Alpha 2 agonists _ clonidine vs dexmed ### . Also compare pentazocine -butorphenol, morphine - fentanyl . Short and crisp with mnemonics or flashcards for md anaesthesia exam .
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I now have comprehensive data from Barash (Clinical Anesthesia), Morgan & Mikhail, and Lippincott. Let me now compose the full answer.
Alpha-2 Agonists, Opioids & Mixed Agonist-Antagonists: MD Anaesthesia Flashcards
🃏 CARD 1: Alpha-2 Agonists at a Glance
Mnemonic: "C is for Clumsy; D is for Dexterous"
Clonidine = older, less selective, oral/transdermal
Dexmedetomidine = newer, more selective, IV infusion only
Dexmedetomidine = newer, more selective, IV infusion only
⚡ CLONIDINE vs DEXMEDETOMIDINE - Master Comparison Table
| Feature | Clonidine | Dexmedetomidine |
|---|---|---|
| α2 : α1 selectivity | 200 : 1 | 1600 : 1 (7x more selective) |
| Type | Partial agonist | Full agonist |
| Route | PO, IV, transdermal, epidural, intrathecal | IV infusion only |
| t½ | Long (~12-16 hr); renal excretion | Short (~2 hr); context-sensitive t½ ~13 min (infusion <8 hr) |
| Onset (IV) | Slow | Fast (~5-10 min) |
| Site of action | Locus coeruleus, spinal cord, peripheral | Locus coeruleus >> medullary vasomotor centre |
| Sedation quality | Mild-moderate | Unique: arousable sedation (mimics natural sleep; responds to voice) |
| Analgesia | Yes (central + spinal) | Yes (but weaker analgesic) |
| Anxiolysis | Yes | Yes |
| Respiratory depression | Minimal / None | Minimal / None (KEY advantage of both) |
| CVS effect | ↓ HR, ↓ BP (no orthostatic hypotension) | Biphasic: initial ↑ BP (peripheral α2B) → then ↓ BP + ↓ HR |
| MAC reduction | ~40-50% | ~40-90% (dose-dependent) |
| Anti-shivering | Yes (thermoregulation threshold ↓) | Yes (lowers thermoregulation threshold) |
| Delirium prevention | Yes | Better evidence; reduces ICU delirium vs propofol/benzodiazepines |
| Withdrawal | Severe rebound HTN if abruptly stopped (tachycardia, diaphoresis) | Less withdrawal risk |
| Hyperglycaemia | Yes (inhibits insulin release) | Less prominent |
| OT-eligible uses | Premedication, regional adjuvant, chronic pain, HTN | ICU sedation, awake fibreoptic, paediatric, OSA patients, TIVA adjuvant |
| Unique use | Complex regional pain syndrome, substance withdrawal | Functional neurosurgery (no EEG suppression); bariatric surgery |
| β-blocker caution | Do NOT use alone in withdrawal (unopposed α1 → worse HTN) | N/A |
Mnemonic for Dexmed's advantages over Clonidine: "7 FARSIES"
- 7x more selective
- Fast acting IV
- Arousable sedation (cooperative patient)
- Respiratory drive preserved even at high doses
- Shorter t½ (titratable)
- ICU delirium reduction
- Effective in OSA/bariatric
- Shivering reduced
🃏 CARD 2: Alpha-2 Receptor Locations - Mnemonic "Pre-Post-Periphery"
| Location | Type | Effect |
|---|---|---|
| Presynaptic CNS (LC) | α2A | ↓ NE release → sedation, analgesia |
| Postsynaptic medullary | α2A | ↓ sympathetic outflow → ↓ BP |
| Peripheral vascular (α2B) | Postjunctional | Initial vasoconstriction → transient ↑ BP (dexmed > clonidine) |
| Spinal cord (dorsal horn) | α2A/C | Analgesia (used as epidural adjuvant) |
🃏 CARD 3: Opioid Receptor Quick Reference
Mnemonic: "MKD" = "My Kidneys Ache Daily"
| Receptor | Effects | Full agonists |
|---|---|---|
| μ (mu) | Supraspinal analgesia (μ1), respiratory depression (μ2), physical dependence, muscle rigidity | Morphine, Fentanyl |
| κ (kappa) | Spinal analgesia, sedation, dysphoria, NO respiratory depression | Morphine, Butorphanol, Nalbuphine |
| δ (delta) | Analgesia, behavioural | Enkephalins |
| σ (sigma) | Dysphoria, hallucinations, respiratory stimulation | Pentazocine, Ketamine |
⚡ MORPHINE vs FENTANYL - Master Comparison
| Feature | Morphine | Fentanyl |
|---|---|---|
| Chemical class | Phenanthrene (natural) | Phenylpiperidine (synthetic) |
| Receptor | μ (primary), κ, δ | μ (primarily, highly selective) |
| Relative potency | 1x (reference) | ~100x more potent |
| Lipid solubility | Low (hydrophilic) | High (lipophilic) |
| Protein binding | ~35% | ~80-85% |
| Onset (IV) | 15-30 min | 1-2 min (fast BBB crossing) |
| Peak effect | 60-90 min (hysteresis!) | 5-10 min |
| Duration | 3-4 hr | 30-40 min (bolus) |
| Context-sensitive t½ | Long; accumulates with infusion | Short initially, INCREASES rapidly with prolonged infusion |
| Metabolism | Hepatic glucuronidation → M6G (active, potent), M3G (hyperexcitatory) | Hepatic (CYP3A4); inactive metabolites |
| Active metabolite | Morphine-6-glucuronide (M6G) - prolongs effect in renal failure | Norfentanyl (inactive) |
| Histamine release | YES (direct mast cell degranulation) | NO (major advantage intraop) |
| Cardiovascular | Bradycardia, hypotension (+ histamine) | Minimal - haemodynamically stable; bradycardia (vagotonic) |
| Chest wall rigidity | Less | HIGH dose → "wooden chest" (glottic + truncal) |
| Neuraxial use | Excellent (hydrophilic = wide spread, long duration) | Less spread (lipophilic = segmental, faster onset) |
| Clinical use | Postop PCA, chronic pain, neuraxial, palliative | Intraoperative (TIVA), procedural sedation, patches (chronic) |
| Dose (IV bolus) | 0.1-0.15 mg/kg; titrate 2 mg q5-10 min in PACU | 1-3 μg/kg intraop; give 5-10 min before stimulus |
| Renal caution | YES - M6G accumulates → prolonged sedation/RD | Safer in renal failure |
Mnemonic: "MORPHINE = Makes Old Receptors Produce Histamine IN Everyone"
Key = histamine release, active metabolite, hydrophilic, long duration
Mnemonic: "FENTANYL = Fast Entry, No Toxin ANd Yielding Lipophilics"
Key = fast onset, no histamine, no active toxic metabolite, lipophilic, 100x potent
🃏 CARD 4: Morphine Unique Points for MCQ
- Hysteresis: Plasma peak ≠ effect peak; peak effect lags by 1-2 hr after IV dose
- M6G (morphine-6-glucuronide): More potent than morphine itself; accumulates in renal failure → prolonged respiratory depression
- M3G (morphine-3-glucuronide): No analgesia; causes hyperalgesia, myoclonus, seizures
- Histamine: Urticaria, bronchospasm, hypotension - treat with antihistamines
- Neuraxial: Preservative-free only; intrathecal 0.1-0.3 mg gives 12-24 hr analgesia
⚡ PENTAZOCINE vs BUTORPHANOL - Mixed Agonist-Antagonists
| Feature | Pentazocine | Butorphanol |
|---|---|---|
| Drug class | Benzomorphan | Morphinan |
| μ receptor | Antagonist (weak) | Weak antagonist / partial agonist |
| κ receptor | Partial agonist | Agonist (primary action) |
| σ receptor | Agonist | Minimal |
| δ receptor | Minimal | Minimal |
| Potency vs morphine | ~1/3 (roughly 0.3x) | ~3-5x more potent |
| Route | PO, IM, IV | IM, IV, intranasal (unique) |
| Analgesia | Moderate; ceiling effect | Good; ceiling effect |
| Sedation | Less | More (κ-mediated) |
| Dysphoria/hallucinations | YES - common (σ agonism) | Less (weak σ) |
| CVS effects | ↑ BP, ↑ HR, ↑ PAP (↑ SVR) - AVOID in MI/CAD | Mild ↑ HR, mild ↑ BP |
| Respiratory depression | Ceiling effect (less than full agonists) | Ceiling effect; naloxone reverses |
| Addiction potential | Lower (but NOT zero) | Lower than full agonists |
| Precipitates withdrawal | YES in opioid-dependent patients | YES |
| Special caution | Dysphoria may need haloperidol; Talwin NX = pentazocine + naloxone (abuse deterrent oral form) | Safe in obstetric analgesia |
| Use in CAD/MI | CONTRAINDICATED (raises cardiac workload) | Use with caution |
Mnemonic: "PENTA = Psycho, Elevates NorTensive Arteries"
(Pentazocine causes dysphoria/hallucinations + raises BP/HR/PAP)
Mnemonic: "BUTO = Better, nasal Use, Twice Or more potent"
(Butorphanol is more potent, available intranasally, fewer psych effects)
🃏 CARD 5: Mixed Agonist-Antagonist Class Rules (Applies to Both)
Mnemonic: "CAWDS"
- Ceiling effect for analgesia (and respiratory depression)
- Avoid combining with full agonists (may precipitate withdrawal or ↓ analgesia)
- Withdrawal precipitated in opioid-dependent patients
- Dysphoria (especially pentazocine via σ)
- Safer respiratory profile than full agonists
🃏 CARD 6: Big Picture - The "Receptor Fingerprint" of Each Drug
Drug μ(analgesia/RD) κ(sedation/spinal) σ(dysphoria)
─────────────────────────────────────────────────────────────────
Morphine +++ + -
Fentanyl ++++ - -
Pentazocine antagonist partial + +++
Butorphanol partial/antag +++ ±
🃏 CARD 7: Clinical High-Yield One-Liners for Exam
- Dexmed > clonidine for α2 selectivity: 1600:1 vs 200:1 (7x difference)
- Only drug that causes arousable sedation = Dexmedetomidine
- Fentanyl = intraoperative opioid of choice; Morphine = postoperative/neuraxial
- M6G (active metabolite of morphine) accumulates in renal failure
- Pentazocine raises BP/HR/PAP - contraindicated in MI
- Butorphanol available intranasally; used in migraine/obstetrics
- Both α2 agonists: no significant respiratory depression - safe in respiratory compromised patients
- Wooden chest with high-dose fentanyl - treat with succinylcholine + intubation
- Clonidine withdrawal = rebound HTN + tachycardia; do NOT use β-blocker alone
- Context-sensitive half-life of fentanyl rises steeply with prolonged infusion (unlike remifentanil)
Sources: Barash's Clinical Anesthesia 9e (p.974-976, p.1553-1556); Morgan & Mikhail's Clinical Anesthesiology 7e (p.348-350); Lippincott Pharmacology (p.700-702)
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