
  • treat with routine, long-acting, nonsedating antihistamines such as fexofenadine and loratadine
40
Q

explain constipation with opioids?

A

common to all opioids

  • effects on CNS, spinal cord, myenteric plexus of gut
  • easier to prevent than to treat, but dietary approach is ineffective
  • bulk forming agents contraindicated, so use stimulant laxative + stool softener (senna + docusate Na)
  • -prokinetic agents are expensive but work, as do osmotic laxatives
41
Q

explain N/V with opioids

A

onset with start of opioids

  • tolerance develops within days
  • prevent or treat with DA-blocking antiemetics (prochlorperazine or metoclopramide)
  • may need alternative opioid
42
Q

what is opioid-induced hyperalgesia?

A

mechanism unclear, but possibly nociceptive sensitization caused by exposure to opioids

43
Q

what is the role of opioids and chronic non-cancer pain?

A

benefits and risks

  • multiple guidelines available based on safety and efficacy
  • widespread prescriptions have resulted in increasing substance abuse
  • use of opiates in CNCP requires caution before starting, contracts and urine testing

MSII Pharmacology (43 decks)

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