Opiods Flashcards
Mu 1 Receptor (location, effects, drugs)
Supraspinal (brain) = periaqueductal or periventricular gray
- Brady (direct central act on vagus nerve)
- Euphoria, miosis, analgesia, hypothermia, urinary retention, psych abuse
- ALL endogenous & exogenous agonists act on Mu1&2
Mu 2 Receptor (location, effects, drugs)
Spinal (SC) = Substantia gelatinosa & dorsal root ganglion
- Brady (direct central act on vagus nerve)
- Pruritis, N/V, constipation, physical dependence
- ALL endogenous & exogenous agonists act on Mu1&2
Kappa Receptor (location, effects, drugs)
Supraspinal & Spinal
- Dysphoria, miosis, sedation, diuresis (inhibit ADH)
- DYNORPHINS work here & Butorphenol (agonist/ant)
Delta Receptor (location, effects, drugs)
Supraspinal & Spinal (modulator of Mu)
- Resp depression, pruritis, constipation (mild), physical dep
- ENKEPHALINS work here
Opiods: CNS Effects
Analgesia, euphoria, sedation, resp ctr depress, miosis, nausea CTZ (NO amnesia/anesthesia)
- DECREASE ICP (modest) in absence of hypo vent
- DECREASE CBF & CRMO2
- Cerebrovascular stability
Opiods: CV Effects
No impairment of CV FUNCTION
-Dec HR (dose dependent)
Dec CO/BP (vasodilation form HISTAMINE release w/MSO4 & meperidine)
Dec CO/BP (venodilation)
Opiods: Resp Effects
- Depression (Dose Dep), Infusion = less depression than bolus;
- Vent depr early < 2h fent/sufent and late 6-12h MSO4
- Hypercarbia ↓CO2 responsiveness;
- Hypoxia
- High airway pressures due to ↑ intrathoracic pressures
compliance ;
↓RR ↑ Vt (Low Dose)
↓RR & Vt (High Dose) - Ventilatory response curve shifted Down & to the Right
What increases the magnitude & duration of reps depression w/opiods?
1) Alkalosis = ↑ % nonionized = ↑ brain penetration.
2) Secondary plasma peaks (Fentanyl & sufentanil) = reuptake into muscle, fat, lungs, & intestines
What factors influence the reap depressant effects of opiods?
Amt of pain/stimulation vs natural sleep, bolus vs continuous infusion, speed of injection, combo w/other anesthetics, age, clearance.
Opiods: Musculature Effects
Muscle Rigidity
Laryngeal
Chest Wall
Pharyngeal
Glottic rigidity and Closure
have been reported
Called Wooden Chest
Tonic/Clonic (Fentanyl)Opiods: Renal/GI/Liver Effects
- ↑ Urine (ADH Blocked) at same time sympathetic blockade of sacral plexus cause urine retention;
- Urine retention after epi/spine more common than IV for ♂;
- ↓ Catecholamine release;
- ↓ Cortisol release;
- Oddi Spasm w/ ↑ biliary pressure (reverse w/ narcan or glucagon 0.25 – 0.5mg IV)
- Constipation
- ↓ Gastric Emptying
Opiod MOA
**All opioids activate inhibitory G proteins. Bind to opioid receptors & produce agonist effects (acting like an opiate)
1) Inhibit adenylyl cyclase → ↓cAMP & ↓ protein phosphorolation.
2) Opioids close voltage-gated Ca⁺⁺ channels on pre-synaptic nerve terminal to inhibit release of excitatory neurotransmitters ACh, Dopa, Norepi, (as well as glutamate & Substance P in the SC) & post-synaptic ↓ in neurotransmission.
3) promote opening of K⁺ channels → ↑K⁺ conduct. & hyperpolarization → ↓activity of post-synaptic cells. Opioids raise pain threshold by interrupting ascending pain pathways in the substantia gelatinosa in the dorsal horn of the SC & ventral caudal thalalamus & also activate descending pathways (periaquaductal gray area in midbrain, rostral ventral medulla) in CNS.
4) ↑ production of Phospholipase A2 = ↑ production of prostaglandins & leukotrienes
**Opioids also ↑ pain threshold by acting on peripheral sensory neurons. They ↓emotional reactivity to pain by acting on limbic areas of CNS.
Describe the various opiod potencies.
Sufentanil (1000x) > Remifentanil (100x) > Fentanyl (100x) > Alfentanil (10-20x) > Dilaudid (5x) > MORPHINE > Demerol (1/10th)
Main characteristics of Morphine
- LEAST lipid soluble, low PB 30%
- Morphine-6-glucoronide (650x more potent)
- CI: asthma, MAOIs, RF
Morphine: DOA, E1/2t, Vd, Peak effects
Morphine:
- DOA 3hrs
- E1/2t 3-5hrs
- Vd 4L/kg
- IV peak 15-30
Morphine DOSE
- 5-15mg IV preop dose
- 01-0.02mg/kg
**Delayed resp del especially w/epidural & spinals
Meperidine unique MOA
- Structure like atropine = antichol effects
- Similar to LAs = bock Na channels
- Alpha 2 agonist
What receptors are activated to dec shivering w/Meperidine?
↓ shivering = Kappa & alpha 2
Meperidine: DOA, E1/2t, Vd
DOA 3hrs
E1/2t 3-5hrs
Vd 4L/kg
Meperidine SE
- Cardiac dep, tachy (catecholamine release)
- Normeperidine = CNS stim, conf, hallucinations, myoclonus & seizures
- Histamine release
Which opiod has the lowest N/V profile?
Meperidine
Which drugs do you avoid w/MAOIs?
Morphine = ↓ metabolism Meperidine = Fetal serotonin syndrome
CI to Meperidine
ASTHMA
Renal Dz
Seizure hx
MAOIs
Which opiods inc ICP?
Fentanyl & Alfentanil
