Barbiturates Class (Dr. E's lecture) Flashcards Preview

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1

How are barbs commercially prepared?

as sodium salts

2

How are barbs prepared with respect to pH? why?

HIGHLY Alkaline formulary (about pH >10)
they're unstable

3

At room temp, what is different about TPL?

prepared TPL is stable and sterile for at least 6 days

4

What types of isomers are in the Barbs?

Racemic Prep, BUT levo isomer is the potent one

5

What are barbiturates derived from? what constitutes this?

Barbituric Acid
Urea + Malonic Acid = Barbituric Acid

6

What makes a barbiturate, chemically speaking with regards to structure? What effects does this cause?

Substitutions at Carbon 2 and 5; have sedative, hypnotic properties

7

What does it mean if there is a branched chain at C # 5 for the structure of Barbs?

-Branched Chain at #5 increases hypnotic activity

8

If there is an Oxygen at Carbon #2 what does this mean?

OXYbarbiturate (Phenobarbital, Pentobarbital, Methohexital)

9

If there is a Sulfur at Carbon #2 what does this mean?

THIObarbiturate (Thiopental)

10

What does it mean if there is a phenyl group at C # 5 for the structure of Barbs?

-Phenyl group at #5 increases ANTIconvulsant activity (phenobarbitol)

11

What does it mean if there is a methyl radical imparted in the structure of Barbiturates?

-Methyl radical imparts CONVULSANT activity (methohexital)

12

What does it mean if there is sulfuration in the structure of barbs?

-Sulfuration=fat soliuble, as lipid solubility increases: shorter duration, more rapid onset, increased potency

13

What is different regarding the long vs straight chain w/r/t the structure/activity relnships of Barbs?

-long branched chain is more potent than a straight chain

14

What are the relative potencies of TPL, Thiamylal, and Methohexital?

TPL: 1
Thiamylal: 1.1
Methohexital: 2.5

15

What is the MOA of Barbiturates?

-decreases the rate at which GABA dissociates from its receptor->increases duration of GABA activated Cl channel opening (enhances GABA)
-Mimics GABA at the receptor
-Decreases POST-synaptic membrane sensitivity to Ach-> some muscle relaxation- NOT surgical depth
-Also Directly decreases the transmission in the sympathetic ganglia-->hypotension
-interaction with GABA receptor produces functional inhibition of the postsynaptic neuron

16

What does Barbs mimic physiologically?

Depresses RAS-> SLEEP

17

What is the onset of barbs?

RAPID onset of action

18

What is important about the redistribution of Barbs?

Redistribution=Rapid termination of Effect

19

Is TPL protein bound?

70-85% protein bound

20

What is the fat: blood partition coefficient? what does this mean?

11= veryyyyy lipid soluble

21

what should you calculate your dosage of barbs based on?

IBW

22

If the patient is alkalotic, what does this do to the barbs?

alkalosis decreases the intensity of Barbs

23

If the patient is acidotic, what does this do to the barbs?

intensifies effect

24

Are barbs acids or bases?

WEAK acids!!!!! remember they are ACIDS, although they are prepared in >10 pH alkaline soln

25

How are oxybarbiturates metabolized?

Hepatic ONLY

26

How are thiobarbiturates metabolized?

Hepatic and some extra hepatic

27

What terminates pharmacologic activity?

side chain oxidation at C#5 to Carboxylic Acid

28

Generally, how are the barbs metabolized?

desulfuration, hydrolysis, opens ring to water soluble combounds

29

How are barbs excreted?

renal primarily; < 1% excreted unchanged

30

Do barbs have active metabolites?

NO active metabolites

31

What is the E 1/2 time of TPL?

11.6 hours

32

What is the E 1/2 time of Methohexital?

3.9 hours

33

Why are the barbs prolonged in pregnancy?

due to increased protein binding

34

Which barb has greater hepatic clearance?

Methohexital

35

What is different between pediatric patients with TPL and the E 1/2 time

In pedi patients, TPL t 1/2 time is shorter than in adults, higher rate of HBF

36

What are the CNS effects of Barbs?

-Depresses level of consciousness
-Cerebrovasoconstriction, Reduced CBF, Decreased ICP and CMRO2
-Can produce isoelectric EEG (flatline the brain=cerebral protection)
-Paradoxical excitement
-Small doses decrease the pain threshold, "anti-analgesic"
-NO skeletal muscle relaxation
-Also decreases IOP
-Does NOT preclude SSEP monitoring

37

What is unique about Methohexital its CNS effects?

-excitatory skeletal muscle movements (myoclonus) and hiccups
-Cerebral protection

38

Do barbs produce skeletal muscle relaxation?

NO

39

What are the cardiovascular effects of Barbs?

-depression of medullary vasomotor center and decreased SNS outflow from CNS->peripheral vasodilation->preload decreases->SBP decreases, Compensatory HR INCREASE in normovolemic pts (activation of SNS peripherally!!!!)
-MINIMAL myocardial depression
-If SNS not intact (like in elderly), OR hypovolemic OR large doses given to decrease ICP, will see significant decreases in BP and myocardial depression
-Histamine release with rapid IV administration
-oral barbs produce minimal CV effects

40

What do barbs cause a release of ?

HISTAMINE release

41

What are the resp effects of Barbs?

-Dose dependent depression of medullary and pontine ventilatory centers
-Decreased ventilatory response to hypoxia and hypercapnia
-Apnea
-Depression of laryngeal and cough reflexes incomplete

42

What is important to note about subdoses of barbs? What does this increase the risk of?

if dose is not large enough can actually see a "Stage 2" like response to a/w manipulation-increased risk of laryngospasm, bronchospasm

43

What do barbs do to hepatic enzymes?

Hepatic enzyme induction with chronic use!

44

Which barb is the most potent inducer of hepatic enzymes?

Phenobarbital

45

What drugs are metabolized more quickly due to barbs?

Oral anticoags
Phenytoin
TCAs
Corticosteroids
Vit. K

46

What pathphysiologic condition is contraindicated with barbiturates? why?

Porphyrias!!!
barbs accelerate the production of heme by stimulation of the enzyme: D-aminolevulinic acid synthetase!!!

47

what can barbs cause vascularly?

venous thrombosis

48

What is a side effect of barbs that is greater than Midazolam and Propfol, but lower than Etomidate, Ketamine and volatiles?

N/V!

49

What can barbs do to metabolism?

can enhance their own metabolism-tolerance builds

50

What can happen if there is an allergic reaction to barbiturates?

Allergy 1:30,000 high mortality
presents as anaphylaxis
Allergy usually atopic patient-multiple allergies, with prior TPL exposure

51

What should you consider with dosing and age?

Decrease dosing in elderly
Increase dosing in peds

52

What is the induction dose of TPL?

3 -5 mg/kg IV
increase in peds (5-6mg/kg and infants 7-8mg/kg

53

What is the induction dose of Methohexital?

1-2 mg/kg IV or 20-30mg/kg PR in peds

54

What is the duration of a single IV induction dose of barbs? Why?

5 - 8 minutes
b/c of redistribution!

55

What medications should Not be in a mixture with barbs?

Dont mix with opioids, catechols, NMBs, midazolam, b/c they are acidic; and
Pancuronium, Vecuronium, Atracurium
Alfentanil, Sufentanil
Midazolam
LR is too acidic->precipitates

56

What solution should you use to reconstitute powder?

sterile H2O or NSS

57

What can occur if barbs are injected intra-arterially? What is the treatment?

-Immediate, intense vasoconstriction and pain
-mechanism-> crystalline precipitation inarterial vessel, inflammatory response, vasoconstriction, microembolization

Treatment:
-dilute with NS
-Phenoxybenzamine (alpha blockers!)
-Prevent thrombosis: heparin, urokinase
-Brachial plexus or stellate ganglion block
-Papaverine 40-80mg in 10-20ml saline or 5-10ml Lidocaine 1%

58

What are the S/S of a Porphyria attack?

-Severe abdominal pain with diarrhea and vomiting
-ANS instability-tachycardia, HTN
-Electrolyte disturbances
-skeletal muscle weakness, respiratory failure
-Seizure
-Neuropsychiatric disturbances

59

What specific drugs should you avoid giving with Porphyrias?

Thiopental
Thamylal
Methohexital
Etomidate
Pentazocine

60

In general, what is characteristic of the porphyrias?

-accumulation of porphyrins, the heme precursors (toxic to tissue in high concentrations)
-any increase in heme requirement (accumulation of the precursors immediately preceding the area of enzyme block