Gruneisen: Nur 638: Intravenous Anesthetic Induction Agents

Front 1

What is barbiturates MOA?

Back 1

Barbiturates depress the reticular activating system by suppressing transmission of excitatory neurotransmitters and enhance transmission of inhibitory ones.

Front 2

What effect does GABA have on the body?

Back 2

GABA is a major inhibitory neurotransmitter

Front 3

What is the RAS (reticular activating system)?

Back 3

A complex polysynaptic network of neurons and regulatory centers that controls several vital functions including consciousness.

Front 4

Where is the RAS located?

Back 4

brainstem

Front 5

In clinical concentrations barbiturates preferentially effect the function of nerve ________ rather than ________.

Back 5

synapses; axons

Front 6

Barbiturates work on excitatory transmitters both presynaptically and postsynaptically. Explain how.

Back 6

Presynaptically by interfering with transmitter release and postsynaptically by stereoselectively interacting with receptors.

Front 7

What is the major excitatory neurotransmitter?

Back 7

Glutamate

Front 8

GABA receptor sites consist of 5 _________ __________. :

Back 8

glycoprotein subunits

Front 9

When GABA receptors are activated, this causes an increase of conductance of _______ channels.

Back 9

chloride

Front 10

GABA and Glutamate are similar in that they both are ____-_______ _______ neurotransmitters.

Back 10

ion-channel linked

Front 11

Barbiturates react with the sub-units of GABA and act as __________; and postsynaptically they ________ or _________ the effect of GABA.

Back 11

agonist; mimic; increase

Front 12

Barbiturates are most frequently administered IV for:

Back 12

induction of general anesthesia

Front 13

Rapid awakening from barbiturates such as thiopental or methohexital is from ___________ .

Back 13

redistribution

Front 14

Barbiturates given rapid IV have an effect-site equalibrium (maximal brain uptake) within ____ seconds.

Back 14

30

Front 15

The brain receives about ___% of the given dose in the first 30-40 seconds and in 5 minutes it is reduced to _____ of the initial peak concentration.

Back 15

10%; half

Front 16

Known as the hallmark barbiturate agent:

Back 16

Sodium thiopental(Sodium pentothal)

Front 17

Sodium Pentothal facts:

Back 17

S-isomer is more potent, but is only available commercially as a racemic mixture
pH 10.5, very alkaline

Front 18

Sodium Pentothal is derived from _______ ______.

Back 18

barbituric acid

Front 19

There is a ______ atom on the #2 carbon atom of the barbituric acid ring; this is known as a ___________.

Back 19

sulfur; thiobarbiturate

Front 20

The addition of a sulfur ring on the #2 carbon atom of barbituric acid makes is more _______ ________.

Back 20

lipid soluble

Front 21

Which barbiturate was used more in veterinary practice and production was stopped in 1990's?

Back 21

Thiamylal

Front 22

__________ is an oxybarbiturate, which means that there is an ______ atom on the #2 carbon of barbituratic acid ring.

Back 22

Methohexital (Brevital); oxygen

Front 23

Which barbiturate has a shorter duration of action and does not decrease seizure threshold?

Back 23

Brevital

Front 24

Sodium Pentothal is more potent than Brevital.
True or False

Back 24

False, Brevital is more potent, therefore takes less drug

Front 25

What is the induction dose of Thiopental?--Brevital?

Back 25

3-5 mg/kg IV; 1-1.5 mg/kg IV

Front 26

Redistribution of barbiturates occurs throughout the body with the highest concentration occuring in the _____, _______, and _______.

Back 26

brain, liver, kidneys

Front 27

What accounts for most of the cessation of hypnotic effects and rapid awakening from barbiturates?

Back 27

Redistribution

Front 28

Oxybarbiturates (Brevital) are metabolized only in _________.

Back 28

hepatocytes

Front 29

Thiobarbiturates break down also in extra-hepatic sites such as _______ and possible the _____.

Back 29

kidneys; CNS

Front 30

Which barbiturates is used to treat increased ICP and seizures?

Back 30

Thiopental

Front 31

Barbiturates have been replaced for preanesthetic medication by __________.

Back 31

Benzodiazepines

Front 32

Metabolites of Barbiturates are usually ________ and are always ______ water soluble than the parent compound.

Back 32

inactive; more

Front 33

Methohexital (Brevital) is metabolized faster than Thiopental because it is ______ lipid soluble and ______ remains in the plasma.

Back 33

less; more

Front 34

All barbiturates are filtered by the _______ _________ ; less than 1% is secreted unchanged in the urine

Back 34

renal glomerulus

Front 35

You can have skeletal muscle relaxation with barbiturates if the dose is high enough.
True or False

Back 35

False; barbiturates have no significant effect on the neuromuscular junction.

Front 36

Barbiturates are poor analgesics and may actually increase the reaction to painful stimuli.
True or False

Back 36

True

Front 37

Barbiturates may cause _________ release and therefore should be avoided in patients with _________.

Back 37

histamine; asthma

Front 38

Barbiturates are very _________ but become weak _______ in plasma.

Back 38

alkaline; acids

Front 39

What is the autosomal recessive or dominant(more often) group of diseases that result in a defect in heme synthesis?

Back 39

Prophyrias

Front 40

The heme pigments are tetrapyrroles that are the essential elements in _________, __________, ___________.

Back 40

hemoglobin, myogloin, and the cytochromes.

Front 41

Those who have porphyria have a partial deficiency in the enzyme needed in one step of the production of ________.

Back 41

heme

Front 42

What is the is the precursor for heme?

Back 42

porphyrins

Front 43

_________ are a chief trigger for prophyrias.

Back 43

Barbiturates

Front 44

Symptoms of a prophyria attack include:

Back 44

confusion, neurological problems, abdominal pain, hypokalemia, hyponatremia, hypomagnesium.

Front 45

A prophyria crisis can be fatal and include:

Back 45

muscle weakness, vomiting, diarrhea, anxiety, seizures, and hallucinations.

Front 46

What percentage of people who suffer from prophyria are photosensitive?

Back 46

80%

Front 47

Among the anesthesia drugs that are considered safe for those who have prophyria are:

Back 47

propofol, nitrous, opiods, and muscle relaxants

Front 48

How do you treat an acute prophyria attack?

Back 48

glucose infusions, correction of electrolyte imbalances, treatment for pain and supportive therapy for respiratory insufficiencies.

Front 49

All benzodiazepines have a _______ ______ and a 7 member _______ _______.

Back 49

benzene ring; diazepine ring

Front 50

What does a benzene ring consist of?

Back 50

a 6-carbon ring with 1 hydrogen attached to each carbon (C6H6).

Front 51

What does a diazepine ring consist of?

Back 51

a 7 member organic ring containing 2 nitrogen atoms in ring positions

Front 52

Potency and biotransformation differences among the benzodiazepines are accomplished by ___________ of various positions on the rings.

Back 52

substitutions

Front 53

What is the MOA of Benzodiazepines?

Back 53

****they enhance the affinity of the receptors for GABA****; opens the gate of chloride gated channels; renders post-synaptic neurons more resistant to excitation.

Front 54

Pharmalogic synergy can be caused by different mechanisms acting on the same receptor.
True or False

Back 54

True; barbiturates, benzos and alcohol can cause a synergistic effect and lead to life-threatening CNS depression.

Front 55

Why are benzos considered to be clinically safe?

Back 55

because they have a limitation to their effect on GABA neurotransmission.

Front 56

Side effects of benzos are:

Back 56

fatigue and drowsiness

Front 57

When given with other CNS depressants, benzos can have _________ effects.

Back 57

synergistic

Front 58

Benzos have dose dependent suppression of the hypothalamic-pituitary adrenal axis; this causes a decrease in __________ levels which may contribute to their use to treat depression.

Back 58

cortisol

Front 59

Even therapeutic doses of benzos may produce dependence.
True or False

Back 59

True

Front 60

What mechanism is involved with benzos effect on platelet aggregation?

Back 60

benzos may inhibit platelet activating factor.

Front 61

What therapeutic benefits do benzos provide?

Back 61

anxiolysis, sedation, anticonvulsant actions, spinal cord mediated skeletal muscle relaxation, anterograde amnesia.

Front 62

Benzos have both amnesic and sedative effects, which effects last the longest?

Back 62

amnesia effects

Front 63

Benzos effect retrograde (stored) memory.
True or False

Back 63

False, benzos do not alter stored memory

Front 64

_________ have replaced barbiturates for preoperative medication and sedation for MAC.

Back 64

Benzos

Front 65

Of these anesthetic agents, which are lipid soluble and which are water soluble?
Versed, Propofol, fospropofol, etomidate, ketamine

Back 65

Water--versed and fospropofol
Lipid--Propofol, etomidate and ketamine

Front 66

Why is versed 2-3 times more potent than valium?

Back 66

Versed's affinity for the benzodiazepine receptor is about twice that of valium.

Front 67

Verseds amnestic effects are more potent than its sedative effects.
True or False

Back 67

True

Front 68

Versed has a unique solubility attribute. Explain.

Back 68

Parenteral versed is clinically buffered to an acidic pH of 3.5, its imidazole ring is pH-dependent and remains open at pH values of < 4, thus maintaiining water solubility, but closes at pH values > 4, as when the drug is exposed to physiologic pH, thus converting it to a highly lipid-soluble drug.

Front 69

Where is versed metabolized and by what and where is it excreted?

Back 69

liver by cytochrome P-450 and excreted via the kidneys

Front 70

Why is versed's Vd, eliimination half-time and clearance not affected by renal failure?

Back 70

because of its extensive hepatic metabolism

Front 71

What is the induction of anesthesia dose of versed?

Back 71

0.2 mg/kg

Front 72

What is the onset, peak effect and duration of sedation of versed?

Back 72

30-60 secs, 3-5 min, and 15-80 minutes

Front 73

Versed can have dose dependent decreases in ventilation and transient apnea with rapid IV doses.
True or False

Back 73

True

Front 74

What is the most common benzo used for pediatric preoperative medication?

Back 74

versed

Front 75

Which benzo is used as an anticonvulsant for grand mal seizures produced by systemic toxicity of local anesthetics?

Back 75

versed

Front 76

__________ is a non-barbiturate, sedative-hypnotic agent.

Back 76

Propofol

Front 77

Propofol is an emulsion that has a pH range of 6.0-8.5 and is a _____ ______ that is _________ at physiologic pH.

Back 77

weak acid; non-ionized

Front 78

Propofol is slightly soluble in water and is therefore formulated in an oil-in-water emulsion.
True or False

Back 78

True

Front 79

What is the pka of propofol?

Back 79

11

Front 80

What other substances are in the propofol emulsion?

Back 80

soybean oil, glycerol, and egg yolk

Front 81

Propofol's half-time elimination is 0.5-1.5 hours; this is the reason for its _______ _________.

Back 81

rapid awakening

Front 82

Why does propofol produce a decrease in BP?

Back 82

Because both CO and SVR are depressed (can decrease BP by 15%-40%); HR is often unchanged despite decrease in BP.

Front 83

The decrease in BP with propofol suggests that it has a ___________ or _________ action.

Back 83

sympatholytic or parasympathomimetic

Front 84

Propofol has profound ________ depressant effects.

Back 84

ventilatory

Front 85

Why is propofol a good antiemetic?

Back 85

It acts on the chemoreceptor zone (CRTZ) and the vomiting center.

Front 86

Propofol has analgesic effects.
True or False

Back 86

False, it has no analgesic effects and unlike the barbiturates it has no antianalgesic effects.

Front 87

Propofol (dec/inc) CBF and cerebral metabolism?

Back 87

decreases

Front 88

How can pain on injection site from propofol be treated?

Back 88

pretreat with lidocaine

Front 89

A rare side effect of propofol is _______, which is involuntary repetitive muscle twitching.

Back 89

dystonia

Front 90

________ movements are common with propofol as with other intravenous hypnotic agents.

Back 90

myoclonic (brief, involuntary twitching)

Front 91

Propofol has been known to trigger both prophyria and malignant hyperthermia.
True or False

Back 91

False, it is porphyria and MH safe.

Front 92

_________ can be used as an effective anti-pruritic in itching associated with neuroaxial opiods.

Back 92

Propofol

Front 93

Some clinical trials have proven that sub-clinical doses of _______ are effective for treating intractable migraine headaches.

Back 93

Propofol

Front 94

Propofol must be administered within ___ hours of opening the vial.

Back 94

6; it is capable of supporting bacterial growth

Front 95

Propofol's MOA is to modulate the GABA receptors. Explain how this is done.

Back 95

The interaction of propofol with specific components of GABA receptors appears to decrease the rate of dissociation of the inhibitory neurontransmitter (GABA) from the receptor thereby increasing the duration of the GABA-activated opening of chloride channel with resulting hyperpolarization of cell membranes. This makes the membranes unable to create a new action potential.

Front 96

How is propofol metabolized?

Back 96

Rapidly in the liver into inactive woter soluble compounds and excreted via the kidneys.

Front 97

Clearance of propofol from the plasma exceeds hepatic blood flow, therefore another form of clearance must exist, what is it?

Back 97

tissue uptake from the plasma, perhaps by the lung is also a form of metabolism of propofol.

Front 98

"First pass" effect of the lungs accounts for __% of propofol uptake and metabolism.

Back 98

30%

Front 99

What is the anesthetic dose for propofol?

Back 99

1.5-2.5 mg/kg

Front 100

What is the typical continuous IV infusion rate for propofol for sedation of an ICU patient?

Back 100

25-100 mcg/kg/min

Front 101

What is the dose for continuous IV infusion of propofol for maintenance of anesthesia?

Back 101

100-300 mcg/kg/min

Front 102

Propofol infusion syndrome is rare but potentially fatal.
True or False

Back 102

True

Front 103

What are the symptoms of propofol infusion syndrome?

Back 103

cardiac dysrhythmia and collapse, metabolic acidosis, acute renal failure, and rhabdomyolysis.

Front 104

At what dose and duration has propofol infusion syndrome occur?

Back 104

long term use over 48 hours at doses higher than 4 mg/kg/hr

Front 105

At subtherapeutic doses, propofol gives feelings of ________ and _______.

Back 105

elation and euphoria

Front 106

Propofol has a wide therapeutic margin.
True or false

Back 106

False, propofol has a narrow margin between effective dose and lethal dose.

Front 107

Propofol is usually abused to treat _________ ________ ______.

Back 107

refractory persistent insomnia

Front 108

What is the water soluble prodrug of propofol?

Back 108

Fospropofol

Front 109

What is the dose of Fospropofol as compared to propofol?

Back 109

Fospropofol 1.86 mg = Propofol 1 mg

Front 110

What is the main differences between fospropofol and propofol?

Back 110

more gradual onset and longer duration; initial dose 6.5 mg and onset 40 seconds with peak effect 3-15 min and duration 20-45 min

Front 111

What are the advantages and disadvantages with Fospropofol as compared to propofol?

Back 111

advantages- less pain of injection site
-less hyperlipidemia with longterm use
-reduced risk of bacteremia
disadvantages- parasthesia in perianal and perineal areas
-pruritis
-hypoxemia and hypotension
-no research on cost effectiveness

Front 112

What drug is a carboxylated Imidazole containing compound?

Back 112

Etomidate

Front 113

*********Etomidate**********

Back 113

Imidazole is an organic compound in which 2 of the 5 atoms that make up the ring are Nitrogen; carboxylated means that a carboxyl group is added(carbon atom double bounded to O2 and single bonded to an OH group)

Front 114

Etomidate is chemically unrelated to any other drug used for the IV induction of anesthesia.
True or False

Back 114

True

Front 115

Due to the Imidazole nucleus, Etomidate is ______ soluble at an acidic pH and ______ soluble at a physiologic pH.

Back 115

water; lipid

Front 116

Which isomer of Etomidate has anesthetic effects?

Back 116

R isomer

Front 117

What is the MOA of Etomidate?

Back 117

Binds to specific sites on the GABA receptor enhancing the affinity of the inhibitory neurotransmitter for the receptors. (does not modulate ligand-gated ion channels like propofol)

Front 118

Etomidate has a large Vd and exists as a ______ _____ at physiologic pH.

Back 118

weak base; pka 4.2; 99% unionized at physiologic pH

Front 119

Etomidate penetrates the brain rapidly due to its high _______ solubility and large percentage of unionized drug accounts for its rapid onset.

Back 119

lipid

Front 120

What is responsible for awakening with Etomidate?

Back 120

redistribution

Front 121

How is Etomidate metabolized?

Back 121

by hepatic enzymes and plasma esterases that hydrolyze it to inactive water soluble metabolites; 85% in urine and 13% bile; 2-3% unchanged in urine

Front 122

What is the induction dose for Etomidate?

Back 122

0.2-0.4 mg/kg

Front 123

When is use of Etomidate a good choice for induction?

Back 123

for cardiac unstable patients and for RSI induction in a patient with precarious hemodynamic balance.

Front 124

Etomidate has good analgesic activity.
True or False

Back 124

False, has no analgesic activity.

Front 125

Why should Etomidate not be used for prolonged sedation?

Back 125

due to suppression of adrenal function and its association with mortality when used in this fashion.

Front 126

What are some of the drawbacks of Etomidate?

Back 126

minor adrenocortical effects even after single induction dose(short term); depresses immune system; 30-40% incidence of N/V; pain on injection; myoclonic movements(can be confused with seizure activity)

Front 127

Benefits of Etomidate are:

Back 127

mild respiratory depressant and minimal change of cardiovascular function.

Front 128

*********Ketamine**********

Back 128

Chiral center that has two opitcal isomers; left side is S isomer (+) ketamine and right is R (-) ketamine.

Front 129

Ketamine is a ________ mixture.

Back 129

racemic

Front 130

What is the MOA of Ketamine?

Back 130

binds noncompetitively to the phencyclidine recognition side on the N-methyl-D-aspartate (NMDA) receptors.

Front 131

NMDA receptors are one of the _________ neurotransmitter receptors.

Back 131

glutamate

Front 132

Glutamate receptors are _________ transmitters with _______-_______ _____ channels

Back 132

excitatory; ligand-gated ion

Front 133

Ketamine might also exert effects on ________, _______, and __________ ________ receptors enabling it to have several effects.

Back 133

opiod, nicotinic; muscarinic cholinergic

Front 134

Ketamine has only weak actions of _______ receptors.

Back 134

GABA

Front 135

Ketamine has _____ onset and ______ duration of action and is highly ______ soluble.

Back 135

rapid; short; lipid

Front 136

Ketamine is distributed quickly to tissues due to the fact that it is not significantly bound to ______ ________.

Back 136

plasma proteins

Front 137

How is Ketamine metabolized?

Back 137

by liver enxymes, CYP-450 is important

Front 138

How is Ketamine excreted?

Back 138

active metabolites are eventually conjugated to more water soluble compounds that are excreted by the kidneys.

Front 139

What is the induction dose of ketamine?

Back 139

1-2 mg/kg IV or 4-8 mg/kg IM

Front 140

When does LOC occur with Ketamine?

Back 140

within 30-60 secs IV or 2-4 min IM

Front 141

What property makes Ketamine useful for induction of anesthesia with asthmatics?

Back 141

bronchodilation properties

Front 142

Does Ketamine induce MH or prophryia?

Back 142

No

Front 143

What type of patients are good candidates for Ketamine use?

Back 143

poor risk patients such as trauma or elderly

Front 144

What are some of the negative results from using Ketamine?

Back 144

emergence delirium, dreams, hallucinations, N/V, hypertonus and nystagmus.

Front 145

Which isomer of Ketamine is used clinically?

Back 145

S-isomer (left sided +)

Front 146

What are some of the reasons that the S-isomer of Ketamine is better to use?

Back 146

more intense analgesia, more rapid metabolism and recovery, less salivation and lower incidence of emergence reactions.