Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Anesthesia Pharm Midterm 2 > Pain and Opioids > Flashcards

Pain and Opioids Flashcards

1
Q

Acute Pain

A
  • the direct result of tissue damage or potential damage and is a symptom
  • well defined onset and clear pathology
  • protect from tissue damage and allow time for healing
  • frequently observable tissue damage
  • usually adequately treated by pharmacological and treatment methods
  • acute pain is useful and protective
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Gaba

A

inhibitory NTM effect on pain

-cerebral cortex, BG, cerebellum and spinal cord- increases Cl- which hyperpolarizes the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Acetylcholine

A

inhibitory NTM effect on pain

-increased K+ conduction in the peripheral parasympathetic NS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Dopamine

A

-most likely inhibitory by acting on adenylate cyclase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Norepi effect on pain

A

-RAS & hypothalamic-inhibitory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Epi effect on pain

A

-RAS- inhibitory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Glycine

A

spinal cord- increases Cl- = hyperpolarizes cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Endorphins

A

-are excitatory for the descending pathways that inhibit pain transmission

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

serotonin

A

-inhibitory in the brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Histamine

A

hypothalamus and RAS-inhibitory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Glutamate effect on pain

A

Excitatory NTM

  • hippocampus, outer layer of cerebral cortex, and SG
  • learning and memory: recall
  • central pain transduction
  • excitotoxic neuronal injury
  • inotropic glutamate receptors: NDMA
  • ligand operated channel opens- influx of cation (Na+), membrane depolarization
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Opioids

A
  • most efficacious analgesic drug available
  • have receptor agonist activity with morphine-like effects at mu receptors throughout the body but also at kappa and delta receptors
  • activation of mu receptor produces analgesia effects and other unwanted SE
  • inhibit NTM, block Ca2+ influx and increase K+ efflux
  • analgesia: absence of pain without loss of consciousness
  • have different bioavailability, efficacy, relatively potency, duration of action, metabolism and metabolite activity
  • may NOT eliminate pain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Opioid MOA

A
  • agonist activity at stereospecific opioid receptors at pre and post synaptic sites in the CNS (brain and spinal cord) and peripheral nerves
  • activate opioid receptors on the primary afferent sensory neurons
  • these neurons are also activated by enkephalins, endorphins, and dynorphins
  • only levi-rotatory opioid molecules exhibit agonist activity
  • opioids need to be ionized for strong binding to the receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Principal effect of opioid receptor activation?

A
  • decreased neurtransmission: this action occurs largely by presynaptic inhibition of the release of neurotransmitters
  • acetylcholine, dopamine, norepi, substance P
  • post synaptic inhibition of evoked activity may also occur
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Opioid receptor occupied by agonist

A
  • increased K+ conductance hyper polarizes membrane
  • or/ and calcium channel inactivation
  • leads to decreased neurotransmitter release
  • opioid receptor mediated inhibition in cAMP is likely a delayed response
  • opioids do NOT alter the responsiveness of peripheral nerves to noxious stimuli nor do they impair impulse transmission
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

The BBB

A

opioids cross the BBB based on:

  1. molecular size (smaller is better)
  2. lipid solubility (lipid soluble is better)
  3. non-ionized is better (more lipid soluble)
  4. protein binding: greater protein binding means less drug available to cross
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Protein binding: which drugs have the highest and lowest?

A

Highest: alfentanil
lowest: morphine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Match receptors with endogenous opioids:

mu, delta, kappa to endomorphins, endorphins, enkephalins, dynorphins

A

Mu: endomorphins and endorphins

Delta: endorphins and enkephalins

kappa: dynorphins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Mu receptors: location (4) and actions (8)

A 
Location:
Brain mu1 in brain
spinal cord: SG
peripheral sensory neurons
intestinal tract
Actions:
sedation
analgesia
physical dependence (mu2)
respiratory depression (mu2)
miosis
euphoria
reduced GI motility
vasodilation
20
Q

Kappa: location (4) and actions (8)

A 
Location:
brain
spinal cord
peripheral sensory neurons
high intensity painful stimulation may be resistant to K receptor effects
Actions:
analgesia
anticonvulsant effects
dissociative and delirium 
diuresis
dysphoria
miosis
sedation
reduces shivering
21
Q

Delta receptor location (1) and actions (4)

A

Location:
Brain
NOT spinal cord*****

Actions:
analgesia
antidepressant effects
convulsant effects
physical dependence
22
Q

Generalized opioid side effects

A

sedation: precursor to respiratory depression
respiratory depression-usually prevented by intense pain
nausea & vomiting: treat with antiemetics
— decrease GI motility and constipation
— decrease secretions
— prescribe a laxative with the opioid

CV:
orthostatic hypotension
bradycardia
peripheral vasodilation– d/t histamine release

23
Q

SIDE NOTE: histamine release on morphine and fentanyl

A

morphine is naturally occurring from poppy seed plant

A LOT more histamine release= more vasodilation than with fentanyl

24
Q

Generalized opioid side effects

A 
-euphoria- meperidine
antitussive (cough syrup w/ codeine)
pupillary constriction-- miosis
pruritis (itching)-- histamine and non histmine
biliary spasm-- gallbladder surgeries
myoclonus/seizures-- high doses
chest wall rigidity-- high/misc. dose
25
Q

Morphine

A

-classic Mu receptor agonist
-influences motivational-effective aspect of pain
-produces analgesia in the:
— brain mu1
— spinal level mu2
Only 23% ionized– able to cross BBB
lipid solubility 1.4 so slow onset of action
t1/2 2-3 hours
duration of actions: 4-6 hrs
opioid: mu agonist, kappa agonist, delta agonist

26
Q

Morphine analgesia

A

central: mu1
- -periaqeductal gray, locus cerelus, medullary nuceli
- -sends descending inhibitory signals

spinal level– mu2
–presynpatic inhibition of primary afferents
–decrease substance P
-post synaptic hyper polarization of interneurons
substancia gelatinosa (Rexed II and V)
-decreases afferent transmission of nociception

–central and spinal synergy
Women have slower onset and slower resolution of analgesia at the same plasma level of morphine
–not observed with Alfentanil or M-G-Glucoronide
–women may require 10-30% more morphine than males

27
Q

Morphine respiratory depression

A

causes respiratory depression

  • -a shift to the right of the CO2 response curve to resting paCO2 and to apnea
  • -classically see slowly respiratory rate and normal TV
  • -with analgesia comes resp depression– protective?

ventilatory response to hypoxia/emia is also decreased
-the onset of respiratory depression with morphine parallels the onset of analgesia (usually the shift in the CO2 curve and hypoxia response protects the patient from too much morphine)

28
Q

Morphine: N&V, muscle rigidity, itching

A
  • induces N&V by direct stimulation of the chemoreceptor trigger zone- studies show no difference in N&V with equal doses of different opioids
  • large doses or rapid administration may cause skeletal muscle rigidity (eliminated with GABA agonists and paralytic agents)
  • result in dose dependent pupillary constriction
  • pruritis (itching) is a mu receptor effect at the medullary dorsal horn, NOT histamine release *** treat with naloxone
29
Q

Morphine: what happens when drug is given to patient over time?

A

Tolerance develops with continued exposure

  • -requires larger doses to produce same level of pain relief
  • hyperalgesia may develop with prolonged use
  • pt shows S&S of withdrawal when morphine is dc’d
  • decreased cough reflex 2/2 direct effect of medullary cough center
  • decreases GI motility, gastric emptying, increases constipation
  • increase biliary pressure by increasing phasic wave frequency of sphincter of do (cholangiograms)
  • triggers release of histamine– allergic reaction
  • reduces centrally mediated SNS activity— peripheral vasodilation
30
Q

Morphine metabolism and elimination

A

metabolized 70% in liver via glucuronidation

  • liver disease has minimal effect on morphine metabolism
  • –reduced liver blood flow reduces morphine clearance
  • –very young (<2 months) and elderly (>60) have reduced liver flow

excretion of metabolites by kidney
M-3-glucuronide 75-85% inactive metabolite– no analgesia– maybe hyperalgesia
M-6-glucuronide 5-10% active metabolite–10X potent than parent morphine

renal disease affects the elimination of morphine

  • M6G is secreted by organic ion transporters in the kidney which is impaired in renal disease. M3G also accumulates
  • a patient receiving high doses of morphine who develops renal insufficiency may develop prolonged sedation or coma due to M6G accumulation
31
Q

Hydromorphone (Dilaudid)

A 
-IV 5X potent than morphine
Onsets 5 minute
peaks 10-20 minutes
1-2 mg dilaudid= 10-20 mg IV morphine
2-4 mg every 4-6 hours
onset 20-40 minutes
peak 1.5 hours
32
Q

Codeine

A

-low affinity for opioid receptors
-analgesic effects are due to 10% conversion to morphine with causes analgesia
-less 1st pass metabolism than morphine when taking orally-so slightly more effective
–tyelnol #3 (30 mg codeine + 300 mg tyelnol)
–tyelnol #4 (60 mg codeine + 300 mg tyelnol)
hydrocodone (vicodin–hydro + acetaminophen)
-oxycodone (percodan)
—-percocet (oxycodone + acetaminophen)
—-oxycontin

33
Q

Oxycodone

A

less 1st pass metabolism than morphine

  • percocet 5 mg oxycodone + 325 mg acetaminophen
  • adults 5-15 mg (1-3 tabs) every 6 hours
  • peds 0.05-0.15 mg/kg every 4-6 hours (beware tylenol limits)
34
Q

Oxycontin

A

-sustained release tablets
10-20mg q12 hours
80-160 mg for opioid tolerant pts (cancer)
sustained release when taken whole
bolus “high” when rushed or chewed– abuse problem

35
Q

Nalaxone

A

competitive antagonist at mu, kappa, delta
IV, IN, SQ admin is effective
peak effect 1-2 minutes IV
metabolized liver (glucuronidation)
excreted urine
half life 65 min (adults), 3 hours (neonates)

standard ampule: 0.4 mg or 400 mcgs
adults dose: 0.5-1.5 mcg/kg (40-100 mcg)
will reverse excessive opioid induced respiratory depression
-give 400 mcg or whole amp in a code blue respiratory depression or narcotic OD (beware of withdrawal, ht., tachycardia, pulmonary edema, PONV)

36
Q

Naltrexone

A

long acting oral opioid antagonist used to treat opioid and alcohol dependent addiction

37
Q

Meperidine

A

1/10th the potency of morphine but more lipid soluble=faster onset
-less bradycardia and less respiratory depression than equianalgesic doses of morphine
-some local anesthetic activity–sensory and motor block (SABs)
-has dysphoric and psychomimetic effects- K receptor
-less biliary pressure effect
>histamine release than morphine
liver metabolism
active metabolite normeperidine T1/2 14-21 hrs
very useful for post operative shivering- K receptor affect

38
Q

Serotonin Syndrome

A

Meperidine inhibits the repute of serotonin
-when given to a patient taking MAO inhibitors or selective serotonin reuptake inhibitors (SSRIs), Meperidine may cause Serotonin Syndrome

Manifests as:

  1. Delirium
  2. Fever
  3. Convulsions

SS does not occur with Meperidine derivatives (Fent)

39
Q

Fentanyl

A

-almost complete mu receptor agonist
50-100X more potent than morphine
100 mcg fent= 10 mg morphine
effects and se similar at equal dose

Onset 3-5 minutes IV

  • more rapid brain equilibration than morphine
  • lipid solubility 816
  • rapid onset of analgesia= rapid resp depression
  • fentanyl induction will reduce your MAC requires of inhaled anesthetic
  • NO direct reduction in myocardial contractility (BP will drop if pain is relieved)
40
Q

Opioid effects on inhaled anesthetic MAC

A
  1. Increased opioid allows reduced ISO
  2. MAC reduction may be >75%
  3. MAC reduction occurs at moderate plasma levels of opioid
  4. Isoflurane can NOT be eliminated
41
Q

Fentanyl

A
  • no histamine release-no vascular tone hypotension
  • synergy with benzodiazepines=respiratory depression
  • 100% hepatic extraction- inactive metabolites
  • clearance directly correlated to liver blood flow
  • decrease with P450 inhibitors

CSHT depends on length of administration
1 minute= t/12 5 minutes
1 hour=t1/2 20 minutes
8 hour infusion=t1/2 250 minutes

infusions:
LD: 8-12 mcg/kg
MD: 1-1.5-2 mcg/kg/hr
transdermal patches used for cancer and chronic pain

42
Q

Alfentanil

A

-almost completely mu receptor agonist
10X as potent as morphine
1/10th-1/4th as potent as fentanyl
1000mcg alfentanil=100 mcg fent=10 mg morphine

extremely rapid onset: 1-2 minutes
90% unbound is unionized at pH 7.4
rapidly crosses the BBB

metabolized in the liver 30-50%
inactive metabolites
clearance is directly proportional to liver blood flow
reduced with P450 inhibitors
lower in elderly and CHF
-CSHT: changes less over time, lower lipid solubility (less redistribution) and higher liver clearance

43
Q

Alfentanil loading dose

A

35-70 mcg/kg
2,500- 5,000 mcg in 70 kg pt
Alfentanil comes in 500 mcg/cc
-maintenance infusion 0.25-0.50 mcg/kg/min
-rapid onset of action= rapid onset of respiratory depression (Beware)

44
Q

Remifentanil

A

-almost completely mu receptor agonist
equipotent to fentanyl
very rapid onset 1 minute
metabolism is by non-specific plasma esterases (NOT pseudocholinesterase)
-clearance is constant and not affected by liver flow, renal failure or length of infusion
-no residual analgesia— need long acting opioid before turned off

infusions– only way to use remifentanyl
LD: 1-2 mcg/kg
infusions: 0.05-0.25 mcg/kg/min
CSHT: 3 minutes
duration: 6-9 minutes after infusion turned off
DOA Policy:
mix 4 mcg/cc (1mg/250 ml) for non intubated cases
mix 10 mcg/cc (1 mg/100 ml) for intubated/GA cases

45
Q

Spinal Opioids

A

Preservative Free

  • spinal mu receptors are present in DH
  • morphine and fentanyl administered spinally is analgesia
  • morphine or fentanyl can be administered intrathecally (directly into CSF) for chronic pain and intrathecally or epidurally (just outside spinal column) for acute pain

When administered spinally or epidurally:
1. Morphine controls pain well and produces less sedation and respiratory depression for same amoutn of analgesia
—but resp depression, N/V, sedation, itching can occur
intrathecal injection: pain relief in 2 minutes
epidural: 20 minutes for onset of relief

46
Q

Opioid Synergism

A

-when admin alone= potent resp depressant
Bezos alone= minimal respiratory depression
propofol= mild resp depression when adminstered as constant infusion of 25-150 mcg/kg/min

Opioid+benzo OR Opioid + propfol= significant synergy and can cause significantly greater respiratory depression, obtundation, and resp arrest at much lower doses than those given when agents administered alone

47
Q 
Active Metabolites:
Morphine
Hydrocodone
Meperidine
Oxycodone
Codeine
Tramodol
A 
Morphine: M6 glucuronide
Hydrocodone: hydromorphone
Meperidine: normeperidine
Oxycodone: oxymorphone
codeine: morphine
tramodol: o-des-methyl tramodol

Anesthesia Pharm Midterm 2 (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions