PHARMACOLOGY | IV Anesthetics Part I Flashcards

Question

Induction dose of Propofol is based on? A. actual body weight B. total body weight C. lean body weight

Answer 1

C. lean body weight

Answer 2

A. Inhibition of baroreceptor reflex

Answer 3

A. >70 mcg/kg.min

Answer 4

A. Increase latency, decrease amplitude

Answer 5

C) Higher incidence of myoclonus

Answer 6

A. Decrease amplitude of SSEP - Correct answer B. Induces malignant hyperthermia - (volatiles, succinylcholine) C. Inhibition of cytochrome p450 - (several, but not propofol) D. Initiation of porphyria - (variety of drugs, but not propofol) E. Inhibition of glucocorticoid function - this is etomidate

Answer 7

FALSE! Does not INHIBIT HPV.

Answer 8

FALSE! The mechanism by which the unconscious state is attained by Propofol is complicated, but primarily occurs via ***enhancement*** of gamma-aminobutyric acid (GABA) inhibitory pathways.

Answer 9

E. 10% Propofol - only 1% of PROPOFOL! PROPOFOL consists: 1% propofol 1.2% egg phospholipid 2.25% glycerol 10% soybean oil emulsifier ethylenediamenetetraacetic acid (EDTA)

Answer 10

FALSE! Propofol binds post-synaptically and enhances GABAergic inhibition. Unconsciousness occurs as this enhanced GABAergic inhibition counteracts ascending arousal inputs to the pyramidal neuron and decreases excitatory activity.

Answer 11

A. increase in alpha and delta activity

Answer 12

A. 3 mcg/mL 8 mcg/mL - BURST SUPRESSION is achieved with this plasma level

Answer 13

* It shortens the duration of seizure It has also been used successfully to treat status epilepticus, thus it is rarely the anesthetic of choice during induction of anesthesia for electroconvulsive therapy (ECT) because it shortens seizure duration.

Answer 14

TRUE The loss of consciousness attributed to Propofol can be partially reversed by the central cholinomimetic properties of physostigmine

Answer 15

Increased * Patients with chronic alcohol abuse, as expected, have an increased induction dose requirement. Morbidly obese patients should have lean body weight used when calculating propofol dosing. * An exaggerated hemodynamic response is likely after induction of propofol in patients with cardiovascular disease.

Answer 16

(E) activation o α 2 adrenergic receptors in the locus ceruleus

Answer 17

A. Nondepolarizing muscle relaxant

Answer 18

B. Depolarizing muscle relaxant

Answer 19

D. Midazolam

Answer 20

B. Myasthenia gravis

Answer 21

D. Erythromycin

Answer 22

D. Etomidate

Answer 23

D. Lipid solubility

Answer 24

TRUE On the opposite end of the spectrum, children typically have a larger than average volume of distribution and quicker clearance, resulting in increased Propofol requirement on a per-kilogram basis. Barash | 9th edit

Answer 25

Primarily because of mitochondrial toxicity and uncoupling of the intracellular respiration chain.

Answer 26

C. excreted predominantly by the bile - FALSE statement Etomidate is metabolized in the liver and excreted predominantly by the kidney (approximately 80%) and in bile (approximately 20%). It is largely protein bound (approximately 75%) and thus affected by pathologic conditions and/or drugs that alter serum proteins.

Answer 27

A. High lipid solubility, non-ionized fraction at physiologic pH

Answer 28

C. 11-deoxycortisol > Cortisol

Answer 29

B. Increases the PA wedge pressure - FALSE Why? * Etomidate has a nonexistent effect on MAP, pulmonary artery (PA) pressure, PA wedge pressure, central venous pressure (CVP), stroke volume, cardiac index, SVR, and pulmonary vascular resistance (PVR). * Etomidate is a reasonable choice for MAC sedation because of the preservation of airway reflexes.

Answer 30

* Etomidate is a reasonable choice for MAC sedation because of the preservation of airway reflexes.

Answer 31

C. adrenocortical suppression Adrenocortical suppression may be the most significant adverse effect of etomidate. Etomidate inhibits the activity of the enzyme 11-beta-hydroxylase and prevents the conversion of cholesterol to cortisol. * Cholesterol to cortisol is inhibited.

Answer 32

(C) a decrease in CMRO2, a decrease in CBF, and an increase in CPP An induction dose of etomidate (0.2–0.4 mg/kg) reduces both cerebral blood flow and CMRO2 by 30–45%. Etomidate also reduces elevated ICP, but unlike induction doses of propofol or thiopental, MAP is preserved without the need or additional vasopressor therapy. As a result, cerebral perfusion pressure is increased (CPP = MAP – ICP), and there is a beneficial net increase in the cerebral oxygen supply-demand ratio. Etomidate is an appropriate agent to use for induction and maintenance o anesthesia during most neurosurgical procedures. Keyword: DECREASE CMRO2, CBF but INCREASE CPP

Answer 33

(D) disruption of intraoperative mapping of seizure foci

Answer 34

(A) a dose-dependent, reversible inhibition of the enzyme 11β -hydroxylase

Answer 35

B. Etomidate Etomidate has the highest incidence of nausea and vomiting, with reports as high as 40%

Answer 36

(B) etomidate Even a single bolus of etomidate can cause adrenal suppression which is not beneficial for a critically ill patient.

Answer 37

(B) increased intraocular pressure

Answer 38

Etomidate does not precipitate in intravenous lines (unlike thiopental, which does in the presence o solutions with low pH).

Answer 39

(D) Allosteric modulation o GABA binding to GABA-A receptor Midazolam (and other benzodiazepines) act at the benzodiazepine receptor on the GABA-A receptor complex. The binding of midazolam results in increased binding affinity of GABA or the GABA-A receptor (allosteric modulation). * GABA-A activation causes influx of chloride ions and hyperpolarization of the cell membrane. Direct activation of the GABA-A receptor can occur with barbiturates and etomidate. NMDA receptor activation alters sodium and potassium conductance. Barbiturates such as thiopental are also thought to act as a competitive inhibitors at CNS acetylcholine (and glutamate) receptors.

Answer 40

TRUE Midazolam can be administered intravenously, intranasally, orally, rectally, and intramuscularly. This flexibility in route of administration also contributes to its popularity

Answer 41

B. High lipophilicity results in a significantly smaller volume of distribution Benzodiazepines are highly protein bound and highly lipophilic. High protein binding renders a smaller free fraction of the drug available to cross the blood–brain barrier, and high lipophilicity results in a larger volume of distribution. High lipid solubility = Large volume of distribution

Answer 42

D. Midazolam

Answer 43

A. Benzodiazepine effect is eliminated more slowly than the effect of flumazenil

Answer 44

A. Midazolam Also, Lorazepam and diazepam are not soluble in water and often cause vein irritation due to the propylene glycol admixture. Alternative formulations are available as a lipid emulsion, but with a decrease in bioavailability.

Answer 45

FALSE It is this enhanced affinity of the GABA-A receptor for the GABA molecule, and subsequent decreased unbinding that produces the so-called “ceiling effect.” Benzodiazepines thus have a dose dependent CNS depressant effect. Because of the ceiling effect of benzodiazepines, an isoelectric EEG or burst suppression is not attained. This is in direct contrast to propofol and thiopental, each of which can achieve burst suppression. Thus, the neuroprotectant effect of benzodiazepines is quite limited, but likely not entirely absent.

Answer 46

A. 0.5 mg/kg

Answer 47

TRUE It has a rapid offset that follows first-order kinetics at the recommended doses due to metabolism by tissue esterases (similar to remifentanil), and thus does not result in accumulation of drug. Remimazolam takes advantage of the hypnotic and amnestic effects of midazolam with a speed and mode of metabolism similar to remifentanil.

Answer 48

A. production of an active metabolites with oxidative metabolism in the liver * Diazepam undergoes oxidative metabolism in liver and has active metabolites --> prolong its sedative effects Also, severe liver disease prolongs the half-life * Lorazepam is directly conjugated to glucuronic acid to form pharmacologic inactive metabolite * Midazolam undergoes oxidative metabolism in liver, but different hepatic enzymes than diazepam. The primary metabolite is 1-hydroxymethyl midazolam - has mild CNS depressive effects

Answer 49

E) pharmacological active metabolite

Answer 50

D) Diazepam

Answer 51

D) all of the above

Answer 52

C. It produces retrograde amnesia

Answer 53

D) increased metabolism of diazepam - it should decrease metabolism Cimetidine - decreases the metabolism of benzodiazepines

Answer 54

D) it has a shorter duration of action than midazolam

Answer 55

B) flumazenil FLUMAZENIL has a shorter elimination half-life than the three commonly used BENZO's

Answer 56

(E) increased Stage 2 sleep Benzodiazepines INCREASE the amount of time spent in Stage 2 sleep. Benzodiazepines usually decrease the amount of time spent in Stage 0, 1, 3, 4, and REM sleep. They also decrease sleep latency and usually increase the number of REM cycles. Overall, benzodiazepines usually increase total sleep time. When benzodiazepines are discontinued, a “rebound” in the amount o REM sleep may occur.

Answer 57

(B) seizures Flumazenil should be avoided in the setting of chronic benzodiazepine use or in cases of tricyclic antidepressant overdose, as seizures have been reported. In general, other side effects of fumazenil administration include tachycardia, hypertension, hearing changes, and nausea.

Answer 58

(C) Isoflurane CVS effect of MIDAZOLAM:

Answer 59

(C) nitrous oxide Etomidate - decrease CBF Midazolam - decrease CBF

Answer 60

(D) It has a shorter duration of action than midazolam * Hence it can cause re-sedation in the ICU when one assumes that benzodiazepine was reversed after a dose of flumazenil.

Answer 61

(C) Ketamine has a relatively low degree of protein binding

Answer 62

(C) Norketamine Ketamine is metabolized in the liver by N-demethylation to form norketamine. This is then hydroxylated to hydroxynorketamine. Both of these intermediate metabolites are conjugated to glucuronide and excreted in the urine. Norketamine apparently has about 70%–80% of the activity of the original drug. Although it does not last very long providing the glucuronidation pathway is not impaired, research does suggest that it contributes somewhat to a prolongation of the effect.

Answer 63

A. Ketamine * Ketamine and Midazolam is have least incidence of drug hypersensitivity intraoperatively. * Most common - NMB > Latex > Hydroxyethyl starch

Answer 64

B. Ketamine Induction dose of 2mg/kg can induce general anesthesia within 30 - 60 seconds.

Answer 65

(D) an increase in right atrial pressure Ketamine is unique among intravenous anesthetics in that it stimulates the cardiovascular system rather than depresses it. Hemodynamic changes following an intravenous induction dose of 0.5–2 mg/kg are seen in the given table. Interestingly, using an equia-nesthetic dose of the S+ enantiomer produces the same effect as the racemic mixture, despite an overall dose reduction of 50%. Moreover, the hemodynamic changes appear NO to be dose-related; a dose of 1 mg/kg appears to produce the same increase in blood pressure, heart rate, etc. as a dose of 2 mg/kg or 0.5 mg/kg. Ketamine appears to act centrally by stimulating the sympathetic system, rather than by a peripheral mechanism such as inhibition of the baroreceptor reflex.

Answer 66

(D) Female sex Several factors have been shown to increase the incidence of emergence reactions. These include female sex, adult (vs. pediatric) patients, and large and/or rapidly administered doses of ketamine. Patients who dream frequently at home may also be at higher risk or vivid dreaming after ketamine anesthesia. Playing music during anesthesia has been postulated by some to increase the incidence due to a possible pro-hallucinatory effect, but this has been disproven. Benzodiazepines (including midazolam, lorazepam, and diazepam) are very effective at reducing the incidence o emergence reactions following ketamine. Ref: Miller RD. Miller’s Anesthesia. 8th ed

Answer 67

D. an increase in right atrial pressure During acute pericardial tamponade, the key problem is restriction of cardiac chamber size during diastole due to the expansion of the pericardial sac. This is especially true of the more compliant, thin-walled right heart. This restriction limits the right-sided stroke volume, which effectively lowers overall cardiac output. The goals of anesthetic management during tamponade are to maintain the preload as much as possible, and to promote the ejection of whatever stroke volume is in the ventricles. This gives rise to the phrase “ fast, full, and forward”—a rapid heart rate and full preload will give the cardiac output a fighting chance until the pressure can be relieved. Bradycardia and a low CVP are not well tolerated in these circumstances Miller | 8th edit

Answer 68

C. The S enantiomer is cleared more rapidly * The induction dose of ketamine is 0.5 to 2 mg/kg for intravenous administration and 4 to 6 mg/kg for IM administration. Barash | 9th edit

Answer 69

B. Liver The liver extensively metabolizes ketamine by demethylation to its principle metabolite norketamine. Norketamine is biologically active but only has 20% to 30% the activity of racemic ketamine. Norketamine is eliminated by renal excretion. * Due to its lipophilicity, ketamine is only partially removed by dialysis.

Answer 70

A. Naloxone Medications that can be used for post-anesthetic shivering: Clonidine Dexmedetomidine Ketanserin( Anti-serotonigenic) Magnesium SO4 Meperidine Tramadol Physostigmine * NALOXONE do not have a role in the post-anesthetic shivering

Answer 71

B. Is suitable for patients with liver disease

Answer 72

C. 0.5 mg/kg The duration of ketamine’s antidepressant effect may last from a couple of days to approximately 2 weeks following a single injection. For treatment of depression, ketamine is typically infused intravenously over 40 minutes at a subanesthetic dose of 0.5 mg/kg. * Ketamine has a rapid effect on depression with decreased depression symptoms and suicidal ideation within 1 hour of administration

Answer 73

FALSE! The excitatory CNS effects of ketamine would increase CMRO2 and increase CBF. However, studies have found that ICP typically remains normal with ketamine administration in neurosurgical patients with controlled ventilation. In fact, ketamine may be neuroprotective. Ketamine is associated with epileptiform activity on EEG; however, these excitement waveforms are not seen in the cortex, and therefore ketamine seems unlikely to precipitate a seizure.