pharmacological consideration in pediatric dentist

1. PHARMACOLOGIC
CONSIDERATIONS IN PEDIATRIC
DENTISTRY
Dr Assjad Ansari

2. CONTENTS
• Introduction
• Applied anatomy & physiology in relation to pediatric
pharmacology
• Pharmacokinetic changes in children
• General principles in pediatric pharmacology

3. • Drug dosage calculation in children
• Conditions that alter pediatric dosage responses
• General considerations in premedication for anxiety
& pain control

4. • Drug compliance
• Poisoning in children
• Conclusion
• References

5. Introduction
• "Pediatrics does not deal with miniature men
and women, with reduced doses and the
same class of disease in smaller bodies, but ...
has its own independent range and horizon."
Dr. Abraham Jacobi

6. Cardiovascular System

7. Cardiovascular System• Heart Rate:
Heart rate of new born ---- 120
By 4 years of age ---- <100
Adult Heart rate ---- 70 by 10-12 years of age
Changes in H R during development
Age Mean H R
New Born 115 – 170
6 months 110 -150
1 year 90 – 135
3 year 80 – 125
5 year 80 – 120
10 year 75 – 110
15 year 70 – 110
Adult 70

8. • Cardiac Output:
Cardiac Output = Heart Rate X Stroke volume
in H R
cardiac output
Hypotension

9. Parasympathetic tone is more marked in immature
nervous system
More prone to significant bradycardias
(with vagal stimulation)
Children undergoing manipulation of air way are
premedicated with Atropine

10.  Blood Pressure
B P throughout childhood
New Born mean systolic B P 75 – 80 mm Hg
First several wks 5 -10 mm Hg
Adult B P 120 mm Hg Early Adolescence
Changes in B P during development
Age Mean systolic B P (mm Hg)
New Born 60 – 75
6 months 80 – 90
1 year 96
3 year 100
5 year 100
10 year 110
15 year 120
Adult 125

11.  DRUG CONSIDERATIONS :
Cardiac output per Kg of body wt is highest in New Born
Gradually declines in first several wks
in cardiac output causes in heart rate
the rate of inhaled anesthetic uptake
As 40% of C O prefuses the brain

12. Depresses the central nervous system
( se in vasomotor tone, peripheral vasodilatation)
Hypotension (assoc with Bardycardia)
To minimize these effects pediatric patients should be
well hydrated prior to procedures.

13. Respiratory System
Anatomic features in obstruction and collapse of airway :
 Narrow nasal passage Partial / complete
 Tongue / oral cavity disproportion airway obstruction
 Decreased airway diameter
Additional risk is generated by:
 A clamped mask over the nares.
 A mouth pack.
 A retractor.
 The secretions and edema

14. Anatomical difference in the child’s chest cage:
Chest wall is more elastic
Lower ventilation pressure are needed to expand lungs
Sternum is less rigid
Ribs and intercostal muscles have less support
Ribs are more horizontal in resting position
Retraction of intercostal muscle ineffiecient

15. Diaphragm is the primary breathing muscle
Anything that limits diaphragmatic excursion should be
therefore be avoided
Supine position Promotes gastric organ pressure
(avoided) on the diaphragm
20 – 30 degree head up position is recommended

16.  Lung infrastructure different
from adults
 Majority of alveoli formed
after birth
 Adult no.- 6 year
 Greater proportion of
alveolar surface area to lung
size

17. Physiology:
Because of relative difference in alveolar surface area
Children have
Greater rate of Alveolar Ventilation (A V) per unit
area
Low Functional Residual Capacity ( F R C)

18. AV / FRC ratio helps to determine the rate at which
changes in inspired gas concentration effect clinical
response

19. Pediatric AV / FRC ratio is 5 times of adult
More rapid reaction to inhaled gases
(eg N2O, Halothane)
Hypotension, Bardycardia, Hypoventilation are the
overdose effect
CAREFUL MONITORING OF VITAL SIGNS IS NECESSARY!

20. Gastrointestinal System
• DECREASED ACIDITY
• Immature gastric mucosa secrets low levels of acid
• Adult level -3 years of age
• Absorption of weakly acidic drugs such as Penicillins and
Cephalosporins
• weakly basic drugs such as Benzodiazepines is delayed

21. Altered Motility:
• Longer gastric emptying time of 8 hours
• Adult values of 2 – 3 hours reaches between 6 – 8
months of age
• Longer emptying time + Irregular peristalsis
Results in slower gastric drug absorption

22. • Altered Hepatic Metabolism:
Infants and children are relatively deficient in hepatic enzyme
High risk for toxicity if not dosed correctly
Low levels of Cytochrome P-450 enzyme
Sluggish oxidation of Diazepam, Phenytoin, Phenobarbital
Prolonged clinical effects in this age group

23. • Glucuronyl transferase-adult level at 1 mon.
• Morphine, Acetaminophen, steroids and Sulfa antibiotics –
caution
• Infant liver -Pseudocholinesterase enzyme-60%of adult levels
• Succinylcholine doses do not reach adult levels until 2 years of
age

24. Renal System
• Sweat, bile, feces.
• Majority -renal excretion
• Because of its immature capacity -kidney is less
competent to excrete drugs
• Glomerular filtration, Tubular transport, or a
combination of both

25. Glomerular Filtration Rate :
• Adult levels are 5 times new born 12months
of age
• Drugs Penicillin, short acting Barbiturates
Phenobarbital
Excreted by GF

26. Tubular transport:
• Morphine, Atropine, Sulfa antibiotics
• Thus have narrower margin of toxicity

27. Blood And Body Fluids
Terminology:
• Total Body Space = Intracellular fluid ( ICF ) +
Extracellular
fluid ( ECF )
Volume of distribution-(Vd)-Plasma
 Physiology:
 Alterations in Body Fluids:
 As child grows, changes in body mass are
accompanied by changes in body fluid compartments

28. • Total Body Water 80% of Infants weight
50 – 60% of normal
adult body weight
Difference in distribution of Body Fluids:
FLUIDS INFANTS ADULT
Total Body Water 80% 50% ( males )
60% (females)
Extracellular Fluid 35 – 40% 20%
Intracellular Fluid 40 – 45% 40%
• As infant weight is water , water soluble drug must be
administered at higher levels per unit of body weight

29. Plasma Protein Difference:
• Plasma protein -transport and render it less physiologically
active when bound
• Serum albumin and Plasma globulin -deficient in New born
and Young infant
• Drugs that are highly protein bound eg warfarin and digoxin
must be dosed at relatively low levels per unit of body weight

30. Body Habitus And Integument
• Smaller drug dose
• Weight based formulas are safer
• Child height triples from birth but weight 20
fold

31. Body Surface Area [ BSA]
• Accurate
• Estimated -height and weight on a nomogram
• Proportional -fluid requirements, oxygen
consumption, metabolic rate and cardiac output

32. Tissue composition of Infants and Child differ
:
• Fat makes up to 10% - 15% of full term new born to 20% -
25% First several months
Toddler and preschool years
Sedatives (Benzodiazepines & Barbiturates)
Serum drug levels
Children with low % of body fat are more sensitive to these
agents

33. • Pharmacokinetics
• pharmacokinetics –Is the quantitative study of drug
movement in,thro & out of the body
• absorption, distribution (including protein binding),
metabolism, and excretion.

34. Routes of drug absorption
• Oral route-not palatable
• IV route
• Intramuscular (IM) absorption
• Percutaneous absorption
• Rectal absorption

35. Absorption
Time-max plasma levels- very young
Gastric ph+ gastric emptying time+ irregular peristalis

36. Distribution
Protein binding:
The binding of drugs to plasma proteins such as
albumin is decreased in neonates
Adult capacity –Few months

37. Metabolism
The liver is the primary organ for most drug
metabolism.
Changes in metabolism & disposition –Function of
age-Variable
Acetaminophen, diazepam, indomethacin,
theophylline, phenytoin, phenobarbital, digoxin,
and meperidine have prolonged elimination half-
lives in neonates

38. Excretion
Kidneys play vital role-Less competent –
reduced GFR &Tubular secretion.
Dose adjusted on basis of renal function

39. Plasma half life and its significance
1)First order kinetics
2)Zero order kinetics
• Most -Exponentially(first order kinetics)
• Single intravenous dose,plasma con.found to fall
exponentially.
• Drug removal-proportional to its plasma con.
• t1/2 –time req for the 50% elimination

40. • Phenytoin,Dicumorol,probenecid,oral propranolol
etc
lower dose
in dose –fixed quantity excreted
Dose dependent or saturation kinetics or zero order
kinetics
• Time of elimination,schedule dose
• A loading dose

41. General Principles Of Pediatric
Pharmacology
• Metric than Ampothecary
• Younger patient –more atypical therapeutic
toxicologic response
• Younger -atypical is the disease
manifestation.Seizures
• Prolonged therapy with agents- affecting endocrine
system

42. General Principles Of Pediatric
Pharmacology
• Childhood –high water turn over –dehydration –high
drug levels
• Excessive use of syrups & Elixirs – caries
• Parental abuse.
• General anaesthesia should be discussed
• Anesthesia -oxygen supply –not less than 20%

43. General Principles Of Pediatric
Pharmacology
• Allerginicity is greater- rapid growth,development &
maturation-skin,eyes,resp,&digestive system
• Tetracycline->5 in females in 1st 6 yrs and for males in
1st 7 yrs
• Genetic heritage-affect drug responsiveness-Hepatic
porphyria

44. Doses For Children
• Clarks Rule weight (lbs)
150
Eg=50 x 300=100 mg
150
• Youngs Rule Age (yr)
Age (yr) + 12
Eg= 4 x 300 = 97mg
4+12
Adult dose
Adult dose
X
X

45. • Dillings formula= agex adult dose
20 Eg=4x300=60mg
20
• Cowling’s rule=age next bday xadult dose
24
Eg=5x300=62.4
24

46. • Catzels rule (For
child.<13)-Safe guide on
BSA for avg adult wt
145 lb
• Not for local anesthetics
Age Wt(lb) %AD
1 22 25
3 33 33.5
7 50 50
12 88 75

47. • Gabius - series of fractions for age 1-1/12, for
age 2-1/8,3-1/6,4-1/4,7-1/3,14-1/2,20-2/3 of
adult dose
• Bastedo rule =Age+3 of adult dose
30

48. • Infant below one year Fried’s rule
=Age in months of adult dose
150
• Body surface area= BSA ( m2 ) Xadult d.
1.7
BSA ( m2 ) = BW (Kg)0.425 X Height (cm)0.725 X
0.007184

49. • Guidelines
for
estimatng
Weight by
age
Age(yr) Age(m
o)
Wt(Kg) Wt(lbs)
0 3-5 7-11
3 5-7 11-15
6 7-8 15-18
9 8-10 18-21
12 10-11 21-24
18 11-12 24-26
2 12-13 26-28
3 13-15 28-33
4 15-17 33-37

50. 5 17-19 37-42
6 19-21 42-47
8 21-25 47-55
10 25-34 55-75
12 34-55 75-120
>12 55+ 120+

51. • Pediatric Calculations- Accurate doses are important
1.1kg=2.2lb
2.Calculate medication dose
a.Calculate daily dose
b.Divide by no. doses to be administered
c.Use ratio proportion to calculate no of tab
Eg=Wt 76lb,150mg Clindamycin q6h.Acc to dose hand
book 8-20mg/kg/day.

52. • 76lb/2.2=34.5kg
• Safe dose-
min;8mg/kg/dayx34.5kg=276mg/day
max;20mg/kg/dayx34.5kg=690mg/day
• 150x4=600mg/day
• 100mg:1tab=150mg:X
=150/100=1.5tab

53. The rule of 10
• Block?
• Better approach
• Age +Tooth no
• Age(4)+Primary 1st molar (4)=8(infiltration)
• Age(7)+Primary 1st molar(4)=11(block)

54. Local Anasthesia
• Dosage calculations
• Lignocaine-2%=20mg/ml
• %con.(mg/ml) x ml/cartridge=total mg/cartridge
• 20mg/mlx1.8ml=36mg/cartridge
• Max dose=300mg
• 300/36=8.3cart.
• 8cart.=288mg

55. Epinephrine
• 1:100,000=1gm/100,000ml=1000mg/100,000
=0.01mg/mlx1.8ml/cart=0.018mg/cart
• Max dose=0.2mg
• 0.018x11=0.198mg

56. Use of Antibiotics
• Should be based on correct diagnosis
• Disrupt the micro organisms-
• Antibiotic therapy should be used as an adjunct &
when systemic signs are evident
• Specialist’s advice should be sought
• Penicillin is the first choice.

57. Commonly Used Antibiotics In Children
And Dosage
Drug Dosage &Route
Amoxicillin Oral-20-40 mg/kg/day tid(
8th hourly)
Cephalexin PO 50-100 mg/kg/day 4
doses (6th hourly)
Erythromycin Oral 30-50 mg/kg/day 4
doses (6th hourly)
Metronidazole Oral 5mg/kg/day tid
Ampicillin Oral-50-100mg/kg/day in 4
doses ie 6th hourly

58. Pain management
Analgesic Availabl Dosage 40lb(18kg) 80lb(36kg)
Acetamino
phen
Elixir160m
g/5cc,325
mg tab,
160 chew
10-
15mg/kg/d
ose 4-6 hr
160mg=1ts
p
160=1
chew
325=1tab
325=2 chew
Ibuprofen Sus
100mg/5cc
,200,400,6
00,800,
4-
10mg/kg/d
ose 6-8h
100mg=1ts
p
200mg=2tsp
200mg=1tab
Tramadol 50mg,100
mg tab
1-
2mg/kg/do
se 4-6h
25mg=1/2
tab
50mg=1tab

59. Analgesic Availabl Dosage 40lb 80lb
Acetamin
ophen &
Codeine
Sus12mg/
5cc
0.5-
1mg/kg/d
ose 4-6 hr
12mg=1ts
p
24mg=2tsp
Mepiridin
e
Syrup50m
g/5cc
50,100mg
tab
0.5-
0.8mg/kg/
dose 4-6h
25mg=1/2
tsp
50mg=1tsp

60. General considerations in Premedication for
Anxiety And Pain control
1. Morning Appointments
2. No break fast
3. Local Anaesthetics-yes
4. Parents should accompany
5. Early arrival
6. Current medical history
7. Facilities for resuscitation & oxygen must be readily
available
8. Pt must never be left alone in the dental chair
9. Parent should plan to keep the child at home
10. Instructions for premedication
11. Close attention for pediatric dosage ie either mg/kg
mg/lb.

61. Preventing Medication Errors
Children are at the highest risk for medication errors.
A study from 1995 to 1999 by the USP.

62. • Prescriptions and orders-
Abbreviations,acronyms & symbols
• Dose-Computer algorithm

63. Adverse drug reactions and toxicity
• Deficient Glucuronyl
transferase
• Kernectirus-Sulfa drugs
• Dermal absorption of
Hexachlorophane –cystic
brain lesions &
neuropathologic
abnormalities
• Boric acid & Analine dye
poisoning-by diapers
• Management-withdrawal

64. Poisoning in Children
• Cough & Decongestant preparations-
Active ingredients
Sympathomimetic agents – largest ingredients
Adverse reactions -Hypertension,reflex
bradycardia,arrythmia,convulsions & coma

65. • Paracetamol & Aspirin make up second largest
group should not be overlooked
• Expectorants- mucosal irritants/stimulants

66. • Oral contraceptive pills -Transient GI upset,Vaginal
bleeding may occur
• Antibiotics- Little adverse effects,transient GI
discomfort.No treatment required
• Benzodiazepines- Most commonly encountered.
Drowsiness,ataxia,hallucinations,confusion
&agitation. Flumazenil,Benzodiazepine antagonist.

67. • Vitamin preparations- generally of low toxicity but
iron content may produce adverse effects
• Topical medicines- Nausea,vomiting & diarrhoea
• Asthma medication- Salbutamol-
tachycardia,agitation etc Theophylline more toxic
encountered infrequently,Activated charcoal if more
than 15mg/kg
• Antihistamines- CNS depression-whole bowel
irrigation- quantities are consumed.

68. Conditions that alter Pediatric dosage
responses
Malignant hyperthermia-
• serious complication of GA with
genetic predisposition
• Mortality-70-80%
• Treatment-Rectal
Aspirin,icebags,chlorpromazine
• GA of choice –N2O
• Preop excitement -curtailed

69. Hyperactivity
• Sign of MBD
• Pediatric dentist should be
vary of unique therapeutic
problems
• Mild sedative –evokes
excitation similar to 2nd stage
of anesthesia
• Coffee

70. Single vs Multiple Drug Dosages
• Chloralhydrate-single dose-elixr-long-GI
irritation,myocardial depression,kidney & liver.
• Triamcenalone paste- minor aphthae
• Antihistamines
• Flouridated water

71. Multiple dosage in Antibiotic coverage
• Children with Rheumatic fever-resistant org.,
long term suffering
• Benign murmurs-high freq.

72. Compliance
• Tending to be excessively obedient or acquiescent
• Disturbingly high (50-75%)
• Higher in chronic conditions
• General measures to improve the compliance
• Remainder calls
• Checking medication -each visit
• Testing urine
• Patients /parents to keep daily records

73. Suggestions for improving patient
compliance
• Respectful communication
• Relationship b/w doctor & patient.
• Precise ,clear instructions.Support oral instructions
with easy to read written information.
• Simplify
• Use mechanical compliance aids

74. Suggestions for improving patient
compliance
• Optimal dosage
• Assess pt literacy and comprehension
• Solutions when physical or sensory disabilities are
present
• Enlist support & assistance from family or care givers
• Use behavioural techniques as goal setting,self
monitoring

76. References
• Pharmacology and pharmacotherapeutic-
R.S.Satoskar & S.D.Bandarkar
• Goodman&Gilman’s –The Pharmacological basis of
therapeutics-Alfred G.Goodman
• Essentials of Medical Pharmacology-KDTripathi
• Pediatric Dentistry;Infancy Through Adolescence-
J.R.Pinkham
• Pediatric Dental Medicine-Donald J Forrester
• Clinical Pharmacology-D.R Laurence & PN Bennett
• DCNA July 2000
• DCNA 46 2002