Barbiturates Flashcards
Uses of Barbiturates
Induction of anesthesia, seizure treatment, short painless procedures (Cardioversion/ECT) treatment of increased ICP
Structure of Barbiturates
Derived from barbituric acid
Structure/Pharmacokinetics of Thiobarbiturates
sulfur atom @ 2nds position
more lipid soluble, greater hypnotic potency, rapid onset, shorter DOA
Structure/PK of Methohexital
methyl group on N (shorter DOA)
Structure/PK of Oxybarbiturates
O2 at 2nd position (long DOA)
Structure/PK of Phenobarbital
phenyl group @ 5th position
Anticonvulsant properites
MOA of Barbiturates
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
PK of Barbiturates
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
PD of Barbiturates (PO)
short amount of drowsiness but residual CNS effects persist
PD of Barbiturates (CNS)
offer good treatment for grand mal seizures, but replaced with benzos in favor of more specific CNS site action
PD of Barbiturates (Resp)
DD depression of medullary and pontine ventilatory centers
Large doses- depressed laryngeal/cough reflexed (but reflexes overall more active as compared to propofol
PD of Barbiturates (CV)
decreased CO, systemic arterial pressure, PVR d/t decreased venous return/peripheral pooling, direct myocardial depression
Thiobarbiturates
Thiopental, Thiamylal
Metabolism of Thiobarbiturates
hepatocytes-> hydroxythiopental (carboxylic acid derivated) which is water soluble and exerts little CNS activity -> renal excretion
Small amount of X is metabolized by kidney/CNS
Thiobarbiturates
Thiopental, Thimylal
SEvere liver dysfunction w/ Thiobarbiturates
affects metabolism due to large reserve capactiy of liver to oxidize
THiobarbiturates and Peds
elimination 1/2 shorter d/t more rapid hepatic clearance
PK of Thiobarbiturates (CNS)
DD changes in median nerve somatosensory evoked responses and brainstem auditory evoked responses
Pk of THiobarbiturates (resp)
decreased sensitivity of medullary ventilatory center to stimulation of CO2, apnea likely especially with other CNS drugs
PK of THiobarbiturates
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
Oxybarbiturates
Methohexital, pentobarbital, secobarbital
Metabolism of Oxybarbiturates
liver -> inactive hydroxy derivatives
clearance higher, more dependent on liver BF than thiobarbiturates. results in shorter elimination 1/2 t
Causes excitatory phenomena (myoclonus, hiccoughs)
Oxybarbiturates
Fix: decrease with opioid
Methohexital is X more potent then thiopental
2.7
PK of Oxybarbiturates (CV)
less effects seen than with thiobarbiturates d/t increased tachycardia reflex response with (methohexital)
Phenobarbital
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
Barbiturates for Induction
minimal no effects on any muscles
lean body mass weight dosing
Thiopental Dosing
3-5mg/kg
pediatrics: 5-6mg/kg
infants: 6-8mg/kg
Methohexital:
1-2 mg/kg
20-30mg/kg rectal in uncooperative or pediatric patients
Neurologic Treatment of Barbiturates
treatment of refractory increased ICP
How do barbiturates treat ICP?
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
Cerebral Protect in Barbiturates
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
Issues of Barbiturates
Acclerated Heme production
Intra arterial injection
Allergy Risk
