GENERAL CLINICAL PHARMACY

DRUG EFFECTS ON THE FETUS The 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 has a 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 showing the classic teratogenic risk assessment. (Adapted from Niebyl, J. [1999])

Effects of nontherapeutic drugs Alcohol 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 include increased 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 THERAPEUTICS Although the major concern about drugs ingested during pregnancy 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 THERAPEUTICS In 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 THERAPEUTICS At birth, some drugs are routinely administered to prevent hemorrhagic disease of the newborn and ophthalmia neonatorum. Hemorrhagic disease of the newborn occurs because the intestinal tract lacks the bacteria that normally synthesize vitamin K. Vitamin K is required for liver production of several clotting factors, including prothrombin. Thus, the neonate is at increased risk of bleeding during the first week of life. One dose of phytonadione 0.5 to 1 mg is injected at delivery or on admission to the nursery.

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 therapy Most 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 therapy IV 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 therapy Children 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 required to accommodate for growth in children receiving chronic 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 GERIATRIC PATIENTS 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

GERIATRIC PATIENTS. 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.

GERIATRIC PATIENTS. 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.

GERIATRIC PATIENTS. Special Considerations Noncompliance 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.