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Summer Pharm (2016) ** > Barbs > Flashcards

Flashcards in Barbs Deck (61):
1

What is more potent, a long branched chain or a straight chain?

Levo-isomers or dextro-isomers?

Long branched chain is more potent

Levo-isomers are twice as potent as dextro-isomers

2

'Sodium something' has a pKa of 3.8.  Will this drug be more than 50% or less than 50% ionized at physiological ph?

Sodium is a positive molecule, so we can assume this is a weak acid (acids unite with positive ions).

A weak acid with a pKa of 3.8 at physiological pH means that we have fewer hydrogen ions than at equilibrium.

The ionized form will dominate.

3

Methohexital dose 

1-2 mg/kg IV (induction)

20-30mg/kg in peds

4

base or acid?

opioids

barbs

benzos

ketamine

propofol

local anesthetics

opioid = weak base

barbs = alkaline in the bottle, acid at physiologic pH

benzos = bases

ketamine = base

propofol = acid

local anesthetics = base

5

Methyl radical on a barbiurates imparts what activity (methohexital)

CONVULSANT activity

6

which patients are at higher risk of allergic rxn

atopic patients (astmathics)

7

Barbiturates with __ at carbon #__ increases hypnotic activity

Barbiturates with __ at carbon #_ increases anticonvulsant activity

Having a _ increases convulsant activity

Branched chain at carbon #5 increases HYPNOTIC activity

Phenyl group at carbon#5 increases ANTICONVULSANT activity (phenobarbital)

Methyl radical increases convulsant activity (methohexital)

8

barbs

inadequate dosages (subtherapeutic) effects

  • stage 2 like response to airway manipulation (high risk of laryngospasm and bronchospasm)
  • paradoxical excitement 

9

Barbiturates are ____ (acidic/alkaline) drugs, but when prepared in ____ solution, they are weak ___

They are acidic drugs

Prepared in highly alkaline solution (bacteriostatic)

Actually are weak acids, not bases

10

Other side effects not mentioned yet of barbs?

  1. Venous thrombosis
  2. Crosses placenta
  3. N/V
  4. Accelerated production of heme
    • by stimulation of an enzyme, D-aminolevulinic acid synthetase
    • caution in porphyria

11

Why is tolerance an issue with barbs?

As good enzyme inducers, they metabolize themselves well, tolerance builds, they need more drug for more effect,

12

Barbiturate MOA?

Decreases rate that GABA dissociates from receptor (increases duration of GABA), Cl channel opens

decreased postsynaptic sensitive to Ach, some muscle relaxation

Mimics GABA at receptor → DIRECTLY

Decreases trasmission in the sympathetic ganglia leading to hypotension

Depresses RAS -> sleep

13

Barbs

intra-arterial injection treatment

  1. dilute with NS
  2. phenoxybenzamine (direct acting alpha blocker)
  3. prevent thrombosis: heparin, urokinase
  4. brachial plexus or stellate ganglion block
  5. Papaverine (opium derivative -> vasodilator) 40-80 mg in 10-20 ml NS
  6. Lidocaine 1% 5-10 ml

14

Will induction be faster or slower when administering Thiopental to an acidotic patient?

Alkalotic?

Thiopental is an acidic drug with a pKa of 7.6

If the patient is acidotic, lower pH, means there are more Hydrogen ions available.  With more ions available, the non-ionized form dominates and induction is FASTER!

If the patient is alkalotic, a higher pH, there are fewer Hydrogen ions available.  With fewer ions available, the ionized form dominates and the induction is SLOWER!

15

All barbiturates are derived from what?

Barbituric acid urea and malonic acid

16

'Something Sulfate' has a pKa of 4.5, will this drug be more than 50% or less than 50% non-ionized at physiological pH?

Sulfate is a negative molecule, so we can assume this is a weak base (bases unite with negative ions).

A weak base with a pKa of 4.5 at physiological pH (above the pKa) means that we have fewer Hydrogen ions (more alkalotic) than at equilibrium.

The non-ionized form will dominate.

17

Induction of GA dosages for TPL and methohexital?

  • TPL 3-5 mg/kg IV (dec dose for elderly and first trimester pregnancy, inc dose for kids)
  • Methohexital 1-2 mg/kg IV or 20-30 mg/kg po in peds

 

Duration 5-8 min (that's when it redistributes)

18

most potent hepatic enzyme inducer of the barbs

phenobarbital

19

Barbiturate respiratory effects?

  1. Depression of medullary and pontine ventilatory centers
  2. decrease response to hypoxia and hypercapnia
  3. APNEA
  4. Incomplete depression laryngeal and cough reflexes (laryngospasm, bronchospasm)

20

Drugs to avoid giving people with porphyria?

  1. Sulfonamide
  2. Etomidate
  3. Nifedipine
  4. Diazepam
  5. Phenytoin
  6. Barbs
  7. Alcohol
  8. Ketorolac

SEND Phil BAK (he's unsafe)

21

Drugs safe in porphyria 

  1. Opioid analgesics
  2. Narcan
  3. Propofol
  4. Ketamine (probably safe)
  5. Nitrous
  6. Succs
  7. Pancuronium
  8. Neostigmine
  9. Atropine
  10. Glycopyrolate
  11. Aspirin
  12. Acetaminophen
  13. Penicillin
  14. Glucocoticoids
  15. Insulin

22

Barbiturate pharmacokinetics?

Rapid onset

Redistribution is rapid, terminates effect

Extensive metabolism

Highly protein bound

Ionization of TPL: pK is 7.6

23

Methohexital contraindications

hx of seizures

pregnancy

porphyria

asthma

LR (it precipitates)

24

phenobarbital DOA

4-10 hrs

25

As a hepatic inducer, barbiturates increase metabolism of what drugs?

  1. Oral anticoagulants
  2. Phenytoin
  3. TCAs
  4. Corticosteroids
  5. Vit K
  6. Muscle relaxants? Look up.

26

phenobarbital onset 

5 min IV

20-30 min PO

27

What happens if barbs are given intra-arterially? 

IMMEDIATE, intense vasoconstriction and pain

Mechanism: crystalline precipitation in artery, inflammatory response, vasoconstriction, microembolization (loss of limb is possible!) 

28

Barbiturates

S.E.: myoclonus, hiccups, seizures

Methohexital

29

Oxybarbiturates

  • have a __ at carbon #___
  • has what metabolism?

Thiobarbiturate

  • has a ____ at carbon #___
  • has what metabolism?

  • Oxy: O2 at carbon #2
    • hepatic metabolism only
  • Thio: Sulfur at carbon #2
    • hepatic and extra hepatic (GI) metabolism

30

phenobarbital peak

30 min with IV

31

What is porphyrin a precursor to?

Heme

which is a component of

  • hemoglobin
  • myoglobin
  • catalase
  • peroxidase
  • respiratory and P450 liver cytochromes

32

Are barbiturates hepatic enzyme inducers?

YES, phenobarb is the most potent inducer

33

methohexitol side effects

  1. induces seizures
  2. excitatory skeletal muscle effects (myoclonus)
  3. hiccups
  4. laryngospasm
  5. cough
  6. vasodilation, reflex tachycardia
  7. decreased CBF, ICP, CMRO2, isoelectric EEG
  8. histamine release (vasodilation, decreased BP, elevated HR)
  9. dose dependent resp depression
  10. decreased thershold for pain (antialgesia)
  11. CYP450 inducer

 

 

34

Barbiturate CNS effects?

  1. Depress LOC
  2. Cerebral vasoconstriction, dec CBF, ICP, CMRO2, IOP
  3. Can produce isoelectric EEG (coma)
  4. Paradoxical excitement (sub-dose)
  5. anti-algesia: decreases pain threshold (small doses)
  6. Methohexital: myoclonus and hiccups
  7. Does NOT interfere with SSEP (somatosensory evoked potentials) monitoring

35

What is porphyria?

Attacks precipitated by events that decrease heme concentration (drugs, hormones, fasting, stress) Autosomal dominant, linked to chromosome 11

36

50% excreted unchanged in the urine

Phenobarbitol

37

phenytoin class

anticonvulsant

antiarrhythmic class 1B

38

Sulfuration increases what?

Sulfuration: fat soluble

As lipid solubility increases you get 

  • shorter duration
  • more rapid onset
  • increased potency

39

barb stimulate production of what enzyme?

D-aminolevulinic acid synthetase

can trigger prophyria

40

Barbs1

metabolism dependent on hepatic enzyme activity, not hepatic blood flow

Thiopental

41

Why is Thiopental stored in a very alkalotic solution?

Because, if Thiopental was stored in an acidic solution there would be more Hydrogen ions available and lead to a dominance of the non-ionized (protonated) form.

This is water insoluble and may form a precipitate.

42

things that barbs don't do

barbs DO NOT

  • take away EEG wave readings in ECT
  • alter SSEP (somatosensory evoked potentials) like inhalational agents do
  • cause muscle relaxation (you'll need muscle relaxants)
  • affect baroreceptors (you'll get reflex tachy due to drop in BP)
  • cause myocardial depression (it's minimal, unless large doses are given, or SNS not intact, or hypovolemia)

 

43

Thiopental side effects

  1. direct vasodilation (depression of medullary vasomotor center and decreased SNS outflow from CNS), reflex tachycardia
  2. decreased CBF, ICP, CMRO2, isoelectric EEG
  3. histamine release (vasodilation, decreased BP, elevated HR)
  4. dose dependent resp depression
  5. decreased thershold for pain (antialgesia)
  6. CYP450 inducer

44

barbs

excreted in the urine and feces

Methohexital

45

barbs redistribution time frame

Fat: blood coefficient is 11:1 → fast redistribution from brain to inactive tisues (muscle, fat)

  1. brain receives 10% of total IV done in 30-40 sec
    1. fast uptake (VRG)
  2. over the next 5 min there is a decrease in brain concentrations
    1. 2​nd uptake, primarily skeletal muscle (MG)
    2. decreased muscle mass = decrease the dose (elderly, trauma)
  3. after 30 min <10% of the initial dose is in the brain
  4. fat concetrantion rises for 30 min

 

46

barbs

drug that is used as an anticonvulsant 

why?

Phenobarbital

has a phenyl group at carbon #5

47

barb with the lowest protein binding

Phenobarbitol 30%

48

E1/2t in TPL vs methohexital?

  • Thiopental (TPL)  11.6h
    • Prolonged in pregnancy due to increased protein binding
  • Methohexital 3.9h

49

barbs

metabolism dependent on C.O. and blood flow

Methohexital

50

Phenobarbital side effects

  1. strongest CYP450 inducer of the barbs
  2. vasodilation with reflex tachycardia
  3. decreased CBF, ICP and CMRO2, isoelectric EEG
  4. dose dependent resp depression
  5. N/V
  6. bone marrow supression
  7. agranulocytosis 
  8. thrombocytopenia
  9. megaloblastic anemia
  10. liver toxicity 
  11. steven johnson syndrome
  12. ataxia

51

barbs

alkalinization of urine doesn't favor excretion, it shifts it to a more ionized state

Phenobarbital

52

Barbiturate metabolism?

Side chain oxidation at carbon 5 to carboxylic acid terminates pharmacologic activity

Desulfuration, hydrolysis opens ring to water soluble compounds

Renal excretion

53

Thiopental dose

3-5 mg/kg IV (induction dose)

5-6 mg/kg IV peds

7-8 mg/kg IV infants 

increase dose in peds

decrease it in elderly and 1st trimester pregnacy

54

Barbiturate CV effects?

  1. Depression of medullary vasomotor center and decreased SNS outflow
  2. peripheral vasodilation (dec afterload), dec preload Dec SBP -> compensatory HR increase
    • baroreceptors remain intact
  3. Minimal myocardial depression (more depression if SNS not intact, hypovolemia, or large doses)
  4. Histamine release with rapid IV admin (more hypotension)

55

phenobarbital metabolism 

50-60% unchanged in the urine

CYP450 hydroxylation and conjugation

56

phenobarbital E1/2t

54-107 hrs

57

Phenobarbital status epilepticus dose

10-20 mg/kg loading

5mg/kg Q 15-30 min until seizure is controlled

max dose 30mg/kg

58

S/S of porphyria attack?

Severe abd pain, diarrhea, vomiting, ANS instability (tachycardia, HTN), electrolyte disturbances, seizure, resp failure, skeletal muscle weakness, neuropsychiatric disturbances

59

Barbs interactions?

  1. Opioids
    1. alfentanil
    2. sufentanil
  2. catecholemines
  3. NMBs 
    1. pancuronium
    2. vecuronium
    3. atracurium
  4. midazolam (these are acidic)
  5. LR solution is too acidic (precipitates)

60

thiopental and pregnancy

prolonged elimination 1/2 t due to increased protein binding

61

N/V of barbs compared to other classes of drugs

Higher incidence than Midazolam and Propofol

Lower incidence than Etomidate, Ketamine and volatile agents