Analgesics Flashcards
what are analgesics?
pain killers
what are prostaglandins (PGs)?
non-opioid analgesics that initiates pain, inflammation, and fever in injured tissue or protect the GI tract and mediate clotting in healthy tissue
PGs are produced from what precursor?
arachidonic acid (AA)
what is the process of PG biosynthesis?
cell damage causes a release of AA
AA is converted to PGs by cyclooxygenase (Cox) 1 and 2
what is Cox 1?
the “good” cox
normal constituent of certain cells
what is the role of Cox 1?
synthesize PGs to protect cells and maintain fxn
which Cox is responsible for platelet aggregation, decreasing acid production, mucus bicarb layer of the gut, and renal vasodilation?
Cox 1
what is Cox 2?
the “bad” Cox
what is the role of Cox 2?
synthesizing Pgs in injured cells that mediate inflammation, pain, and fever
what are the therapeutic classifications for non-steroidal anti-inflammatory drugs (NSAIDs)?
analgesic (pain killer), anti-pyretic (anti-fever), anti-inflammatory
what is an anti-pyretic?
a fever reducing drug
what does a non-selective (traditional) NSAID block?
both Cox 1 and 2
are aspirin, ibuprofen, and naproxen non-selective or selective NSAIDs?
non-selective NSAIDs
what does a selective NSAID block?
just Cox 2
are celecoxib (celebrex) and Meloxicam (mobic) selective or non-selective NSAIDs?
selective NSAIDs
are Cox 2 inhibitors selective or non-selective NSAIDs?
selective NSAIDs
what are the only 2 selective NSAIDs on the market by prescription in the US?
celecoxib (celebrex) and Meloxicam (mobic)
what is the mechanism of action of NSAIDs?
they block Cox 1 and/or 2 to stop the conversion of AA into PGs
what are some examples of non-selective NSAIDs?
aspirin, ibuprofen (Motrin and Advil), naproxen (Aleve), ketoprofen, piricam (feldene), and indomethacin (indocin)
do selective or non-selective NSAIDs inhibit pain, fever, and inflammation and cause GI damage and increase clotting risk?
non-selective NSAIDs
what results from long-term Cox-1 inhibition from non-selective NSAIDs?
decrease in GI mucosa and GI damage
decrease in clotting mechanism and increased bleeding risk
what are common indications for Aspirin?
headache, fever, arthritis, tooth aches, body aches, and after an MI
why is baby aspirin used after an MI?
bc low doses of aspirin provide them with good clot prevention
in what age range is baby aspirin good for prevention of CVD?
50-59 yo
should other NSAIDs be taken while taking baby aspirin? why or why not?
no, bc higher doses of NSAIDs will block the cardioprotective effect
why is resistance training unsafe while taking daily aspirin?
bc the aspirin increases the risk of internal bleeding
describe the absorption of aspirin
absorbs rapidly from the GI tract
transformed into salicylate in the stomach and liver
may cross the placenta and into breast milk
what is the bioavailability of aspirin?
50-70%
what is the 1/2 life of aspirin?
2 hours
how is aspirin eliminated?
depends largely on hepatic biotransformation
renal excretion of unchanged drugs is usually small (<5% of the dose)
describe the absorption of ibuprofen
oral dose is rapidly absorbed
does ibuprofen undergo a lot of the 1st pass effect?
no
what is the bioavailability of ibuprofen?
90-99%
how is ibuprofen eliminated?
rapidly by the kidneys w/ 95% eliminated w/in 4 hours
what is the 1/2 life of ibuprofen?
1.8-2 hours
what is the peak plasma concentration of ibuprofen?
1-2 hours after a single dose
what are the side effects of non-selective NSAIDs?
headache, dizziness
GI irritation
bleeding
peripheral edema
renal dysfxn, tinnitus, confusion, metabolic acidosis
Reye’s syndrome (pediatrics)
pseudoarthosis following a spinal fusion
when non-selective NSAIDs are used long term, what should be taken with it?
proton pump inhibitor (PPI) to reduce stomach acids
misoprostol (synthetic PG)
what can result from bleeding from non-selective NSAID use?
anemia and abnormal bleeding
what is Reye’s syndrome?
relatively rare pediatric condition from use of aspirin in children 4-12
swelling in the brain and liver
what are the s/s of Reye/s syndrome?
lethargy, confusion, vomiting, seizures
why isn’t Reye’s syndrome very common anymore?
bc asprin is not routinely given to children anymore
what are the advantages of topic NSAIDs?
min side effects
relief of local superficial pain without changes to good PGs
what is pseudoarthrosis?
slow fusion or nonunion
why does pseudoarthrosis occur with non-selective NSAID use?
bc it stops Cox 2 mediated osteogenesis
non-selective NSAIDs should be avoided for how many months post-op?
6
after opioids are no longer needed post-op, what meds are recommended for pain?
Tylenol
are Cox 2 inhibitors selective or non-selective NSAIDs?
selective
how do Cox 2 inhibitors work?
by selectively inhibiting the synthesis of inflammatory PGs
what are the therapeutic effects of Cox-2 inhibitors?
analgesic (pain reducer), antipyretic (reduce fever), and antiinflammatory
same as non-selective NSAIDs
t/f: cox 2 inhibitor have a lower incidence of gastric irritation
true
t/f: cox 2 inhibitors allow for normal platelet activity
true
what NSAID is preferred in pts at risk for bleeding (pts on blood thinners)?
Cox 2 inhibitors
why are cox 2 inhibitors recommended for pts at risk for bleeding?
bc they allow for normal platelet activity
are cox 2 inhibitors slow or fast absorbing?
fast
when is the peak concentration of Cox 2 inhibitors?
about 3 hours
are cox 2 inhibitors metabolized by the liver?
yes
t/f: cox 2 inhibitors have extensive distribution
true
what is the 1/2 life of cox 2 inhibitors?
8-12 hours
what are the side effects of Cox 2 inhibitors?
some GI distress
increased CV incidents (acute heart attack, stroke, sudden coronary death) with long term use (over 9 mo)
contraindicated in pts with CABG
decreased effectiveness of ACE inhibitors
what is acetaminophen?
a non-NSAID analgesic and antipyretic
is acetaminophen an antiinflammatory/anticoagulant?
no!
what is the mechanism of action of acetaminophen?
unique mechanism not clearly defined
t/f: acetaminophen has fewer side effects than NSAIDs
true
how long does the onset of action of acetaminophen take?
orally less than 1 hour
t/f: acetaminophen is rapidly and well absorbed in the GI tract
true
t/f: acetaminophen crosses the placenta and breast milk
true
what is the 1/2 life of acetaminophen in adults?
1-3 hours
what is the 1/2 life of acetaminophen in neonates?
4-10 hours
can young children take acetaminophen? why or why not?
yes bc it is free of the risk of Reye’s syndrome
when is the peak concentration of acetaminophen?
about 2 hours
t/f: acetaminophen is metabolized by the liver
true
t/f: high doses of acetaminophen can lead to liver toxicity
true
how is acetaminophen usually excreted?
by the kidneys
what are the side effects of acetaminophen?
nausea, vomiting, constipation
headache
rash
hepatic toxicity/failure
renal failure w/high dosage/chronic use
leukopenia, neutropenia, and pacytopenia
what is leukopenia?
reduced WBCs
what is neutropenia?
reduced neutrophils (a type of WBC)
what is pancytopenia?
reduced WBCs and RBCs
can acetaminophen be used safely in pts with liver disease?
yes, as long as the pt doesn’t consume alcohol
why is acetaminophen often preferred in pts with liver disease over NSAIDs?
bc of the absence of platelet impairment, GI toxicity, and nephrotoxicity associated with NSAIDs
t/f: pts with chronic liver disease have a prolonged 1/2 life of acetaminophen
true
what are the therapeutic effects of NSAIDs?
analgesic, antipyretic, anti-inflammatory, antithrombotic/anticoagulant, and anticancer (not well supported)
what are the therapeutic effects of acetaminophen?
analgesic
antipyretic
combining NSAIDs and acetaminophen is advantageous for ____ to ____ pain
mild, moderate
what are some other non-opioid analgesics?
anticonvulsants
SNRIs (serotonin NE reuptake inhibitors)
tricyclic antidepressants (TCAs)
how do anticonvulsants, SNRIs, and TCAs work to relieve pain?
they are membrane stabilizing drugs so they make it less likely that an AP with be fired to cause pain
what is the downside of TCAs?
they can have an anticholinergic effect in higher doses
what drugs are involved in CNS pharmacology?
opioids, antiparkinsonism drugs, pyschopharmacology, antiepileptic drugs, and antispastic drugs
what are opioid analgesics?
very powerful analgesics
how do opioids work?
they use endogenous peptides already in the system (enkephalin, B-endorphins, dynorphins)
what are the endogenous peptides?
enkephalin, B-endorphins, dynorphins
t/f: opioid use the body’s built in anti-nociceptive system
true
where are the opioid receptors?
on the presynaptic terminals of C and a delta fibers (pain fibers)
what were opioids originally used as?
sleep aids
how do opioids work?
by blocking the pain-mediating NTs
what are the 3 opioid receptors?
mu, kappa, and delta
what are mu receptors?
the primary target of opioids
located primarily in the BS and med thalamus
primary effect: analgesic
side effects: euphoria, respiratory depression, bradycardia, decreased GI motility, and dependence
what receptor is the primary target of opioids?
mu receptors
what is the primary effect of the mu receptors?
analgesic
what are the side effects of the mu receptors?
euphoria, respiratory depression, bradycardia, decreased GI motility, and dependence
what are k (kappa) receptors?
located in the limbic and other diencephalon areas, BS, and SC
primary effect: spinal analgesia
side effects: sedation, respiratory depression, dependence
where is the primary location of mu receptors?
in the BS and med thalamus
where is the primary location of k receptors?
in the limbic system and other diencephalon areas, BS, and SC
what is the primary effect of k receptors?
spinal analgesic
what are the side effects of k receptors?
sedation, respiratory depression, dependence
what are delta receptors?
primarily located in the brain
effects: psychotomimetric, analgesia
what are the effects of delta receptors?
psychotomimetric, analgesia
what are psychotomimetric effects?
effects that mimic the symptoms of psychosis or schizophrenia
can opioids be selective and nonselective to certain receptors?
yes
what is the mechanism of action of opioids?
has actions at several levels of the NS
inhibition of NT released
increase K+ outward current
activation of descending inhibitory controls in the midbrain
what are common opioid agonists?
morphine
fentanyl
hydromorphone (Dilaudid)
oxycodone/hydrocodone
codeine
methadone
buprenorphine
opioid agonists treat ___ to ____ pain
moderate, severe
what is morphine?
an analgesic
what is fentanyl?
a very potent anesthetic
fentanyl is ___ times more potent than morphine
80
what is hydromorphone?
an analgesic, antitussive, and anti diarrhea
what does antitussive mean?
reduced coughing
what is oxycodone/hydrocodone?
analgesic with greater risk for addiction and dependency
dif ions associated with each
what is codeine?
an analgesic and antitussive
weak agonist w/low affinity for mu receptors
lower potency
codeine is __ as potent as morphine
1/2
what is methadone?
analgesic
used for withdrawal and addiction
weak agonist w/low affinity for mu receptors
unique synthetic opioid (can be used in ppl with opioid allergies)
what is buprenorphine?
used for ppl w/opioid addiction to reduce the drug craving
what opioid agonists can be used for withdrawal and addiction?
methodone, buprenorphine, and codeine
what are schedule drugs?
drugs that have a risk for dependency
are all opioids schedule drugs?
yes
is a schedule 1 or schedule 5 drug more dangerous?
schedule 1 drug
t/f: the lower the schedule number in schedule drugs, the more dangerous they are
true
what are common opioid antagonists?
Naloxone (Narcan)
Naltrexone
what does Naloxone (Narcan) do?
blocks all types of opioid receptors
what is Naltrexone used for?
opioid and alcohol abuse to treat w/drawal symptoms
what does PO mean?
oral
what does SQ mean?
subcutaneous
what does IM mean?
intramuscular
what does IV mean?
intravenous?
t/f: patches are transdermal
true
t/f: patches have a much longer onset of action
true
are patches meant for acute or chronic pain?
chronic
after the removal of a fentanyl patch, how long can the effects last?
up to 24 hours
what precaution should PTs know about their pts with fentanyl patches?
don’t directly touch the patch with your bare skin
what are the consequences of opioid use?
tolerance
dependence
addiction
what is tolerance?
the need for more of the drug to achieve a particular effect
pts will respond to the same amount of a drug for ___ weeks after stopping a drug
1-2
what is dependence?
the need for the receptors to be occupied (stimulated), resulting is w/drawal upon removal of the drug
is dependence physiological or psychological?
it can be either or both
what addiction?
disease of the brain reward and motivation pathways
pathological pursuit of addiction substance knowing they have a problem
when are drugs most addictive
when they are taken in a way other than as prescribed (ie snorting an oral med)
t/f: taking opioids for more than a few days increase the risk for abuse
true
pts are more likely to become addicted after only __ days of opioid use
5
what is the most common side effect of opioids?
sedation
what are the side effects of opioids?
sedation
nausea
respiratory depression
delirium/confusion (psychosis symptoms)
bowel dysfunction (mostly constipation)
miosis (constricted pupils)
pruritis (intense itching)
what are the s/s of opioid withdrawal?
sweating
shaking
headahce
nausea, vomiting, diarrhea
abdominal cramping
inability to sleep
confusion, agitation, depression, anxiety, and other behavioral changes
allodynia and hyperalgesia
neonatal abstinence syndrome
what is neonatal abstinence syndrome?
babies born from a mother w/opioid abuse problems
w/drawal from a drug as a newborn bc they become detached from mom who had been on opioids
what are the contraindications for opioid use?
hx of substance abuse
hypersensitivity
IBS/Chron’s
uncontrolled asthma
why would someone with a hypersensitivity be contraindicated for opioids?
bc opioid can increase pain sometimes (don’t really know why but may have to do with genetics)
why would someone with IBS/Chron’s be contraindicated for opioids?
bc of the GI issues related to opioid use
why would someone with uncontrolled asthma be contraindicated for opioids?
bc respiratory depression is a common side effect of opioids
what are medications used for opioid use disorder?
methadone
naltrexone
buprenorphine
(weaker opioid agonists to reduce w/drawl symptoms)
what do meds for opioid use disorder do?
they substantially reduce w/drawal symptoms
decrease relapse rates and time to relapse
reduce risk for death
what is opioid use disorder characterized by?
maladaptive use of opioid causing harm to the patient
what is a common comorbidity of opioid use disorder?
chronic musculoskeletal conditions
what is a patient controlled analgesia (PCA)?
a button that can be used and controlled by the patient to release pain killers
what drug is primarily used in PCAs?
opioid analgesics
what is demand dose in PCAs?
the dose delivered when the button is pressed by the pt
what is the lockout interval in PCAs?
the few minutes when the PCA will not release more drugs even if the patient is pressing the button
what conditions are PCA’s used in?
acute surgical pain, cancer pain, and chronic pain
t/f: PCAs provide a safer and more effective way to reduce pain
true
t/f: opioid work better for improving pain related functioning than non-opioids
false
what is the most effective pain relief pharmacologically?
ibuprofen with acetaminophen
why do we believe that opioids are so much stronger?
when given IV, opioids have no ceiling effect
psychotherapeutic effects of opioids relieve emotional distress of pain and is likely much stronger than the pain relieving effects
the WHO pain ladder
marketing
t/f: children have differences in pharmacodynamics and pharmacokinetics with opioid analgesics
true
do infants have more or less opioid receptors?
more
what is the consequence of infants having more opioid receptors?
they are more sensitive to opioids
why does opioid dosing in children vary with body surface area?
bc in children, body surface area I used rather than weight to estimate metabolism
what non-pharmacological interventions can PT counsel pts in?
relaxton techniques, mediation, pain management team, etc
what are precautions PTs should be aware of with pts on opioids?
psychosis, respiratory depression, constipation, bradycardia, nausea and vomitting, sedation (fall risk), hyperalgesia, and allodynia
is neuropathic pain responsive to NSAIDs?
no
what is the first line of treatment in neuropathic pain?
antidepressants
why are antidepressants used to treat neuropathic pain?
bc they are membrane stabilizers that work by modifying the sensitization of the pain fibers
what are some drugs used for the pharmacological management of neuropathic pain?
opioids, local anesthetics, anticonvulsants, NMDA antagonists
what are the descriptors of neuropathic pain?
burning, electric shock-like, tingling, choosing, numbness and tingling, paresthesias
what are common populations affected by neuropathic pain?
pts with diabetes, post-herpetic neuralgia, CRPS, HIV, MS, fibromyalgia, and amputations
why may analgesics fail to work?
overestimating efficacy of the drug
underestimating the analgesic requirement of the pt
lack of knowledge in analgesics
pt noncompliance due to drug fears
pt wants to pls the PT by not complaining when the meds aren’t working as intended
what do PTs need to do in pain management?
ID pts at high risk for developing persistent pain
lower pt dependence on pain meds by providing and actively engaging them in a more sustainable plan (AKA PT!)
t/f: pts with depression are more at risk for developing an addiction
true
t/f: women are more at risk for more debilitating symptoms
true
