Opioids Flashcards
Basic Pharmacology
Structure, activity
Semi synthetic (morphine modified): codeine, hydromorphone, hydrocodone, oxycodone
Full synthetic meperidine: fentanyl, alfentanil, sufentanil, remifentanil
In general: highly protein bound, highly soluble, weak bases, ionized at physiologic pH
Mu agonists are most effective in treating “second pain”, carried by slow conducting unmyelinated C fibers
Mechanism
Opioid-R: G protein coupled, opioid agonist bind -> activates G protein -> effects (inhibitory); hyperpolarize = reduced neuronal excitability
Inhibit release of substance P: from primary sensory neurons (dorsal horn) -> decrease pain sensation to brain
Brainstem: modulate nociception in dorsal horn via descending inhibitory pathways
Probable actions in forebrain
Acts on “reward structures”
Receptors
Mu: endogenous ligand = endorphin/endomorphin. Supra/spinal anesthesia. Vent depression. GI and sedation
(Morphine,fentanyl)
Delta: endogenous ligand = enkephalins. Supra/spinal anesthesia.
Kappa: dynorphine. Supra/spinal. GI and sedation
(Buprenorphine)
Metabolism
General: hepatic microsomal
Active metabolites; morphine and meperidine
Context sensitive half time CSHT - time req for 50% reduction in concentration after stopping a continuous steady-state infusion
Pharmacodynamics
Mainly Mu agonists have same PD with important PK differences.
I.e. Their efficiency as analgesics and propensity to produce vent depression are essentially indistinguishable
Top down:
Supraspinal analgesia
Sedation and euphoria
Miosis
N/V (stim area postrema, 4th ventricle, exacerbated by movement)
Cough suppression (medulla)
Spinal analgesia
Vado-D (depress vasomotor centers [brainstem] and > direct effect on vessels)
Brady (increased vagal tone - brainstem)
Vent depression (medulla- response to CO2)
Delayed gastric emptying (tonic contraction of GI smooth muscle)
Increased biliary pressure (GB and sphincter of Odi contraction)
Ileus
Urinary retention (decreased detrusor tone and increased urinary sphincter tone, esp w/ intrathecal and epidural)
Muscle rigidity
Depressed cellular immunity (inhibit IL2)
Drug interactions
Most important PK:
-IV opioid + propofol = higher opioid concentrations
Most important PD:
- synergy with sedatives
- w/ volatile anesthetics = dramatic reduction in MAC (as much as 75%). Occurs at moderate opioid doses
- applies with combination with propofol for TIVA
Codeine
Prodrug -> morphine
Metabolized by liver (CYP2D6)
10% of white people lack CYP2D6
Morphine
Prototype
Assoc with histamine release and this hypotension
Slow onset: it’s pKa makes it ionized at physiologic pH, also low lipid solubility = prolonged latency to peak effect. Penetrates CNS slowly (risk of overshooting and “stacking”)
Active metabolite; MG6, excreted by kidney
First pass metabolism with PO = high MG6
Potentially toxic levels in HD patients
Dosing:
PO 15-30mg q4 - peak 60min, duration 4-5hrs
IV 2.5-10mg q2-6
Epidural 1-6mg (start 3-5mg)
Angina/MI 2-5mg
Renal dosing
t1/2 2-4hrs
Pedi
Intra op 50-100 mcg/kg post op 50 mcg/kg
Fentanyl
IV, transdermal, transmucosal, transnasal, transpulmonary
Doses
GA 50-100 mcg/kg (low dose for PTs > 65)
Pedi 1-3mcg/kg q1-4hr
Post op pain 50-100mcg IV/IM q1-2hr
Renal dosing
t1/2 3-4
Peak 3-5 min, effect site t1/2 30 min
Remifentanil
Loses mu receptor agonist activity upon ester hydrolysis
CSHT - 5min
Slightly less potent than fentanyl
Dosing
Induction 0.5-1 mcg/kg
Maintenance 0.05-2 mcg/kg/min
t1/2 3-10min
Peak 90sec
Hydromorphone (dilaudid)
Rapid onset
Peak effect 5-10min
8 x more potent than morphine
— 1mg = 8mg of Morphine
Pedi
10-20mcg/kg
Elimination half life 2.5hrs
Meperidine (Demerol)
Peak effect 15min Lasts 2-4hrs *actuve metabolite = normeperidine -> lower seizure threshold and Renault excreted Tx shivering Anticholinergic - tachy Avoid with MAOI's Histamine release
Dose
50-100mg PO/SC/IM q3-4hrs
