Drugs for Pain Flashcards
Mechanism of action of local anesthetics
Block Na+ channels on the AXON = inability to conduct an action potential
What are the two classes of local anesthetics?
esters & amides
Which class of local anesthetics have a higher allergic reaction rate?
esters
How are the two classes of local anesthetics metabolized?
esters = plasma esterases
amides = hepatic enzymes
s/s of local anesthetic toxicity
CNS = seizures progressing to coma and death
CV = bradycardia, heart block, decreased contractility, cardiac arrest, vasodilation
adverse effects of local anesthetics
local anesthetic systemic toxicity (LAST)
allergic reactions
methemoglobinemia (only benzocaine)
List some ester local anesthetics
procaine
chloroprocaine
cocaine
tetracaine
List some amide local anesthetics
lidocaine
bupivicaine
ropivicaine
mepivicaine
What is the general mechanism of action of many of the general anesthetics
chloride influx (via GABA inhibition) & hyperpolarization of neuronal membranes
= depression of CNS activity
Life threatening adverse effect of inhalation anesthetics?
malignant hyperthermia
Common side effects of most of the inhaled anesthetics
hypotension
respiratory depression
post-operative nausea & vomiting
mechanism of action of propofol
promote GABA release
(hyperpolarization of membranes of the CNS, decrease neuronal transmission)
adverse effects of propofol
respiratory dpression
hypotension
can have bradycardia or reflex tachycardia
injection site pain
propofol infusion syndrome w/ long term infusion
Positive outcomes of COX inhibition
decreased inflammation
decreased pain
decreased fever
The production of which substances is inhibited with COX inhibition?
prostaglandins
prostacyclin
thromboxane A2
Major adverse effects of COX inhibition
increased gastric acid secretion = ulcer development
decreased vasodilation of renal artery = decreased renal blood flow
decreased platelet aggregation = bleeding risk **can be positive effect or adverse effect
Effects of COX1 inhibition
gastric erosion & ulceration
bleeding
renal impairment
BUT also decreased platelet aggregation (which can prevent MI/CVA, which is good)
Effects of COX2 inhibition
decreased inflammation
decreased pain
decreased fever
BUT also decreased vasodilation, which can promote MI/CV (which is bad)
What is another term for the first generation COX inhibitors
nonselective COX inhibitors
List some first generation COX inhibitors
aspirin
ibuprofen
naproxen
ketorolac
indomethacin
Who are first generation COX inhibitors contraindicated in?
peds (aspirin)
pregnancy
renal disease
PUD or GI bleeding
bleeding disorders
How is aspirin different than the other first generation COX inhibitors?
binding is irreversible (higher platelet inhibition)
How are the second generation COX inhibitors different from the first generation?
only inhibit COX2
What is the major risk that is present ONLY for second generation COX inhibitors?
CV events
- no suppression of platelet aggregation
- inhibition of vasodilation
Name a second generation COX inhibitor
celecoxib
mechanism of action of acetaminophen
COX inhibition only in the CNS (not peripherally)
How are the effects of COX inhibitors and acetaminophen different?
acetaminophen = no anti-inflammatory, no decreased platelet aggregation, no GI issues, no decrease in renal blood flow
site of metabolism of acetaminophen
liver
how does toxicity occur in high dose acetaminophen?
too much of the toxic metabolite builds up without enough glutathione to convert it.
This toxic metabolite can lead to liver damage
Treatment of acetaminophen toxicity
acetylcysteine (antidote to acetaminophen that can convert the toxic metabolite to inactive form)
what is the max dose of acetaminophen
4g in 24hrs
*this max dose may be lower in those w/ preexisting liver disease or EtOH use
What are the 3 opioid receptors?
mu
kappa
delta
What are the effects of mu agonism
analgesia
respiratory depression
sedation
euphoria
physical dependence
decreased GI motility
what are the effects of kappa agonism
analgesia
sedation
decreased GI motility
What do pure opioid agonists do?
agonize mu and kappa
What do opioid agonist-antagonists do?
either agonize or antagonize mu and do the opposite at kappa
How do the effects of opioid agonists/antagonists compared with the pure agonists?
ceiling effect to analgesia
less respiratory depression
less euphoria
lower abuse potential
*can precipitate withdrawal in those w/ physical dependence
What do the opioid antagonists do?
antagonize mu & kappa
What are the effects of the opioid antagonists
(NO analgesia)
reverse most effects of opioids
(can precipitate withdrawal symptoms in those w/ physical dependence)
Which two effects of opioids do patients NOT develop a tolerance to?
miosis
decreased GI motility
respiratory effects of opioids
depression (decreased RR)
cough suppression
hemodynamic effects of opioids
can slow HR d/t decreased SNS
orthostatic hypotension
GI/GU effects of opioids
constipation
urinary retention
CNS effect of opioids
euphoria or dysphoria
sedation
tolerance/physical dependence
pupillary effects of opioids
miosis (constriction)
what is tolerance
larger doses are required to produce same response
what is physical dependence
state in which abstinence syndrome will develop if the drug is abruptly stopped
how to avoid withdrawal symptoms of opioids
taper down doses over time
s/s of opioid withdrawal
mild = yawning/rhinorrhea/sweating
severe = sneezing/weakness/N/V/diarrhea/abdominal cramps/muscle pain/spasms
List a few pure opioid agonists
fentanyl
morphine
meperidine
methadone
hydromorphone
sufentanil
remifentanil
How is meperidine different than the other pure opioid agonists
toxic metabolite build up occurs with prolonged use
interacts with MAO inhibitors = excitation/seizures
How is methadone different from the other pure opioid agonists
very long 1/2 life
- can treat addiction
- can also lead to drug accumulation
also prolongs the QTc
What is the active metabolite of codeine
morphine
Why do some people not have analgesic effects from codeine
genetic variation in the CYP450 enzyme that metabolizes it
list some opioid agonist-antagonists
nalbuphine
butorphanol
buprenorphine
List some opioid antagonists
naloxone
methylnatrexone
naltrexone
What is naloxone used for
opioid OD reversal
Duration of action of naloxone
1hr
what is methylnatrexone used for
opioid-induced constipation that hasn’t responded to other interventions
what is naltrexone used for
to block the euphoric effects of opioids (so for opioid/alcohol abuse)
How does tramadol work
weak mu agonism
antagonism of NE & serotonin reuptake
adverse effects of tramadol
sedation
dizziness/HA
constipation
seizures
suicidal ideation
When increasing opioid dosing when treating cancer pain, what is a major concern?
constipation
