2. Pediatrics age
NEONATE
First 4 week of life
INFANCY
Up to 1 year of age
TODDLER
1-3 year of age
PRESCHOL
3-6 years of age
SCHOLE AGE OF CHILDERN
6-12 years of age
ADOLESCENTS
12-18 years of age
3. Drug therapy in Pediatrics
• Pharmacokinetic process
1. Absorption
2. Distribution
3. Biotransformation
4. Elimination
• Pharmacodynamic
• Pediatric dosage forms and compliance
4. Pharmacokinetic process in pediatric patients
• Absorption:
GI factors altering drug absorption:
• Prolonged gastric emptying time and irregular gut motility
interfere with achievement of peak plasma conc of drug.
• Reduced transit time in upper intestine
• Presence of food decreases absorption of penicillin,
paracetamol and ampicillin.
• High protein diet and low carbohydrate diet increases
clearance of theophylline.
• Absorption of lipid soluble drugs reduced in infants as they
have low conc of lipase and bile acid.
5. Oral absorption of various drugs in neonate compared
with older children & adults
Drugs
• Acetaminophen
• Ampicillin
• Diazepam
• Digoxin
• Penicillin G
• Sulfonamides
• Phenobarbital
• Phenytoin
Oral absorption
• Decreased
• Increased
• Normal
• Normal
• Increased
• Normal
• Decreased
• Decreased
6. DISTRIBUTION
• The reversible transfer of drug from one location
to another within the body (or) which involves
reversible transfer of a drug between
compartments.
7. FACTORS AFFECTING DRUGS
DISTRIBUTION
1)Physicochemical properties of the drug
• Molecular size
• Oil water partition coefficient (Kow)
• Degree of ionization that depends on pKa
2) Physiological factors
• Organ or tissue size
• Blood flow rate
• Physiological barriers to the diffusion of drugs
- blood capillary membrane
8. .
- cell membrane
- specialized barriers
- blood brain barrier
- blood cerebrospinal fluid barrier
- placental barrier
- blood testis barrier
3) Drug binding in the blood
4) Drug binding to the tissue and other macromolecules
5) Miscellaneous factors related in mother e.g.
a) Age
b) Pregnancy
c) Obesity
d) Diet
e) Disease states
f) Drug interactions
9. Plasma protein binding
• Albumin α-glycoprotein and lipoproteins.
• Higher fraction of unbound (free) drug due to:
1. Reduced concentration of plasma proteins in infancy
2. Decreased affinity for drug binding e.g. digoxin,
theophylline,
3. High conc of endogenous compounds such as bilirubin,
hormones transferred through placenta
4. Reduced plasma proteins e.g. PEM, nephritic syndrome.
5. Decreased binding of drugs in disease states.
10. Blood brain barrier
• In predicts Blood brain barrier is not well developed,
so drug penetration is more in CNS e.g. bilirubin, lipid
soluble drugs, morphine etc.
• Disease states in newborn & infants confound
enhanced penetration e.g. Acidosis, hypoxia,
hypothermia and hypoglycemia.
11. Biotransformation of drugs
• Drug metabolizing enzymes & immature in neonates, so drug
metabolizing capacity limited.
• Phase 1 oxidation reaction & glucoronidation are immature at birth
hence increased toxicity e.g. chloramphenicol produces gray baby
syndrome.
• Plasma esterase reduced in infants leading to prolonged apnoea due
to succinylcholine.
• Sulfat reaction more active in infants & children leading to more
toxic metabolite of paracetamol.
• Metabolism is faster for certain drugs after 1st year so reduced t½.
E.g. theophylline, phenytoin, carbamazapine, phenobarbitone.
12. Elimination
• GFR is low and tubular transport not fully developed
• Drugs eliminated by kidney should be reduced in infants e.g.
aminoglycosides, diuretics.
• t1/2 of theophylline and prednisolone & reduced due to high
plasma clearance.
• t1/2 of ampicllin, digoxin & certain increased due to reduced
renal clearance
• In patients with renal insufficiency dosage guides are based
on serum creatinine levels.
13. Pediatric drug dosage
• Dose calculation on the basis of age, surface area
and weight
• Based on age (young’s rule)
• Dose = Adult dose x Age ( years)
Age +12
• Based on weight
• Dose = Adult dose x weight(kg)
150
14. Pediatric dosing is commonly based on body surface area (BSA)
Approximate dosage for a child =
Body surface area of the child × adult dose
1.73 m²
Dose Approximation based on Body Surface Area
15. Drug Therapy in Pediatric Patients:
Promoting Adherence to a Medication Regimen
Patient/ caregiver/ family need to know:
• Name of medication
• Purpose of medication
• Dosage size and timing (r/t meals, other meds,
time of day, symptom onset, and so forth)
• Administration route and technique
• Special considerations
• Treatment duration
• Drug storage- safety for children in household
• Nature and time course of desired responses
• Nature and time course of adverse effects.
19. Drugs selection in Geriatric
• Pharmacokinetic process
• Pharmacodynamic
20. Effects of Absorption in geriatric
Physiologic change
Decreased gastric acidity
Decreased gastrointestinal blood flow
Delayed gastric emptying
Slowed intestinal transit time
General clinical effect
Passive diffusion: for most drugs decreased
Decreased active transport: Decreased bioavailability for
some drugs
Decreased first-pass effect: Increased bioavailability for
some drugs
21. Effects of Distribution in geriatric
Decreased Total body water
• Increased Plasma Conc. of water soluble drugs
• Lower doses are required: Lithium, digoxin, ethanol, etc
Decreased Lean body mass
• Increased Volume Distribution, Longer (t½) of water soluble drugs
• Accumulation into fat of lipid soluble drugs
Decreased Serum Albumin
• Increased unbound fraction of highly protein bound drugs
• Binds acidic drugs: warfarin, phenytoin, digitalis, etc
Decreased Alpha1 Acid glycoprotein
• Increased unbound fraction of highly protein bound drugs
• Binds basic drugs: lidocaine and propranolol, etc
22. Effects of metabolisms in geriatric
Difficult to predict, depends on
• General health & nutritional status
• Use of alcohol, medications
• Long term exposure to environmental toxins/pollutants
• Decreased liver mass/ hepatic blood flow
• Delayed/reduced metabolism of drugs
• Higher plasma levels
• Changes in phase 1 reaction those carry out microsomal p450
• Decline in liver ability to recover from injury
• Lower serum protein levels
• Loss of protein binding
23. Effects of elimination in geriatric
Physiologic change
• Decreased GFR
• Decreased renal blood flow
• Decreased renal mass
General clinical effect
• Decreased clearance
• Increased (t½) of renal eliminated drugs
24. Pharmacodynamic changes in the elderly
• Changes in receptor affinity
• Changes in receptor number
• Post-receptor alteration
• Age-related impairment of homeostatic mechanisms
• Example: decreased baro-receptor reflexes
25. Age-related changes:
• Sensitivity to sedation and psychomotor impairment with
benzodiazepines
• Level and duration of pain relief with narcotic agents
• Drowsiness with alcohol
• Sensitivity to anti-cholinergic agents
• Cardiac sensitivity to digoxin
26. Behaviour and lifestyle change
• Cognitive changes associated with vascular and other
pathology
• Economic stresses with reduced income or due
increased expenses of illness
• Loss of spouse
27. Major adverse drugs reactions in elderly
• Positive relationship between number of drugs taken and
incidence
• Prescribing errors
• Polypharmacy
• Drug interactions with other prescriptions
• Unawareness of age related physiologic changes
• Drug usage errors
OTC
28. Factor contribute adverse drugs reactions
• Polypharmacy
• How many prescription medications are too many?
>4 or >5 Many elderly people receive 10 - 12
medications per day
• Heart
• Kidney
• Liver
• Thyroid
29. Economic factors
• Choose between food and medications
• OTC instead of expensive doctor visits
• Use of outdated medications
• Use of home remedies
• Share medications
• Nutritional supplements may affect how body
metabolizes of medications
30. Polypharmacy
• Use of multiple medications
• Consume 30% of all prescription drugs [average
person takes 4-5 prescription meds]
• Consume 40% of OTC
• Excessive use of drugs
• Overdose of a drug
31. Risks of problems:
• Polypharmacy primary reason for adverse reactions
• Medication errors
• Wrong drug, time, route
• Adverse effects from each drug
• Adverse interactions between drugs
32. Major group drugs reactions
Sedative and hypnotic drugs
• Half life of many drugs benzodiazepine & barbiturates
increases 50% between age 40 - 70
• Adverse reactions like Ataxia & motor impairment
mostly present
39. Ant arrhythmias drugs
• Treatment of arrhythmias in elderly is particularly
challenging due to
• Lack of good hemodynamic reserves
• Frequency of electrolyte disturbance
• High prevalence of coronary disease
• Confusion
• Slurred speech
• Light-headedness, seizures
• Hypotension
41. Drugs use in Alzheimer's disease
• Progressive impairment of memory and cognitive function,
• Prevalence increases with age
• Pathological changes includes increased deposits of myeloid
beta peptide in cerebral cortex due to progressive loss of
neurons especially cholinergic neurons
42. Drugs use in glaucoma and mucosa dermatitis
• Cholinomimetics drugs because of evidence of loss of
cholinergic neurons
• Tacrine, donepezil, rivastigmine & galantamine are used
as these are cholinesterase inhibitors
• ADRs nausea, vomiting & peripheral cholinomimetics
effects
43. Optimal pharmacotherapy
• Balance between overprescribing and under
prescribing
• Correct drug
• Correct dose
• Targets appropriate condition for the patient Avoid “a
pill for every ill”
• Always consider non-pharmacologic therapy
44. Patients factors of ADEs
• Polypharmacy
• Multiple co-morbid conditions
• Prior adverse drug event
• Low body weight or body mass index
• Age > 85 years
• Estimated CrCl <50 mL/min
45. Drug - drug interactions
• Absorption may be increased or decreased
• Drugs with similar effects can result additive effects
• Drugs with opposite effects can antagonize each
other
• Drug metabolism may be inhibited or induced
48. Principles of drugs prescribing in
elderly
• Avoid prescribing prior to diagnosis
• Start with a low dose
• Avoid starting 2 agents at the same time
• Reach therapeutic dose before switching or adding
agents
• Consider non-pharmacologic agents
49. Preventing Polypharmacy
• Review medications regularly & each time a new
medication started or dose is changed
• Maintain accurate medication records (include
vitamins, OTC & herbals)
50. Client taking meds regulatory
1. Suggest physician prescribe combination drugs or
long-acting forms
2. Fewer pills to remember
3. Suggest re-evaluation of medications periodically
4. Encourage client to use one pharmacy
5. New medications
6. Good information
7. Encourage follow up
51. Compliance
• Prescriber must recognize
• Forgetfulness
• Prior experience
• Physical disabilities
• Recommendations to improve compliance
• Take careful drug history
• Prescribe only for a specific & rational indication
• Define goal of drug therapy
• High index of suspicion regarding drug reactions & food
interactions
• Simplify drug regimen
52. Enhancing Medication Advance
• Avoid newer, more expensive medications
• Prescribe less expensive, generic drugs
• Simplify the regimen
• Utilize pill organizers or drug calendars
• Educate patient on medication purpose, benefits,
safety & potential ADEs
53. Therapeutic drugs monitoring
Most drugs have narrow therapeutic windows and thus
toxicity is unlikely at 'normal doses'.
• Phenytoin
• Phenobarbital
• Warfarin
• Carbamazepine
• Gentamicin
• Vancomycin
• Digoxin
• Theophylline
