Knowledge

Collections of knowledge containing reference notes.

  • Oxycodone

     

    Oxycodone is a semi-synthetic opioid commonly used as an oral, rectal or intravenous analgesic (subcutaneous, intramuscular & intranasal also possible). Trade names include Endone™, OxyContin™ and OxyNorm™.

    A. Physiochemistry

    • Semi-synthetic opioid; thebaine derivative. First synthesised in 1916.

    B. Pharmacokinetics

    1. Dose
      • Oxycodone po conversion from morphine IV 2:1 (oxycodone:morph).
      • (NB: oral to IV morphine 3:1)
      • 10 mg of oral oxycodone is equivalent to 20 mg of oral morphine.
      • 10 mg of oral oxycodone is equivalent to 5 mg of IV/IM morphine.
      • 10-15 mg of parenteral oxycodone (IV/IM) is equivalent to 10-15 mg parenteral morphine (ie. morphine up to 50% more potent)
    2. Absorption - orally up to 87%
    3. Distribution - 2.6 L/kg
    4. Protein binding
    5. Onset - within 10-15 min orally, peak 45-60 minutes; Offset ~2-3h.
    6. Metabolism - ß1/2 ~3-4hrs, metabolised principally to noroxycodone, noroxymorphone and oxymorphone (p450 system). Oxymorphone has some activity
    7. Clearance - 0.8 L/min; predominately renally excreted.

    C. Pharmacodynamics

    • Oxycodone is a full opioid agonist with no antagonist properties whose principal therapeutic action is analgesia.
    • It has affinity for kappa, mu and delta opiate receptors in the brain and spinal cord.
    • Oxycodone is similar to morphine in its action. Other pharmacological actions of oxycodone are in the central nervous system (respiratory depression, antitussive, anxiolytic, sedative and miosis), smooth muscle (constipation, reduction in gastric, biliary and pancreatic secretions, spasm of sphincter of Oddi and transient elevations in serum amylase) and cardiovascular system (release of histamine and/or peripheral vasodilation, possibly causing pruritus, flushing, red eyes, sweating and/or orthostatic hypotension).
    • Strong potentially for tolerance, dependence and abuse.
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  • Buprenorphine

     

    A. Physiochemistry

    • Semi-synthetic thebaine derivative (like oxycodone).
    • Partial µ-agonist.

    B. Pharmacokinetics

    1. Dose: 0.5 mg q6h IV/IM
      • 30x morphine potency
      • 200mcg-400mcg sublingual qid  for analgesia
    2. Absorption - IV, IM, s/l, epidural (po undesirable as ++ 1st pass met)
    3. Distribution - 3 L/kg
    4. Protein binding - 96%
    5. Onset 30 min; Offset 4 h (longer latency & duration than morph)
    6. Metabolism - ß½ 5 h; hepatic dealkylation & glucuronidation. Excreted in bile & hydrolysed by GIT bacteria.
    7. Clearance - 14 mL/min/kg (dec 30% by GA)

    C. Pharmacodynamics

    1. Mechanism: µ partial agonist.
      • 50x greater mu rec affinity than morphine.
      • May be used to treat heroin/morphine dependence.
      • Greater lipid solubility than morphine.
      • Ceiling effect to both analgesia & respiratory depression.
      • Long duration as slow to dissociate from receptor & thus difficult to reverse.
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  • Remifentanil

     

    A. Physiochemistry

    • pKa - 7.3 (58% nonionised @ 7.4)
    • Octanol water coeff - 18
    • phenylpiperidine opioid
    • contain 2 ester bonds so hydrolysed by non-specific tissue esterases.
    • Preparation contains 'glycine', so cannot be used epidurally.
    • White powder for reconstitution with water - 1, 2, 5 mg packs

    B. Pharmacokinetics

    1. Dose: (100x morphine potency, ~equal to fent)   - TCI: 3-8 ng/mL     - (up to 15 ng/mL for very stimulating procedures)     - Spontaneous ventilation returns @ 1-2 ng/mL   - 0.1-0.3 mcg/kg/min infusion (with propofol 80 mcg/kg/min (= 34 mL/h for 70 kg).
      • 0.01-0.05 mcg/kg/min spont vent
      • dilute 1 mg to 50 mL = 20 mcg/mL, or 5 mg in 50 mL = 100 mcg/mL.
      • paeds: 0.03 mg/kg in 50 mL then 1 mL/h = 0.01 mcg/kg/min.
      • Or paediatric whole-ampoule dilutions when advanced pumps are unavailable:
      • 1mg in 16.7mLs
      • or 2mg in 33.3 mLs
      • or 3mg in 50mLs 
      • → to give a dilution of 60mcg/mL
      • then for a patient of XYkg running at X.Y mLs/hr is 0.1mcg/kg/min. eg. for a 42kg patient running at 0.1mcg/kg/min will be 4.2mLs/hr which over 4 hrs uses 16 mL so a 1mg ampoule would be sufficient.
      • 1 mcg/kg IV bolus to blunt pressor resp to intubation, better than fentanyl. (equiv. fent 2 mcg/kg, alfent 20 mcg/kg)
      • 3-5 mcg/kg for intubation with propofol 2 mg/kg.
      • 0.2-0.8 mcg/kg bolus for PCA analgesia (++SEs: sedation, desaturation)
    2. Absorption - IV
    3. Distribution - 0.5 L/kg (small)
    4. Protein binding - 70-90%
    5. Onset 1-4 min; Offset 4 min (offset due to metab not redist)
    6. Metabolism - ß½ ~10 min. (CSHT-8h only 4 min!) Metabolised by non-specific plasma esterases to almost-inactive metabolites (GR90291: 1/4600 activity! / t½ 2h).
      • Minor pathway - N-dealkylation. NOT metabolised by plasma cholinesterase.
    7. Clearance - 42 mL/min/kg (30-50% CO)

    C. Pharmacodynamics

    1. Mech - highly selective mu agonist.
    2. CVS - dec MAP & HR 20-30%. (? low dose glycopyrrolate to attenuate brady).
      • No histamine release.
    3. CNS
      • max MAC reduction ~ 85% (0.1-0.2 mcg/kg/min = 60-70% MAC reduction).
      • To avoid awareness keep propofol @ at least 80 mcg/kg/min or volatile 0.3 MAC.
      • Sedation.
      • Beware rapid Opioid Induced Hyperalgesia.
    4. Resp - ⇣ RR & MV; apnoea. Spontaneous respiration occurs at blood concentrations of 4 to 5 nanogram/mL in the absence of other anaesthetic agents; for example, after discontinuation of a 0.25 microgram/kg/minute infusion of remifentanil, these blood concentrations would be reached in two to four minutes.
    5. GIT - dec CTZ stimulation as rapidly metabolised; no ion trapping.
    6. Muscle - muscle rigidity similar to alfentanil, though more than fentanyl.
      • May cause chest wall rigidity (inability to ventilate) after single doses of > 1 microgram/kg administered over 30 to 60 seconds or infusion rates > 0.1 microgram/kg/minute.
      • Administration of doses < 1 microgram/kg may cause chest wall rigidity when given concurrently with a continuous infusion of remifentanil.
    7. Foetal - little effect as rapidly metabolised by foetus.
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  • Suxamethonium

     

    Suxamethonium chloride (suxamethonium, succinylcholine or sux) is a depolarising muscle relaxant that produces rapid-onset, short-duration, deep muscle relaxation. First identified in 1906 and used medically in 1951, it is one of the oldest anaesthesia drugs still widely used. Due to its unique properties and low cost, it remains on the World Health Organisation's List of Essential Medicines

    A. Physiochemistry

    • (CH3)3-N-CH2CH2-OCO-CH2CH2-OCO-CH2CH2-N-(CH3)3
    • pH 3.5
    • Shelf life 3 years at 4°C, though only 'months' at 20°C.

    B. Pharmacokinetics

    1. Dose - ED95 0.5 mg/kg, IV 1.5 mg/kg, IM 2.5-4 mg/kg.
    2. Absorption - IM, IV.
    3. Distribution - >0.2 L/kg; crosses placenta slightly but little effect on foetus.
    4. Protein binding ?
    5. Onset 30s IV, 2-3 min IM; Offset 3-5 min.
    6. Metabolism - PChE to succinylmonocholine (5% activity) & choline -> succinic acid & choline.
      • tß½ 5 minutes

    C. Pharmacodynamics

    1. Mechanism - binds to alpha subunit of nicotinic ACh receptor, producing persistent depolarisation (phase 1 & phase 2 blocks).
    2. CNS - ⇡ intra-ocular pressure (4-8 mmHg rise), ⇡ intra-celebral pressure (to 30 mmHg at 2-4 min).
    3. CVS - arrhythmias (both bradycardia & tachycardia possible), ⇡ systolic blood pressure, (both negative inotropic and chronotropic effects).
    4. Resp - 'sux apnoea' pharmacogenetic diversity (94% normal, 3.8% heterozyg (10 min duration of effect), <1% homozog (1-2h duration))
    5. Renal - hyperkalaemia due to K+ release from muscle; beware in neuromuscular conditions, denervation, and extensive burns.
    6. GIT - ⇡ intragastric pressure, ⇡ secretions, salivation.
    7. SEs - anaphylaxis, malignant hyperthermia, sux apnoea, muscle pains, masseter spasm.
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