Pharmacology

Question 1

Routes of Rx Admin

Answer 1

IV  - most reliable
PO - most utilized pre op
IM  -  poorly tolerated
IN/INH -  poorly tolerated
Rectal - variable absorption with contents/pH

Question 2

Available Inhalation Meds

Answer 2

N - narcan A - atropine V - valium E - epinephrine L - lidocaine

Question 3

Hepatic Performance with Rx - Factors that decr metab

Answer 3

1 - CP450 in decr concentration
2- decr liver blood flow
3 - decr CP450 activity
4 - decr phase 2 conjugation with decr gluc-transferase (affects benzos, opioids)

Question 4

Key Concepts in Peds Pharms

Answer 4

1 - greater amount of water (ECF % BW) alters Vd
2 - decr PRO amounts and function alters rx binding/duration
3 - decr fat/muscle content decr tissue available for drug ReD
4 - immature hepatic and renal functions alter rx metab and elimation

Question 5

Rx Distribution Influences (x5)

Answer 5

1 - body composition (% water, % fat)
2 - tissue --> rx permeability
3 - cardiac output
4 - regional blood flow
5 - rx distribution between blood  tissue (pKa, lipid soluble, pro binding)

Question 6

Hepatic Maturity

Answer 6

Increased to mature/adult fxnl levels @ 2-3yrs, incr conc/activity of DME, incr hepatic blood flow, large liver:body size ratio

Question 7

Protein Binding

Answer 7

Albumin –> binds acidic rx (benzos, barbs)
AAG –> binds basic rx (LA, opioids, propofol
Protein presence: Neo < Infant < child in amount and rx binding ability

Question 8

Volume of Distribution Definition

Answer 8

Rx dose:plasma concentration
Small Vd = rx confined to intravasc space/plasma = likely water soluble
Large Vd = rx easily ReD to tissue, leaves intrvasc space/plasma = likely lipid soluble

Question 9

Peds and Vd and Rx Type

Answer 9

Larger Vd with water soluble Rx as increased amount of ECF with neo/nb/infants. More Rx needed as expanded carrier space, and desire rapid effect.
Smaller Vd with lipid soluble Rx as decreased %BW/composition of fat/muscle. Increased BMR requires incr dosing of induction Rx. Tends to stay in VRG longer.

Question 10

Induction/Sedation Drugs

Answer 10

Propofol: Infant 3-3.5 mg/kg, Child 2.5-3 mg/kg
Ketamine: IV 2 mg/kg, IM 5-6 mg/kg, PO/PR 3-6 mg/kg
Versed PO 0.5-.75 mg/kg, max 20mg, IV 0.1-0.2 mg/kg
Methohexital PR 20-30 mg/kg, IV 1-2 mg/kg (5hr duration)
Chloral Hydrate PO/PR 50-75 mg/kg

Question 11

Problems with Opioid Use

Answer 11

1 - reduced clearance rates, especially with morphine & metabolites, incr age = incr clearance
2 - morphine crosses BBB easily d/t degree of ionization
3 - Fent class with incr action d/t low PRO binding in neo/inf
4 - No demerol as has long, active metabolites = seizures, atropine like structure yields tachycardia

Question 12

NeuroMuscular Junction Immature d/t:

Answer 12

1 - decr nerve conduction velocity w/ incomp myelination
2 - immature Ach receptors (alpha/beta/gamma vs epsilon)
3 - decr Ach stores
4 - Ion channels open longer with each activation as a safety measure of immature muscles

Question 13

Rationales for Peds NDMR dosing x3

Answer 13

1 - immature NM junction
2 - decr metab and elimination of Rx
3 - decr muscle mass

Question 14

NDMR monitoring

Answer 14

Must use adductor poll as is = to diaphragm paralysis. Orbicularis occ = laryngeal muscles
Neos have decr TOF response and possible baseline fade d/t limited Ach storage

Question 15

Muscle Relaxant Doses

Answer 15

Succs: infant IV 2-2.5 mg/kg IM 5 mg/kg
child IV 1.5-2 mg/kg IM 4 mg/kg
Panc/Vec IV 0.1 mg/kg Roc IV 0.6-1.2 mg/kg
Cis IV 0.15 mg/kg

Question 16

Succinylcholine Characteristics

Answer 16

Higher dose required due to large volume of distribution
Probable longer duration with decr psuedocholinesterase activity in peds pt
IV dose likely to produce bradycardia, metab into Ach like structure producing cholinergic mediated bradycardia
Assoc with rhabdo, hyperkalemia, masseter spasm, MH

Question 17

ExtraJunction Ach Receptors

Answer 17

Neurologic motor defects, direct muscle trauma, thermal injury, disease atrophy, sepsis, and prolonged use of relaxants can markedly increase the number of normal ACh receptors and, more important, the number of extrajunctional ACh receptors

Question 18

NDMR: Pancuronium

Answer 18

Vagolytic property, incr HR/BP

80% excreted by kindey, unchanged, with major metabolite 3-D panc 50% active.

Question 19

NDMR: Vecuronium

Answer 19

Hepatic metab with biliary/urinary excretion. Active metabolite 3-17D vec 10% active

Question 20

NDMR: Rocuronium

Answer 20

Excretion via bile, mostly unchanged, useful for RSI

Question 21

NDMR Reversal

Answer 21

Routinely reverse muscle relaxation, unless post op ventilation is planned.
Neostigmine 0.07 mg/kg, Edrophonium 1mg/kg
Glyco 0.01 mg/kg, atropine 0.02 mg/kg
Admin separately to know anti Ach is on board
Prob use atropine in pt < 1mo, incr vagal dominance
Atropine incr HR > glyco, crosses BBB while glyco doesn’t

Question 22

Local Anesthetics

Answer 22

Metabolism of both esters (PChe) and amides (Hepatic) reduced in neo/infants.
Bound by AAG (basic rx), limited amounts in neo/inf = incr free rx

Question 23

LA Max Doses:

Answer 23

Lidocaine: 7-10 mg/kg w/ epi // 5 mg/kg plain
Bupivicaine: 2.5-3 mg/kg w/ epi // 2-2.5 plain
Tetracaine: 1.5 mg/kg
Mepivicaine: 7 mg/kg w/ epi // 5 mg/kg plain

Question 24

Epinephrine Max dose w/ halothane & dilutions

Answer 24

5 mcg/kg per 10m // 10 mcg/kg per 20m

1: 100,000 = 10 mcg/ml
1: 200,000 = 5 mcg/ml
1: 400,000 = 2.5 mcg/ml
1: 500,000 = 1.25 mcg/ml

Question 25

FA/FI rise in Peds is increased d/t:

Answer 25

Increased minute ventilation increase speed of alveolar saturation of inhalation agents. Induction and recovery occurs rapidly in neo/infants. Exposes immature CV system to potent depressants with narrow safety margin.

Question 26

Reasons that support slower sleep/induction time in neonates x3

Answer 26

1- inhalation agents slightly more soluble in peds blood, increased solubility allows increased blood fraction depressing FA rise.
2- MAC is higher in peds, reflective of BMR, translating to higher dose needs longer time of induction
3- Increased CO carries agent away from alveoli at increased speed, reducing FA and therefore brain concentration and slowing induction

Question 27

Inh Agents: CV effects

Answer 27

Dose Dependent decr SVR, myocardial depressant, blunt baroreceptor response, decrease venous tone, decr SNS outflow (already immature)

Question 28

Inh Agents: Resp effects

Answer 28

Dose Dependent decr vent response to hypercarbia (already immature resp), rapid shallow breathing (decr MVe req assist vent w/ induction), bronchodilation, impaired HPV.
Des/Iso - resp irritant, not for inh induction, also Iso too slow

Question 29

Oxygen Administration

Answer 29

Hyperoxia produces free radical –> o2 toxicity induced ARDS/BPD, ROP incr retinal vasc overgrowth. Excess O2 admin can suppress ventilatory drive.

Question 30

Nitrous Oxide

Answer 30

Easily diffuses and expands closed air spaces. Decr MAC of 2nd agents used, limited second gas effect with fast acting Sevo.

Question 31

Desflurane

Answer 31

Limited use d/t pungent odor and resp irritation. Decr SVR in dose dep manner, can also increase SNS activity from irritation/high concentrations. Assoc w/ ED poss from rapid offset.

Question 32

Sevoflurane

Answer 32

Low gas solubility = rapid rise in FA. CV stable w/ minimal AW irritation. Low flows < 2l/min may produce nephrotoxic Compound A.

Question 33

MAC Values:

Answer 33

Des: Neo = 9.2 / Inf = 9.4 / Child/Ad = 5.8
Sevo: Neo = 3.3 / Inf = 3.2 / Child/Ad = 2.0
Iso: Neo = 1.45 / Inf = 1.6 / Child/Ad = 1.15

Question 34

Emergence Delirium/Agitation Risk Factors

Answer 34

Age: 2-5 years // Pre-op anxiety incr risk // More soluble agents Sevo/Des // Shorten/Fast emergence/awakening time