DRUG THERAPY FOR PAEDIATRICS

                                   DRUG THERAPY FOR INFANTS AND CHILDREN (PEDIATRICS)

1. PEDIATRIC DOSAGE FORM AND COMPLIANCE: .SOLID DOSAGE FORM AND AEROSOL INHALATIONS ARE DIFFICULT TO ADMINISTER TO YOUNG CHILDREN.SO MANY DRUGS PREPARED FOR CHILDREN ARE IN THE FORM OF ELIXIRS AND SUSPENSIONS.

2. CHILDREN ARE GROWING AND ARE SUSCEPTIBLE TO SPECIAL ADVERSE EFFECT---

# E.G. SUPPRESSION OF GROWTH CAN OCCUR WITH CORTICOSTEROIDS, ANDROGENS—STUNTED GROWTH

#TETRACYCLINE DEPOSITED IN GROWING TEETH AND DISCOLOUR AND DEFORM THEM

#DYSTONIC REACTIONS TO PHENOTHIAZINES ARE COMMON IN CHILDREN

3. PHARMACODYNAMIC: SPECIAL PHARMACODYNAMIC FEATURES IN NEONATE

#ADMINISTRATION OF INDOMETHACIN CAUSES THE RAPID CLOSURE OF A PATENT DUCTUS ARTERIOSUS, WHICH WOULD OTHERWISE REQUIRE SURGICAL CLOSURE IN AN INFANT WITH A NORMAL HEART.

#INFUSION OF PROSTAGLANDIN E1 CAUSES DUCTUS ARTERIOSUS TO REMAIN OPEN, WHICH CAN BE LIFE SAVING IN AN INFANT WITH TRANSPOSITION OF THE GREAT VESSELS  OR TETRALOGY OF FALLOT.

4.PHARMACOKINETIC:

A. DRUG ABSORPTION: DRUG ABSORPTION IN INFANTS AND CHILDREN FOLLOW THE SAME PRINCIPLE AS IN ADULTS

1. NEONATES HAVE LOW CONCENTRATION OF BILE ACIDS AND LIPASE, WHICH MAY DECREASE THE ABSORPTION OF LIPID SOLUBLE DRUGS.

2. IN NEONATES TRANSDERMAL ABSORPTION IS FASTER BECAUSE SKIN IS THIN AND MORE PERMEABLE.

3. DRUG ABSORPTION DEPENDS ON:

I)  FOR PARENTRAL (I.M., S.C.)                                                                                 

A) ON BLOOD FLOW AT THE SITE OF DRUG ADMINISTRATION: BLOOD FLOW DEPENDS ON THE PHYSIOLOGIC STATUS OF INFANT AND CHILD:

#PHYSIOLOGICAL CONDITIONS LIKE CARDIOVASCULAR SHOCK AND VASOCOSTRICTION CAUSE DIMINISHED PERIPHERAL PERFUSION TO THESE AREAS (I.M., S.C.).IN SUCH CASES ABSORPTION BECOME IRREGULAR AND DRUG REMAIN IN MUSCLE AND ABSORBED SLOWLY.

#IF PERFUSION SUDDNLY INCREASES THERE CAN BE SUDDEN AND UNPREDICTABLE INCREASE IN ABSORPTION OF DRUG WHICH CAUSE TOXICITY.(E.G. CARDIAC GLYCOSIDE,AMINOGLYCOSIDE ANTIBIOTICS)

II) FOR ORAL: GASTROINTESTINAL FUNCTION—IT DEPEND ON GASTRIC PH AND GIT TRANSIT.

A) GASTRIC ACID SECRETION:

#IN FULL TERM INFANT, GASTRIC SECRETIONS BEGINS SOON AFTER BIRTH AND INCREASE GRADUALLY OVER SEVERAL HOURS

#IN PREMATURE INFANTS, THE SECRETION OF GASTRIC SECRETION IS MORE SLOWLY AND HIGH CONC. ON FOURTH DAY OF LIFE.

SO IN BOTH CASES DRUG WHICH IS INACTIVATED BY LOW PH OF GASTRIC CONTENT SHOULD BE AVOIDED ORALLY.

B) GIT TRANSIT: INCREASE IN GIT MOTILITY DECREASE IN EXTENT OF ABSORPTION.

GASTRIC EMPTYING TIME IS PROLONGED IN FIRST DAY OF LIFE. THEREORE DRUGS THAT ABSORBED FROM STOMACH ARE ABSORBED MORE COMPLETELY THAN ANTICIPATED.

#IN THIS CASE DRUG ABSORBED IN THE SMALL INTESTINE---THERAPEUTIC EFFECT MAY BE DELAYED.

ABSORPTION OF DRUGS IN NEONATES AS COMPARED  TO ADULTS
PENICILLIN-G, AMPICILLIN	INCREASED
PHENOBARBITAL, PHENYTOIN	DECREASED

DRUG DISTRIBUTION:

A.       WATER CONTENT: IN NEONATES THERE IS HIGH WATER (70-75%) CONTENT IN THE BODY AS COMPARED TO THE ADULTS (50-60%). SO IN NEONATES THERE IS LARGE VOLUME OF DISTRIBUTION OF WATER SOLUBLE DRUGS LIKE AMINOGLYCOSIDES.

WATER PERCENTAGE IN THE BODY OF ADULT, NEONATE AND PREMATURE NEONATE:

IN ADULTS	IN NEONATES		PREMATURE NEONATE
50-60%	70-75%		85%
EXTRACELLULAR WATER
IN ADULTS-----20%		IN NEONATES----40%

B.       FAT CONTENT: IN PREMATURE NEONATES (1%) THERE IS LESS FAT CONENT THAN FULL TERM INFANTS (15%). SO LIPID SOLUBLE DRUG IN PREMATURE NEONATES LESS ACCUMULATES AS COMPARE TO THE FULL TERM NEONATES.

C.       ALBUMIN CONTENT: IN NEONATES THERE IS LESS ALBUMIN CONTENT. SO PROTEIN BINDING OF SOME DRUGS DECREASES LIKE DIAZEPAM, PHENYTOIN, AND AMPICILLIN. FREE CONCENTRATION OF THESE DRUGS INCREASE IN PLASMA WHICH CAUSES TOXICITY.

D.       COMPETITION B/W DRUG AND BILIRUBIN FOR BINDING TO SERUM ALBUMIN: E.G.WHEN SULFONAMIDE ANTIBIOTIC GIVEN TO NEONATE IT COMPETES WITH BILIRUBIN FOR BINDING TO ALBUMIN. SULFONAMIDE DISPLACES BILIRUBIN. DUE TO PERMEABILITY OF BBB IN NEONATES BILIRUBIN ACCUMULATE IN BRAIN AND CAUSE KERNICTERUS.

DRUG METABOLISM: hepatic drug metabolizing system is inadequate.

DURING IST YEAR OF LIFE DRUG METABOLISM IS FASTER THAN ADULTS E.G. THEOPHYLLINE, PHENYTOIN, CARBAMAZEPINE T1/2 IS SHORTER IN CHILDREN AND DIGOXIN DAILY DOSE IS INCREASED E.G. 8-12 MICRO GRAM/KG COMPARED TO ADULT DOSE OF 3-5 M.G/KG

 E.G. GLUCURONIDE CONJUGATION IN NEONATES REACHES TO ADULT VALUE IN 3 TO 4 YEARS. THAT’S WHY chloremphenicol cause gray baby syndrome IN NEONATES WHEN ADULT DOSE IS GIVEN.

HALF LIFE OF VARIOUS DRUGS IN NEONATES AND ADULTS
DRUG	NEONATAL AGE AND T1/2 IN HOURS	ADULT T1/2 IN HOURS
PHENOBARBITAL	0-5 DAYS -----       200 5-15 DAYS----          100 1-30 MONTHS----        50	64-140
PHENYTOIN	0-2 DAYS----         80 3-14 DAYS----         18 14-50 DAYS----          6	12-18
DIGOXIN	60-70	30-60

DRUG EXCRETION: LOW GLOMERULAR FILTERATION RATE IN NEONATES (30-40% OF ADULTS) --- T_1/2 OF DRUG INCREASES THAT EXCRETED THROUGH G.F.R E.G. GENTAMICIN.                                                                 

2. TUBULAR TRANSPORT IS IMMATURE------tubular secretion is prolonged by 3-5 times e.g. penicillin

DRUGS THAT DEPEND ON RENAL FUNCTION FOR ELIMINATION ARE CLEARED FROM THE BODY VERY SLOWLY IN THE IST WEEK OF LIFE.

DOSE OF AMPICILLIN FOR A NEONATE LESS THAN 7 DAYS OLD	50-100 MG/KG/D IN TWO DOSAGES AT 12 HOUR INTERVAL
DOSE OF AMPICILLIN FOR A NEONATE OVER 7 DAYS OLD	100-200 MG/KG/D IN THREE DOSAGES  AT 8 HOUR INTERVAL
DOSE OF GENTAMICIN FOR A NEONATE LESS THAN 7 DAYS OLD	5  MG/KG/D IN TWO DOSAGES  AT 12 HOUR INTERVAL
DOSE OF GENTAMICIN FOR A NEONATE OVER 7 DAYS OLD	7.5 MG/KG/D IN THREE DOSAGES  AT 8 HOUR INTERVAL