Opiods Agonist/Antagonists Flashcards
(201 cards)
1
Q
3 types of Opioids class
A
Opioid agonist Opioid antagonist Opioid agonist-antagonists
2
Q
Opioids derived from
A
Opium, meaning juice
3
Q
Narcotic is a greek word for
A
Stupor
4
Q
Why is opiod unique?
A
Produces analgesia without loss of proprioception, touch or consciousness
5
Q
Bind to receptor site to elicit a response definition
A
Agonist
6
Q
ONLY this form have an AGONIST ACTIVITY
A
LEVOROTATORY
7
Q
Blocks agonist from binding
A
Antagonist
8
Q
Opiod agonist-antagonists
A
partially bind to mu receptors produces a limited response (partial Agonist) or no effect (competitive antagonist)
9
Q
SEMI SYNTHETIC OPIOIDS are (CHOO)
A
Codeine Heroin Hydromorphone Oxycodone
10
Q
Semisynthetic opiods are
A
modified morphine molecule
11
Q
Synthetic opiods are FSAR MMT
A
Fentanyl, Sufentanyl, Alfentanyl, Remifentanyl Methadone, Meperidine, Tramadol
12
Q
Mechanism of action : opiods in ______State bind stroly at _______opioid receptor site
A
ionized; anionic
13
Q
Opioid agonists and neurotransmitters
A
inhibit neurotransmitters pre and post synaptic
14
Q
IN CNS opioid action is
A
Brainstem and spinal cord
15
Q
IN PNS opioids on
A
Primary afferent neurons
16
Q
Opioids on primary afferent neurons are activated by 3 endogenous peptide opioid receptor ligands which are?
A
Enkephalins Endorphins Dynorphins
17
Q
Opiods and endogenous ligands?
A
they mimic the endogenous ligands
18
Q
Raphe magnus ligand
A
Enkephalin
19
Q
Periventricular nuclei and periaqueductal grey
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Morphine and dynorphin
20
Q
What is the principal effect of opiod receptor activation?
A
Decrease neurotransmission
21
Q
How do opiods prevent neurotransmitter release?
A
Due to presynaptic inhibition of Ca2+ channels which reduce the neurotransmitter release.
22
Q
Opiods block the release of these neurotransmitters (ADNSS)
A
Ach, Dopamine, Norepinephrine, Substance P, Serotonin
23
Q
Pre-synaptic opioid receptor is a
A
GPCR
24
Q
What is the mechanism of presynaptic activity?
A
Leads to a decrease in cAMP decrease in Ca2+ ion influx and inhibits the release of excitatory neurotransmitters
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Excitatory neurotransmitters blocked, (2)
Glutamate Susbtance P
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Post synaptic opioid receptor action
Inhibit DEPOLARIZATION of neuron by inhibiting the production of adenylate cyclase , thereby inhibiting ion channel (Na and Ca) Inactviation of K+ channels lead to hyperpolarization of the cell
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All opioid receptors are
G protein coupled receptors that INHIBIT ADENYLATE CYCLASE leading to decrease in cAMP
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With opiod the resting MP becomes more ______ leading to \_\_\_\_\_\_\_of neuron to propagate a signal. There is ________ neuronal activity
negative, inability; decrease
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The receptors mu, kappa and delta are all
GPCR with same mechanism of action, decrease cAMP
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Mu and Morphine types of anesthesia
Supra spinal spinal
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Mu 1 produces analgesia with ELMUH
Euphoria, low abuse potential, miosis, URINARY RETENTION, Hypotethermia
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Mu 1 and Mu 2 agonist are EMS
Endorphins Morphine Synthetic opioids
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Mu 2 responsible for CHAP marked
Constipation marked, hypoventilation, analgesia (spinal) and physical dependence
34
Kappa receptors responsible for (low SAD MD)
Low abuse potential, SEDATION, Analgesia (s+s) DYSPHORIA, MIOSIS, DIURESIS
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Kappa agonist receptors - dynorphins inhibit
N-type Ca2+ channels leading to analgesia
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Kappa agonists \_\_\_\_\_Respiratory depression
Less
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Kappa agonists may cause
DIURESIS and DYSPHORIA
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May be resistant to analgesic effect of Kappa
High intensity painful stimulation
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On which receptor does OPIOD AGONIST- ANTAGONIST act principally?
KAPPA receptors
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Delta receptors responsible for (PACUVA) minimal
Physical dependence, analgesia S+S, constipation minimal, urinary retention, ventilatory depression, antidepressant
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Receptor to have ONLY SPINAL anesthesia efect
Mu 2
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Receptor associated with marked constipation
Mu 2
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Receptors associated with urinary retention
Mu 1 and delta
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Receptor associated with low abuse potential
Mu 1 and kappa
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Receptor associated with SEDATION
Kappa
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Receptor associated with DIURESIS and DYSPHORIA
Kappa
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Receptor associated with EUPHORIA
Mu 1
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Opioids receptors are in the
Brain and spinal cord
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Where in the brain are opiods receptors (PACH)
Periaqueductal gray matter of brainstem, amygdala, corpus striatum, and hypothalamus
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Where in the spinal cord are opiods receptors
SUBSTANTIA GELATINOSA dorsal horn
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Principal receptor in spinal cord
Mu
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Endorphins inhibit release of
Neurotransmitters
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Opiods given Neuraxial are not associated with
SNS denervation, Skeletal muscle weakness, loss of proprioception
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Epidural dose vs subarachnoid which is stronger
Epidural 5-10 times subarachnoid dose
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Epidural separated by
Dura and arachnoid
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Path of opiods in epidural space
Undergoes uptake in epidural fat --\> systemic absorption --\> diffusion across the dura into CSF
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What penetrates dura faster? (solubility / molecular weight)
HIghly lipid soluble, low molecular weight.
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CSF concentration of sufentanyl peaks in
6 min
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CSF concentration of Fentanyl peaks in
20 min
60
CSF concentration of MORPHINE peaks in
1-4 hours
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Spinal cord ends at
L1
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What is the most common location for epidural
LUMBAR spine, (largest region)
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Epidural administration of morphine, sufentanyl and fentanyl mimics
IM injection
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When Epinephrine administered with opioid it
Decreases systemic absorption
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Subarachnoid (Intrathecal) LIPID soluble opiods? meaning Absorption in CSF is
Fentanyl , rapid absorption in CSF
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Subarachnoid (Intrathecal) WATER Soluble opiods meaning Absorption in CSF is \_\_\_\_\_\_\_\_\_, meaning may cause \_\_\_\_\_
MORPHINE , no absorption, float in CSF, may cause delayed apnea
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When subarachnoid morphine and EPINEPHRINE
Increase block density Decrease intravascular absorption Prolong duration of action of lipid soluble anesthetics no effect on protein bound LA.
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Side effects of Neuraxial (PNUDS CVS NeWa)
Pruritus, N/V, Urinary retention, depression of ventilation, sedation, CNS excitation, viral reactivation, sexual ocular, GI thermoregulation, water retention, neonatal morbidity.
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The side effects seen with neuraxial opiods administration is caused by
opiods in CSF and in systemic circulation
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Side effect of neuraxial opiods that are dose dependent PNUR
Pruritus, N/V, Urinary retention, Respiratory depression
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The most common out of the side effect of neuraxial opiods? characterized by
PRURITUS Localized FUN (localized in face, upper thorax, neck)
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What can neuraxial opiod related pruritus treated wtih
BUPRENEX, treat without reversing analgesia
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Urinary retention with neuraxial more common with
Young males
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What is the mechanism of urinary retention with neuraxial opioid?
Interaction of the opiod with sacral spinal cord PNS sacral inhibition, detrusor muscle relax, increase bladder capacity,---\> ↑ retention
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Morphine can cause marked detrusor relaxation in ______ can last \_\_\_\_
15 min 16 hours
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Most serious side effect of opioid
Respiratory depression
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No respiratory depression after
24 hours
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What is the respiratory depression caused by ?
Cephalad migration of opioid in CSF and interaction with receptors in ventral medulla
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Increase risk of respiratory depression
-Concomittant use of opiod of sedative use -High opiod use, low lipid solubility of opiod - Lack of opiod tolerance, advanced age - Increased intrathoracic pressure
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Diagnosis of respiratory depression
↓ MV, ↓RR, ↓SPO2, somnolence →apnea, CP arrest
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Sedation effect is dose related more common with
SUFENTANYL
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What is the sedation effect of sufentanyl caused by?
Due to interaction with non-opioid receptors in brainstem and Basal ganglia →Blocks glycine or GABA inhibition
83
Viral reaction and opioid in OB patients
Theres been a link found between OB patients with REACTIVATION of herpes virus with EPIDURAL MORPHINE
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For Epidural,use only
preservative free
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Morphine : dull vs sharp pain
Better for dull
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In absence of pain, morphine causes
DYSPHORIA rather than Euphoria
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Morphine peak IV
15-30 mins rapid onset
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Morphine Peak IM
45-90 mins
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Hyperventilation will make blood more _______ and Increased \_\_\_\_\_\_\_fraction, increase passage to CNS
Alkaline, nonionized
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Hypoventilation (respiratory acidosis) will \_\_\_\_\_\_nonionized portion may lead to higher CNS concentration due to \_\_\_\_\_\_\_CBF and \_\_\_\_\_\_\_CO2 levels
increase; increase; increase
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Morphine rapidly accumulated in
liver, kidneys, skeletal muscles
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Metabolism of morphine : What is the principal pathway
Conjugation with GLUCURONIC ACID in hepatic, and extra hepatic (kidneys)
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Metabolism of morphine: Principal metabolite
Morphine-3- Glucuronide 75-80% inactive
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Metabolism of morphine: metabolite more potent than morphine
Morphine -6- Glucuronide 5-10%
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Morphine vs M6G
More potent, longer duration
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MAOIs and morphine
MOAI inhibit formation of glucuronide metabolites →exaggerated effects (can't metabolize)
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Morphine metabolites excreted via
Urine
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\_\_\_\_\_Significant contribution to total metabolism
Renal metabolism
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Renal impairment and morphine
Accumulation of metabolites and UNEXPECTED resp depression.
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With morphine, decrease in plasma concentration after initial distribution is due to
METABOLISM
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Greater analgesis potency of morphine in
women
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Higher post op consumption in
Men
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Morphine high dose? will it have major effect on supine normovolemic patient?
1mg/kg; UNLIKELY to cause myocardial depression
104
Change to supine to standing may cause \_\_\_\_and \_\_\_\_\_\_\_why?
Hypotension + syncope impairment of compensatory sympathetic NS response ↓vasomotor tone leading to ↓preload, CO and BP
105
How to reduce morphine induced bradycardia
caused by histamine release give 5mg/min, supine, well hydrated patient
106
Bradycardia associated with morphine mechanism
↑ activity of vagal nerve ↑stimulation of vagal nuclei Decrease SA node to AV conduction
107
Produce histamine release substantially
1mg/kg over 10 min
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Which dose of opiods not causing histamine release?
Fentanyl 50mcg/kg over 10min
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What prevents the histamine release
Pretreatment w/ H1 and h2 blockers, does not prevent release but prevent changes in SVR and BP
110
Opiods and nitrous may cause
CV depression
111
All opiods cause dose dependent + depression of ventilation why?
Due to agonist effect @ MU2, ↓ brainstem ventilatory center characterized by ↓ responsiveness to CO2
112
Codeine effect on cough
↓cough by effect on MEDULLARY COUGH center
113
Morphine action on airway
↑ airway resistance ↑ Bronchial smooth muscle contraction ↑ histamine release
114
With HYPOVENTILATION , morphine \_\_\_\_CBF and ICP
INCREASE
115
With HYPERVENTILATION , morphine \_\_\_\_CBF and ICP
DECREASE
116
Rapid administration of morphine may lead to \_\_\_\_\_\_\_
Skeletal muscle rigidity
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Risk from Greatest to least as far as skeletal or abdominal and thoracic rigidity
Fentanyl \> Remifentanyl \> Morphine
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Opiods and the biliary tract
may cause spasm of biliary tract Increase intrabiliary pressure associated with epigastric distress and biliary colic
119
Equal doses of opiods increase bile duct pressure percentage for each agent
Fentanyl 99% Meperidine 61% Morphine 53%
120
What my reverse opiod induced biliary smooth muscle spasm
Glucagon 2mg IV
121
Morphine and peristaltic
Decrease peristaltic contraction, increase tone of pyloric sphincter
122
First mechanism of opiod induced N/V due to
Direct stimulation of chemoreceptor trigger zone in floor of fouth ventricle
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2nd mechanism of opioid induced NV due to
may act as partial dopamine agonist
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3rd MOA of opioid induced NV
Caused by increase GI secretions and delayed passage of interstinal contents.
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Why erythemia and urticaria at injection site
Histamine release
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Morphine cause neonatal resp depresion because
immature BBB, chronic opioid use by mom
127
Giving narcan to mother can
lead to life threatening NEONATAL ABSTINENCE SYNDROME
128
Morphine and drug interaction. Respiratory depression exaggerated by (TAMP)
TCAs Amphetamines MAOIs Phenothiazine
129
Tolerance and physical dependence can happen with
All opiods
130
How long does tolerance takes to develop
2-3 weeks
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Tolerance develops to \_\_\_\_\_, \_\_\_\_\_\_, \_\_\_\_\_\_\_, _______ (SEDA-em)but not to \_\_\_\_\_\_And \_\_\_\_\_\_\_\_\_
Sedation, euphoric, depression of ventilation, analgesia , and emetic NOT to MIOSIS and CONSTIPATION
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Initial withdrawal symptoms are DYL RIC
Diaphoresis, yawning, lacrimation, restlessness, insomnia, coryza
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When does the abd pain, NV peak
72 hours
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Prevention of withdrawal with \_\_\_\_\_\_MOA?
Clonidine - diminishes transmission in sympathetic pathway in the CNS and prevent withdrawal
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What is the principal manifestation of overdose
Respiratory depression
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Pupils are ____ and\_\_\_\_\_Unless there is severe hypoxemia \_\_\_\_\_
symmetric; miotic; mydriasis
137
What is the triad of OPIOD overdose (MCH)
MIOSIS HYPOVENTILATION COMA
138
Overdose treatment
Mechanical ventilation Narcan 0.4 - 2mg q 2-3 mins
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After \_\_\_\_Mg of narcan question diagnosis
10
140
Continuous infusion of narcan dose
0.8mg/kg/hr (may cause withdrawal)
141
What are analogues of Meperidine --\> FSAR
Fentanyl, Sufentanyl, Alfentanyl, Remifentanyl
142
Meperidine potency vs morphine
1/10 th
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Duration of meperidine
2-4 hours
144
Meperidine metabolism
90% to NORMEPERINE via demethylation
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Route elimination for meperidine
urinary
146
Renal failure and meperidine
accumulation of NORMEPERIDINE metabolites → increase risk for Seizures
147
Normal kidney meperidine clearance? kidney issues?
15 hours \>35 hours
148
Meperidine half time
3-5h
149
Meperidine protein binding is \_\_\_% which in elderly
60; decrease binding, increase plasma
150
Principally use for analgesia during L&D
Meperidine
151
What are responsible for the anti-shivering effect of Meperidine?
Stimulation of kappa 10% of drug activity also a potent alpha 2 agonist
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Also use for post op shivering
Clonidine
153
Side effects of MEPERIDINE
Orthostatic hypotension (worse than morphine)
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Meperidine may also cause
Serotonin syndrome ( HTN, Diaphoresis, hyperthermia)
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Fentanyl potency compared to morphine
100 times more potent
156
Onset and duration of fentanyl compared to morphine
Rapid onset and shorter duration of action due to its rapid redistribution to tissue
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Fentanyl upon administration : % undergoes
75% undergoes rapid 1st pass PULMONARY uptake limiting amount reaching systemic circulation
158
Effect equillibration time of fentanyl
6.4 min
159
Fentanyl metabolism
N-demethylaton --\> Norfentanyl , detectable for 72 hours, NOT ACTIVE
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Elderly have increase half time due to
Decrease clearance, Decrease Hepatic blood, decrease albumin, decrease hepatic enzymes activity
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2 hours continuous infusion
FASR graph, saturation of inactive tissues with prolonged infusion
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Cardiopulmonary bypass
Decrease plasma concentration of opioids Decrease greater with fentanyl, less with alfentanyl and sufentanyl
163
Fentanyl dose for analgesia
1-2mg/kg
164
As adjunct to inhaled anesthetics to blunt tachy and HTN associated with laryngoscopyq
2-20mcg/kg
165
High dose produce surgical anesthesia
50-150mcg/kg
166
High dose of fentanyl produce
stable hemodynamic, no CV depressant , no histamine release
167
No histamine release with
Fentanyl
168
Fentanyl depresses
Carotid sinus baroreceptor reflex control of heart rate
169
Morphine and fentanyl more bradycardia with
Fentanyl
170
Increase in ICP with
Fentanyl and sufentanyl
171
Sufentanyl potency
5-10 more potent than fentanyl
172
Effect site equillibration of Sufentanyl
6.2 min
173
Protein binding of Sufentanyl
92.5% low Vd, significant 1st pass metabolism
174
Termination of action of sufentanyl via
Redistribution
175
Dose of Sufentanyl
0.1 -0.4mcg/kg
176
Compared to fentanyl, sufentanyl cause
longer analgesia, less ventilatory depression, Rapid induction , early emergence
177
SE of Sufentanyl
Chest wall rigidity, N/V , bradycardia
178
Alfentanyl potency
1/5 - 1/10 less potent
179
Use of Alfentanyl
Laryngoscopy Retro bulbar block
180
Alfentanyl ; Rapid effect equilibration time of \_\_\_\_\_Why?
1.4min ; cause of low pKa 90% in NI form
181
Do not use in parkinson patients
Alfentanyl
182
General dose of Alfentanyl
5-15mcg/kg q5-20 min
183
Remifentanyl acts on which recepotr
Mu receptor
184
Potency of remifentanyl
15-20 times more than alfentanyl similar potency to fentanyl
185
Metabolism of REMIFENTANYL
Hydrolysis by non-specific plasma tissue esterases
186
What is the only opiod metabolized by the liver? and also not affect by ?
REMIFENTANYL ; renal disease
187
3 REASONS remifentanyl is good
rapid onset , short duration of action NON cum effect Rapid recovery after d/c
188
How long does it take for remifentanyl to reach steady state ______ complete offset in ______ clearance rapid at \_\_\_\_L/min
10 mins; 6-8 min; 3
189
Use for transient analgesia with retra bulbar block
1 mcg/kg over 60-90 sec
190
Disadvantage of REMI
Short duration,POST OP PAIN SIGNIFICANT
191
Codeine half life equivalent to asa Histamine release : y/n
3-3.5 hr 60 mg to 650 ASA 120mg IM = 10mg yes
192
Dilaudid potency to morphine
8 times more potent, shorter duration (every else as morphine)
193
Tramadol is a
Central acting, moderate on mu, weak on kappa and delta
194
Tramadol compared to morphine MOA Dose Disadvanage:
5-10 times less potent than morphine Inhibit NE and serotonin neuronal uptake 3mg/kg Ceiling effect seizure
195
OPIOD AGONIST - ANTAGONIST
Butorphanol- stadol Nalbuphine - NUBAIN
196
Narcan
HIGHER affinity to opiod receptor, prevent agonists from binding
197
Pruritus treated with
Narcan , nalbuphine
198
Dose of NARCAN
1-4mcg/kg
199
Narcan metabolized by
LIVER
200
Vomiting occurs with narcan but
It occurs with awakening, meaning patient can protect their airway.
201
GRAPH for Context (FASR)
