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50 Cards in this Set
- Front
- Back
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What is "context-sensitive" half life?
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is defined as the time necessary for the effect-compartment (i.e., effect site) concentration to decrease by 50% in relation to the duration of the infusion. The context-sensitive half-time becomes particularly important in determining recovery after prolonged infusions of sedative-hypnotic drugs
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factors affecting anesthetic drug's disposition?
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the degree of protein binding, the efficiency of hepatic and renal elimination processes, physiologic changes with aging, pre-existing disease states, the operative site, body temperature, and drug interactions (e.g., coadministration of volatile anesthetics
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high hepatic clearance IV anesthetics
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propofol, etomidate, ketamine
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intermediate hepatic clearance IV anesthetics
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methohexital, midazolam
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low hepatic extraction IV anesthetics
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diazepam, lorazepam, thiopental
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hepatic blood flow decreases with:
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age, administration of volatile anesthetics, upper abdominal surgery, laparoscopic surgery, liver disease, hypocapnia, congestive heart failure, intravascular volume depletion, acute alcohol intoxication, circulatory collapse, increase intra-abdominal pressure, β-adrenergic blockade, and norepinephrine administration
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How does liver disease influence hepatic clearance?
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(1) altering the plasma protein content and changing the degree of protein binding, (2) decreasing hepatic blood flow and producing intrahepatic shunting, and (3) depressing the metabolic enzymatic activity of the liver.
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Which IV anesthetic has minimal histamine release?
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Etomidate
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List the barbiturate IV agents
and their molecular structure |
Thiopental (Pentothal) and thiamylal (Surital) are thiobarbiturates, while methohexital (Brevital) is an oxybarbiturate.
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Barbiturates precipitate with?
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Rocuronium, LR
- will occlude the IV |
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Effects of intra-arterial injection of barbiturates:
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Intra-arterial injection of thiobarbiturates is a serious complication as crystals can form in the arterioles and capillaries, causing intense vasoconstriction, thrombosis, and even tissue necrosis. Accidental intra-arterial injections should be treated promptly with intra-arterial administration of papaverine and lidocaine (or procaine), as well as a regional anesthesia-induced sympathectomy (stellate ganglion block, brachial plexus block) and heparinization.
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Induction dose of thiopenthal
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3 to 5 mg/kg in adults, 5 to 6 mg/kg in children, and 6 to 8 mg/kg in infants
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Induction dose and potency of methohexital
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Because methohexital is approximately 2.7 times more potent than thiopental, a dose of 1.5 mg/kg is equivalent to 4 mg/kg of thiopental in adults
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Why is TIVA not advisable w/ thiopental
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Thiopental infusion is seldom used to maintain anesthesia because of the long context-sensitive half-time and prolonged recovery period. Plasma thiopental levels necessary to maintain a hypnotic state range between 10 and 20 mg/mL.
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Effect of thiobarbiturates on CBF
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Barbiturates produce a proportional decrease in CMRO2 and CBF, thereby lowering ICP. The maximal decrease in CMRO2 (55%) occurs when the EEG becomes isoelectric (burst-suppressive pattern). An isoelectric EEG can be maintained with a thiopental infusion rate of 4 to 6 mg/kg/hr. Improves cerebral blood flow and compliance.
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Describe thiobarbiturates and their role in neuroprotection.
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It has been suggested that barbiturates also possess “neuroprotective” properties secondary to their ability to decrease oxygen demand. Alternative explanations have been suggested, including a reverse steal (“Robin Hood effect”) on CBF, free-radical scavenging, stabilization of liposomal membranes, as well as excitatory amino acid receptor blockade. Given the lack a demonstrable neuroprotective effect, use of barbiturates during cardiac surgery is not recommended. Use of moderate degrees of hypothermia (33 to 34°C) might provide superior neuroprotection to the barbiturates without prolonging recovery.
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Methohexital and effect on epileptogenic activity
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Methohexital has well-established epileptogenic effects in patients with psychomotor epilepsy. Low-dose methohexital infusions are frequently used to activate cortical EEG seizure discharges in patients with temporal lobe epilepsy. It is also the IV anesthetic of choice for electroconvulsive therapy
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Cardiovascular effects of thiopental
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decreases in cardiac output, systemic arterial pressure, and peripheral vascular resistance. The depressant effects of thiopental on cardiac output are primarily a result of a decrease in venous return caused by peripheral pooling, as well as a result of a direct myocardial depressant effect, which assumes increasing importance in the presence of hypovolemia and myocardial disease
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Cardiovascular effect of methohexital
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Less hypotension than thiopental, causes tachycardia
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structure of propofol
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alkylphenol compound
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Propofol metabolism, clearance, context-sensitive half life, and what is it metabolized to.
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Rapidly cleared by hepatic metabolism.
context-sensitive half-life for propofol infusions up to 8 hours is <40 minutes. Propofol is rapidly and extensively metabolized to inactive, water-soluble sulphate and glucuronic acid metabolites, which are eliminated by the kidneys. Propofol's clearance rate (20–30 mL/kg/min) exceeds hepatic blood flow, suggesting that an extrahepatic route of elimination (lungs) also contributes to its clearance. |
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Propofol induction dose
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1.5-2.5 mg/kg
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Propofol CNS effects
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Propofol decreases CMRO2 and CBF, as well as ICP.40 However, when larger doses are administered, the marked depressant effect on systemic arterial pressure can significantly decrease CPP.
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Propofol and epileptogenic activity
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decreases seizure activity
Propofol has been reported to decrease spike activity in patients with cortical electrodes implanted for resection of epileptogenic foci and has been used successfully to terminate status epilepticus. |
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Propofol effect on evoked potentials
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Propofol produces a decrease in the early components of somatosensory and motor-evoked potentials but does not influence the early components of the auditory-evoked potentials.
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Propofol cardiovascular effects
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Propofol's cardiovascular depressant effects are generally considered to be more profound than those of thiopental. Both direct myocardial depressant effects and decreased systemic vascular resistance have been implemented as important factors in producing cardiovascular depression. Direct myocardial depression and peripheral vasodilation are dose- and concentration-dependent. In addition to arterial vasodilation, propofol produces venodilation. Negative inotropic effect.
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propofol effect on nausea and pruritus
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decreases both.
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what is propofol infusion syndrome
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myocardial failure, metabolic acidosis, and rhabdomyolysis. The etiology of this syndrome may be related to the large lipid load associated with prolonged infusions of the current formulations of propofol
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benzodiazepine metabolism
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Benzodiazepines undergo hepatic metabolism via oxidation and glucuronide conjugation
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diazepam metabolism
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Diazepam is metabolized to active metabolites (desmethyldiazepam, 3-hydroxydiazepam), which can prolong diazepam's residual sedative effects because of their long t1/2 β values. These metabolites undergo secondary conjugation to form inactive water-soluble glucuronide conjugates.
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Diazepam's oxidation is prolonged w/ which drug?
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Cimetidine H2 blocker
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Diazepam's metabolism and liver disease
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Severe liver disease reduces diazepam's protein-binding and hepatic-clearance rate, increases its volume of distribution, and thereby further prolongs the t1/2β value.
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Etomidate structure
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Etomidate is a carboxylated imidazole-containing anesthetic compound (R-1-ethyl-1-[a-methylbenzyl] imidazole-5-carboxylate) that is structurally unrelated to any other IV anesthetic. Only the d-isomer of etomidate possesses anesthetic activity.
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Etomidate and reaction to injection.
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The aqueous solution of etomidate (Amidate) is unstable at physiologic pH and is formulated in a 0.2% solution with 35% propylene glycol (pH 6.9), contributing to a high incidence of pain on injection, venoirritation, and hemolysis
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Etomidate induction dose
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0.2–0.3 mg/kg IV
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Etomidate clearance
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The high clearance rate of etomidate (18 to 25 mL/kg/min) is a result of extensive ester hydrolysis in the liver (forming inactive water-soluble metabolites).
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Etomidate effect on ICP
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Analogous to the barbiturates, etomidate decreases CMRO2, CBF, and ICP.
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Etomidate side effect
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adrenocortical suppression
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Etomidate and evoked potentials
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Etomidate also produces a significant increase of the amplitude of somatosensory-evoked potentials while only minimally increasing their latency. Consequently, etomidate can be used to facilitate the interpretation of somatosensory-evoked potentials when the signal quality is poor.
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Etomidate's effect on cardiovascular system
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Etomidate causes minimal cardiorespiratory depression even in the presence of cardiovascular and pulmonary disease.63 The drug does not induce histamine release and can be safely used in patients with reactive airway disease. Consequently, etomidate is considered to be the induction agent of choice for poor-risk patients with cardiorespiratory disease, as well as in those situations in which preservation of a normal blood pressure is crucial (e.g., cerebrovascular disease). However, etomidate does not effectively blunt the sympathetic response to laryngoscopy and intubation unless combined with a potent opioid analgesic.
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Etomidate and nausea
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increases incidence of post-op nausea
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Etomidate, mechanism of adrenosuppression
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Etomidate inhibits the activity of 11-β-hydroxylase, an enzyme necessary for the synthesis of cortisol, aldosterone, 17-hydroxyprogesterone, and corticosterone. Even after a single induction dose of etomidate adrenal suppression persists for 5 to 8 hours
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Etomidate adverse effects
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nausea, vomiting, adrenosuppression, inhibits platelet function, increases bleeding time
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Ketamine structure
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arylcyclohexylamine that is structurally related to phencyclidine
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Ketamine metabolism and clearance
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Ketamine is extensively metabolized by hepatic microsomal cytochrome P450 enzymes and its primary metabolite, norketamine, is one third to one fifth as potent as the parent compound. The metabolites of norketamine are excreted by the kidney as water-soluble hydroxylated and glucuronidated conjugates. Analogous to the barbiturates and propofol, ketamine has relatively short distribution and redistribution half-life values. Ketamine also has a high hepatic clearance rate (1 L/min) and a large distribution volume (3 L/kg), resulting in an elimination half-life of 2–4 hours. The high hepatic extraction ratio suggests that alterations in hepatic blood flow can significantly influence ketamine's clearance rate.
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Ketamine effect on CNS
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electrophysiologic inhibition of thalamocortical pathways and stimulation of the limbic system
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Ketamine induction dose
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1 to 2 mg/kg IV
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Duration of ketamine anesthesia
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The duration of ketamine-induced anesthesia is in the range of 10 to 20 minutes after a single induction dose; however, recovery to full orientation may require an additional 60 to 90 minutes. Emergence times are even longer following repeated bolus injections or a continuous infusion
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Ketamine effect on ICP and seizure activity
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increases ICP
suppresses seizure activity, although causes myoclonus in normal patients on induction ( sometimes) |
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Induction dose, onset, duration, pain on injection, heart rate and BP for
Thiopental Methohexital Propofol |
T: 3-6 , < 30 sec, 5-10 min, 0 pain, ^ HR, lowers BP
M: 1-3 < 30, 5-10, +1 pain, ^^ HR, lowers BP P: 1.5-2.5, 15-45 sec, 5-10 min, +3pain, less HR, lowers BP |
