Week 7: Pain Flashcards
Local anesthetics: Classes
- Esters
- Ester linkage
- Metabolized by plasma esterases
- Higher allergic reaction rates - Amides
- Amide linkage
- Metabolized by hepatic enzymes
- Lower allergic reaction rates
Cocaine: Class, indications, MOA (2), AE (11), PK (2)
Class: Esters
Indications: Localized pain relief
MOA: Block Na+ channels in the axonal membrane -> Unable to conduct an AP
- Also blocks NE reuptake by adrenergic neurons → CNS and CV stimulation
AE: LAST (Local Anesthetic Systemic Toxicity)
- CNS excitation (seizures) → CNS depression (coma, death)
- CV: Bradycardia, heart block, decreased contractility, cardiac arrest, vasodilation
- Allergic reactions (esters more than amides)
- L&D: fetal toxicity due to placenta ion trapping, prolong labor
- Preexisting CV disease (tachycardia, dysrhythmia, MI)
PK: Metabolized by plasma esterase
- Avoid intravascular injection in the doses we use for nerve blocks
Chloroprocaine // Benzocaine: Class, indications, MOA, AE (10), PK (2)
Class: Esters
Indications: Localized pain relief
MOA: Block Na+ channels in the axonal membrane -> Unable to conduct an AP
AE: LAST (Local Anesthetic Systemic Toxicity)
- CNS excitation (seizures) → CNS depression (coma, death)
- CV: Bradycardia, heart block, decreased contractility, cardiac arrest, vasodilation
- Allergic reactions (esters more than amides)
- L&D: fetal toxicity due to placenta ion trapping, prolong labor
PK: Metabolized by plasma esterase
- Avoid intravascular injection in the doses we use for nerve blocks
Benzocaine: What’s unique?
Risk of methemoglobinemia (topical benzocaine)
- Converts Hgb → MetHgb (can’t release O2 to tissues)
- Contraindicated in <2yrs (due to % body surface area)
Chloroprocaine: What’s unique?
Short DOA
Lidocaine: Class, indications, MOA, AE (10), PK (2)
Class: Amide
Indications: Localized pain relief
MOA: Block Na+ channels in the axonal membrane -> Unable to conduct an AP
AE: LAST (Local Anesthetic Systemic Toxicity)
- CNS excitation (seizures) → CNS depression (coma, death)
- CV: Bradycardia, heart block, decreased contractility, cardiac arrest, vasodilation
- Allergic reactions (esters more than amides)
- L&D: fetal toxicity due to placenta ion trapping, prolong labor
PK: Metabolized by hepatic enzymes
- Avoid intravascular injection in the doses we use for nerve blocks
Inhalation anesthetics: Indications, MOA (3), AE (10), PK
Indications: Loss of consciousness → decreased response to pain stimuli
MOA: Enhancing GABA + GABA receptor binding in the CNS
- Results in Cl- influx = hyperpolarization of the postsynaptic neuron
- Harder to elicit an AP = depression of CNS activity
AE:
- Aspiration risk
- Post-op nausea/vomiting
- Respiratory and cardiac depression (extreme → cardiac arrest)
- Sensitize myocardium to catecholamines → increase risk of dysrhythmia
- Postoperative N/V
- Malignant hyperthermia: Temp elevation (109), muscle rigidity, CO2 production, tachycardia/ dysrhythmias, acute kidney injury
Propofol: Class, indications, MOA, AE (5), PK (4)
Class: IV general anesthetic
Indications: Low dose for sedation, very high doses for anesthesia
MOA: Enhance GABA + GABA receptor binding → Cl- influx (hyper polarization) → Harder to elicit AP → Increased CNS depression
AE:
- Profound respiratory depression (apnea)
- Profound hypotension
- Reflex tachycardia OR bradycardia
- Injection site pain
- Propofol infusion syndrome
PK:
- Formulated in lipid based medium, risk for bacterial growth
- Ultrashort DOA due to redistribution
- Rapid onset
- Low doses for sedation, VERY high doses for anesthesia
Propofol infusion syndrome: Symptoms (5) and screening guidelines
Symptoms:
- Metabolic acidosis
- Cardiac failure
- Renal failure
- Rhabdomyolysis
- Can be fatal
Screening: Check CPK levels for indication of muscle injury (also give lowest dose possible)
Ketamine: Class, indications (2), MOA, AE, PK
Class: IV general anesthetic
Indications:
- Analgesia!
- Dissociative anesthesia
MOA: Decreased NMDA transmission → decreased CNS excitation
AE: CNS disturbances (hallucinations, bad dreams)
PK: Rapid onset
Actions of COX inhibitors (7)
- Dec. inflammation and pain receptor sensitization
- Inc. gastric acid secretion
- Dec. platelet aggregation
- Dec. vasodilation
- Dec. renal blood flow
- Mediation of fever and dec. perception of pain (CNS)
- Dec. term uterine contractions
COX 1 (4) vs COX 2 (6)
COX 1: “the good COX”, mediates beneficial processes
Inhibition results in:
- Gastric erosion & ulceration
- Bleeding tendencies
- Renal impairment
- Decreased platelet aggregation
= MI
& CVA protection
COX 2: “the bad COX”, mediates harmful processes
Inhibition results in:
- Suppression of inflammation
- Alleviation of pain
- Reduction of fever
- Protection against colorectal CA
- Renal impairment
- Suppression of vasodilation =
promotion of MI & CVA
Asprin // Ibuprofen: Class, indications, MOA, AE (10), PK
Class: First generation NSAIDs (nonselective COX inhibitors)
Indications:
- Suppression of inflammation (rheumatoid arthritis, osteoarthritis, etc.) *doses for this use are higher than those for pain/fever
- Analgesia of mild/moderate pain (desensitize pain receptors)
- Fever reduction
- Suppression of platelet aggregation
- CA prevention (colorectal decrease tumor growth & metastases)
MOA: Dec. COX activity
- Dec. conversion of arachidonic acid to prostaglandins, prostacyclin, and TXA2
AE:
- GI effects: heartburn, nausea, occult bleeding
- Bleeding
- Avoid in those w/ bleeding disorders
- Avoid in those w/ propensity for bleeding: surgical patients, laboring women
- Renal impairment
- Reye syndrome (children + aspirin, especially with influenza or chickenpox) AVOID in peds
- Toxic to fetus: can cause premature ductus arteriosus closure. Also associated with other birth defects
- Hypersensitivity reactions (rare)
PK: Act locally, they don’t affect sites distant from where they’re made
- Irreversible binding = high levels of inhibition of platelet aggregation
NSAIDs and drug interactions (5)
- Anticoagulants -> bleeding risk
- Glucocorticoids -> gastric ulceration risk
- Alcohol -> gastric bleeding risk
- ACE inhibitors and ARBs -> increased impairment of renal function
- Vaccines -> response can be blunted d/t decreased immune response
Celecoxib: Class, indications, MOA, AE
Class: Second-generation NSAIDs (COX2 selective)
Indications:
- Osteoarthritis, rheumatoid arthritis
- Ankylosing spondylitis
- Acute pain
AE:
- GI ulceration: would expect this to be low. Some data support this and some don’t
- Renal impairment (same as nonselective)
- CV EVENTS: BIGGEST CONCERN (BLACK BOX WARNING)
- Increased MI/CVA/other CV events
- Avoid in heart disease & coronary artery bypass
Acetaminophen: Class, indications, MOA, AE, PK
Class: COX inhibitor
Indications: Acute pain
MOA: Inhibition of COX only in the CNS
AE: Potential for acute toxicity
PK:
- Major metabolism = conjugation w/ glucuronic acid
nontoxic metabolites
- Minor metabolism = CYP450 oxidation TOXIC metabolite (N-acetyl-p-benzoquinoneimine)
- Not much at therapeutic doses (most through other pathway)
- Toxic metabolite is rapidly converted to nontoxic form by glutathione
- High doses = run out of glutathione accumulation of toxic metabolite liver damage
Acute toxicity of acetaminophen: Cause, incidence, symptoms (4), treatment, guidelines
Cause: Liver damage and death due to accumulation of toxic metabolite
Incidence: Leading cause of acute liver failure in the US
Symptoms:
- Early = Nausea/vomiting, diarrhea, sweating
- Later (48-72hrs post overdose) = Hepatic injury
Treatment: acetylcysteine (specific antidote to acetaminophen). Acts as a substitute for the depleted glutathione, converts toxic metabolite
- Given within 8-10 hours of OD = 100% prevention of severe liver injury!
Guidelines: Max dose = 4g/24 hrs or lower in those with preexisting liver disease or EtOH use
Effects of Mu receptor stimulation (6)
- Analgesia
- Resp. depression
- Sedation
- Euphoria
- Physical dependence
- Dec. GI motility
Effects of Kappa receptor stimulation (3)
- Analgesia
- Sedation
- Dec. GI motility
Endogenous opioid peptides vs exogenous opioids
Endogenous: Agonize all 3 of main receptors (mu, kappa, delta)
Exogenous: Agonize only mu and kappa receptors
Locations of opioid receptors (4)
- Spinal cord
- Brainstem
- Thalamus
- Cortex
Morphine: Class, MOA, AE (11), PK
Class: Opioid agonist
MOA: Agonize mu and kappa receptors
AE:
- Respiratory depression (Mu agonism)
- Constipation (Mu agonism)
- Orthostatic hypotension
- Urinary retention
- Emesis
- Euphoria/dysphoria
- Sedation
- Miosis
- Birth defects
- Neurotoxicity
- Tolerance and physical dependence
PK:
- Poorly lipid soluble (higher doses needed to cross BBB to CNS)
- High first-pass effect (usually given IV)
Fentanyl: Class, MOA, AE (11), PK
Class: Opioid agonist
MOA: Agonize mu and kappa receptors
AE:
- Respiratory depression (Mu agonism)
- Constipation (Mu agonism)
- Orthostatic hypotension
- Urinary retention
- Emesis
- Euphoria/dysphoria
- Sedation
- Miosis
- Birth defects
- Neurotoxicity
- Tolerance and physical dependence
PK: 100x as potent as morphine
Codeine: Class, MOA, AE (11), PK
Class: Opioid agonist
MOA: Agonize mu and kappa receptors
AE:
- Respiratory depression (Mu agonism)
- Constipation (Mu agonism)
- Orthostatic hypotension
- Urinary retention
- Emesis
- Euphoria/dysphoria
- Sedation
- Miosis
- Birth defects
- Neurotoxicity
- Tolerance and physical dependence
PK: 10% of dose is converted to morphine in liver via CYP2D6
- Some people lack this gene = cannot gain analgesic effect
