Analgesics Flashcards
Analgesia that affects peripheral nociceptors: 3
Opioids
Local anesthetics
Anti inflammatory agents (COX-2-specific inhibitors, nonselective NSAIDs)
Analgesia that affect peripheral nerve:
Local anesthetic
Analgesia that affect spine: 4
Opioids
Local anesthetic
Alpha2 agonists
COX-2-specific inhibitors
Analgesia that affect brain: 4
Opioids
Alpha2 agonists
Centrally acting analgesics
Anti inflammatory agents (COX-2-specific inhibitors, nonselective NSAIDs)
Where are the opioid receptors located?
CNS and peripheral tissues
What are the 4 major receptors?
Mu
Kappa
Delta
Sigma
What is the G protein coupled mechanism of action?
Agonist leads to membrane hyperpolarization
Inhibition of AC
Reduction in cAMP
Activation of PLC
Opioid mechanism of action:
Inhibits presynaptic release and post synaptic response to excitatory NTs which are released by nociceptive neurons
Clinical action depends on which receptor acting upon (4):
Affinity at receptor
Agonist or antagonist or combo effect
Butorphanol : ag/antagonists weaker than full agonist
May antagonize action of full agonist
How is post synaptic neuron inhibited?
Open K channels to hyerpolarize
How is analgesia produced?
Binding to the G protein coupled receptors located in brain and spinal cord regions (some peripheral sensory nerve endings)
What is opioid induced hyperalgesia?
Persistent administration of opioid can increase sensation of pain
Which drugs can cause opioid induced hyperalgesia?
Morphine
Fentanyl
Remifentanil
Is the first pass right high or low with PO?
High
How does this impact PO to IV ratio for dosing?
Needs higher dose for PO to get same affect as IV
What is fentanyl transdermal patch for?
Chronic pain
What is intrathecal used for?
Spinal analgesia
What does opioid distribution half life depend on?
Lipid solubility and other characteristics
What is morphines half life?
Low- slower onset compared to fentanyl and sufentanil
How does redistribution to other compartments affect duration of action?
Limits it with single dose/small dose
What plays a role in longer administrations?
Metabolism
Metabolism of opioids?
Converted by liver to polar metabolites than excreted by kidneys
What is hepatic P450 metabolism?
Phenylpiperidine opioids extensive degradation to metabolites, only small amount of parent life for renal excretion
Morphine structure:
Codeine
Oxycodone
Hydrocodone
Remifentanil structure
Ester
What is morphine metabolized by?
CYP2D6
What is remifentanil hydrolyzed by?
Plasma esterases
What is the elimination half life of remifentanil?
10min
Is remifentanil affect by pseudocholinesterase deficiency?
NO
What can kidney failure due to morphine excretion?
Prolong duration of action
What can accumulation of M3G and M6G in patients with renal failure lead to?
Prolonged affects including respiratory failure
What does normeperidine increased in renal failure lead to?
Seizures
What receptors in the CNS are central mediated?
Mu
Inhibition of what leads to respiratory depression?
Brainstem respiratory mechanisms
What causes chest wall rigidity?
Rapid IV dose of opioid may make difficult ventilation with bag/mask due to inhibition of nigrostriatal GABA release
What does mu receptor agonist lead to in regards of temperature
Hyperthermia
What does kappa receptor agonist lead to in regards to temperature?
Hypothermia
How does opioid affect cerebral perfusion?
Reduce cerebral oxygen consumption, CBF, ICP, but less than propofol or barbiturates
What would you give antishivering effect?
Meperidine low does most effective 25mg IV
CV affects with opioid
Minimal direct effects
What does meperidine do to CV?
May cause atropine effect (increase HR)
Which combo may reduce CO?
BZ + fentanyl or sufentanil
When does histamine release?
Bolus of morphine, hydromorphone, meperidine
How do you reverse respiratory depress with regional analgesia (epidural and spinal)?
Naloxone
What is opioid adverse affects? (7)
Respiratory depression Nausea and vomiting Pruritus Urticaria Constipation Urinary retention Delirium
Measure of necessary amount of drug to produce effect of a given magnitude?
Potency
Ability of drug to illicit pharmacological response when interacts with receptor (relationship between response and occupancy of receptor)?
Efficacy (intrinsic activity)
What is full agonist efficacy?
1
What is partial agonist efficacy?
0-1
What is competitive antagonist efficacy?
0
Extent or fraction to which drug binds to receptors at any given drug concentration
Affinity
How is affinity, potency, and efficacy related?
Affinity is inversely proportional with potency
Affinity is independent of efficacy
Common morphine agonists?
Mu and kappa
Common fentanyl agonists?
Mu
Common sufentanil agonist?
Mu, delta, and kappa
Common alfentanil agonists?
Mu
Common remifentanil agonists?
Mu
Common meperidine agonists?
Mu
Common hydromorphone agonists?
Mu
What is naloxone?
Antagonist only at mu, kappa, and delta
Naloxone onset?
1-3min
Onset of fentanyl
Almost immediate
Duration and half life of fentanyl
.5-1hr
2-4hr
Metabolism of fentanyl
Phase 1 via CYP
Remifentanil onset
Almost immediate
Remifentanil duration and half life
5-10min
10-20min
Remifentanil metabolism
Hydrolysis of ester linkage; nonspecific esterases
Morphine onset
5-10min
Morphine duration and half life
4hr
2-4hr
Morphine metabolism
Primarily phase II glucuronidation
NSAIDs mechanism of action
Inhibition of cyclooxygenase (COX), which is key step in prostaglandin synthesis
Receptors are widely distributed in body including gut and platelets (causing bleeding)
COX1
Produced in response to inflammation
COX2
COX non selective agents affect:
Fever
Inflammation
Pain
Thrombosis
COX2 selective
Increase risk of MI, thrombosis, stroke
What does aspirin and acetaminophen do?
Inhibit COX
Nonselective NSAIDs available for IV use:
Ketoroloac
Ibuprofen
Diclofenac
What are potential negative effects of nonselective NSAIDs?
Bone healing and anastomotic leak after colorectal surgery
What is Ketorolac NSAID?
Parental
Only short term for mild to moderate pain
Renal insufficiency (elevated sCr)
Inhibition of platelet aggregation
Acetaminophen does what?
Inhibits COX1 and COX2
How is acetaminophen administered?
PO and IV
Max does of acetaminophen?
4g/24hrs
Hepatic impairment of acetaminophen?
Low dose <2-3g/day causation about other factors (alcohol, nutritional status, renal function)
Severe impairment: contraindicated
