PECULIARITIES OF DRUG PECULIARITIES OF DRUG THERAPY IN PEDIATRICS THERAPY IN PEDIATRICS

AND GERONTOLOGYAND GERONTOLOGY

DRUG EFFECTS ON THE FETUSThe fetus, which is exposed to any drugs circulating in maternal blood, is very sensitive to drug effects because it is small, has few plasma proteins that can bind drug molecules, and hasa weak capacity for metabolizing and excreting drugs. Once drug molecules reach the fetus, they may cause teratogenicity (anatomic malformations) or other adverse effects.

DRUG EFFECTS ON THE FETUS

Drug teratogenicity is most likely to occur when drugs are taken during the first trimester of pregnancy, when fetal organs are formed. For drugs taken during the second and third trimesters, adverse effects are usually manifested in the neonate (birth to 1 month) or infant (1 month to 1 year) as growth retardation, respiratory problems, infection, or bleeding.

The gestational clock showingthe classic teratogenic risk assessment.

(Adapted from Niebyl, J. [1999])

Effects of nontherapeutic drugsAlcohol is contraindicated during

pregnancy; no amount is considered safe. Heavy intake may cause fetal alcohol syndrome, a condition characterized by multiple congenital defects and mental retardation.

Caffeine. Although ingestion of moderate amounts has not been associated with birth defects, spontaneous abortions, preterm

births, and low birth weights have occurred. In addition, high doses may cause cardiac dysrhythmias in the fetus.

Effects of nontherapeutic drugs

Cigarette smoking. Effects includeincreased fetal, neonatal, and infant

mortality; decreased birth weight and length; shortened gestation; and increased complications of pregnancy (eg, placental abruption, spontaneous abortion; preterm delivery). These effects are attributed to decreased flow of blood and oxygen to the placenta and uterus.

Effects of nontherapeutic drugs

Cocaine, marijuana, and heroin are illegal drugs of abuse, and their use during pregnancy is particularly serious.

Cocaine may cause maternal vasoconstriction, tachycardia, hypertension, cardiac dysrhythmias, and seizures. These effects may impair fetal growth, impair neurologic development, and

increase the risk of spontaneous abortion during the first and second trimesters.

FETAL THERAPEUTICSAlthough the major concern about drugs ingested

duringpregnancy is adverse effects on the fetus, a few

drugs are given to the mother for their therapeutic effects on the fetus.

These include digoxin for fetal tachycardia or heart failure, levothyroxine for hypothyroidism, penicillin for exposure to maternal syphilis, and prenatal corticosteroids to promote surfactant production to improve lung function and decrease respiratory distress syndrome in preterm infants.

NEONATAL THERAPEUTICSIn the neonate, any drug must be used

cautiously. Drugs are usually given less often because they are metabolized and excreted slowly. Immature liver and kidney function prolongs drug action and increases risks of toxicity.

Also, drug therapy should be initiated with low doses, especially with drugs that are highly bound to plasma proteins. Neonates have few binding proteins, which leads to increased amounts of free, active drug and increased risk of toxicity.

NEONATAL THERAPEUTICSAt birth, some drugs are routinely administered to preventhemorrhagic disease of the newborn and ophthalmianeonatorum. Hemorrhagic disease of the newborn occursbecause the intestinal tract lacks the bacteria that

normallysynthesize vitamin K. Vitamin K is required for liver

production of several clotting factors, including prothrombin.

Thus, the neonate is at increased risk of bleedingduring the first week of life. One dose of phytonadione0.5 to 1 mg is injected at delivery or on admission to thenursery.

NEONATAL THERAPEUTICS

Ophthalmia neonatorum is a form of bacterial conjunctivitisthat may cause ulceration and blindness. It may be caused by several bacteria, most commonly Chlamydiatrachomatis, a sexually transmitted organism. Erythromycin

ointment 0.5% is applied to each eye at delivery.

It is effective against both chlamydial and gonococcal infections.

Pediatric drug therapyMost medications are commercially available only in adult dose forms. Preparing pediatric doses from adult tablets or capsules can be very difficult and may require special skill on the part of the pharmacist. For some drugs it is simpler to administer the intravenous (IV) preparation orally than to develop a preparation from the oral medication.

Pediatric drug therapyIV drug administration is most effective in children when given via a pump infusion system close to the site of IV insertion. Because of the small size of many pediatric doses and the fact that some drugs adhere to IV tubing, a significant percentage of the drug can be lost if it is given using techniques usually reserved for adults.For many prematures and newborns, the volume of administration is also critical and therefore much more easily managed by IV infusion pumps.

Pediatric drug therapyChildren with chronic illnesses require special

consideration.Patients with cystic fibrosis have increased hepatic

metabolism and therefore increased drug clearance.This may necessitate the administration of increased drug dosages.

Calculation of pediatric dosages is usually done on

the basis of weight (e.g., milligrams per kilogram) for infants and toddlers and on the basis of weight or body surface area (milligrams per square meter) for older children.

Repeated increases in drug dosage are requiredto accommodate for growth in children receivingchronic drug therapy.

SUMMARY Drug administration must be tailored

to meet the unique needs of children at their varied stages of development.

Special attention must be given to unexpected drug actions and adverse reactions in these patients, who are maturing at variable rates.

DRUG DISPOSITION IN GERIATRICPATIENTS

It is difficult to predict the response among 80-year-olds.

It is apparent that an increase in life span is accompanied by an increase in chronic illnesses such as hypertension, congestive heart failure, arthritis, and diabetes. The pharmacological management of these conditions, especially when the same person has several diseases, becomes increasingly complex.

Physiological changes in elderly patients, when taken together, may contribute to impairments in drug clearance

GERIATRICPATIENTS. Adverse Drug

Effects Inappropriate drug use has been noted in

almost half of hospitalized elderly patients. One-fourth of these patients were receiving

contraindicated drugs, and three-fourths were receiving unnecessary drugs.

Delirium and cognitive impairment are common adverse reactions in the elderly.

The risk increases with the number of drugs the patient is receiving, reaching a 14-fold increase in risk for patients taking more than 6 drugs.

GERIATRICPATIENTS. Special

Considerations Drugs should be prescribed only if

nonpharmacological techniques are ineffective, such as for problems like sleeplessness and anxiety.

When drugs are prescribed for these conditions, they should be given for a limited time and the patient closely monitored for adverse effects.

GERIATRICPATIENTS. Special

ConsiderationsNoncompliance is a significant problem, with almost 50% of elderly patients failing to take their medications as prescribed. Some of the reasons for noncompliance are inability to pay for the drug, side effects, mental impairment, and inability to understand complex instructions.