Obinoscopy:
PEDIATRIC PHARMACOLOGY
Children takes drugs thus we need to take special consideration of how the drug works in their body. The way drug works in kids is different from the way it works in an adult. This is because as the organs and systems within the child develops (ontogeny), the pharmacokinetics and pharmacodynamics of drugs changes.
When a child is born until he gets to 1 month he/she is called a neonate. Then from 1 month to 24 months (2 years) he/she is called an infant. From 2 years till 12 years he is called a child. Adolescents are those from 12 years till 18 years. I personally don't see Adolescents as Children but I see them as young adults. Thus my focus will be mostly on those less than 12 years (neonates, infants and children).
Like I said earlier, the organs and systems of a child undergoes different developmental changes from birth till maturity. This changes affect drug disposition when consumed by the child. The most dramatic changes occur in the first 18 months of life. Organs such as the liver and the kidney which play a very critical role in drug metabolism are not fully functional at birth. Also the activities of enzymes such as CYP450 and UGT isoforms is not at maximum. Thus we need to be careful when administering drugs affected by the liver or kidney or the enzymes (CYP & UGT) such as erthromycin, saquinavir, ritonavir, codeine, carbamazepine, etc. to children. A typical example of a pharmacokinetic consideration due to altered renal drug clearance in newborns and infants is in the adminstration of gentamicin. Gentamicin is given every 18-24 hours in neonates and every 6 hours in young children. This is as opposed to how its given to adolescents and young adults (given 8 hourly).
Another factor that contributes to the different drug disposition in kids is the poorly developed Blood Brain Barrier (BBB). Some drugs are crosses the BBB very easily while others don't. Thus this must be taken into consideration when treating a child.
It is also worthy of note that the volume of distribution (Vd) is increased in Infants of 6 months or less. This needs to be taken into account when administering drugs to kids.
The GIT of children is different from those of an adult. For example, gastric pH changes during ontogeny (stomach pH is higher than the adult value due to the immaturity of parietal cells). This is the reason why peroral bioavailability of acid-labile drugs such as penicillin, ampicillin is increased and peroral bioavailability of weak organic acids such as phenobarbital, phenytoin is reduced in kids. Also gastric emptying time is prolonged throughout infancy and childhood due to reduced motility. This delayed emptying time can affect the absorption of drugs with limited water solubility (phenytoin, carbamezepine). Neonates and young infants have problem absorbing fat-soluble vitamins because they don't have adequate bile acids.
ADVERSE DRUG REACTION IN CHILDREN
Drugs can cause adverse reactions when taken by adults and children. This is especially so in children as they don't fully have the body mechanism to deal with these drugs the way adult does. A child is susceptible to ADR indirectly in the womb or during lactation (due to maternal drug exposure) or directly when given a medication.
An example of ADR from maternal drug exposure is the neonatal abstinence syndrome due opioids. Example of ADRs that occur in children are Reyes Syndrome (caused by Aspirin), Serum Sickness (caused by cefaclor), cutaneous toxicity (caused by lamotrigine), hepatotoxicity (caused by valproic acid or paracetamol), cartilage and tendon toxicity (caused by fluoroquinolones).
DRUG USE DURING LACTATION
As I said earlier, a child can indirectly be exposed to a drug during lactation. Fortunately, the concentration of drug achieved in the breast is usually low for most drugs. For these drugs, it is advised that the mother continues breast feeding the child as the benefit of breast feeding outweights the risk. This is because it is known that formula feeding is associated with higher infant morbidity and mortality. For example, in developing countries, HIV mothers who are taking anti-retrovirals should still breast feed their children. This is because the risk of exposing the child to the HIV virus and to the HIV drugs is low compared to the risk of the child dying from not being breast fed.
However there are some drugs that are not to be taken during lactation because they are present in large toxic concentration in the breast milk. These drugs are amiodarone (can affect the child's thyroid function), chloral hydrate (cause drowsiness in the child), chloramphenicol (bone marrow suppression), heroin/methadone (neonatal narcotic dependence), radio active iodine (thyroid suppression), tetracycline (teeth staining), atenolol, niroprusside, clonidine, guanfacine (hypotension), etc.
The following drugs have minimal effect during lactation and thus can be taken by the nurisng mother. They include: penicillins, isoniazid (must be taken with pyridoxine supplement), acyclovir, aspirin, paracetamol, ibuprofen, antacids, albendazole, caffeine, warfarin, oral contraceptives, propranolol, metoprolol, labetalol, enalapril, captopril, methyldopa, nifedipine, amlodipine, cholorothiazide, spironolactone, hydralazine, digoxin chlorpromazine, etc. It is advisable to take the drugs 30 - 60 minutes after breast feeding and 3 - 4 hours before the next feeding.
It is worthy of note that even the drugs that present in large toxic concentration in breast milk can be taken by the lactating mother if prescribed by the doctor. This is especially if the drug is taken for a very short period of time and the mother and baby are properly monitored. Also the drug clonidine has been used off-label as a single post partum dose as a neuraxial analgesia.
Antibiotics such as penicillins, cephalosporins, macrolides and metronidazole are mostly safe. Tetracyclins and flouroquinolones are not safe and should be taken only if benefit outweighs risk and if taken for a short period of time under prescription and proper monitoring of the physician.
Antimalarials such as artesunate, artemether, lumefantrine, quinine, chloroquine are safe to be taken by lactating mothers. They can be taken for prophylaxis or treatment. Also the child being breastfed should be given antimalarials if he has the signs/symptoms. However care should be taking when giving these antimalarials to lactating mothers who's breastfeeding children weighs less than 5kg.
POSOLOGY
People make the mistake of viewing children as little adults. They make adjustments to the dose for a child based on his age (Young's Rule) or weight (Clark's Rule). This is wrong as it may lead to under- or over-dosage. A more reliable way of calculating drug dosage for a child is based on his/her surface area. Aside the surface area, it is important to know the differences in the child's metabolic system compared to an adult as this will enable the doctor and/or the pharmacist to determine the accurate dosage for the child.
Reference
Briggs , Freeman RK, Yaffe SJ: Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th ed. Wolters Kluwer/Lippincott Williams & Wilkins, 2015.
de Wildt SN et al: Ontogeny of midazolam glucuronidation in preterm infants. Eur J Clin Pharmacol 2010;66:165.
Katzung BG, et al. Basic and Clinical pharmacology, 12 edn. McGraw-Hill, 2012.
Kliegman R, et al. Nelson textbook of pediatrics (Edition 20.). Phialdelphia, PA: Elsevier, 2016.
Koren G. Medication Safety during Pregnancy and Breastfeeding; A Clinician’s Guide, 4th ed. McGraw-Hill, 2006.
So guys this is my piece on pediatric pharmacology. I might do a little writeup on diabetes and hypertension in children as an offshoot of this piece. But that will be at a latter date. Please feel free to let me know if I made any mistake in my writeup as I am not perfect and am amenable to learning. Thanks. nice bro Keep the good work up! |
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