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2nd Quarter > Pharm Quiz #8 > Flashcards

Pharm Quiz #8 Flashcards

1
Q

How are barbiturates classified(3)?

A
  1. ultrashort barbiturates
  2. short/medium-acting barbiturates
  3. long-acting barbiturates
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2
Q

What are ultra-short acting barbiturates used for?

A

for anesthesia-short duration of action allows for emergence(Brevital)

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3
Q

What are short/medium-acting barbiturates used for?

A

for anesthesia purposes, anxiety and insomnia(mostly oral agents)

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4
Q

what are long-acting barbiturates used for?

A

for anticonvulsants, not for insomnia because of residual “hang-over” effect(phenobarbital).

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5
Q

What are barbiturates derived from?

A

barbituric acid

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6
Q

What is a significant characteristics of all barbiturates?

A

all have long periods of “hand-over”

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7
Q

What percentage of barbiturate solution is used?

A

Available as 2.5% solutions only-5% solutions too caustic to vessels

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8
Q

Can barbiturates be mixed in the same line as opioids, catecholamines and neuromuscular blockers?

A

No….if given together they will react causing precipitation.

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9
Q

Are all barbiturates racemic mixtures?

A

yup

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10
Q

Levorotary isomers of thiopental and thiamylal are ___ as potent as dextrorotary isomers.

A

twice as potent

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11
Q

Does barbituric acid have any CNS activity?

A

no

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12
Q

Substitution of which carbons determine drug characteristics?

A

2 and #5

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13
Q

Characteristic of sulfuration.

A

greater lipid solubility

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14
Q

Characteristic of phenyl groups.

A

anti-convulsant properties

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15
Q

Characteristic of methyl group.

A

convulse activity

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16
Q

Are the sedative and anti-vonvulsant effects of barbiturates the same affect?

A

No they are separate effects

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17
Q

Prompt awakening from single dose barbs due to ___?

A

redistribution

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18
Q

What inhibitory neurotransmitter does barbiturates interact with?

A

gamma-amino butyric acid(GABA) in CNS

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19
Q

How does barbs affect GABA receptors?

A

Barbs decrease GABA dissociation from receptors

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20
Q

In relation to barbiturates affect on GABA, what action does it create?

A

Causes increased duration of GABA activated openings of chloride ion channels.

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21
Q

What causes quick awakening from barbiturates?

A

from redistribution

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22
Q

How do barbiturates affect the reticular activating system? What is the reticular activating system?

A

Barbs depress the reticular activating system. The reticular activating system is the used to maintain wakefulness.

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23
Q

How do barbiturates contribute to lowered blood pressures?

A

Barbs depress SNS ganglia transmissions.

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24
Q

What does redistribution have to do with barbs?

A

Prompt awakening from single dose barbs due to redistribution.

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25
Q

The effect-site equilibration time for thiopental and methohexital is?

A

Rapid-time between dose and clinical effect is brief. Asleep in 15-20 seconds

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26
Q

Barbiturate complete elimination from the body depends upon?

A

Metabolism

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27
Q

Protein binding of barbs parallels?

A

lipid solubility

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28
Q

Barbiturate lipid solubility is determined by solubility of the _____ molecule. Why?

A

Non-ionized molecule; Ionized barbiturate molecules are poorly lipid soluble

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29
Q

What is the greatest plasma bound barbiturate? How bound is it?

A

Thiopental; 72 - 86%

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30
Q

If a patient is on a higher protein bound medication how will that affect barbiturates given?

A

It will cause the barbiturates to have a greater affect.

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31
Q

What is an example of patients being on a high protein bound medication and what is the affect?

A

Patients on highly bound meds like ASA and phenytoin-increased thiopental effects.

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32
Q

What is a great determiner of how lipid soluble a barbiturate is?

A

if its ionized or non-ionized

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33
Q

Of ionized and non-ionized which are most lipid soluble?

A

non-ionized

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34
Q

Which causes greater anesthetic potency ionized or non-ionized?

A

non-ionized

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35
Q

How does redistribution affect barbs?

A

quick wake up after a single dose of barbs due to redistribution

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36
Q

What affect do barbiturates have on patients with cirrhosis and why?

A

causes an exaggerated response to barbs cut to hypoalbuminemia—>results in increased plasma concentrations.

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37
Q

What 3 factors affect barbiturate distribution?

A
  1. lipid solubility
  2. protein binding
  3. ionization
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38
Q

How does less plasma protein binding affect barbiturates in neonates - 1/2 of adults?

A

less plasma protein binding means greater unbound pharmacologically active fraction.

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39
Q

What helps determine the delivery of barbiturates to the tissues?

A

tissue blood flow

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40
Q

Why are exaggerated effects of barb seen in cases of shock?

A

decreases in skeletal muscle perfusion as well as maintained brain and heart perfusion. So less dilution—>causing exaggerated effects!

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41
Q

Thiopental, thiamylal and methohexital have maximum brain uptake how soon?

A

within 30 seconds(rapid effect site equilibration)

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42
Q

What is the principle mechanism for barbiturate early awakening?

A

redistribution

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43
Q

Where is the main initial site for distribution of barbiturates?

A

Skeletal muscle

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44
Q

What affect does distribution of barb by skeletal muscle have on the plasma concentration?

A

Initially decreases in plasma concentration of thiopental due to skeletal muscle uptake.

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45
Q

What is the only body compartment where thiopental concentrations continue to increase 30 minutes post injection?

A

fat

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46
Q

What can be done to prevent slow wakeup from thiopental?

A

Thiopental dosages calculated by lean patient weight avoids slow wakeup from fat accumulation.

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47
Q

What effects does cardiopulmonary bypass have on barbiturates?

A

decreased systemic clearance of barbs due to hypothermia and decreased perfusion makes the effects of barbiturates prolonged and exaggerated.

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48
Q

How does ionization affect barb distribution?

A

NON-IONIZED barbs have greater CNS access, greater lipid solubility.

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49
Q

How does acid base balance affect barbiturate effects?

A

Acidosis increases barbiturate effects, alkalosis decreases barbiturate effects due to alterations in non-ionized fractions

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50
Q

What are the 3 principle pathways for metabolism of barbiturates?

A
  1. hepatic
  2. Kidney
  3. CNS
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51
Q

What barbiturates are involved with hepatic metabolism only?

A

Oxibarbiturates

52
Q

What barbiturates are involved mainly with hepatic metabolism but also kidneys and CNS?

A

Thiobarbiturates

53
Q

The capacity of the liver to metabolize barbs is ____.

A

Large; Hepatic dysfunction must be extreme before prolonged barbiturate effects are seen from poor metabolism.

54
Q

Is Thiopental redistribution slow or rapid?

A

Rapid

55
Q

How is Thiopental metabolism?

A

It is slow; 10-24% being metabolized every hour, this explains “hangover” effect

56
Q

How much of Thiopental is metabolized?

A

over 99%

57
Q

How does cirrhosis affect barbiturate metabolism?

A

minimal difference in barb plasma clearance than healthy patients

58
Q

How is methohexital metabolism in comparison to thiopental?

A

Methohexital has a more rapid metabolism than thiopental, lower lipid solubility so less is llama protein bound-more available for metabolism

59
Q

How does methohexital hepatic clearance in comparison to thiopental?

A

Methohexital hepatic clearance is 4 X greater than thiopental, hence the name Brevital for brevity of action.

60
Q

The rapid awakening from a single dose of Methohexital is due to ___?

A

REDISTRIBUTION

61
Q

While redistribution determines _____, metabolism determines complete _____?

A

awakening, recovery

62
Q

Due to increased metabolism, methohexital has a _____ recovery time with repeated doses than thiopental.

A

quicker

63
Q

All barbiturates are filtered by renal glomeruli but what limits its filtration?

A

high protein binding limits filtration, High barbiturate lipid solubility favors reabsorption of filtered drugs back into blood.

64
Q

Compare the distribution 1/2 time and the volume of distribution of thiopental and methohexital.

A

distribution 1/2 time and volume of distribution are similar-so you go to sleep in a similar fashion, but metabolism differs so patients have less hanover with Brevital.

65
Q

Compare the elimination 1/2 time and the clearance of thiopental vs methohexital.

A

elimination 1/2 time of thiopental greater in obese patients due to greater volume of distribution from fat storage. Elimination 1/2 time and clearance of thiopental and methohexital are different.

66
Q

How does age of the patient affect how barbiturates act?

A

Increased age results in slower passage of barbs from CNS to periphery resulting in greater anesthetic effects.
Pediatric patients have a faster recovery from barbs due to more hepatic clearance.

67
Q

Clinical use of barbs declining to benzo because of:

A
  • lack of specificity in CNS effects
  • therapeutic index less
  • greater tolerance effects
  • greater liability for abuse
  • high risk of drug interactions
68
Q

Do barbiturates provide analgesia and why or why not?

A

Barbs don’t reliably provide sedation in the presence of pain due to risk of paradoxical reaction. Small barb doses LOWER the pain threshold, making it easier for the patient to feel pain.

69
Q

Do barbiturates provide skeletal muscle relaxation?

A

nope

70
Q

What is the primary advantage of propofol over barbs.

A

Residual CNS effects(hangovers) persist for several hours-hence propofol

71
Q

Barbs were THE induction drug from 1934 until —–?

A

propofol replaced thiopental for induction when rapid awakening is essential.

72
Q

Methohexital has increased risk for excitatory phenomena like _____ and _____.

A

myoclonus and hiccups; methohexital excitatory effect are dose related.

73
Q

What is the induction dose of Thiopental?

A

3-5 mg/kg

74
Q

What is the induction dose of Methohexital?

A

1-1.5 mg/kg

75
Q

Methohexital __________ mg/kg PR used to induce anesthesia in peds or the uncooperative.

A

20 - 30

76
Q

In what cases are barbs used as the sole anesthetic(3)?

A

ECT
retrobulbar block
cardioversion

77
Q

Which barb would you use for an ECT and why?

A

For ECT don’t use a barb exempt for methohexital @ doses of 1 mg/kg or less to avoid reduction of seizure activity.

78
Q

What is Methohexital used for in epilepsy patients undergoing temporal lobe resection?

A

used to induce seizure activity

79
Q

How does barbiturates affect cerebral blood flow and ICP.

A
  • Barbs given to decrease ICP UNRESPONSIVE to diuresis and hyperventilation
  • Barbs DECREASE cerebral blood volume by cerebral vascular vasoconstriction
80
Q

Why are barbiturates good drug for high ICP?

A

Decreased cerebral blood flow & an increased perfusion to metabolism ratio make thiopental good for high ICP patients.

81
Q

At what percentage do barbiturate induced isoelectric EEG show maximal depression for cerebral metabolic oxygen requirements?

A

By 55%

82
Q

What is the hazard of using high dose barbiturates to lower ICP?

A

hypotension, which worsens cerebral perfusion pressures

83
Q

What is a side affect of thiopental doses that gives isoelectric EEGs?

A

causes peripheral vasodilation and myocardial depression

84
Q

Why are barbiturates preferred over volatile agents at producing isoelectric EEGs?

A

isoflurane affords less hemodynamic stability so barbs are preferred over isoflurane for EEG suppression.

85
Q

If a barbiturate is used to induce a isoelectric EEG for CPB it increased the need for _____?

A

post cardiopulmonary bypass inotropic support

86
Q

Brain complications from CPD due to embolism clear more rapidly if_____?

A

thiopental is given to maintain isoelectric EEGs

87
Q

Barbiturate decreases in cerebral metabolic oxygen requirements _____ decreases in cerebral blood flow so it really _____ protect the brain.

A

EXCEED, DOES

88
Q

What is a preferential treatment over barbs that is used for brain protection during CPB and why is it preferred?

A

Hypothermia @ 33-34 celsius may provide superior neuro protection without raising inotropic requirements.

89
Q

What does the administration of barbiturates protect the patient from during carotid endartectomies, thoracic aneurysm or profound hypotension cases?

A

Provides protection against focal ischemia but not global ischemia.

90
Q

Why are barbiturates given?

A

Barbiturates are given exclusively to produce CNS depressant effects.

91
Q

What are 4 undesirable side effects of barbiturates?

A
  1. cardiovascular depression
  2. ventilatory depression
  3. enzyme induction
  4. physical dependence
92
Q

What effects are seen in a normovolemic patient that receives 5mg/kg of thiopental?

A

produces a brief 10-20 mmHg drop in MAP that is offset by a 15-20 > HR

Methohexital and Thiopental have similar cardiovascular effects in equal potent doses**

93
Q

At what dosage dose Thiopental have no visible myocardial depression in healthy patients?

A

@ 5 mg/kg

94
Q

Negative inotropic effects of barbiturates see in in high doses as with ICP treatment(T/F)?

A

true

95
Q

What are the effects of lower BP ween with barbs?

A
  • lower preload
  • peripheral vasodilation due to depressed medullary vasomotor centers
  • reduced SNS outflow from the CNS
  • Results in capacitance vessel dilation
96
Q

Histamine release can occur with IV barbs(T/F)?

A

true

97
Q

What does barbiturate cutaneous and skeletal muscle vasodilation contribute to?

A

radiant heat loss

98
Q

What type of patients are less able to compensate for the peripheral vasodilatory effects of barbiturates?

A

hypovolemic patients and those receiving beta blockers and/or central acting anti-hypertensive drugs.

Hypovolemic patients-vulnerable to decreases in BP from barbiturates administration(SO DON’T USE THEM)

99
Q

Does slow barbiturate administration decrease the effects?

A

No slow administration does not work. Rapid or slow administration of barbs produces similar decreases in BP and increases in HR…slower administration also results in higher total doses so GIVE IT QUICK!

100
Q

What affect dose barbiturates given IV for anesthesia induction produce?

A

produce dose-dependent DEPRESSION of medullary and pontine ventilatory centers.

101
Q

Does barbs increase or decrease the sensitivity of the medullary center to stimulant effects of CO2?

A

decrease, hypercapnea will not make you breath.

102
Q

Is laryngeal reflexes depressed with IV induction doses of barbiturates?

A

Laryngeal reflexes are not depressed with IV induction doses of barbiturates.

103
Q

Is cough reflexes depressed with IV induction doses of barbiturates?

A

Cough reflexes are not depressed with IV induction doses of barbiturates.

104
Q

Can thiopental be used for evoked potential monitoring?

A

yes

105
Q

Do barbiturates doses that produce isoelectric EEG interfere with evoked potential monitoring?

A

Even doses that produce isoelectric EEG don’t interfere with evoked potential monitoring.

106
Q

How does Thiopental affect hepatic blood flow?

A

produces clinically insignificantly decreases in hepatic blood flow

107
Q

After sustained use of barbiturates what happens after 2-7 days? Which drug has the greatest affect?

A

Barbiturates stimulate enzyme induction after 2-7 days of sustained use…phenobarbital the greatest.

108
Q

At maximal enzyme induction what happens to the rates of metabolism?

A

At maximal enzyme induction, rates of metabolism are doubled.

109
Q

Are fetal barbiturate concentrations higher or lower than the moms?

A

much lower than the mom’s

110
Q

At what dose does Thiopental not result in excessive fetal levels?

A

4 mg/kg

111
Q

How does tolerance to sedative effects compare to the tolerance to anti-convulsant and lethal effects of barbs?

A

Tolerance to sedative effects occurs sooner and is greater than tolerance to anti-convulsant and lethal effects.
Its how people die from barbiturate use**

112
Q

How long does enzyme induction stimulation from barbs persist after last dose?

A

for up to 30 days

113
Q

Enzyme induction results in greater metabolism of other drugs like(5)?

A
  • coumadin
  • phenytoin
  • tricyclics
  • corticosteroids
  • vitamin K
114
Q

What is porphyria?

A

Disease of accelerated heme production resulting in jaundice.

115
Q

What effect does barbiturates have on those who have porphyria?

A
  • barbiturates stimulate activity of mitochondrial(not microsomal) enzyme called D-aminolevulinic acid synthetase-a hemoglobin precursor
  • D-aminolevulinic acid synthetase increases hem production
  • If barbiturate induced D-aminolevulinic acid synthetase mediated increased heme production occurs with patients with porphyria increased heme production, porphyria symptoms are exaggerated.
116
Q

What are the symptoms of porphyria?

A
  • abdominal pain
  • neuropathies
  • psychiatric symptoms

barbiturates are contraindicated for porphyria patients

117
Q

Are barbiturates contraindicated for patients with porphyria?

A

yes

118
Q

What are the signs and symptoms of intra-arterial Thiopental and what can occur as a result?

A

S/S: immediate intense vasoconstriction and excruciating pain

Can result in gangrene and never damage

Risk of vascular damage increased if concentrations greater than 2.5% are given

119
Q

What is the mechanism of damage of intra-arterial Thiopental injection?

A

precipitation of Thiopental crystals leading to arteritis.

120
Q

What is the treatment of intra-arterial injection of Thiopental?

A

Should immediately attempt to #1 dilute via saline administration through the catheter where barbiturate was given—>so don’t pull a-line. #2 Lidocaine, papaverine or phenoxybenzamine should be given to prevent arterial spasm and to maintain perfusion.

Intra-arterial 2.5% thiopental causes much less damage than 5% solution thiopental

121
Q

Venous thrombosis after barbiturate administration reflects what?

A

DEPOSITION OF BARBITURATE CRYSTALS…..not alkaline pH issues

Barbiturate crystal formation in viens is less hazardous than in arteries because of ever increasing vein diameter .

122
Q

Tolerance to sedative effects occurs at greater rates than anti-convulsants & lethal effects, so barbiturate therapeutic index _____ as tolerance _____.

A

decreases, increases

Tolerance and physical dependence on barbiturates are closely related

123
Q

Severity of withdrawal syndrome relates to amount of _____ and rate of barbiturate _____.

A

tolerance, elimination

124
Q

What is the thiopental allergic reaction rate?

A

1:30000

Thiopental allergic reactions mortality is high

125
Q

Allergic reaction see in patients with?

A

IgE mediated hypersensitivity disorders such as:

  • hay fever
  • asthma
  • infantile eczema
  • some types of urticaria
  • food reactions
126
Q

What is probably the best advantage of thiopental over propofol?

A

Thiopental is strongly bactericidal

Propofol strongly supports growth of E. Coli and C. Albicans and must be used within 6 hours of handling.

2nd Quarter (27 decks)

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