Exam 1: General Barbiturates

Question 1

Barbiturates are commercially prepared as:

Answer 1

Highly alkaline sodium salts

Racemic mixture

Question 2

Once prepared, barbs are:

Answer 2

Stable and sterile at room temp for 6 days

Question 3

Isomers:

Answer 3

Levo and dextro; levo isomer is the potent one

Question 4

Derived from:

Answer 4

Barbituric acid (urea + malonic acid)

Question 5

Addition that ↑ hypnotic activity:

Answer 5

Branched chain at #5

Brain BRANCHES off into sleep

Question 6

Addition that ↑ anticonvulsant activity:

Answer 6

Phenyl group at #5

PHENobarb is anticonvulsant

Question 7

Addition that ↑ convulsant activity:

Answer 7

Methyl radical at #5

METHohexital used in ECT as it doesn’t dampen EEG

Question 8

Effect of sulfuration:

Answer 8

More lipid soluble and thus more potent, more rapid onset, shorter duration

Question 9

More potent: long branched chain or straight chain?

Answer 9

Long branched chain

Question 10

Two classes of barbs based on carbon #2:

Answer 10

Oxygen at #2: oxybarbiturate

Sulfur at #2: thiobarbiturate

Question 11

Relative potencies of three main barbiturates:

Answer 11

Thiopental: 1
Thiamylal/Surital: 1.1
Methohexital/Brevital: 2.5

Question 12

MoA (5):

Answer 12

↓ rate of GABA dissociation
Mimics GABA
↓ transmission in SNS ganglia (hypotension)
↓ postsynaptic membrane ACh sensitivity (sub-surgical depth muscle relaxation)
Functional inhibition of RAS neurons (sleep)

Question 13

General PK:

Answer 13

Rapid onset and short duration
Moderately high protein binding (70-85%)
Weak acids at physiologic pH (pK 7.6)

Question 14

Metabolism of oxybarbiturates:

Answer 14

Hepatic

Question 15

Metabolism of thiobarbiturates:

Answer 15

Hepatic + extrahepatic (renal, CNS)

Question 16

Biotransformation that terminates pharmacologic activity:

Answer 16

Carbon #5 side chain oxidized to carboxylic acid

Question 17

CNS effects:

Answer 17

↓ LOC
Cerebral vasoconstriction and ↓ CBF, ICP, IOP, CMRO₂
Isoelectric EEG at high doses
No effect on SSEPs
Small doses: "anti-analgesic" effect

Question 18

CV effects:

Answer 18

↓ SVR, preload, SBP
↑ HR
If SNS not intact: ↓ BP, myocardial depression
Histamine release with rapid IV admin

Question 19

Reason for peripheral vasodilation:

Answer 19

Depression of medullary vasomotor center and ↓ SNS outflow

Question 20

Respiratory effects:

Answer 20

Depression of pontine and medullary ventilatory centers
↓ response to hypoxia, hypercapnia
Incomplete depression of laryngeal reflexes

Question 21

Complication with too-small dosing:

Answer 21

“Stage 2”-like response to airway manipulation

↑ risk of spasm

Question 22

Metabolic effects:

Answer 22

Chronic use induces hepatic enzymes

Accelerates heme production

Question 23

Other system effects:

Answer 23

N/V potential higher than midaz/prop (less than etomidate)

Allergy (1:30,000, high mortality)

Question 24

Induction dosing of thiopental:

Answer 24

3 - 5 mg/kg IV
↓ for elderly, 1st trimester
↑ for kids (5-6mg/kg) and infants (7-8mg/kg)

Question 25

Induction dosing of methohexital:

Answer 25

1 - 2mg/kg IV

Peds: 20-30 mg/kg PR

Question 26

Do not mix barbiturates with:

Answer 26

Acidic drugs:
Opioids
Catecholamines
NMBs
Midazolam
LR

Question 27

Effects of intra-arterial injection:

Answer 27

Immediate vasoconstriction and pain

Question 28

Treatment for intra-arterial injection:

Answer 28

Dilute with NSS
Phenoxybenzamine, paperavine (40-80mg) or lidocaine
Heparin or urokinase to prevent thrombosis
Brachial plexus or stellate ganglion block for pain