Basic Science Clinical

Anatomy Physiology Pharmacology Pathology

Pain & Anesthesia Pharmacology

What Do You Need to Know?

Neuropathic pain agents — gabapentin/pregabalin (α2δ Ca channel subunit), SNRIs (duloxetine), TCAs (amitriptyline), carbamazepine (first-line for trigeminal neuralgia)
Opioid receptors — mu (analgesia, respiratory depression, constipation), kappa (dysphoria), delta (spinal analgesia); naloxone = competitive antagonist; tramadol lowers seizure threshold and causes serotonin syndrome
Local anesthetics — Na channel blockade; esters (pseudocholinesterase) vs amides (hepatic CYP); toxicity = CNS first then cardiac for lidocaine (bupivacaine cardiotoxicity may precede CNS); B fibers (autonomic) blocked first, Aα (motor) last
General anesthetics — volatile agents enhance GABA-A and increase ICP; propofol (GABA-A, decreases ICP); ketamine (NMDA antagonist) — classic teaching of ICP elevation; modern TBI/ICU data in sedated/ventilated patients generally do NOT show reliable ICP elevation and may preserve CPP; caution in uncontrolled intracranial hypertension but not absolute prohibition; etomidate = least hemodynamic effect
Neuromuscular blockers — succinylcholine (depolarizing) causes hyperkalemia in burns/denervation/SCI and triggers malignant hyperthermia; rocuronium (nondepolarizing) reversed by sugammadex
Malignant hyperthermia — RYR1 mutation + volatile anesthetics or succinylcholine; treatment = dantrolene (blocks ryanodine receptor Ca release from SR)
Procedural sedation — methohexital activates seizure foci (used in Wada test); thiopental suppresses cortical activity (burst suppression); propofol can activate foci on ECoG

🚩 Don’t Miss — Test-Day Priorities

Meperidine → normeperidine seizures: AVOID chronic use & in renal failure — toxic metabolite normeperidine accumulates and causes tremor, myoclonus, seizures (not reversed by naloxone); also serotonin syndrome with MAOIs/SSRIs.
Methadone — QT prolongation + NMDA antagonism: baseline + follow-up ECG required; long & variable half-life (15–60 h) → delayed respiratory depression; NMDA blockade makes it useful for neuropathic pain and opioid rotation; CYP3A4/2B6 interactions.
Tramadol & tapentadol — serotonin syndrome + seizures: mixed μ agonist + 5HT/NE reuptake inhibition; AVOID with SSRIs, SNRIs, MAOIs, TCAs; lowers seizure threshold (especially with renal impairment or bupropion).
Opioids in renal failure: AVOID morphine and codeine (active metabolites accumulate — M6G → neuroexcitation/myoclonus). Hydromorphone is safer than morphine but H3G can accumulate (neuroexcitation) — dose reduce + monitor. Prefer fentanyl, methadone, or buprenorphine when CrCl < 30.
Buprenorphine = partial μ agonist + κ antagonist: ceiling effect on respiratory depression; can precipitate withdrawal in opioid-dependent patients; high receptor affinity blocks full agonists — preferred for NAS & opioid use disorder in pregnancy.
Naloxone vs naltrexone: naloxone = short-acting (IV/IM/IN) for acute overdose — repeat dosing/infusion needed for long-acting opioids (methadone, ER fentanyl); naltrexone = long-acting oral/depot for relapse prevention — must be opioid-free 7–10 days or precipitates severe withdrawal.
Bupivacaine cardiotoxicity → INTRALIPID rescue: high lipid solubility → refractory ventricular arrhythmias & arrest that precede CNS toxicity; rescue = 20% lipid emulsion 1.5 mL/kg bolus then 0.25 mL/kg/min infusion; prilocaine/benzocaine → methemoglobinemia → methylene blue.
Acetaminophen hepatotoxicity: > 4 g/day (or lower with chronic alcohol/malnutrition) → NAPQI depletes glutathione → centrilobular necrosis; rescue = N-acetylcysteine (most effective < 8 h); preferred analgesic in pregnancy.
Duloxetine = only evidence-based agent for CIPN: ASCO guideline — chemotherapy-induced peripheral neuropathy responds to duloxetine; gabapentin/pregabalin/TCAs have not shown benefit in CIPN trials.
Ketamine — NMDA antagonist: low-dose infusions for refractory neuropathic pain, opioid-induced hyperalgesia, treatment-resistant depression; AE = dissociation, emergence reactions, hypertension, chronic use → ulcerative cystitis. ICP teaching: classic caution remains, but modern TBI/ICU data in sedated/ventilated patients generally do NOT show reliable ICP elevation and may preserve CPP — caution in uncontrolled IH but not absolute prohibition.
Gabapentinoids — renal dosing + abuse potential: bind α2δ subunit of voltage-gated Ca channels → ↓ presynaptic glutamate; pregabalin is Schedule V (euphoria, abuse); both cause sedation, dizziness, weight gain, peripheral edema; renally cleared.

🔍 Buzzwords & Pathognomonic FindingsMechanism · Adverse effects · Use / pearls

Mechanism

Gabapentin / pregabalin → bind α2δ subunit of voltage-gated Ca2+ channel → ↓ presynaptic glutamate release
Methadone → μ agonist + NMDA antagonist + SNRI activity (and hERG blockade → QT)
Tramadol / tapentadol → μ agonist + 5HT/NE reuptake inhibition (mixed mechanism)
Buprenorphine → partial μ agonist + κ antagonist (high affinity, ceiling effect)
Ketamine → non-competitive NMDA receptor antagonist
Capsaicin → TRPV1 agonist → substance P depletion & C-fiber desensitization
Local anesthetics → voltage-gated Na channel blockade (use-dependent; ester vs amide)
NSAIDs / celecoxib → COX1/COX2 inhibition → ↓ prostaglandins (celecoxib COX2-selective)
Acetaminophen → central COX inhibition; metabolized to NAPQI by CYP2E1

Adverse effects / toxicity

Normeperidine seizures + serotonin syndrome → meperidine (especially renal failure or with MAOI/SSRI)
QT prolongation + torsades → methadone (dose-dependent; ECG monitoring required)
Serotonin syndrome + lowered seizure threshold → tramadol / tapentadol
Myoclonus + neuroexcitation in renal failure → morphine (M6G); hydromorphone safer than morphine but H3G can still accumulate — dose reduce + monitor
Refractory cardiac arrest rescued by intralipid → bupivacaine toxicity
Methemoglobinemia → methylene blue → benzocaine / prilocaine
NAPQI hepatic centrilobular necrosis → N-acetylcysteine → acetaminophen overdose
Anticholinergic toxicity + orthostatic hypotension + QT → amitriptyline (TCA) — avoid in elderly
GI bleeding + AKI + cardiovascular risk → NSAIDs (diclofenac, rofecoxib withdrawn)
Dissociation + emergence reactions + ulcerative cystitis → ketamine
Peripheral edema + weight gain + sedation → gabapentinoids
Precipitated withdrawal in opioid-dependent patient → buprenorphine or naltrexone initiation

Use / pearls

Chemotherapy-induced peripheral neuropathy (CIPN) → duloxetine — only evidence-based agent (ASCO)
Diabetic neuropathy first-line (ADA / AAN) → duloxetine, pregabalin, gabapentin, amitriptyline
Postherpetic neuralgia — focal → lidocaine 5% patch or capsaicin 8% patch
Opioid use disorder in pregnancy → buprenorphine (less severe NAS than methadone in some trials) or methadone
Acute opioid overdose → naloxone IV/IM/IN — repeat dosing/infusion for long-acting opioids (methadone, ER fentanyl)
Refractory neuropathic pain or opioid-induced hyperalgesia → IV ketamine infusion cycles; rotate to methadone (NMDA antagonism)
Bupivacaine LAST (local anesthetic systemic toxicity) → 20% intralipid 1.5 mL/kg bolus then 0.25 mL/kg/min
Acetaminophen overdose → N-acetylcysteine (most effective within 8 h); pregnancy preferred analgesic
Renal failure (CrCl <30) — preferred opioids → fentanyl, methadone, buprenorphine; AVOID morphine, codeine, meperidine; hydromorphone safer than morphine but H3G can accumulate (neuroexcitation) — dose reduce + monitor
Treatment-resistant depression + chronic pain → ketamine / esketamine infusions
Trigeminal neuralgia first-line → carbamazepine (oxcarbazepine alternative)
Long-term opioid relapse prevention → naltrexone (oral or depot Vivitrol) — require 7–10 days opioid-free

Neuropathic Pain Agents

Drug / Class	Mechanism	Indications	Key Side Effects / Notes
Gabapentin / Pregabalin	Bind α2δ subunit of voltage-gated Ca2+ channels → ↓ presynaptic glutamate release	Diabetic neuropathy, postherpetic neuralgia, fibromyalgia (pregabalin)	Sedation, dizziness, edema; renally cleared; pregabalin has linear pharmacokinetics
Duloxetine / Venlafaxine (SNRIs)	Serotonin + NE reuptake inhibition → descending pain inhibition	Diabetic neuropathy (duloxetine FDA-approved), fibromyalgia	Nausea, HTN (venlafaxine at high doses); serotonin syndrome risk
TCAs (amitriptyline, nortriptyline)	Na channel blockade + serotonin/NE reuptake inhibition	Neuropathic pain, migraine prophylaxis	Anticholinergic effects; QT prolongation; nortriptyline better tolerated than amitriptyline
Carbamazepine	Na channel blockade (use-dependent)	First-line for trigeminal neuralgia; glossopharyngeal neuralgia	SIADH; agranulocytosis; SJS/TEN (screen HLA-B*1502); CYP3A4 autoinduction
Topical lidocaine (5% patch)	Local Na channel blockade	Postherpetic neuralgia, localized neuropathic pain	Minimal systemic absorption; well tolerated
Capsaicin (topical)	TRPV1 agonist → C-fiber desensitization; depletes substance P	Postherpetic neuralgia (8% patch), diabetic neuropathy	Initial burning; high-concentration patch applied in clinic

Board Pearl

Carbamazepine is first-line for trigeminal neuralgia. Lancinating facial pain in V2/V3 triggered by chewing or touch = carbamazepine. Oxcarbazepine is an alternative with fewer drug interactions. Screen HLA-B*1502 in patients of Southeast Asian descent before starting.

Opioid Pharmacology

Opioid Receptors

Receptor	Endogenous Ligand	Key Effects	Drugs
Mu (μ)	β-endorphin, enkephalins	Analgesia, euphoria, respiratory depression, miosis, constipation, dependence	Morphine, fentanyl, oxycodone, hydromorphone; buprenorphine — partial mu agonist (high affinity, can precipitate withdrawal in opioid-dependent patients); kappa antagonist; ceiling effect on respiratory depression. Naloxone/naltrexone (antagonists)
Kappa (κ)	Dynorphin	Spinal analgesia, dysphoria, sedation, diuresis	Butorphanol, pentazocine (mixed agonist-antagonist)
Delta (δ)	Enkephalins	Spinal analgesia, mood modulation	Research targets

All opioid receptors are Gi-coupled → ↓ cAMP, ↓ Ca2+ influx, ↑ K+ efflux → hyperpolarization
Tolerance: develops to analgesia, euphoria, respiratory depression; does NOT develop to miosis or constipation
Withdrawal: lacrimation, rhinorrhea, piloerection, diarrhea, mydriasis — uncomfortable but not life-threatening (unlike alcohol/benzo withdrawal)

Commonly Used Opioids

Drug	Key Features
Morphine	Prototype mu agonist; histamine release (pruritus, hypotension); active metabolite M6G accumulates in renal failure
Fentanyl	80–100x more potent than morphine; highly lipophilic; rapid onset; chest wall rigidity with rapid IV bolus
Oxycodone	Oral; often combined with acetaminophen; intermediate potency
Hydromorphone	5–7x more potent than morphine; less histamine release; safer than morphine in renal impairment but H3G metabolite can accumulate (neuroexcitation) — dose reduce + monitor; fentanyl/methadone/buprenorphine preferred when CrCl <30
Methadone	Long half-life; NMDA antagonist + QT prolongation added risks; used for chronic pain and opioid maintenance. Equianalgesic conversion is non-linear — conversion ratio increases with higher morphine equivalent doses; high overdose risk during rotation

Opioid Antagonists & Special Agents

Naloxone: competitive mu antagonist; IV/IM/intranasal; short half-life (30–90 min) — may need redosing for long-acting opioids
Naltrexone: oral, long-acting mu antagonist; used for opioid and alcohol use disorder
Tramadol: weak mu agonist + SNRI activity — lowers seizure threshold; risk of serotonin syndrome (especially with SSRIs/MAOIs); CYP2D6 metabolism

Board Pearl

Tramadol has dual risk: lowers the seizure threshold AND causes serotonin syndrome with serotonergic drugs. Patient on SSRI who develops clonus, hyperthermia, and altered mental status after starting tramadol = serotonin syndrome. Tolerance does NOT develop to opioid-induced constipation or miosis.

Local Anesthetics

Mechanism: block voltage-gated Na channels from the intracellular side → prevent depolarization and AP propagation
Preferentially block open and inactivated channels (use-dependent blockade) — rapidly firing neurons more susceptible
Must cross membrane in uncharged (base) form, then ionize to bind — acidic/infected tissue reduces efficacy

Esters vs Amides

Feature	Esters	Amides
Examples	Procaine, tetracaine, cocaine, benzocaine	Lidocaine, bupivacaine, ropivacaine, prilocaine
Metabolism	Pseudocholinesterase (plasma)	Hepatic CYP (P450)
Allergy	More common (PABA metabolite)	Rare; safe if ester allergy
Memory aid	One "i" in name (procaine)	Two "i"s in name (lidocaine)

Order of Nerve Fiber Blockade

B fibers (small myelinated autonomic/preganglionic sympathetic) blocked FIRST → sympathetic blockade (warmth, vasodilation, BP drop)
Then C fibers (unmyelinated) and Aδ (small myelinated pain/temperature) → loss of pain and temperature
Then Aβ fibers → touch and pressure
Aα (large myelinated motor) blocked LAST → motor function
Clinical correlate: autonomic block (warmth, BP drop) precedes pain block, which precedes motor block

Local Anesthetic Toxicity (LAST)

Lidocaine: CNS toxicity (perioral numbness, tinnitus, metallic taste, tremor, seizures) precedes cardiac toxicity
Cardiac toxicity: arrhythmias, cardiovascular collapse
Exception — Bupivacaine: cardiotoxicity may occur with or before CNS toxicity due to tight Na-channel binding ("fast in, slow out"); highest cardiotoxicity risk
Treatment of severe LAST: IV lipid emulsion (Intralipid 20%) — "lipid sink"

Board Pearl

Esters = pseudocholinesterase; Amides = hepatic CYP. Pseudocholinesterase deficiency prolongs ester anesthetics (and succinylcholine). Local anesthetics work poorly in infected tissue because the low pH keeps the drug ionized, preventing membrane crossing. For lidocaine, CNS toxicity (seizures) precedes cardiac — but bupivacaine cardiotoxicity may occur with or before CNS toxicity due to tight Na-channel binding.

General Anesthetics

Volatile (Inhaled) Agents

Agent	Mechanism	Key Features
Isoflurane	Enhance GABA-A and glycine; activate TREK/TASK two-pore K channels	Widely used; increases ICP (cerebral vasodilation); cardiovascular depression
Sevoflurane	Same as isoflurane (GABA-A, glycine, TREK/TASK)	Non-irritating → preferred for mask induction (pediatrics); rapid onset/offset
Desflurane	Same as isoflurane (GABA-A, glycine, TREK/TASK)	Fastest onset/offset (lowest blood-gas partition coefficient); pungent, airway irritant; tachycardia
Nitrous oxide (N₂O)	NMDA antagonist (NMDA antagonism shared with xenon and ketamine)	Weak anesthetic (adjunct); inactivates methionine synthase via irreversible cobalt oxidation in B12 → subacute combined degeneration (SCD) — dorsal columns + lateral corticospinal tracts; megaloblastic anemia rare; treat with B12 + cessation. Expands closed gas spaces (contraindicated in pneumothorax, pneumocephalus)

All volatile agents increase ICP via cerebral vasodilation and are malignant hyperthermia triggers
MAC (minimum alveolar concentration): concentration at which 50% of patients won’t move to incision; lower MAC = more potent

Intravenous Anesthetics

Agent	Mechanism	ICP	Key Features
Propofol	GABA-A	↓	Rapid onset/offset; hypotension; antiemetic; propofol infusion syndrome (prolonged high-dose: metabolic acidosis, rhabdomyolysis, cardiac failure)
Ketamine	NMDA antagonist	Classic teaching: ↑; modern TBI/ICU data (sedated/ventilated): generally no reliable ICP elevation, may preserve CPP — use caution in uncontrolled intracranial hypertension	Dissociative anesthesia + analgesia; maintains airway reflexes and respiratory drive; sympathomimetic; emergence delirium; bronchodilator
Etomidate	GABA-A	↓	Least hemodynamic effect — RSI in unstable patients; adrenal suppression (11β-hydroxylase); myoclonus
Thiopental	GABA-A (barbiturate)	↓	Burst suppression in refractory SE; cerebral protection; porphyria contraindication
Methohexital	GABA-A (barbiturate)	↓	Activates epileptiform foci on ECoG; used for ECT and Wada test

Board Pearl

Classic teaching: ketamine raises ICP (all other IV anesthetics decrease it). Modern TBI/ICU data in sedated/ventilated patients generally do NOT show reliable ICP elevation and may preserve CPP — use caution in uncontrolled intracranial hypertension but it is no longer an absolute prohibition. Ketamine uniquely provides analgesia and maintains respiratory drive. Etomidate = agent of choice for RSI in hemodynamically unstable patients. Watch for propofol infusion syndrome with prolonged high-dose use (metabolic acidosis + rhabdomyolysis + cardiac failure).

Neuromuscular Blockers

Depolarizing vs Nondepolarizing

Feature	Depolarizing (Succinylcholine)	Nondepolarizing (Rocuronium, Vecuronium, Cisatracurium)
Mechanism	Sustained depolarization → fasciculations then phase I block	Competitive antagonist at nicotinic ACh receptor; no fasciculations
Onset / Duration	Fastest (30–60 sec); ultra-short (5–10 min); pseudocholinesterase metabolism	Slower (1–3 min); intermediate to long; hepatic/renal metabolism
Reversal	None — wait for pseudocholinesterase	Neostigmine (+ glycopyrrolate) or sugammadex (encapsulates rocuronium/vecuronium)
Key risks	Hyperkalemia, malignant hyperthermia, bradycardia	Residual paralysis; prolonged block in organ failure

Succinylcholine Hyperkalemia — Contraindications

Burns, denervation injuries (stroke, SCI, peripheral nerve injury) — upregulation of extrajunctional ACh receptors
Prolonged immobilization / ICU myopathy
Muscular dystrophies (especially Duchenne) — rhabdomyolysis risk
Mechanism: extrajunctional nicotinic receptor upregulation → massive K+ efflux upon depolarization → cardiac arrest
Timing: Safe in first 24–48 hours after acute injury; risk window ~5 days through 1–2 years (or longer in chronic denervation/SCI)
Stroke: avoid after ~1 week post-stroke (safe in hyperacute phase); use rocuronium thereafter

Clinical Pearl

Succinylcholine is contraindicated in burns, denervation, SCI, and muscular dystrophy due to extrajunctional ACh receptor upregulation causing fatal hyperkalemia. Sugammadex allows rapid reversal of rocuronium, making it a viable RSI alternative to succinylcholine in these patients.

Malignant Hyperthermia

Genetics: autosomal dominant; RYR1 mutation (ryanodine receptor type 1 on skeletal muscle SR)
Triggers: volatile anesthetics (isoflurane, sevoflurane, desflurane, halothane) + succinylcholine
Pathophysiology: uncontrolled Ca2+ release from SR → sustained contraction → hypermetabolism
Early signs: masseter rigidity, unexplained tachycardia, ↑ end-tidal CO₂ (earliest and most sensitive sign)
Progression: temperature >40°C, rigidity, mixed acidosis, hyperkalemia, rhabdomyolysis, DIC
Confirmatory test: caffeine-halothane contracture test (CHCT/IVCT) — muscle biopsy, gold standard
RYR1 / CACNA1S genetic testing adjunctive (sensitivity ~50–70%); CHCT/IVCT remains gold standard

Treatment

Dantrolene = definitive treatment — blocks the ryanodine receptor (RYR1), preventing Ca2+ release from SR
Immediately discontinue all triggering agents; hyperventilate with 100% O₂
Active cooling; treat hyperkalemia
Dantrolene dosing: 2.5 mg/kg IV bolus, repeat q5–10 min up to cumulative 10 mg/kg (higher if persistent symptoms); maintain at 1 mg/kg q6h × 24–48 h
Safe agents for MH-susceptible patients: propofol, etomidate, opioids, benzodiazepines, nitrous oxide, nondepolarizing NMBs

Board Pearl

Malignant hyperthermia = RYR1 + volatile anesthetic or succinylcholine. Earliest sign = unexplained ↑ EtCO₂. Treatment = dantrolene (blocks ryanodine receptor). Dantrolene is also used for NMS, though NMS is from dopamine blockade (not a channelopathy). Know the safe anesthetic alternatives for MH-susceptible patients.

Procedural Sedation in Neurology

Agent	Effect on Seizure Foci	Neurologic Use
Methohexital	Activates epileptiform discharges	Wada test (intracarotid injection for language/memory lateralization); ECT
Propofol	Activates foci at low doses; suppresses at high doses	Intraoperative ECoG (identifies epileptogenic zone); burst suppression in refractory SE
Thiopental	Suppresses; does NOT activate foci	Burst suppression; cerebral protection (↓ CMRO₂ and ICP)
Pentobarbital	Suppresses	Prolonged burst suppression for super-refractory SE (pentobarbital coma)
Midazolam	Suppresses	First-line IV infusion for refractory SE; least hemodynamic compromise

Wada test: intracarotid methohexital (or amobarbital) anesthetizes one hemisphere → tests language dominance and memory before temporal lobectomy
Refractory SE escalation: midazolam → propofol → pentobarbital coma (continuous EEG targeting burst suppression)

Clinical Pearl

In refractory status epilepticus, midazolam has the least hemodynamic effect but highest breakthrough rate; pentobarbital is most reliable for burst suppression but causes the most hypotension. All require continuous EEG monitoring.

Non-Opioid & Adjuvant Analgesics

Drug / Class	Key Features
Acetaminophen	Max 3–4 g/day; hepatotoxicity (NAPQI metabolite); NAC for overdose; chronic ETOH/malnutrition → lower max dose
NSAIDs	GI bleeding, renal injury, cardiovascular risk (esp COX-2 selective); avoid in CKD, heart failure, peptic ulcer disease
Tapentadol	Mu agonist + NRI; lower opioid burden; less constipation; CrCl considerations for dose adjustment
Suzetrigine (Journavx)	NaV1.8 inhibitor — FDA-approved Jan 2025 for moderate-severe acute pain; first non-opioid acute pain analgesic in decades

Muscle Relaxants

Cyclobenzaprine — TCA-related (anticholinergic side effects)
Methocarbamol, baclofen (GABA-B), tizanidine (alpha-2), diazepam (BZD), dantrolene (RYR1 blockade — used in MH and spasticity)

Cannabinoids

Dronabinol, nabilone — synthetic THC
CBD (Epidiolex) — FDA-approved for refractory seizures (Dravet, Lennox-Gastaut, TSC)
Medical cannabis — variable evidence in chronic pain

Codeine + CYP2D6

Prodrug activated to morphine by CYP2D6
Ultra-rapid metabolizers (UM) → morphine toxicity/death — FDA labeling contraindicates codeine in all children <12 yr (for pain or cough); codeine AND tramadol are contraindicated in patients <18 yr after tonsillectomy/adenoidectomy; FDA recommends AGAINST both codeine and tramadol during breastfeeding (serious infant toxicity / respiratory depression / death)
Poor metabolizers → no analgesic effect

Opioid-Induced Hyperalgesia (OIH)

Paradoxical pain sensitization from chronic opioid use (NMDA-mediated central sensitization)
Treatment: opioid rotation/taper + ketamine or buprenorphine + adjuvants (gabapentinoids, SNRIs)

Chronic Pain Syndromes

Complex Regional Pain Syndrome (CRPS)

Stellate ganglion / lumbar sympathetic block
Ketamine infusion for refractory cases
Bisphosphonates (early, within 6–12 weeks)
Spinal cord stimulation (SCS) and dorsal root ganglion (DRG) stimulation

Fibromyalgia — FDA-Approved Agents

Duloxetine (SNRI)
Milnacipran (SNRI)
Pregabalin (α2δ)

Phantom Limb Pain

Gabapentin, TCAs, mirror therapy; opioids and ketamine used selectively

Interventional / Device Therapies for Refractory Pain

Intrathecal pump (morphine, ziconotide, baclofen)
Spinal cord stimulation (SCS) — failed back surgery syndrome, CRPS, diabetic neuropathy
Dorsal root ganglion (DRG) stimulation — focal neuropathic pain

OUD Pharmacotherapy & Reversal Agents

Opioid Use Disorder (OUD)

Drug	Mechanism / Notes
Methadone	Full mu agonist; clinic-dispensed; QT prolongation
Buprenorphine/naloxone (Suboxone)	Partial mu agonist + naloxone (antagonist deters injection); ceiling effect on respiratory depression
Naltrexone (Vivitrol IM monthly)	Mu antagonist; requires opioid-free 7–10 days prior to initiation to avoid precipitated withdrawal
Naloxone (Narcan / Kloxxado)	OD reversal; intranasal/IM/IV
Lofexidine	Alpha-2 agonist; treats opioid withdrawal symptoms

Sedation & Reversal Agents

Dexmedetomidine — alpha-2 agonist; ICU sedation; preserves arousability; bradycardia/hypotension; no respiratory depression
Flumazenil — BZD reversal; precipitates withdrawal in dependent patients; caution in mixed overdose with TCAs / seizure history (can precipitate seizures)
Sugammadex — encapsulates rocuronium / vecuronium for rapid reversal of nondepolarizing block

Anesthesia in Neurosurgery / IONM

TIVA (total IV anesthesia — typically propofol ± remifentanil) preferred for intraoperative neuromonitoring (IONM) — volatile agents suppress evoked potentials (MEPs, SSEPs)
Avoid neuromuscular blockade during MEP monitoring
Ketamine and etomidate can augment cortical SSEP amplitude

Quick Reference

Pain & Anesthesia Pharmacology — At a Glance

Category	Key Drug / Concept	Board-Yield Feature
Trigeminal neuralgia	Carbamazepine (first-line)	Na channel blocker; screen HLA-B*1502
Neuropathic pain	Gabapentin/pregabalin	α2δ Ca channel subunit; renal dosing
Opioid overdose	Naloxone	Short half-life; may need redosing
Tramadol risks	Seizures + serotonin syndrome	Weak mu + SNRI; avoid with SSRIs/MAOIs
Ester vs amide	Pseudocholinesterase vs hepatic CYP	Amides have two "i"s; esters have one
LA toxicity	CNS first, then cardiac	Bupivacaine = highest cardiotoxicity; IV lipid emulsion
Nerve block order	B (autonomic) first → C / Aδ (pain) → Aβ (touch) → Aα (motor) last	Autonomic block precedes pain; motor last
ICP and anesthetics	Volatiles + ketamine ↑ ICP	Propofol, etomidate, thiopental ↓ ICP
Etomidate	Least hemodynamic change	RSI in unstable patient; adrenal suppression
Succinylcholine	Hyperkalemia risk	Burns, denervation, SCI, muscular dystrophy; MH trigger
Sugammadex	Reverses rocuronium/vecuronium	Encapsulates drug; alternative to neostigmine
Malignant hyperthermia	RYR1 + volatiles/succinylcholine	Earliest sign = ↑ EtCO₂; treat with dantrolene
Wada test	Methohexital (or amobarbital)	Activates foci; lateralizes language/memory
Burst suppression	Thiopental / pentobarbital	Suppresses cortical activity; refractory SE

References

Ropper AH, Samuels MA, Klein JP, Prasad S. Adams and Victor’s Principles of Neurology. 12th ed. McGraw-Hill; 2023.
Bhatt A. Ultimate Review for the Neurology Boards. 3rd ed. Demos Medical; 2016.
Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 14th ed. McGraw-Hill; 2023.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail’s Clinical Anesthesiology. 7th ed. McGraw-Hill; 2022.
Dworkin RH, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007;132(3):237–251.
Rosenberg H, et al. Malignant hyperthermia: a review. Orphanet J Rare Dis. 2015;10:93.

🔒

Continue reading — sign in

The full note has more clinical pearls, tables, and board-focused tips. Free account, no fee.