Barbiturates

Question 1

Uses of Barbiturates

Answer 1

Induction of anesthesia, seizure treatment, short painless procedures (Cardioversion/ECT) treatment of increased ICP

Question 2

Structure of Barbiturates

Answer 2

Derived from barbituric acid

Question 3

Structure/Pharmacokinetics of Thiobarbiturates

Answer 3

sulfur atom @ 2nds position

more lipid soluble, greater hypnotic potency, rapid onset, shorter DOA

Question 4

Structure/PK of Methohexital

Answer 4

methyl group on N (shorter DOA)

Question 5

Structure/PK of Oxybarbiturates

Answer 5

O2 at 2nd position (long DOA)

Question 6

Structure/PK of Phenobarbital

Answer 6

phenyl group @ 5th position

Anticonvulsant properites

Question 7

MOA of Barbiturates

Answer 7

increase affinity of GABA at its binding site, increased duration of GABA a activated opening of chloride channel
Can also mimic GABA action via direct activation of GABA a receptors in high doses
Also works at glutamate, adenosine, neuronal nicotinic acetylcholine receptors

Question 8

PK of Barbiturates

Answer 8

rapid onset and wake d/t rapid uptake and redistribution out of brain to tissues (similar to other highly liphophilic drugs)
Elimination depends on metabolism
INcrease Context sensitive half times d/t drug sequestering in fat, skeletal muscle and then re-entering circulation

Question 9

PD of Barbiturates (PO)

Answer 9

short amount of drowsiness but residual CNS effects persist

Question 10

PD of Barbiturates (CNS)

Answer 10

offer good treatment for grand mal seizures, but replaced with benzos in favor of more specific CNS site action

Question 11

PD of Barbiturates (Resp)

Answer 11

DD depression of medullary and pontine ventilatory centers

Large doses- depressed laryngeal/cough reflexed (but reflexes overall more active as compared to propofol

Question 12

PD of Barbiturates (CV)

Answer 12

decreased CO, systemic arterial pressure, PVR d/t decreased venous return/peripheral pooling, direct myocardial depression

Question 13

Thiobarbiturates

Answer 13

Thiopental, Thiamylal

Question 14

Metabolism of Thiobarbiturates

Answer 14

hepatocytes-> hydroxythiopental (carboxylic acid derivated) which is water soluble and exerts little CNS activity -> renal excretion

Question 15

Small amount of X is metabolized by kidney/CNS

Answer 15

Thiobarbiturates

Thiopental, Thimylal

Question 16

SEvere liver dysfunction w/ Thiobarbiturates

Answer 16

affects metabolism due to large reserve capactiy of liver to oxidize

Question 17

THiobarbiturates and Peds

Answer 17

elimination 1/2 shorter d/t more rapid hepatic clearance

Question 18

PK of Thiobarbiturates (CNS)

Answer 18

DD changes in median nerve somatosensory evoked responses and brainstem auditory evoked responses

Question 19

Pk of THiobarbiturates (resp)

Answer 19

decreased sensitivity of medullary ventilatory center to stimulation of CO2, apnea likely especially with other CNS drugs

Question 20

PK of THiobarbiturates

Answer 20

infusion not great opt d/t long context sensitivity 1/2 time, long recovery
not great for inductino, same time to wake up as propofol, but increased incidence of N slower to reach recovery milestones

Question 21

Oxybarbiturates

Answer 21

Methohexital, pentobarbital, secobarbital

Question 22

Metabolism of Oxybarbiturates

Answer 22

liver -> inactive hydroxy derivatives

clearance higher, more dependent on liver BF than thiobarbiturates. results in shorter elimination 1/2 t

Question 23

Causes excitatory phenomena (myoclonus, hiccoughs)

Answer 23

Oxybarbiturates

Fix: decrease with opioid

Question 24

Methohexital is X more potent then thiopental

Answer 24

2.7

Question 25

PK of Oxybarbiturates (CV)

Answer 25

less effects seen than with thiobarbiturates d/t increased tachycardia reflex response with (methohexital)

Question 26

Phenobarbital

Answer 26

increased liver microsomal protein content (enzymes) = enzyme induction s/p 2-7 days of sustained drug administeration affects PO anticoagulants, phenytoin, TCAs, endogenous corticosteroids/bile salts/ vitamin K

Question 27

Barbiturates for Induction

Answer 27

minimal no effects on any muscles | lean body mass weight dosing

Question 28

Thiopental Dosing

Answer 28

3-5mg/kg pediatrics: 5-6mg/kg infants: 6-8mg/kg

Question 29

Methohexital:

Answer 29

1-2 mg/kg | 20-30mg/kg rectal in uncooperative or pediatric patients

Question 30

Neurologic Treatment of Barbiturates

Answer 30

treatment of refractory increased ICP

Question 31

How do barbiturates treat ICP?

Answer 31

decreases CBV via cerebral vascoconstriction and decreased CBF which increases perfusion to metabolism ratio 55% decrease in CMRO2= burst suppression in EEG DOse required can cause significant hypotension and has not really been shown to improve outcomes

Question 32

Cerebral Protect in Barbiturates

Answer 32

thought to be due to reversal steal of CBF, free radical scavenging, stabilizing liposomal membrane, excitatory amino acid receptor blockade Utilized for incomplete brain ischemia situations (CEA, CPB) however such have been shown to be more effective

Question 33

Issues of Barbiturates

Answer 33

Acclerated Heme production Intra arterial injection Allergy Risk