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.
    reference

    expand and show 6 more articles

  • 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.
    reference

    expand collection

  • Ketamine

     

    Ketamine is a dissociative anaesthetic & potent analgesic.

    • "Dissociative anaesthesia" refers to dissociation of thalamocortical and limbic systems on the EEG.

    A. Physiochemistry

    • phenylcyclidine (PCP) derivative
    • pKa 7.5, weak acid (like thiopentone 60% nonionised @ pH 7.4)
    • highly lipid soluble (4x thio)
    • ampoule: 200 mg in 2 mL
    • acidic solution of i) ketamine hydrochloride with ii) benzethonium chloride (preservative - neurotoxic !)
    • 2 optical isomers - S(+)d ketamine has i) more rapid emergence due to higher metab, ii) less emergence SEs, iii) less cardiac depression, iv) 3x analgesic potency.

    B. Pharmacokinetics

    1. Dose - 1.5-2 mg/kg IV, 10 mg/kg IM
      • oral premed: 6-7 mg/kg po (15-30 min onset)
      • Rx: asthma 20 mcg/kg/min
      • analgesia: 0.1-0.3 mg/kg/h (no dysphoria @ 0.1, sometimes pleasant dreams @ 0.2 mg/kg/h). -[HPH 400mg in 50mL]
      • TIVA: 10-50 mcg/kg/min
    2. Absorption - IV, IM, oral or PR
    3. Distribution - 8 L/kg
    4. Protein binding - 25% (thiopentone 75%, propofol 98%)
    5. Onset IV: 45-60s, peak 60s; IM: 3-5 min; Offset 15-30 min
    6. Metabolism - alpha∆ 11 min, ß ∆ 2.5 h. Hepatic p450 to N-demethylation to norketamine, hydroxylated to hydroxynorketamine, conjugated to water sol glucuronide derivatives.
      • Norketamine has 1/5 activity of ketamine (? post-op S/Es).
    7. Clearance - 18 mL/kg/min (prop 25, thio 4 mL/kg/min)

    C. Pharmacodynamics

    1. Mech - non-competitive NMDA antagonism (PCP site on NR1 subunit); anti-muscarinic; anti-monaminergic; inhibits peripheral reuptake of catecholamines; S+ enantiomer has some mu receptor activity; inhibits NO synthesis; inh non-NMDA glutamate rec.
    2. CNS - analgesia, amnesia, dissociative anaesthetic (thalamocortical - limbic system); inc CBF, CMRO2, ICP & IOP.
    3. CVS - direct cardiac depressant, but inc SNS outflow - inc CO, HR, MAP. Variable Vc & Vd.
    4. Resp - unaltered response to CO2; bronchodilator; inc salivary secretions; airway reflexes intact.
    5. GIT- inc BSL
    6. SEs - PONV, emergence delerium, ++ secretions, uterine hypertonicity at > 1.5 mg/kg
    7. Interactions - halothane prolongs duration by delaying its redistribution and metabolism.

    Ketamine produces a dissociative state (unconsciousness where in cataleptic state, disconnected from surroundings associated with functional and electrophysiological dissociation between thalamo-neocortical and limbic system)

    • Characteristically : eye open, slow nystagmus, varying purposeful movement and hypertonus unrelated to stimuli
    • Advantages: sympathetic stimulation with preservation of BP esp in hypovolaemic state, preservation of airway reflexes, bronchodilation and intense analgesia
    • Disadvantages: can theoretically precipitate myocardial ischaemia (increasing both workload and O2 requirements) increases CBF, increases PVR, emergence delirium (also anaesthetic end-point unclear and uncontrolled movements).
    reference

    expand and show 1 more article

  • 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.
    reference

    expand collection

  • Sufentanil

     

    Sulfentanil is a potent, short-acting synthetic opioid used in anesthesia and critical care. First synthesized by Janssen Pharmaceutica in 1974. It is the most potent opioid licensed for use in humans.

    • OWC 1800
    • pKa 8.0
    • Potency 5-10x fentanyl, 500x morphine.
    • Vd 3 L/kg
    • Protein binding 93%
    • Clearance 12 mL/kg/min
    • tß½ 3 hours
    • CSHT(8h) 30 min (alfentanil ~60 m)
    • mu agonist, also stimulates serotonin release and at high dose has local anaeshetic effect.
    • Structurally different from fentanyl, with a methoxymethyl group on the piperidine ring (increases potency and reduces duration of action) and thiophene instead of phenyl ring.
    reference

    expand collection

What will the 'Medical Journal of You' look like?

Start your free 21 day trial now.

We guarantee your privacy. Your email address will not be shared.