Analgesic in pedo

1. Pediatric Drug Dose
Presented By:
Dr. Vani Bais
P.G 1st year
Guided By:
Dr . Navneet Agrawal
Professor & HOD

2. • Drug is any substance or product that is used or is intended to
be used to modify or explore physiological systems or
pathological states for the benefit of recipient.
• Children experience large amounts of growth and
development during early childhood which can dramatically
affect the pharmacokinetics of different drugs.
• Route and rate of drug administration , dosage , onset and
duration of action ,and possibility of toxicity are all influenced
by unique physiology of childhood

3. • The different drug effects seen in children can
be toxic, as seen with valproate hepatotoxicity
and tetracycline-stained tooth enamel, or
enhanced, as seen with some treatments for
leukaemia .
• Drugs with a wide safety margin are good
options for treating children as
pharmacokinetic changes are unlikely to result
in toxicity or ineffectiveness.

4. Paediatric population is divided into:
• Preterm newborn
• Newborn (0–28 days)
• Infant (>28 days–12 months)
• Toddler (>12 months–23 months)
• Preschool child (2–5 years)
• School age child (6–11 years)
• Adolescents (12–18 years)
Batchelor HK, Marriott JF. Paediatric pharmacokinetics: key considerations. Br J
Clin Pharmacol. 2015 Mar;79(3):395-404. doi: 10.1111/bcp.12267. PMID:
25855821; PMCID: PMC4345950.

5. • Factors that influence tissue drug
concentrations over time include absorption,
distribution, metabolism and excretion
(ADME).
• These ADME processes differ in paediatric
populations compared with adults and have
consequences on the pharmacokinetic profile
of a drug.
• An understanding of these ADME differences
and likely outcome is important to ensure
effective therapy in paediatric populations.

6. Absorption
• It is the movement of drug from its site of
administration into the circulation
• Application of heat and muscular exercise
accelerate the drug absorption by increasing
blood flow,while
vasoconstrictor,e.g.adrenaline injected with
drug (local anaesthetic )retard absorption.
Essential of Medical Pharmacology, K.D.Tripathi

7. Absorption
• The composition of intestinal fluids and
the permeability of the gut vary during childhood.
• Absorption of orally administered drugs is affected by
changes in gastric pH which decreases during infancy
to reach adult values by two years of age.
• Infants are at higher risk of toxicity via skin
absorption due to a larger surface area to volume ratio
and they also absorb more of a drug across skin due to
their thinner stratum corneum.
• This explains why infants have an increased risk of
methaemoglobinaemia with topical anaesthetics.8

8. • Methemoglobin is the result of the oxidation of
ferrous ion (Fe+2) of hemoglobin to the ferric ion
(Fe+3). Methemoglobin is incapable of binding
and transporting oxygen. Benzocaine induced
methemoglobinemia was first described by BM
Bernstein in 1950 . The occurrence of drug
induced methemoglobinemia is rare but
potentially fatal.
Hall DL, Moses MK, Weaver JM, Yanich JP, Voyles JW, Reed DN. Dental
anesthesia management of methemoglobinemia-susceptible patients:
a case report and review of literature. Anesth Prog. 2004;51(1):24-7.
PMID: 15106687; PMCID: PMC2007462.

9. For EMLA®, when it is not accompanied by the administration of any other local anesthetic,
the following rules should be used to guide maximal doses:( max. dose, max. area,
max.time)
Infants ≤3 mo of age or <5 kg: 1 G, 10 cm2 for ≤1 h,
Infants from 4 to 12 mo of age and 5 to 10 kg: 2 G, 20 cm2for ≤4 h,
Children from 1 to 6 yr of age and >10 kg but ≤20 kg: 10 G, 100 cm2,
Children from 7 yr of age and >20 kg: 20 G and 200 cm2.
Guay, Joanne MD, FRCPC. Methemoglobinemia Related to Local Anesthetics: A Summary
of 242 Episodes. Anesthesia & Analgesia: March 2009 - Volume 108 - Issue 3 - p 837-845
doi: 10.1213/ane.0b013e318187c4b1

10. • Steele and Spink reported using methylene
blue (also known as methylthionine chloride)
to treat methemoglobinemia in 1933.
• Ockliz reported a case of methemoglobinemia
attributed to a local anesthetic, and its
treatment with thionine in 1949.
Guay, Joanne MD, FRCPC. Methemoglobinemia Related to Local Anesthetics: A
Summary of 242 Episodes. Anesthesia & Analgesia: March 2009 - Volume 108 - Issue 3
- p 837-845 doi: 10.1213/ane.0b013e318187c4b1
Methylene blue is contraindicated in patient with G6PD
deficiency

11. • Because it is impossible to predict which
individuals will be susceptible to develop
methemoglobinemia after benzocaine
exposure, and also because there is no
therapeutic window(between the doses
required to produce a therapeutic effect and
those producing toxicity) in susceptible
individuals, the clinical use of benzocaine
should be abandoned.
Guay, Joanne MD, FRCPC. Methemoglobinemia Related to Local Anesthetics: A
Summary of 242 Episodes. Anesthesia & Analgesia: March 2009 - Volume 108 -
Issue 3 - p 837-845 doi: 10.1213/ane.0b013e318187c4b1

13. Methylene Blue
• Usual Pediatric Dose for Methemoglobinemia
• Drug-Induced Methemoglobinemia:
Methylene blue injection 1%:
0.1 to 0.2 mL/kg IV very slowly over a period of several
minutes; may repeat in one hour if necessary
Acquired Methemoglobinemia:
Methylene blue injection 0.5% [Provayblue (TM)]:
1 mg/kg IV over 5 to 30 minutes; if the methemoglobin
level remains greater than 30% or if symptoms persist, a
repeat dose of 1 mg/kg IV may be given one hour after the
first dose; if methemoglobinemia does not resolve after 2
doses, consider alternative interventions

14. Distribution
• The volume of distribution changes
throughout childhood as stores of fat and
water change.
• Infants have a higher percentage of
extracellular water, and stores of body fat
increase throughout childhood. Changes in
volume of distribution can alter the
drug’s half-life, requiring adjustment of the
dosing interval.
Björkman, S. Prediction of Cytochrome P450-Mediated Hepatic Drug
Clearance in Neonates, Infants and Children. Clin Pharmacokinet 45,
1–11 (2006).

15. • Dosing information for obese children is limited
and has been identified as an area for research.
Obese children can be dosed using ideal body weight
and the dose adjusted based on clinical effect. They are
at higher risk of toxicity from drugs such as
paracetamol that do not distribute into fat, if actual
weight is used to calculate the dose.
• Infants have lower concentrations of circulating plasma
proteins reducing protein binding.
• This results in higher distribution and lower peak
concentrations of protein-bound drugs

16. Metabolism
• The metabolism of drugs is the most
complex difference between adults and
children.
• The pattern of active enzymes changes over
the first few months of life to reach or exceed
adult levels at around two years of age.
• Liver blood flow may be relatively high in
infants. This could affect first-pass metabolism
particularly for drugs .

17. • Many drugs are metabolized by the liver.
• Hepatic enzyme may act to detoxify a drug or
alter it into a more potent metabolite . But
infants and young children are relatively
deficient in these enzymes so are at high risk
of toxicity.

18. Elimination
• Excretion is an important step in the final
removal of the drug and any metabolites from
the body.
• Because of immature capacity the young
kidney is less competent to excrete drugs.
• Preterm neonates develop renal excretion
pathways more slowly than term neonates.
Björkman, S. Prediction of Cytochrome P450-Mediated Hepatic Drug
Clearance in Neonates, Infants and Children. Clin Pharmacokinet 45,
1–11 (2006).

19. • These differences in body composition have
important implications regarding drug effect,
loading dose, interval of dosing and drug
metabolism.
• For example, if one is giving a medication that is
highly water soluble and therefore rapidly
redistributed in this large water compartment,
then one might have to give a higher initial dose
on a mg/kg basis compared with older patients

20. • If one considers the neonate in particular, not
only do they look different on the outside
compared with a more mature infant they also
look different on the inside. For example if one
examines total body water, in a premature infant
this accounts for approximately 85% of the
patient’s weight.
• In a term infant this is about 75%, whereas in the
6 month old and older, the total body water only
accounts for 60% of body weight . Likewise, there
are marked changes in fat and muscle content as
the infant matures.

21. Developmental pharmacokinetics
• Slower GI but faster IM absorption in infancy
• More body water vs. lipid in early life
• Limited protein binding in infants
• Larger liver/body weight ratio in infants
• Immature enzymes in neonates
• Larger brain/body weight ratio and higher blood–
brain barrier permeability in younger children
• Immature renal function in infants
Stephenson T. How children's responses to drugs differ from adults. Br
J Clin Pharmacol. 2005 Jun;59(6):670-3. doi: 10.1111/j.1365-
2125.2005.02445.x. PMID: 15948930; PMCID: PMC1884865.

22. Drug Dosage Formula
AGE
Young’s Rule
Dilling’s Rule
Brunton’s Rule
Fried ‘s Rule
Cowling’s Rule
BODY WEIGHT
Clarke’s rule
BODY SURFACE
AREA
Clarke’s SA rule
In the calculation of dosages, weight has a more direct bearing on the dose than any
other factor, especially in the calculation of pediatric doses. The rule governing
calculation of pediatric doses for newborns and young infants with a normal lean body
mass and normal body development is Clark's Rule. For toddlers use Fried’s Rule, and for
older children Young’s Rule is used.

23. Age Based Drug Formula

24. Body weight based Drug Formula
Paediatric dose= weight(in kg)x Adult dose
70

25. Body Surface Area based Drug Formula

26. Analgesics
 Analgesic is a drug that relieves pain by acting in the
central nervous system or on peripheral pain
mechanisms.
Widely prescribed for pain relief, especially after a
dental surgical procedures, pulpitis, gingival infections
and peri-apical infections , dental extractions and
teething.

27. Analgesic
•

28. Common Properties of Analgesic

29. • There are two cyclooxygenase isoenzymes , COX-1
and COX-2.
• COX-1 gets constitutively expressed in the body,
and it plays a role in maintaining gastrointestinal
mucosa lining, kidney function, and platelet
aggregation.
• COX-2 is not constitutively expressed in the body;
and instead, it inducibly expresses during an
inflammatory response.

30. • However, COX-2 selective NSAIDs (ex.
celecoxib) only target COX-2 and therefore
have a different side effect profile.
Importantly, because COX-1 is the prime
mediator for ensuring gastric mucosal
integrity and COX-2 is mainly involved in
inflammation, COX-2 selective NSAIDs should
provide anti-inflammatory relief without
compromising the gastric mucosa

31. Mechanism of Action

32. Indication
•Mild to moderate pain
•Fever
•Inflammation
•Dysmenorrhoea
•Thromboembolism
•Patent ductus arteriosus

33. Contraindication
• Asthma.
• Gastritis.
• Congestive heart failure, hypovolemia, hepatic
cirrhosis, renal disease, those receiving
diuretics and anti-hypertensives.
• Renal effects of NSAIDS leading to Na+
retention and oedema.
• Chronic liver disease.

35. Commonly used Analgesic in Pediatric
patients
• Mild/Moderate Pain
Acetaminophen
Ibuprofen
Naproxen
• Moderate/Severe Pain
combination of Paracetamol and Ibuprofen

36. PARACETAMOL/ACETAMINOPHEN
• It is analgesic ,anti-pyretic with poor anti-
inflammatory action
• Paracetamol (acetaminophen) is generally
considered to be a inhibitor of the synthesis of
prostaglandins (PGs)
• Paracetamol half-life (t ½) is short, ranging
from 2 to 2.5 h

37. FORMS
TABLETS
RECTAL SUPPOSITORIES
DISPERSIBLE TABLET
INJECTABLE
SUSPENSION

38. • Usual oral dosage:
 Children <12 years: 10-15 mg/kg/dose every
4-6 hours as needed (maximum 75 mg/kg/24
hours, but not to exceed 4 g/24 hours)
Children >12 years and adults: 325-650 mg
every 4-6 hours OR 1,000 mg 3-4 times daily
as needed (maximum 4 g/24 hours)

39. DOSAGE
(mL)
2mL (C120)
3mL (C120)
5mL (C120)
3mL (C240)
5mL (C240)
7mL (C240)
8mL (C240)
10mL (C240)
1mL of Crocin 120 consist of 24mg of paracetamol
1mL of Crocin 240 consist of 48mg of paracetamol

40. Doses
• For infants and Children-100mg,120mg,240mg
suspensions are available
• For Children and Adults-500mg,625mg & 325
mg is available in combination with other
drugs

41. Trade Name
1. .
Calpol 100,120,250 oral suspension-Gsk
Crocin 120,240 oral suspension-Gsk
Paracip 250 oral suspension-Cipla
Tab.Calpol 500,650-Gsk

42. Paracetamol toxicity
• Both acute and chronic doses of acetaminophen are
associated with hepatotoxicity in children.
• Acute paracetamol poising occurs in small childrens
who have low hepatic glucuronide conjugation ability.
• Early manifestation are just
nausea,vomiting,abdominal pain and liver
tendernesswith no impairment of consciousnes.
• Fatal at >250mg/kg in adult
• Fatal at>150mg/kg in children

43. • Treatment-
If patient is brought early vomiting is induced &
and activated charcoal is given orally.
Specific treatment is N-Acetylcysteine should be
infused i.v

44. Management
algorithm for
paracetamol
overdose in
children.

45. IBUPROFEN
• Propinoic acid derivative
• Non-selective COX inhibitors
• T1/2 life is 2-4 hr
• Contraindicated in pregnancy (cross placenta
barrier) and should be avoided in peptic ulcer
patients.
• Analgesic & Antipyretic
• antiinflammatory

46. • Do not use ibuprofen in children who are less
than 6 months old . This is because it has not
been found to be safe in children less than 6
months old. The use of the medicine in
children less than 6 months is also not
approved by the FDA.

47. • Forms: Liquid, tablet, injectable

48. Doses
• For infants and Children-100mg suspensions
are available
• For Children and Adults-200mg & 400 mg Tab
is available
• It is also available in combination with other
drugs

49. Usual oral dosage:
• Infants and children <50 kg: 4-10 mg/kg/dose
every 6-8 hours as needed (maximum single dose
400 mg; maximum dose 40 mg/kg/24 hours)
• Children >12 years: 200-400 mg every 4-6 hours
as needed (maximum 1.2 g/24 hours)
• Adults: 200-400 mg/dose every 4-6 hours as
needed (maximum 1.2 g/24 hours)OR 600-800
mg every 6-8 hours as needed (maximum 1.2
g/day - 3.2 g/day)

50. DOSAGE
(mL)
2.5mL (100)
3.5mL (100)
5mL (100)
7mL (100)
10mL (100)
12.5mL (100)
15mL (100)
1ml of Ibugesic consist of 20 mg of Ibuprofen

52. Trade names
• Ibugesic Oral Suspension- Cipla
• Brufen Oral Suspension- Abbott
• Icparil Oral Suspension- Icpa
• Tab.Brufen 200 -Abbott
• Tab.Ibulgesic 200-Cipla
• Tab.Brufen 400-Abbott
• Tab.Ibulgesic 400-Cipla

53. Ibuprofen + Paracetamol
• The combination of two analgesics with
different modes of action results in an additive
rather than a synergistic effect; the efficacy of
the combination in acute pain is roughly
similar to the sum of the efficacies of
individual agents.

54. • Comparative studies have found that
paracetamol/ibuprofen combinations offer
similar pain relief to that of codeine-based
analgesics in acute pain, with generally
improved tolerability.
Daniels SE, Goulder MA, Aspley S, et al. A randomised, five-parallel-group, placebo-
controlled trial comparing the efficacy and tolerability of analgesic combinations
including a novel single-tablet combination of ibuprofen/paracetamol for
postoperative dental pain. Pain 2011;

55. Ibuprofen + Paracetamol
Age group Dosage
Infants 3 - 6 months
(weighing more than 5 kg) *
2 - 2.5ml dose may be taken 3 times daily
>6 months – 12 months 2 - 2.5ml dose may be taken 3 to 4 times daily
1- 4 years 4 - 4.5ml dose may be taken 3 to 4 times daily
4 - 7 years 4 - 8ml dose may be taken 3 to 4 times daily
7 - 10 years 8 - 10ml dose may be taken 3 to 4 times daily
10 -12 years 8 - 15ml dose may be taken 3 to 4 times daily
*Infants under 3 months of age or weighing less than 5 kg should not take Ibuprofen due to
lack of data on safety and efficacy.
1mL of Ibugesic Plus consist of 20mg of ibuprofen+32.5 mg of Paracetamol

56. Doses
• For infants and Children-A suspensions of
paracetamol 162.5mg +Ibuprofen 100mg is
available
• For Children and Adults- Tablets of
Paracetamol 325mg+Ibuprofen 400mg
is available
• It is also available in combination with other
drugs

57. Trade names
• Imol suspension-Zydus
• Combiflame suspension-Sanofi India Ltd
• Ibulgesic Plus- Cipla
• Tab.Combiflam-Sanofi India Ltd
• Tab.Flexon-Aristo pharma.
• Tab.Ibulgesic Plus-Cipla

58. Ketorolac
• It is potent analgesic and modest anti-
inflammatory activity.
• In post operative pain it has equalled the
efficacy of morphine ,but does not interact
with opioid receptors and is free of opioid
side effect.
• It is highly plasma protein bound
• Its plama t1/2 life is 5-7 hrs

59. • Ketorolac is versatile, as it is available in
multiple-dose forms: oral, nasal spray, IV, or
IM
• Dosage Formulations
• Ketorolac tromethamine IV injection solution:
15 mg/mL; 30 mg/mL
• Ketorolac tromethamine IM injection solution:
60 mg/2 mL
• Oral tablets: 10 mg
Ahmad N. Mahmoodi1; Peggy Y. Kim2. University of
Wisconsin, StatPearls Publishing; 2022 Jan

60. • Adult Dosing
• IV and IM dosing for adults are recommended
at 30 mg single dose or 30 mg every 6 hours, not
exceeding 120 mg in 24 hours.
• The recommended oral dosing in adults is a 20
mg single dose after IV or IM therapy, then 10 mg
every 4 to 6 hours, not exceeding 40 mg in 24
hours.
• Half-life: 5.6 hours for a single 30 mg IM or
single 10 mg oral dose

61. • Pediatric Dosing (off-label for acute moderate to severe
pain; ketorolac has no approval for use under the age of 17)
 Less than two years -Not recommended
 2 to 16 years-
• Single-dose: 0.5 mg/kg IV/IM once; not to exceed 15 mg
• Multiple-dose: 0.5 mg/kg IV/IM q6h; not to exceed 5 days
 Over 16 years, less than 50 kg –
 IV: 15 mg in a single dose or 15 mg every 6 hours; do not
exceed 60 mg/day
 IM: 30 mg in a single dose or 15 mg every 6 hours; do not
exceed 60 mg/day
 PO: 10 mg once after IV/IM therapy, then 10mg every 6
hours; do not exceed 40 mg/day

62. • Geriatric Dosing: Because this group is more
sensitive to the dose-related adverse effects of
NSAIDs, and ketorolac may be eliminated
more slowly by the elderly, extreme caution
and reduced dosages with careful clinical
monitoring must be used when treating the
elderly with ketorolac tromethamine.

63. Dosage (mg)
NR
NR
NR
3mg
5mg
6.25mg
7.5mg
10mg
NR – Not Recommended
The recommended oral dosage is 0.25 mg/kg to a maximum of 1.0 mg/kg/day,
with a maximum duration of 5 days
Maximum dose: 40 mg/day

64. • The majority of ketorolac and its metabolites
are eliminated via the kidneys. Around 92% of
a dose is excreted in urine as 60% as
unchanged ketorolac and 40% as metabolites.
According to Kidney Disease Improving Global
Outcomes guidelines (KDIGO Guidelines), all
NSAIDs should be avoided in patients with
creatinine clearance less than 30 mL/min.

65. • Orally it is used in a dose of 10-20 mg 6 hourly
for short term management of moderate pain.
• In post operative dental pain it is rated
superior to aspirin 650mg,paracetamol 600mg
and equivalent to ibuprofen 400mg.
• Continuous use more than 5 days is not
recommended.
• It should not be used as pre-anesthetic
medication.

66. • Ketorolac tromethamine tablets are not
indicated for use in pediatric patients and they
are NOT indicated for minor or chronic painful
conditions.
• Increasing the dose of ketorolac
tromethamine tablets beyond a daily
maximum of 40 mg in adults will not provide
better efficacy but will increase the risk of
developing serious adverse events.

67. • ketorolac increase the risk of premature
closure of the fetal ductus arteriosus in the
3rd trimester; therefore, beginning at 30
weeks gestation, pregnant women should
avoid ketorolac.
• Due to serious Adverse effects related to renal
function and to the gastrointestinal system,
use of ketorolac has been limited to five days
duration.

68. • The pharmacokinetics of ketorolac differ in children
compared with adult patients after surgery
• In children, the volume of distribution (Vd) of ketorolac is
increased by as much as 2-fold relative to that in adults.
The plasma clearance (CL) of ketorolac is also higher in
children, probably because of lower binding to plasma
proteins. However, the elimination half-life (t 1/2 beta) of
ketorolac is similar in children and adults because t 1/2
beta is directly proportional to Vd but inversely
proportional to CL.
• These pharmacokinetic differences indicate that a higher
relative dosage is required in children, but the dosage
interval is similar in children and adults
Forrest JB, Heitlinger EL, Revell S. Ketorolac for postoperative pain
management in children. Drug Saf. 2007 May;16

69. • The recommended oral dosage is 0.25 mg/kg
to a maximum of 1.0 mg/kg/day, with a
maximum duration of 5days
• Ketorolac is not recommended for use in
infants aged < 1 year.
• Older children may require somewhat lower
dosages, while infants and young children may
require slightly higher dosages to achieve the
same level of pain relief.
For e.g.-If a patient weighs about 60 kg then recommended oral
dosage is 0.25mgx 60=15mg

70. Trade Name
• Ketorol-DT(10mg)-Dr.Reddy’s
• Ketoford-DT(10mg)-Leeford
• Dentaforce-DT(10mg)-Best Biotech
• Inj.Ketorol-30mg/mL-Dr.Reddy’s
• Topical Ketorol Gel-DrReddy’s
• Nasal spray-Sprix

71. Ketorolac Overdose
• Common symptoms of ketorolac overdose
include nausea, vomiting, epigastric pain,
gastrointestinal bleeding, lethargy and
drowsiness.
• More rare symptoms of overdose include
acute renal failure, hypertension, respiratory
depression, and coma.

72. Treatment
• There are no specific antidotes. Emesis and/or
activated charcoal (60 g to 100 g in adults, 1
g/kg to 2 g/kg in children) and/or osmotic
cathartic may be indicated in patients seen
within 4 hours of ingestion with symptoms or
following a large oral overdose (5 to 10 times
the usual dose). Forced diuresis, alkalization of
urine, hemodialysis or hemoperfusion may
not be useful due to high protein binding.