Module 3 - Special Considerations: Pediatrics, Pregnancy/Lactation, Older Adults
N609

Describe the differences in pharmacokinetics among pregnant women, neonates, children, and adults.
Describe the unique challenges neonatal and pediatric patients pose to the medication system, including drug selection and dosages.
Explain the potential and strategies for the prevention of medication errors in neonatal and pediatric patients.
Identify strategies to determine safe medication use in pregnancy based on available literature.
Determine the drug-related factors that would help guide safe and effective medication use in breast- feeding women.

Effect on a drug's absorption, distribution, metabolism, and excretion based on the ongoing maturation and development in pediatric patients or the altered physiologic changes in the mother.
Interpatient variabilities may be attributed to physiologic changes throughout childhood or pregnancy.
Short- and long-term effects that the prescribed drug will have on a pediatric patient's growth and development.

The placental-fetal unit, which affects the amount of drug that crosses the placental membrane, the amount of drug metabolized by the placenta, and the distribution and elimination of the drug by the fetus.
Effects of underlying congenital, chronic, or current diseases on the prescribed drug, and vice versa.

Changes in pediatric patient's body proportions and composition
Relative size of the liver and kidneys
Changes in intracellular and extracellular body water, fat, and protein

Gastric pH
Gastric emptying time and surface area
Gastrointestinal enzymes and microorganisms

Rectal absorption
Intramuscular and subcutaneous absorption
Percutaneous absorption
Mucosal absorption
Pulmonary absorption

Vascular perfusion
Body composition
Tissue-binding characteristics
Physicochemical properties
Plasma protein binding
Route of administration

Two phases of drug metabolism in the liver
Phase I: oxidation, reduction, and hydrolysis reactions
The P-450 cytochrome (CYP) is the most important component.
Phase II: conjugation reactions
Phase II glucuronidation reaction is deficient in neonates and infants.

Glomerular filtration rate (GFR; passive diffusion)
GFR increases quickly during the first 2 weeks of postnatal life and does not approach adult rates until age 2.
Plasma clearance of many drugs via the kidneys is altered.
Tubular secretion (energy-dependent channels or pumps)
Rates do not reach adult values until age 5 to 7 months.

A health care practitioner is prescribing penicillin for an infant. Which age-related factor should be considered when dosing drugs for this population?
A. Tubular secretion is decreased in infants.
B. Cardiac output to the kidney is increased in infants.
C. Tubular reabsorption rates are increased in infants.
D. GFR approaches adult rates at 6 months of age.

A. Tubular secretion is decreased in infants.
Rationale: Decreased tubular secretion in neonates and infants can lengthen the elimination half-life of antibiotics, such as the penicillins and sulfonamides. Tubular secretion and reabsorption rates do not reach adult values until age 5 to 7 months, and the GFR increases quickly during the first 2 weeks of postnatal life but does not approach adult rates until age 2. This immaturity of the renal system in neonates and infants results from restricted blood flow and a resultant decrease in cardiac output to the kidneys.

Placental transfer of medications
Placental and fetal metabolism
Fetal physiology
Teratogenicity of medications

Human breast milk as a drug delivery system
Blood flow to the breast
Plasma pH (7.45) and milk pH (7.08)
Mammary tissue composition
Breast milk composition
Physiochemical properties of the drug
Extent of drug-protein binding in plasma and breast milk
Rate of breast milk production

Risks and benefits
Long-term effects
Dosage formulation
Dosage
Obesity

Determine the patient type (i.e., neonate, pediatric, and adolescent).
Assess the appropriateness of the drug therapy selected in this patient type, patient population, and/or disease state.
Establish the appropriate dose, route, formulation, and frequency based on the recommended references mentioned in the following section.
If all resources have been exhausted or further information is needed, contact a pharmacist.

An oncologist is calculating a dosage of an antineoplastic drug for a child. What is the best basis for an accurate dosage for this patient?
A. Weight
B. Concurrent drug therapy
C. Body surface area (BSA)
D. Stage of development

C. Body surface area (BSA)
Rationale: Although body weight-based dosing is the most common method for pediatric dosing, drug dosages based on a patient's BSA are usually used for antineoplastic agents or critically ill patients. BSA correlates closely with many factors that influence drug elimination, including cardiac output, respiratory metabolism, blood volume, extracellular water volume, GFR, and renal blood flow.

A health care practitioner is prescribing an aerosol medication for a 3-year-old with asthma. What device would be most appropriate for this patient?
A. Breath-actuated metered-dose inhaler (MDI)
B. Dry-powder inhaler
C. Valved holding chamber (VHC) + face mask
D. MDI without spacer or VHC

C. Valved holding chamber (VHC) + face mask
Rationale: A VHC with a face mask is appropriate for a patient under 4 years old. A breath-actuated MDI is used for a patient 5 years or older. A dry-powder inhaler is appropriate for a 4-year-old or older, and a metered-dose inhaler without a spacer or valved holding chamber is appropriate for a patient 5 years or older.

Describe the various physiological changes that occur in the older adult that affect pharmacokinetic and pharmacodynamics responses.
Identify at least four drugs that are problematic to use in the older adult.
Discuss safe prescribing practices for the older adult.
Describe the behavioral and psychological symptoms of dementia.

Unique physiology
Multiple chronic comorbid conditions (polypharmacy)
Cognitive and social issues affecting adherence
Lack of testing of pharmaceuticals for this population

Falls
Fractures
Delirium

Oropharyngeal muscle dysmotility and altered swallowing
Reduction in esophageal peristalsis and lower esophageal sphincter pressure
Delayed motility and gastric emptying
Decreased propulsive motility of the colon
Decreased gastric secretion
Impairment of the mucous-bicarbonate barrier

Muscle shifts to increased fat stores.
Body water content decreases.
Serum albumin is reduced by approximately 20% leading to increase in free drug concentration of some drugs.
Change in serum proteins causes potential toxicity.
Body mass changes lead to changes in body content of drugs.
Increase in Vd can lead to increased half-lives and drug accumulation.

Decrease in hepatic blood flow and size of liver
Decrease in phase I metabolism, particularly oxidation causing decreased total body clearance; however, phase II metabolism by conjunction not affected by age
Decrease in renal blood flow and drop in glomerular filtration rate

When prescribing drugs for an older adult, what factor affecting elimination of drugs does NOT need to be considered?
A. The kidney is the major organ of drug metabolism for older adults.
B. Phase II metabolism of drugs by conjugation
C. Aging produces an increase in hepatic blood flow.
D. Increased oxidation of drugs occurs with aging.

B. Phase II metabolism of drugs by conjugation
Rationale: The phase II metabolism of drugs by conjugation, which promotes drug elimination by breaking the drug into water-soluble components, is not affected by age. The liver is the major organ of drug metabolism in the body. With aging comes a decrease in blood flow and liver size. Decreased oxidation of drugs results in a decreased total body clearance.

Increased central nervous system effects of drugs
Increased sedative effects of agents
Changes in cardiovascular system may occur causing orthostatic hypotension
Risk for syncopal episode with drugs lowering blood pressure

Varied symptoms and complaints associated with multiple chronic illnesses
Pressure on practitioner to "prescribe something"
Prescribing cascade
Patient stockpiling of medications
Patients sharing medications
Polyproviders
Self-prescribing of over-the-counter medications by patients

Alcohol and recreational drugs
The combination of comorbid conditions, physiological changes with age, and concomitant medications is often potentiated with alcohol and drug usage.
Caffeine and nicotine use
Caffeine and nicotine are among some of the most commonly used products that have the potential to interact with certain drugs, thereby altering efficacy and therapeutic drug levels.

Cost factors
Side effects
Physical and mental changes
Self medication issues

Falls and medication
Antipsychotics
Anxiolytics
Antidepressants
Other disorders and drug therapies

Prevent initiation of inappropriate use of psychotropic medications in residents.
Taper and discontinue inappropriate psychotropic medications, to ensure that use of the medications is appropriate and that monitoring and documentation are properly conducted.
Improve disruptive behaviors while limiting/diminishing the use of psychotropic medications, by educating and encouraging prescribers and nursing facility staff to adopt a more structured and broader approach to management of behavioral symptoms.

Establishing daily routines in a structured environment
Consistently providing the same caregiver for bathing and hygiene assistance
Avoiding overstimulation from activities
Limiting social visits
Scheduling quiet time with rest or naps

Severe or persistent pain
Urinary incontinence, urinary tract infections (UTIs)
Respiratory infections
Constipation

Beer's criteria
Choosing wisely initiative
"Things Providers and Patients Should Question"
AMDA-The Society for Post-Acute and LTC Medicine

Dementia and behavioral and psychological symptoms of dementia (BPSD)
Screening and medication management
Antibiotic use
Diabetes management
Nutritional management

Not prescribing cholinesterase inhibitors without periodic assessment for cognitive and gastrointestinal (GI) effects
Assessing the use of chemical and physical restraints
Not using antipsychotic medications for BPSD in individuals with dementia as first choice or without an assessment for an underlying cause of the behavior
Not using benzodiazepines or other sedative-hypnotics as first choice for insomnia, agitation, or delirium
Avoiding use of physical restraints for hospitalized older adults when delirium was called out

A health care practitioner is caring for an older patient diagnosed with dementia. Which measure is appropriate for this patient?
A. Ordering physical restraints to prevent falls
B. Ordering antipsychotic medication for BPSD as first-line therapy
C. Periodically assessing a patient who is taking a cholinesterase inhibitor
D. Treating insomnia with benzodiazepines

C. Periodically assessing a patient who is taking a cholinesterase inhibitor
Rationale: Cholinesterase inhibitors should not be used for dementia without periodic assessment for perceived cognitive benefits and adverse GI effects. Antipsychotic medications should not be prescribed for BPSD in individuals with dementia as first choice or without an assessment for an underlying cause of the behavior. Physical and unnecessary chemical restraints such as treating insomnia with benzodiazepines should be avoided if possible.

Screening and medication management
Antibiotic use
Diabetes management
Nutritional support
Exploring alternatives to medication
Simplifying the regimen
Educating adults and caregivers
Reviewing medications

Which action by the interdisciplinary team member is appropriate for an older adult diagnosed with dementia?
A. Not using chemical restraints to manage symptoms of dementia.
B. Using antibiotics only when bacterial infection is clearly indicated.
C. Requesting urine analysis frequently for early treatment of UTI.
D. Using sliding scale insulin (SSI) for diabetes management.

B. Using antibiotics only when bacterial infection is clearly indicated.
Rationale: Both the American Geriatrics Society and AMDA recommend not to use antimicrobials to treat bacteriuria in older adults unless specific urinary tract symptoms are present. Chemical restraints should be used to manage symptoms of dementia. Urine analysis should not be requested unless there is a clear indication of bacterial infection. Diabetes should be managed through the use of HgbA1c target and regularly scheduled antidiabetic medications thus avoiding SSI.

Three quotes summarize best practice:
"Any symptom in an elderly patient should be considered a drug side effect until proved otherwise"
Medications in older adults should "start low and go slow".
"A medication only works if the patient takes it"

Arcangelo, V. (2022). Pharmacotherapeutics for Advanced Practice: A Practical Approach. 5th ed.
Wolters Kluwer. Philadelphia, PA