Opioids Flashcards
2 opioid structures
Phenanthrenes and benzylisoquinolines
Natural opioid
Semisynthetic opioids
Natural: morphine
Semi: heroin, dilaudid, codeine
Synthetic opioids
Exogenous. Fentanyl, sufentanil, alfentanil
Phenylpiperidines
5
Meperidine, fentanyl, alfentanil, sufentanil, remifentanil
What it means to be a partial agonist, example
Buprenorphine. Regardless of dose cant produce full mu receptor fx. Safer, less abuse
What it means to be mixed agonist/antagonist and ex
Nalbuphine. Agonist at one receptor (kappa) antagonist at mu, reverses resp depression
All endogenous and exogenous agonists act where
Mu receptors
Mu 1 receptor
5 main effects
Analgesia, euphoria, miosis, bradycardia, urinary ret
Mu 1
Where it primarily acts
What works here
Supraspinal, spinal to lesser degree.
All endogenous and synthetic agonists
Mu 2 receptor
3 main effects
Where it primarily works
What works here
Hypoventilation, phys dependence, constipation. Spinal. Endog/exog agonists
Kappa receptor
Where they are
Only what works here
Supraspinal and spinal
Dynorphins
Kappa receptor
4 main effects
Dysphagia, sedation, miosis, diuresis
Delta receptor
Where they are
What works here
Supraspinal and spinal
Enkephalins
Delta receptor
4 Main effects
Hypoventilation, phys dependence, constipation (minimal), and urinary retention
Opioid MOA
Net effect
Inc K conductance, ca ch inactivation, both decrease NT release
Opioid MOA
Activation of receptors does what
Decreases neurotransmission or inhib release of excitatory NTs
What affects onset of opioids
Higher % unionized, higher % unbound. Both = faster onset
Opioids: what pH, what part works
Weak base. Only unionized and unbound can diffuse from blood to tissues
Alfentanil vs morphine onset
Alf- 98% unionized, rapid onset
Morph- 23% unionized, slower onset
Neonate vs elderly in opioid dynamics
Neonate- dec elim d/t immature cyp 450. Elderly have greater brain sensitivity to drug
How to dose opioids, how not to
Based on ideal body weight (lean body mass) not actual weight in kg
Spinal analgesic effects produced by what
Receptor activation in SC and DRG
Supraspinal analgesia produced by what
Receptor activ in periaqueductal gray matter in brain
CNS effects of opioids
Analgesia, euphoria, sleep, resp dep, miosis, nausea, modest dec ICP, dec CBF
CNS effects
How nausea is produced
Doesnt do what 2 things
Chemoreceptor trigger zone
Amnesia or anesthesia
Advantages Of opioids in neuro anesthesia
Hemodynamic and cerebrovascular stability
CV effects
Doesnt impair function. Bradycardia (dose dep), dec co and bp, vasodilation
CV effects specific to meperidine
Tachycardia and myocardial depression
Vent effects
Resp dep (dose dep), dec chest wall compliance, constriction of pharyngeal/laryngeal muscles, hypercarbia, hypoxia
Bad effects on resp sys
Low dose
High dose
Low- dec rr, inc vt
Hi- dec rr and vt
Bad effects resp sys
Dec hypoxic vent drive and vent response curve reduced and shifted right
Resp depression onset and duration: morphine vs fentanyl
Onset slower for morphine and lasts longer than fentanyl
Factors that inc magnitude and duration of opioid resp depression: 8
Inc dose, bolus v gtt, speed of injec, admin of other anesthetics, dec clearance, age, alkalosis, reuptake from muscle/fat/lung tissue/intestine
Skeletal muscle effects
Rigidity (laryngeal, inhib of gaba, inc in dopamine). Can make vent difficult
Renal/gi/liver effects
Urgency GU, block catecholamine release and cortisol, sphincter of oddi spasm, constipation, prolonged gastric emptying
Opioids in epidural space undergo uptake into where
Fat, systemic absorption, diffusion into CSF
Penetration into CSF depends on what
Lipid soluble. More soluble= quicker peak concentration
How lipid solubility affects movement in CSF
Highly= limited migration d/t SC uptake
Less soluble= remains in CSF for cephalic transfer
How lipid solubility affects vascular absorption of opioids in neuraxial anesthesia
More lipid soluble- quicker peak in blood.
SE neuraxial opioids
4
Pruritis most common, NV, urine retention, vent depression (faster w lipophilic)
Morphine
Solubility, binding, ionization
Poor lipid solubility, high protein binding. Highly ionized
Morphine
Effects 8
Analgesia, sedation, euphoria, nausea, pruritis, dry mouth. Vent depression
Morphine
IM and IV peak
DOA
IM- 45 min. IV- 15-30 min
DOA- 4 hrs
Morphine
How bradycardia caused, other CV effect
Stim vagus directly, inhib SA node
Morphine
Metab by what
Metabolite and potency
Liver. Active morphine 6 glucuronide, more potent than morphine sulfate
Morphine
Metabolism: other role and affected by what
Kidneys do extrahepatic metab. Renal failure will impact d/t metabolite
Meperidine
Structural similarity to what
___ effects
Atropine and LA (blocks Na ch). Muscarinic.
Meperidine
Potent at which receptors
DOA
A2
2-4 hrs
Meperidine
Effects, similarity to
Euphoria, sedation, analgesia, same amt as morphine
What is normeperidine
Active metabolite. Lasts 3 days, 1/2 as potent. Seizures reported
Meperidine
Used postop for what
Potency compared to morphine
Shivering (kappa and A2 receptors). 1/10th as potent as morphine
Hydromorphone
Potency and effects compared to morphine
Dosing
5x more potent, more sedation but less euphoria than morphine. Rapid elim, q4 dosing
Fentanyl
Comparison to morphine: solubility, duration, potency
More lipid soluble, shorter duration, 100x more potent
Fentanyl
Where its taken up
75% 1st pass pulmonary uptake. Also fat, muscle
Fentanyl
Dose for bolus
Dose for lollipop, when
1-20 mcg/kg
5-20 mcg/kg 45 min before induction
Sufentanil
Comparison to fentanyl and to morphine
2x as lipid soluble and 10x more potent than fent. 1,000x more potent than morphine
Sufentanil
Binding
Metabolism
Highly protein bound. Pulm 1st pass. Metab in liver. Weak active metabolite desmethylsufentanil
Clinical use of sufentanil
Quicker induction and earlier emergence/extubation than morphine and fent. Good for output surgery
Alfentanil
Onset, binding
Fast onset, 90% unionized, 1.4 min. Highly protein bound
Alfentanil
Comparison to fentanyl and morphine
Even tho more protein bound, higher diffusable fraction than fentanyl. 1/5 as potent as fentanyl. 10-20x more potent than morphine
Alfentanil
Useful for what
Rapid onset to blunt hemodynamic response to pain. Outpt surgery
Remifentanil
Metabolism, onset, duration
Metab by tissue/plasma esterases. Fast onset/duration, smal Vd
Remifentanil
Potency compared to fent and morphine
Sim to fent, 100x more than morphine
Remifentanil
Clinical use
Blunts pain. Use gtt for interm-long surgeries when rapid recovery needed. Neuro or O/P
Agonist/antagonist
Where receptor effects are, use, may cause what
Mu antagonist/partial agonist, partial agonist at kappa. Ltd vent dep, low dependence chance. Dysphoria possible.
Nalbuphine
Works where, how, class
Agonist antagonist. Kappa and sigma receptors. Antagonizes resp dep but maintains analgesia. Reverses oddi spasm.
Butorphenol
Class, acts where, analgesia
Agonist at kappa, antagonist or partial agonist at mu. 5x > potent than morphine. Nasal for migraines
Naloxone
Class, where it acts
Opioid antagonist at mu, kappa, and delta
Naloxone
Duration, onset
Less than most opioids, 1-2 min
Naloxone
Adverse effects
Tachycardia, htn, dysrhythmias, pain, pulm edema (cv disease pts or healthy)
Demerol dose
50-100 mg IV
Fentanyl dose
1-3 mcg/kg
Remifentanil dose
1-2 mcg/kg
Alfentanil dose
10-20
Sufentanil dose
0.1-0.3 mcg/kg
Gtt for fent
.01-.05 mcg/kg/min
Gtt for sufentanil
0.0015-0.01 mcg/kg/min
Gtt for alfentanil
.25-.75 mcg/kg/min
Gtt for remifentanil
0.05-.25 mcg/kg/min
Alfentanil: loading dose, bolus
25-100 mcg/kg
5-10 mcg/kg
Sufentanil
Loading dose
Bolus
- 25-2 mcg/kg
2. 5-10 mcg
Fentanyl
Loading dose
Bolus
4-20 mcg/kg
25-100 mcg
Remifentanil
Loading dose
Bolus
1-2 mcg/kg
.1-1 mcg/kg
Potency of opioids
Sufent > remifent > fent > alfent > dilaudid > mso4 > demerol
