Pharm Unit 2 Flashcards
(299 cards)
1
Q
What can be given for pre-eclampsia?
A
Magnesium sulfate
2
Q
What organs are a part of the vessel rich group (VRG)? What % of CO goes to the VRG?
A
brain, heart, kidney, liver
75%
3
Q
What is included in the muscle group? What % of CO goes to the muscle group?
A
skeletal muscle and skin
18%
4
Q
How much of CO is administered to fat?
A
5%
5
Q
What is included in the vessel-poor group? What % of the CO is used?
A
bone, tendon, cartilage
2%
6
Q
What are the 5 components of anesthesia?
A
Hypnosis, analgesia, muscle relaxation, sympatholysis and amnesia
7
Q
What are the 4 stages of anesthesia?
A
- Analgesia
- Delerium
- Surgical anesthesia
- Medullary paralysis
8
Q
What stage of anesthesia includes laryngospasm?
A
Stage 2 - delirium
9
Q
What stage of anesthesia includes responses to stimulation that are exaggerated and violent?
A
Stage 2 - delirium
10
Q
Which stage of anesthesia includes absence of all reflexes and flaccid paralysis with hypotension and a weak pulse?
A
Stage 4 - medullary paralysis
11
Q
What stage of emergence should you extubate in?
A
Stage 1 - analgesia
12
Q
What are the 4 protective airway reflexes?
A
sneezing, coughing, swallowing, gagging
13
Q
How do barbiturates exert their effect?
A
Potentiating GABA-a channels, also act on glutamate/adenosine/neuronal nicotinic ACh receptors
14
Q
What do barbiturates do the CBF/CRMO?
A
Act as a cerebral vasoconstrictor, reduce CBF and CRMO by about 55%
15
Q
Why do you want to avoid infusions of barbiturates?
A
Prolonged context-sensitive half time. They also rapidly redistribute into other tissues - fat and protein reservoir
16
Q
What is the effect on redistribution if the drug has a high protein binding capacity?
A
Longer duration of action
17
Q
How well do barbituates bind to protein? Which protein?
A
albumin 70-85%
18
Q
What are the 2 types of barbiturates? Which one is more lipid soluble?
A
Oxybarbiturates and Thiobarbiturates (more lipid soluble)
19
Q
Which drugs are Oxybarbiturates and Thiobarbiturates?
A
Oxybarbiturates: Methohexital, Phenobarbital, Pentobarbital
Thiobarbiturates: Thiopental, Thiamylal
20
Q
Why is it that: “the greater the ratio of fat to body weightthe less is the blood volume (ml/kg)?” Adipose tissue has….
A
Decreased blood supply
21
Q
The greater the ratio of fat to body weight→ the_____ is the blood volume (ml/kg).”
A
less
22
Q
__________ describes the distribution of a given agent at equilibrium, between two substances at the same temperature, pressure, and volume
A
Partition coefficient
23
Q
__________ describes the distribution of an anesthetic between blood and gas at the same partial pressure
A
Blood-gas coefficient
24
Q
A higher blood-gas coefficient correlates with ______ solubility of anesthetic in blood and thus ______ the rate of induction
A
higher, slowing
25
Dose of Thiopental?
4 mg/kg IV
26
Dose of methohexital?
1.5 mg/kg IV
27
How does methohexital affect seizures?
Lowers seizure threshold = easier to have one, making it an ideal drug for ECTs
28
Basic effects of barbiturate's on ventilation?
Dose-dependent depression (less sensitive to CO2) with slower frequency and lower tidal volume, similar to narcotics
29
What happens during intra-arterial injection of a barbiturate?
Immediate intense vasoconstriction and pain - permanent nerve damage
- Treat with vasodilators: lidocaine or papaverine
30
What medications are affected by barbiturates? Why?
- Enzyme induction approx. 2 to 7 days of infusion
- Accelerated metabolism of anticoagulants, phenytoin, TCAs, digoxin corticosteroids, bile salts, and vit. K.
- May persist for 30 days
31
List the induction, conscious sedation and maintenance doses of propofol
Induction = 1.5 - 2.5 mg/kg IV
CS = 25 - 100 mcg/kg/min
Main = 100 - 300 mcg/kg/min
32
What are the disadvantages to propofol?
- Support bacterial growth.
- Causes increased plasma triglyceride concentrations (in prolonged IV infusions).
- Pain on injection
33
Describe Ampofol and Aquavan relative to Propofol
Ampofol = low-lipid emulsion with no preservative, higher incidence of pain on injection (good d/t less effect on triglycerides)
Aquavan = prodrug that converts into active form, no pain on injection, by has unpleasant sensation related side effects
34
Describe Propofol MOA
Selective modulator of GABA-a = increased Cl conductance and hyperpolarized cell
35
What are the elimination and context-sensitive half-times of propofol?
- Elimination half-time: 0.5-1.5 hours
- Context-sensitive half time: 40 minutes (8 hour infusions)
36
How does the liver metabolize propofol?
CP450 - converted to water-soluble sulfate and glucuronic acid metabolites to be excreted by kidneys
37
Describe the BP/HR changes with propofol, etomidate and ketamine
P = decreased BP and HR
E = no change to BP and HR
K = increased BP and HR
38
T/F: Propofol is safe for alcoholic patients?
T: awakening time does not change with healthy vs ETOH patients
39
How does the dose of Propofol change with children vs elderly?
Children = increased dose, elderly = decreased dose (by 25-50%)
40
Why is Propofol advantageous as a sedative?
Prompt recovery, low PONV, anti-convulsant, amnestic, anti-oxidant. Does not provide analgesia however
41
What is the sub-hypnotic dose of Propofol?
10-15 mg IV followed by 10 mcg/kg/min
42
Anti-pruritic dose of Propofol?
10 mg IV
43
What effect does Propofol have on the airway?
Bronchodilation
44
Anti-convulsant dose of Propofol?
1 mg/kg IV
45
Effects on CRMO with Propofol?
Decreases CRMO, CBF and ICP. D/t autoregulation, CBF and PaCO2 are maintained
46
Propofol doesn't induce seizures but can result in involuntary muscle movements, aka ________
myoclonus
47
What kind of EEG waves do we want in anesthesia?
Delta
48
Black box warning for Propofol?
Profound bradycardia leading to asystole in healthy patients
49
How does propofol work as an anti-emetic agent?
Depresses subcortical pathways and has a direct depressant effect on the vomiting center
50
Effects of propofol on the CV system
- decreased SBP - SNS inhibition, decreased SVR
- bradycardia
51
Describe Propofol infusion syndrome including dose
Dose > 75 mcg/kg/min longer than 24 hours.
s/s: severe refractory bradycardia in children, lactic acidosis, brady-dysrhythmias, and Rhabdomyolysis; green urine
52
What medication can you give with propofol to prevent bradycardia and asystole?
Antimuscarinic agent - atropine
53
Propofol (does or does not) affect the hypoxic pulmonary vasoconstriction response
does not - stays intact
54
What does it mean when urine is green or cloudy with propofol administration?
No alteration in renal function/NBD
- green = phenols
- cloudy = uric acid crystallization
55
Propofol ______ IOP
decreases
56
Etomidate MOA?
Selective modulator of GABA-a
57
_______ is the only drug with direct systemic absorption in oral mucosa that bypasses hepatic metabolism
etomidate
58
Drugs that are highly protein bound have _____ duration of action
longer
59
Etomidate is a weak _____; it is _____ soluble at physiologic pH
base, lipid
60
Etomidate is 35% propylene glycol →
pain at injection and venous irritation
61
What % of PO medication is metabolized during hepatic first pass?
50%
62
Onset, peak, and half-life of etomidate?
onset - 1 min
peak - 2 min
half-life - 2-5 hours
63
Etomidate is metabolized via ______
Hydrolysis (hepatic microsomal enzymes & plasma esterases)
64
Etomidate is ___% albumin bound, but ______ is 5x faster than thiopental
76%, clearance (prompt awakening)
65
Etomidate elimination is ___% in urine and ___% in bile
85% in urine & 10-13% in bile
66
Dose for Etomidate?
0.3 mg/kg IV
67
Best indication for etomidate?
In an unstable CV patient (esp with little to no cardiac reserve)
- min changes to HR, SV, CO, contractility
- mild decrease MAP d/t ↓ SVR and PAP
68
Etomidate has ______ analgesic effects
no
69
What is the big side effect of etomidate?
Myoclonic movements, very common. Can be prevented with fentanyl 1-2 mcg/kg IV
- caution pt with seizure hx
70
Contraindication to etomidate?
Adrenal suppression - it makes it worse so you lose your stress response
71
How does etomidate cause adrenal suppression?
Dose-dependent inhibition of the conversion of cholesterol to cortisol → ✕ stress response
- Severe hypotension, longer mechanical ventilation hours, etc.
72
What patients should etomidate be used cautiously in?
seizure hx, sepsis, hemorrhage
73
Relationship of CRMO/CBF to etomidate?
Decrease CBF, CRMO and ICP by 35-45% via cerebral vasoconstriction
↓ ICP
74
Etomidate effects on ventilation?
- Is a depressant but less so than barbiturates.
- Vt decreases are offset by compensatory increases in RR (transient 3-5 min)
- stimulates CO2 medullary centers
75
Minute ventilation =
Vt x RR
76
What are the advantages of ketamine over etomidate/Propofol? Cons?
- No pain on injection and profound analgesia at subanesthetic doses.
- Does have delirium concerns and abuse potential.
77
What preservative is used for ketamine?
Benzethonium Chloride
78
S/S of ketamine use
- "Dissociative anesthesia"
- resembles cataleptic state in which eyes remain open with slow, nystagmic gaze
- non-communicative, but wakefulness is present; hypotonus and purposeful skeletal muscle mvmt
79
What is the street equivalent of ketamine?
PCP or angel dust
80
Compare isomers of ketamine
S (the left or -) = more intense analgesia, more rapid recovery, less salivation, lower incidence of emergence reactions
R = (right or +) = cocaine like effect, less fatigue, less cognitive impairment
81
Where does ketamine work?
NMDA receptors (prevents glutamate from activating them), all opioid receptors (mu, delta and kappa) and weak actions at GABA-a and sigma opioid receptors. Also affects calcium and neuronal nicotinic ACh channels (analgesic effect)
82
What is the peak, duration, and half-time of ketamine?
peak: 1 min
duration: 10-20 min (60-90 min to return to full orientation)
half-time: 2-3 hours
83
Ketamine has a Vd of ______
3 L/kg (large)
84
Does ketamine have inactive or active metabolites?
Norketamine: active metabolite (1/3 – 1/5 potency); prolonged analgesia
85
What is the hepatic clearance rate of ketamine? How is it excreted?
1 L/min
kidneys
86
Ketamine has _____ lipid solubility
high
87
Induction doses IV and IM of ketamine?
IV = 0.5 - 1.5 mg/kg
IM = 4 - 8 mg/kg
PO = 10 mg/kg
88
Maintenance doses of IV/IM ketamine?
IV = 0.2 - 0.5 mg/kg
IM = 4 - 8 mg/kg
89
Subanesthetic/analgesic dose of ketamine?
0.2 - 0.5 mg/kg IV
90
Post op sedation/analgesia dose of ketamine?
1 - 2 mg/kg hour
91
Neuraxial Analgesia dose for ketamine?
- 30 mgs Epidural
- 5 - 50 mg in 3 mLs of saline Intrathecal/Spinal/Subarachnoid
92
What anti-sialagogue do you give with ketamine?
Glycopyrrolate
93
Ketamine LOC to fill consciousness times
- LOC effect: 30 secs – 1 min (IV); 2 to 5 mins (IM)
- Return of consciousness (ROC): 10 to 20 minutes
- Full consciousness: 60 to 90 minutes.
- Amnesia persists after ROC: 60 to 90 minutes
94
What is the coronary artery disease cocktail (include dosages)?
Valium = 0.5 mg/kg IV
Ketamine = 0.5 mg/kg IV
Ketamine infusion of 15-30 mcg/kg/min
95
Avoid or caution use of ketamine in patients with
- Pulmonary: Systemic/pulmonary HTN
- Neuro: Increased ICP
96
Ketamine clinical uses
- Acutely hypovolemic patients
- Asthmatic & MH patients
- CAD cocktail
- pediatric induction
- burn pts, reverse opioid tolerance
- psych disorders - depression, PTSD, OCD, restless leg syndrome
97
How does ketamine affect ICP? At what dose does the ICP effect plateau?
Potent cerebral vasodilator = 60% increase in CBF, no further increase in ICP at 0.5 - 2 mg/kg IV
- myoclonus, increased amp SSEP, does not alter seizure threshold
98
Ketamine effects on CV system?
Increased CO, BP, HR, PAP, MRO2
- increases catecholamine levels
99
Decreased CO and BP in patients with ketamine can be treated with ______
epi - depleted catecholamine stores
100
Effects of ketamine on ventilation?
No depression of ventilation, airway reflexes are maintained, increase in salivary secretions, bronchodilator
101
Ketamine s/sx of emergence delirium
- Psychedelic Effects in 5% to 30% of patients
- S/Sx: visual, auditory, proprioceptive, and confusional illusions
- Morbid & vivid dreams (in color) and hallucinations up to 24H
102
What is the MOA of how ketamine causes psychedelic effects?
MOA: depression of the inferior colliculus and medial geniculate nucleus
103
What can be given with ketamine to prevent emergence delerium?
Benzos, Clonidine and Dexmedetomidine
104
What are the side effects of ketamine on other systems?
- Inhibits platelet aggregation
- Inhibits cytosolic free calcium concentration - Enhances non-depolarizing NMBDs
- Inhibit plasma cholinesterase's - Prolongs apnea from sux
105
What is the relationship of ketamine to volatiles, NMBDs and Sux?
NMBD = enhanced effect
Sux = prolonged
V = hypotension
106
Which induction agent has the highest analgesic properties?
ketamine
107
What is Ketafol?
mixing ketamine and propofol - not recommended bc propofol is not chiral and ketamine is (not stable - lipid bubbles)
108
Differentiate between the two components of pain
1. sensory-discriminative - Ascending → spinothalamic & trigemino-thalamic tracts → cerebral cortex → perception of pain
2. motivational-affective - attention/arousal, somatic/autonomic reflexes, endocrine responses, and emotional changes
109
_______ is the experience of pain with a series of complex neurophysiologic processes
Nociception
110
Define hyperalgesia and allodynia
Hyper = increased pain sensations to normally painful stimuli
A = perception of pain in response to non-painful stimuli
111
Where does transduction, transmission, modulation and perception occur in nervous system?
Transduction = signals starting at the nerve endings
Transmission = travel of the electrical impulses to the nerve body connecting to the dorsal horn
Modulation = process of altering pain (inhibitory/excitatory) transmission mechanisms at the dorsal horn
Perception = thalamus acting as the central relay station and discrimination of stimuli in the somatosensory cortex
112
What medication classes act at peripheral nociceptors or rather affect transduction?
LAs and NSAIDS
113
What medication classes act on transmission of nerve signals? Where?
LAs and on the a-delta and c-fibers
114
What medication classes act on modulation and where does this occur?
LAs, opioids, ketamine a2-agonists and in the spinal cord, primarily in the dorsal horn
115
What medication classes act on perception and where does this occur?
Opioids, a2-agonists, GAs. In the brain -> somatosensory cortex
116
Describe the process a stimulus would take to travel throughout the CNS
Stimulus → Nociceptor → Resting Threshold → Transmission → Modulation → Interpretation
117
Describe the physiology of c-fibers and type 1 (a-beta) and type 2 (a-delta) fibers including speed
C-fiber (unmyelinated) = burning pain and sustained pressure pain (2 meters/second)
AB = heat, mechanical and chemical pain
AD = heat
Both alpha = much faster
118
What are the 7 chemical mediators of pain?
- Peptides (substance P, calcitonin, bradykinin, CGRP)
- eicosanoids
- Lipids (PGAs, thromboxane, leukotrienes and endocannabinoids),
- neutrophins
- cytokines
- chemokines
- extracellular proteases/protons
119
What are peptide mediators of pain?
Substance P, calcitonin, bradykinin, CGRP
120
What are lipid mediators of pain?
PGAs, thromboxane, leukotrienes and endocannabinoids
121
What are the receptors and ion channels of the dorsal root ganglion and peripheral terminals?
- Purinergic
- Metabotropic
- Glutamatergic
- Tachykinin
- TRPV I
- Neurotrophic
- Ion channels
122
Define primary vs secondary hyperalgesia
P = at the original site of injury, decreased pain threshold, increased response to stimuli, spontaneous pain and expansion of receptive field
SH = uninjured skin surrounding the injury that has been sensitized by central neuronal circuits
123
Basic function of the dorsal horn
Relay center for nociceptive and other sensory activity
124
What do the ascending pathways do?
Transmit sensations such as pain to the brainstem and forebrain
125
What fibers would you find in lamina I (marginal layer)?
Afferent C-fibers
126
What would you find in Lamina II (substantia gelatinosa)?
afferent c-fibers, also where opioids can exert their effect
127
Where does substance P work?
Lamina III and IV - NKI receptor
128
Where would you find myelinated fibers in the cord? What do they innvervate?
Lamina I, IV, VII and the ventral horn, and they innervate muscles and viscera
129
Describe the gate theory of pain
If the gate is open, the pain is projected to supraspinal brain regions, if the gate is closed, pain is not felt with simultaneous inhibitory impulses
130
What happens if you rub an injured area?
The a-beta fibers deliver information about the rubbing/touching which override the slower information from a-delta and c-fibers regarding pain
131
What does the limbic cortex and thalamus do with pain information?
They are involved with perception of motivational-affective pain components
132
What does the PAG and RVM (rostro-ventral medulla) do with pain information?
Depress or facilitate the integration of pain information in the spinal dorsal horn
133
What does tissue injury release?
Substance P and glutamate
134
What are things damaged cells can release that cause pain?
Bradykinin, histamine, PGAs, serotonin, hydrogen ions and lactic acid
135
What are some excitatory impulses? Inhibitory?
E = glutamate, calcitonin, neuropeptide Y, aspartate, substance P
I = GABA, glycine, enkephalins, norepi, dopamine
136
What information travels the spinothalamic tract? Lamina?
Pain, temperature and itch, I VII and VIII
137
What information travels the spinobulbar tract? Lamina?
Behavior towards pain, I V and VII
138
What information travels the spinohypothalamic tract? Lamina?
Autonomic, neuroendocrine and emotional aspects of pain, I V VII and X
139
Describe the descending inhibitory pain pathway
Originate in PAG → RVM → dorsolateral funiculus → synapse in dorsal horn
140
What are the neurotransmitters used in the descending inhibitory tracts?
Endorphins, enkephalins, serotonin
141
What happens when you hyperpolarize a-delta and c-fibers?
Decreased release of substance P via opening of K channels and closing of Ca channels
142
What are the 2 descending pathways of pain modulation?
- Descending Inhibition Pathway (DI)
- Descending Facilitation Pathway (DF)
143
What are the opioid receptors for the PAG-RVM system?
Mu, Kappa and Delta receptors
144
Treatment for neuropathic pain?
Common to have allodynia and hyperalgesia, opioids, gabapentin, anti-depressants and cannabis
145
Describe visceral pain
Diffuse and poorly localized, if it is referred to the muscle/skin it become somatic pain
146
What are some causes of visceral pain?
ischemia, stretching of ligamentous attachments, spasms, distention
147
________ are a variety of painful conditions following injury in a region with impairment of sensory, motor, and autonomic systems
Complex Regional Pain Syndromes
148
When does pain become perceivable in an neonate?
23 weeks
149
What are the CV responses to pain?
HTN, ↑HR, myocardial irritability, ↑ SVR, compromised LV (↓ CO, myocardial ischemia)
150
What are the pulmonary responses to pain?
- ↑ total body O2 consumption/CO2 production → ↑ Vm and work of breathing
- Splinting
- Decreased movement of chest wall →
Atelectasis and Intrapulmonary shunting
- Impaired coughing
151
What are the GI/GU responses to pain?
- Enhanced sympathetic tone, ↑ sphincter tone, and ↓ motility (Ileus and urinary retention)
- Hypersecretion of acid (Stress ulceration and aspiration)
- N/V
- Abdominal distention
152
What are some endocrine responses to pain?
↑ catabolic hormones (catecholamines, cortisol, glucagon)
↓ anabolic hormones (insulin, testosterone)
combined effects = negative nitrogen balance, carb intolerance, and increased RAAS
153
What are the hematologic responses to pain?
Stress-related - platelet adhesiveness, reduced fibrinolysis, and hypercoagulability
154
What are the immune responses to pain?
Stress-related - Leukocytosis and depressed reticuloendothelial system (increased infection)
155
What are some examples of phenanthrenes?
Morphine, codeine and thebaine
156
What are some examples of benzylisoquinolines?
Papaverine and noscapine
157
How do opioid agonists work?
Inhibit ACh, dopamine, norepi and substance P, they increase K conductance (hyperpolarize), inactivate Ca channels and decrease neurotransmission
158
Where would you find opioid receptors in the Brain, spinal cord and outside the CNS?
B = PAG, locus ceruleus, RVM and hypothalamus
SC = dorsal horn at the substantia gelatinosa (lamina II)
Outside CNS = sensory neurons and immune cells
159
What is the only opioid receptor that is not supraspinal?
Mu2
160
What effects would you expect from Mu1 vs Mu2 receptors?
1 = analgesia, euphoria, low abuse, miosis, bradycardia, hypothermia and urinary retention
2 = analgesia, ventilatory depression, physical dependence, constipation
161
Is there any difference in the agonists/antagonists of Mu1/Mu2?
No, they are all the same.
Ago = endorphins, morphine and synthetics. Antag = naloxone, naltrexone and nalmefene
162
What effects occur at Kappa?
Analgesia, dysphoria/sedation, low abuse potential, miosis, diuresis
163
What effects occur at delta?
Analgesia, depression of ventilation, physical dependence, constipation, urinary retention
164
What are the body's endogenous agonists of kappa and delta?
K = dynorphins, D = enkephalins
165
What opioid receptors depress ventilation?
Mu2 and delta
166
What opioid receptors have dependence issue?
Mu2 and delta
167
What opioid receptors have low abuse potential?
Mu1 and kappa
168
What opioid receptors cause miosis?
Mu1 and kappa
169
What opioid receptors cause urinary retention?
Mu1 and delta
170
What opioid receptor has the most effects?
Mu1
171
What opioid receptors cause euphoria? Dysphoria/sedation?
Eu = Mu1
Sedation = kappa
172
What drug could you give to help reverse the opioid ventilation s/e but keep the analgesia going?
Physostigmine - increases ACh
173
What are the CNS effects of opioids?
- Decreased CBF and possibly ICP
- Caution with head injury: wakefulness, miosis, PaCO2, BBB
- Myoclonus with large doses
174
Which opioids cause cough suppression?
- Codeine
- Dextromethorphan: no analgesia
175
What are the ventilation effects of opioids?
- Decreased responsiveness of ventilation centers to CO2
- increased in resting PaCO2 (Shift to the right)
- Depression (mu2): rhythm (decreased rate with compensatory increase in tidal volume), pauses, periodic breathing
- **APNEA, aka overdose: miosis, hypoventilation & coma**
176
What are the CV effects of opioids?
- Decreased SNS tone in peripheral veins
- decrease in venous return, CO, & BP
- orthostatic hypotension & syncope
- Bradycardia or Histamine release → decreased BP
- + N20 or benzo = CV depression (CO & BP)
- Benefit: cardioprotective from myocardial ischemia
177
What skeletal issues do opioids have?
Can make the muscles rigid, treat with a muscle relaxer or naloxone
178
What is spasm of biliary smooth muscle called?
Sphincter of oddi spasms
179
What is the primary concern with Oddi spasms?
delayed gastric emptying and constipation, N/V, inc GI secretions
180
Treatment for sphincter of Oddi spasm?
Glucagon 2 mg, naloxone 40 mcg, atropine 0.2 mg, Nalbuphine 10 mg, NTG (nitroglycerin) 50 mcg
181
How long does tolerance generally take to occur?
2-3 weeks
182
What are initial symptoms vs after 72 hours of opioid withdrawal?
- Initial symptoms: yawning, diaphoresis, lacrimation, or coryza. Insomnia and restlessness.
- 72 hrs: Abdominal cramps, N/V, and diarrhea.
183
What opioids have the shortest onset, peak intensity and duration?
Demerol and fentanyl
184
What opioid(s) have the longest onset, peak intensity and duration?
Methadone
185
Intraop and postop doses for morphine
I = 1 - 10 mg
P = 5 - 20 mg
186
Intraop dose of fentanyl?
1.5 - 3 mcg/kg
187
Intraop dose of sufentanil?
0.3 - 1 mcg/kg
188
Intraop dose of remifentanil?
load 0.5-1 mcg/kg over 1 min
189
Intraop and postop dose of dilaudid
I = 1-4 mg
P = 1.5 - 5 mg
190
Infusion rate for sufentanil?
0.5 - 1 mcg/kg/hr
191
Infusion rate for remifentanil?
0.125 - 0.375 mcg/kg/min
192
What type of pain does morphine relieve?
Visceral/skeletal, joints, and integumental, dull > sharp, intermittent pain
193
_______ is the gold standard of opioids
morphine
194
_______ is the greek god of dreams
Morpheus
195
IV onset and peak of morphine?
O: 10-20 min
P: 15 - 30 min
196
How is morphine metabolized?
Via glucuronidation into 2 metabolites: Morphine-3 (75-95% but inactive) and morphine-6 (active)
197
Compare the analgesic potency and speed of offset of morphine in women vs men
Women > men: analgesic potency and slower speed of offset
198
Compare demerol potency to morphine
Demerol 1/10th the potency,
199
Dose for demerol in post-op shivering?
12.5 mg
200
What receptors does demerol hit?
kappa and A2 receptors
201
What is the metabolism and elimination of demerol?
- Duration: 2 to 4 hours
- Hepatic 1st pass: 80%
- Metabolism: 90% hepatic → normeperidine
- Protein-bound: 60% (elderly considerations)
- Elimination: renal, acidic urine can speed elimination
- Elimination ½ time: 3 to 5 hours (35 hours with renal failure)
202
What are the signs of Demerol toxicity?
delirium (confusion, hallucinations) myoclonus & seizures
203
Compare fentanyl to morphine
75 - 125x potency
204
Fentanyl has lung-first pass of ___% and a _____ Vd
Lung-first pass: 75%
large Vd
205
List the context sensitive half times of all fentanyl's from least to greatest
Remifentanil -> sufentanil -> alfentanil -> fentanyl
206
List the analgesia, induction and inhaled anesthetic doses of fentanyl
A = 1 - 2 mcg/kg IV
Ind = 1.5 - 3 mcg/kg IV
Inh = 2 - 20 mcg/kg IV
207
What is the surgical anesthesia dose of fentanyl?
50 - 150 mcg/kg IV
208
Intrathecal dose of fentanyl?
25 µg
209
Transdermal dose of fentanyl?
75 - 100 mcg over 18 hours
210
Transmucosal (oral) dose of fentanyl?
- 5 to 20 µg/kg
Rapid dissolving film/lozenge in peds
- 2 to 8 yo: 15-20 µg/kg PO 45 minutes prior
- 1 mg of PO Fentanyl = 5 mgs of IV Morphine
211
Advantage of fentanyl vs morphine in terms of s/e?
No histamine release, no significant bradycardia though can decrease BP and CO
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Fentanyl CNS s/e?
- Seizure like activity
- SSEP and EEG (>30 µg/kg IV)
- Modest increase in ICP (6 to 9 mmHg)
213
What was morphine originally derived from?
Poppy (Papaver Somniferum)
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Why is fentanyl discouraged in cardiopulmonary bypass?
You can lose some to the circuit
215
How much does fentanyl increase ICP?
6-9 mmHg
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What is fentanyl synergistic with?
Benzo's and Propofol (this can be a good thing, combined you could lower the dose of the propofol)
217
List the fentanyl in order of least to most potent
Alfentanil < Remifentanil and Fentanyl (both the same) < Sufentanil
218
Which is more potent, fentanyl or sufentanil?
Su: 5 - 12x more potent than fentanyl
219
Lung first pass and protein binding of sufentanil
- 60% lung first-pass uptake
- 92.5% protein binding (smaller Vd < fentanyl)
220
What does sufentanil bind to (not receptors)?
A1-acid glycoprotein
221
Give the analgesia, induction, intra-op and infusion doses of sufentanil
A = 0.1 - 0.4 mcg/kg IV
Ind = 18.9 mcg/kg IV
Intraop = 0.3 - 1 mcg/kg IV
Inf = 0.5 - 1 mcg/kg/hr IV
222
Compare and contrast potency and onset of fentanyl and alfentanil
Alfentail is 1/5 less potent, but has a faster onset of 1.4 minutes
223
Which 2 fentanyl's have the same protein binding?
Alfentanil and sufentanil
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What is the induction, induction alone and maintenance dose of alfentanil?
Ind = 15 - 30 mcg/kg IV (90 sec prior)
Ind A = 150 - 300 mcg/kg IV
M = 25 - 150 mcg/kg/hour IV
225
Alfentanil is ___% nonionized at normal pH
90% -> low lipid solubility
226
What is a contraindication to alfentanil?
Parkinsons and other neuromuscular disorders (MG, muscular dystrophy etc)
227
Remifentanil is a selective ___ opioid agonist
µ
228
Remifentanil potency compared to alfentanil and fentanyl
15 to 20 times as potent as alfentanil (same as fentanyl)
229
Remifentanil has an _____ structure; hydrolysis by _______
ester
Hydrolysis by nonspecific plasma and tissue esterases
- rapid onset and offset
230
What fentanyl is dosed in IBW?
Remifentanil
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Which fentanyl rapidly reaches steady state?
Remifentanil
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Give the induction and maintenance dose of remifentanil
I = 0.5 - 1 mcg/kg IV
M = 0.25 - 1 mcg/kg IV or 0.005 - 2 mcg/kg/min IV
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Which fentanyl is not recommended for spinal/epidural use?
Remifentanil
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Remifentanil has synergistic depression of ventilation with ________
propofol
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Remifentanil clearance and elimination half-time?
Clearance: 3L/min (8x more rapid > alfentanil)
Elimination half-time: 6.3 minutes (99.8%)
236
Before stopping Remifentanil, give what?
longer-acting opioid
237
Compare hydromorphone and morphine
Hydromorphone is 5x more potent, less hydrophilic, no histamine release and does have an active metabolite
238
Dose range for dilaudid?
0.5 - 4 mgs IV
239
Why is codeine not given IV?
histamine-induced hypotension
240
Elimination half-time of codeine?
3-3.5 hours
241
Cough suppressant and analgesia dose range for codeine?
CS = 15 mg
A = 60 - 120 mg
242
Dose of tramadol? Primary drug interaction?
3mg/kg PO and interacts with coumadin
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Which opioids have the greatest and least context sensitive half times?
Greatest = fentanyl
Least = remifentanil
244
Which opioids have the highest protein binding? Least?
High = Su, al and remifentanil
Low = morphine
245
Which opioids have the highest and lowest Vd?
High = fentanyl
Low = alfentanil
246
Which opioids have the highest/lowest VD?
High = fentanyl
Low = alfentanil
247
Which opioids have the highest/lowest partition coefficient?
High = sufentanil
Low = morphine
248
Which opioids have the highest/lowest E1/2?
High = fentanyl
Low = remifentanil
249
Which opioids have the highest/lowest blood/brain equilibration times?
High or longest = fentanyl
Low or shortest = remifentanil
250
What are the advantages of opioid agonist-antagonists?
Provide analgesia, limited depression of ventilation, low chance of dependence and ceiling effect prevents additional responses
251
What receptors does pentazocine work on?
Delta and kappa
252
Describe pharmacokinetics of pentazocine
1/5th as potent as nalorphine, antagonized by naloxone, may have withdrawal s/sx
253
What OAA crosses the placental barrier?
Pentazocine
254
Dosage of PO and IV pentazocine?
IV = 10 - 30 mg
PO = 50 mg
255
General CV effects of pentazocine?
Increased HR, BP, PA and LV-EDP
256
Compare butorphanol and pentazocine potency
Butorphanol is 20x more potent agonist and 10 - 30x more potent antagonist relative to pentazocine
257
Describe receptor affinity for pentazocine
low affinity for Mu and sigma, moderate for kappa
so low antagonism and dysphoria, but can produce analgesia and anti-shivering effects
258
What is the caution for use of Butorphanol?
Do not use with other opioid agonists
259
What is the only OAA that does not increase CV effects?
Nalbuphine
260
What OAA would you use in cardiac cath lab?
Nalbuphine
261
List the OAA from least to most potent
Nalbuphine < Pentazocine < Nalorphine < Butorphanol
262
Which OAA has 50x more affinity for mu receptors relative to morphine?
Buprenorphine
263
Why isn't Nalorphine used?
High incidence of dysphoria (sigma receptor)
264
Which OAA is more potent than morphine?
Buprenorphine
265
Which antagonist can increase myocardial contractility?
Naloxone
266
Dose of Naloxone?
1 - 4 mcg/kg IV
(40-80 mcg)
267
Duration of Naloxone?
30 min
268
Dose of Naloxone in continuous infusion, shock and epidural
CI = 5 mcg/kg IV
S = greater than 1 mg/kg IV
E = 0.25 mcg/kg/hour IV
269
Use of naltrexone?
ETOH, lasts for 24 hours
270
Dose of Nalmefene? potency relative to naloxone?
15 - 25 mcg q 2-5 min, same potency
271
What is methylnaltrexone used for?
Gastric emptying and antagonizing N/V
272
What is Alvimopan used for?
Post-op ilieus
273
What is the only drug listedin lecture here to be metabolized by the gut flora?
Alvimopan
274
What are some of the tamper or abuse resistant opioids?
Suboxone (buprenorphine and naloxone), Embeda (ER morphine and naltrexone) and Oxynal (oxycodone and naltrexone)
275
How much does fentanyl reduce MAC of Iso or des?
50%
276
How much does su, al and remifentanyl reduce mac?
Su = 70 - 90%
Al = up to 70%
Remi = 50 - 91%
277
With neuraxial opioids, what are you targeting?
The opioid receptors in the substantia gelatinosa
278
How much more drug do you give with an epidural relative to a spinal?
5 - 10x more
279
What can you do to prevent systemic absorption of an epidural?
Add epinephrine
280
List in order of increasing lipid solubility: sufentanil, fentanyl, morphine
Morphine < fentanyl < sufentanil
281
If you had a left hip replacement with the hip up, right hip down, would you want a high or low baracity (hypobaracity) epidural?
Low so that it would float
282
If you had a left hip replacement with the hip down and right hip up, would you want a high or low baracity epidural?
High so that it would sink down to the hip
283
Which opioid would experience the most cephalad movement in the CSF?
Morphine
284
Common s/e of neuraxial opioids?
Pruritis, N/V, urinary retention (more so in males)
285
What is the most reliable sign of decreased ventilation with neuraxial opioids? Treatment?
Decreased LOC secondary to hypercarbia. 0.25 mcg/kg/hour IV of naloxone
286
What do you base barbiturate dosing on?
Lean body weight due to its propensity to go into other tissues
287
Why are barbiturates no longer used as a pre-medication in pre-op?
They are notorious for having a bad hangover effect
288
Which isomer of barbiturates are more potent?
S-isomers, though they are only marketed as a racemic mixture
289
How much do barbiturates generally decrease HR/BP?
10 - 20 mmHg drop in BP, 15 - 20 reduction in HR
290
For what drug class is SSEP monitoring required?
Barbiturates
291
What are the plasma levels of unconscious vs awake of propofol?
Unconscious = 2-6 mcg/ml
Awake = 1 - 1.5 mcg/ml
292
Where would you find nociceptors?
Skin, muscles, joints, viscera and vasculature
293
Where would you find the NKI receptor where substance P would act?
Lamina III and IV
294
Which opioids have the highest incidence rates of spasm of the oddi sphincter?
Fentanyl > Demerol > Morphine
295
All the fentanyl's are derivatives of what opioid?
Demerol
296
Which fentanyl's bind to A1-Acid glycoprotein?
Al and Sufentanil
297
Which fentanyl has a very rapid onset/offset with minimal tissue accumulation?
Remifentanil
298
What is the common reason to use an OAA?
If the patient cannot tolerate a pure opioid agonist
299
What OAA is resistant to narcan?
Buprenorphine
