Question

1. Why is it important to take into account the growth and development stage in the administration of medicines in the child and in the old adult?

2. How are pharmacokinetics and pharmacodynamics affected in children?

3. How are pharmacokinetics and pharmacodynamics affected in the elderly?

4. Compare the pharmacokinetic and pharmacodynamic processes in the child and in the elderly.

Answer 1

1. Why is it important to take into account the growth and development stage in the administration of medicines in the child and in the old adult?

Medications that are generally safe and effective for adults may be unsafe or ineffective—or both—for some or all pediatric age groups or may require changes in dosing forms, calculations, or schedules to be safe and effective.

Basic Aspects of Developmental Pharmacology

1) The visible changes that occur as a newborn infant grows into a toddler, child, adolescent, and then a young adult are well known.

• As knowledge of the biology underlying this normal growth and development has increased, so has the recognition that these changes significantly affect the responses of growing children to medications.
• Such changes require evidence-based methods for selecting safe and effective doses of medications for children at different stages of development and for engineering appropriate delivery systems for these medications.
• Adjustments in dosing are often more complicated than simply scaling down the dose determined for adults on the basis of a child’s age or weight.

2)Once administered, drugs undergo biochemical changes that allow their absorption, distribution, metabolism, and removal from the body (processes collectively referred to as the pharmacokinetics of a drug).

• These biochemical changes may occur in the intestinal tract, liver, or other organs through the action of drug-metabolizing enzymes may facilitate absorption or elimination. (Some of these enzymes are not fully active at the time of birth, especially premature birth).
• After a drug is absorbed into the bloodstream, it can quickly move throughout the body.
• After a drug is moved or distributed throughout the body, its concentration in the blood generally decreases.
• The extent to which a drug is distributed throughout the body depends on a number of factors, including how readily it dissolves in water.

3) For drugs that are water soluble, this lowering of the concentration by dilution in body water is particularly important in premature newborns, who have proportionately more body water than do adults and older children.

4) In developing children, the individual enzymes for drug metabolism and conjugation usually do not mature at the same rate, nor does the maturation of an individual enzyme occur at a constant rate.

5) For newborns and young children, the dose of a drug is often adjusted to the child’s body weight or body surface area to take into account not only size but also the maturation of enzymes that occurs with growth.

6) As children move from infancy through childhood and adolescence, their developmental maturity, as it affects responses to drugs more closely approaches that of adults.

7) Adolescent development is, however, highly variable. The onset of puberty in children who are living in similar environments and have no medical conditions that could accelerate or delay puberty may vary by as much as 4 to 5 years.

The treatment of the elderly

Medical care for the elderly is an integral part of a general practitioner's (GPs) everyday work and is challenging for many reasons:

• Older people often experience multiple chronic diseases concurrently (comorbidity, multimorbidity) and they often have deteriorated organ function and decreased physiological reserves due to the natural aging process.
• The choice of appropriate medication for each particular disease is a complex process and can cause "therapeutic confusion", especially among younger GPs in the field.
• Elderly people are prone to develop adverse side-effects to usual dosages of medications and the side-effects are even 7 times more frequent in elderly than in younger patients.
• Moreover, in therapy for elder patients, a responsible clinician always needs to think about potential drug to drug interactions and possible compromised pharmacokinetic dynamics in the aging body.
• When prescribing drugs for the elderly, GPs should take into account the specificities of the elderly, their biological and chronological framework and should always apply the principles of rational, conservative and evidence-based pharmacotherapy.

2. How are pharmacokinetics and pharmacodynamics affected in children?

• The PHARMACOKINETICS AND PHARMACODYNAMICS of most medications, when used in children, especially neonates, differ from those in adults.
• Children exhibit different pharmacokinetics (PK) and pharmacodynamics (PD) from adults because of their immature renal and hepatic function, different body composition, altered protein binding, distinct disease spectrum, diverse behavior, and dissimilar receptor patterns.
• PK differences necessitate modification of the dose and the interval between doses to achieve the desired clinical response and to avoid toxicity.
• In addition, some medications may displace bilirubin from its protein binding sites and possibly predispose an infant to kernicterus.
• The capacity of the end organ, such as the heart or bronchial smooth muscle, to respond to medications may also differ in children compared with adults (PD effects).

. 3) How are pharmacokinetics and pharmacodynamics affected in the elderly?

Pharmacotherapy in the elderly is one of the most challenging aspects of patient care. It is important to understand the pharmacological properties of drugs in elderly patients. Different parts of pharmacokinetics such as distribution, metabolism and renal elimination are affected by age.

• Renal elimination may be measured or estimated (glomerular filtration rate), whereas other changes are difficult to measure.
• Pharmacodynamic changes with aging affect both beneficial and adverse effects in most organs.
• These age-related changes make elderly patients at greater risk of adverse drug effects.
• Adjustment in choice of drugs and dosage is advisable.
• Starting at a low dose and titrating slowly followed by careful evaluation of effects may minimise the risk of adverse effects.
• It is important to choose the lowest dose required for clinical effect.

Pharmacodynamics

• Pharmacodynamics affects not only therapeutic effects but also toxic and adverse effects. Pharmacodynamics depends on the concentration of the drug at the receptor, the response at the receptor, postreceptor events within cells and homeostatic mechanisms. All these parts of pharmacodynamics may be affected with aging.
• Usually, there is an increased sensitivity to the effects of drugs but for some drugs there is a decrease in responsiveness.
• The same plasma concentration of a drug may be associated with a higher risk of adverse effects in older patients compared to younger patients.
• All organ systems are affected by these changes.

Pharmacokinetics

• Pharmacokinetic alterations are easier to measure since they affect the plasma concentration of the drug.
• The bioavailability of a drug depends on many factors including absorption, distribution, metabolism and elimination.
• For many drugs, the facts about pharmacokinetics are based on studies on younger adults although mainly elderly patients will use these drugs.

4. Compare the pharmacokinetic and pharmacodynamic processes in the child and in the elderly.

Pharmacokinetics and pharmacodynamics are very different in children and adults. For the majority of drugs, in children as well as adults, a relationship exists between pharmacokinetics and pharmacodynamics.

• The pharmacokinetics of many drugs vary with age. For instance, because of the rapid changes in size, body composition, and organ function that occur during the first year of life, clinicians, as well as pharmacokineticists and toxicologists, are presented with challenges in prescribing safe and effective doses of therapeutic agents.
• Studies with adolescents reveal even more complexity in ding metabolism and differences in drug metabolism between the sexes.
• The therapeutic value of understanding differences in pharmacokinetics because of developmental factors thus relies on an ability to understand better the dose versus concentration versus effect profile for a specific drug in patients of various ages.
• In turn, recognition of differences in pharmacokinetics because of developmental factors can be invaluable for interpretation of data and improving and guiding the design of clinical trials on drug disposition and efficacy.