Pharm: Opioid Drugs Flashcards
Meperidine (Demerol) MOA
Synthetic opioid
Structural similar to atropine
Metabolite = normeperidine
Causes CNS stimulation @ high risk for seizures
Meperdine (Demerol) dosing
2.5-5mg/kg
Meperidine (Demerol) onset and duration
onset: 5min
duration: 2-3hrs
Meperidine (Demerol) potency
0.1
Meperidine (Demerol) cautions and other uses
Orthostatic hypotension
Mydriasis
IV Demerol decrease postop shivering (Kappa)
Serotonin syndrome with MAO inhibitors
Morphine MOA
Opium poppy derivative
Inhibits ascending pain pathway
Morphine dosing
0.1-1mg/kg
Morphine onset and duration
onset: 20min
duration: 4-5hrs
Morphine potency
1.0
Morphine cautions and other uses
Orthostatic hypotension
Resp depression
Reduces MAC 50%
Histamine release
Alfentanil (Alfenta) MOA
Analog of fentanyl
1/5 as potent
Metabolized in liver
Alfentanil (Alfenta) loading and maintenance doses
loading: 25-100mcg/kg
maintenance: 0.5-2mcg/kg/min
Alfentanil (Alfenta) onset and duration
Onset: immediate
Duration: 15 m
Alfentanil (Alfenta) potency
10-25
Alfentanil (Alfenta) cautions
admin slowly over 1-3m
monitor for bradycardia
hypotension
Fentanyl (sublimaze) MOA
Structurally r/t meperidine
50-100 x more potent than morphine
High lipid solubility
Fentanyl (sublimaze) loading, maintenance and bolus dosing
Loading:
3-5 mcg/kg
Maintenance:
2-10 mcg/kg/hr
Bolus:
25-100 mcg
Fentanyl (sublimaze) onset and duration
Onset: 2-5 m
Duration: 30-60 m
Fentanyl (sublimaze) potency
75-125
Fentanyl (sublimaze) cautions
Stiff chest syndrome
Remifentanil loading, maintenance, bolus dosing
Loading:
1-2 mcg/kg
Maintenance:
0.1-1 mcg/kg/hr
Bolus:
0.1-1 mcg/kg
Remifentanil onset and duration
onset: 1min
duration: 5-10min
Remifentanil potency
250
Sufentanil (sufenta) MOA
Analog of fentanyl 5-10 x as potent
Sufentanil (Sufenta) loading, maintenance, bolus dosing
Loading:
0.25-2 mcg/kg
Maintenance:
0.5-1.5 mcg/kg/hr
Bolus:
2.5-10 mcg
Sufentanil (sufenta) onset and duration
onset 1-3min
duration: dose dependent
Sufentanil (sufenta) potency
500-1000
Sufentanil (sufenta) cautions
Dose-related bradycardia
HypoTN and HTN
Resp dep
Chest wall rigidity
N/V
Dilaudid dosing
0.015mg/kg
Q3-6hrs
Dilaudid onset and duration
onset 1-3 min
duration 4-5hrs
Dilaudid cautions
Bradycardia/
tachycardia
Flushing of face
Agitation, dysphoria
MOA of opioids
: Agonist binds with stereospecific opioid receptors on the CNS (spinal & supraspinal) and periphery
🡺 Produce analgesia at CNS receptors that respond to endorphins, enkephalins, & dynorphins
🡺 Opiate-receptor activation inhibits pre-synaptic release and postsynaptic response to excitatory neurotransmitters (Ach, substance P) from nociceptive neurons
Classifications of pain
neuropathic
somatic
visceral
opioid receptors: Mu-1
analgesia (supraspinal, spinal), bradycardia, euphoria, hypothermia, miosis, urinary retention, low abuse
- Agonist: endorphins, morphine, synthetics
- Antagonist: naloxone, naltrexone, nalmefene
opioid receptors: Mu-2
analgesia (spinal), respiratory depression, bradycardia, euphoria, miosis, N/V, constipation, urinary retention, physical dependence
- Agonist: endorphins, morphine, synthetics
- Antagonist: naloxone, naltrexone, nalmefene
opioid receptors: Kappa
analgesia (supraspinal, spinal), possible resp depression, sedation/dysphoria, diuresis (vasopressin), low abuse
- Agonist: dynorphins
opioid receptors: delta
analgesia (supraspinal, spinal), modulation of Mu receptors, selective of endogenous enkephalins, resp depression, urinary retention, physical dependence
- Agonist: enkephalins
Opioid receptors: Sigma
dysphoria, hallucinations, tachycardia, mydriasis, resp stimulation
- Agonist: nalorphine, pentazocine, ketamine?
Pain modulation: Gate Theory
large-diameter myelinated afferents (Aβ) conveying pressure and touch information have “faster” conduction speed than Aδ fibers or C fibers conveying painful information to the dorsal horn
🡺 the application of light peripheral mechanical stimuli resulting in excitation of Aβ fibers can activate the inhibitory interneurons in the dorsal horn and thus close the “gate” to the simultaneous incoming pain signals carried by Aδ and C fibers
Pain modulation: tolerance
over time, a drug loses its effectiveness, and a larger dose is required to produce the same physiologic response
Pain modulation: physical dependence
set of physiological changes that disrupts homeostasis
🡺 withdrawal = diaphoresis, insomnia, restlessness, N/V, diarrhea, abd cramps
Classifications of opioids: Natural Opium alkaloids
(Phenanthrene derivatives)
- morphine
- codeine
(Benzylisoquinolone)
-papaverine
Classifications of opioids: synthetic
(Phenylpiperidines)
- alfentanil
- fentanyl
- sufentanil
- remifentanil
- meperidine
- naloxone
(Morphinans)
- nalbupine
(Phenylheptylamines)
- methadone
Clinical effects of opioids: CNS
analgesia, sedation, and euphoria
opioid induced hypercarbia
Clinical effects of opioids: Respiratory depression
acts on Mu and Delta receptors in the brainstem
-reduce responsiveness to increasing CO2 and decreasing O2
-Shift to the right
Clinical effects of opioids: Cardiac
-Via medullary vagal stimulation
-Dose-dependent vasodilation
-Hypotension related to histamine release (morphine, codeine, and meperidine)
Clinical effects of opioids: Miosis
pinpoint pupils
-Opioid depression of GABA interneurons leads to stimulation of Edinger-Westphal nucleus = parasympathetic signals to CN III
Clinical effects of opioids: GI
Decreased GI motility and intestinal propulsive activity, prolong gastric emptying time, and reduce GI secretory activity
-Postoperative issues can include constipation and ileus
Clinical effects of opioids: PONV
emetic effect – opioids stimulate the chemoreceptor trigger zone (CTZ) in the Area Postrema of the medulla
-Primary receptors in this area include serotonin type 3 (5-HT3) & dopamine type 2 (D2)
-dose-dependent increase in biliary duct pressure and sphincter of Oddi tone
Clinical effects of opioids: Muscle Rigidity
generalized hypertonus of skeletal muscle, especially with higher dosing
-Truncal rigidity, chest-wall constriction/loss of compliance, pharyngeal & laryngeal muscle constriction possible (fentanyl, sufentanil, remifentanil, alfentanil)
Clinical effects of opioids: Endocrine
Reduce the stress response to surgery, have immunosuppressant effect
-Release vasopressin and inhibit stress-induced release of corticosteroids & gonadotropins from the pituitary
Clinical effects of opioids: GU & antitussive
GU: increases urinary sphincter tone
Antitussive effect: cough suppression (codeine is among best suppressant)
Cyclooxygenase inhibitors (NSAIDS) MOA
inhibit COX
*COX 1: inhibition decreases thrombosis (aspirin, irreversibly inhibits and is effective 7 days)
*COX 2: produced in response to inflammation (acetaminophen, celecoxib, ketorolac)
Multimodal analgesia: NSAIDS
*Aspirin = salicylic acid, antiplt
*Ketorolac = acetic acid derivative, can change lithium level, can promote postop bleeding, NO resp dep, need adequate renal fn
*Ibuprofen = propionic acid derivative
*Celecoxib: heterocyclic derivative
Multimodal analgesia: Tylenol (Ofirmev)
*10 mg/mL, admin 1000 mg over 15 minutes for > 50 kg
*MUST DRAW UP appropriate dose from the vial and placed into a separate container for < 1000mg
*<50 kg 15mg/kg q 6 (max 75mg/kg/day)
*Max 4 g/day
*Warnings -> hepatic injury and hypersensitivity
