Drug Therapy Across the Lifespan

Why is pediatric pharmacology research limited?

Most studies use adult samples or healthy children due to reluctance among parents & less funding

What percentage of drugs have federally approved indications for children?

50%

What happens to drug absorption as children age?

Absorption becomes more effective → dosage + administration adjustments

What factors could slow absorption in adolescents? (3)

• Poor nutrition

• Changes in physical maturity

• Hormones (adolescence)

Considerations for oral absorption in children and adolescents? (3)

• GI motility unpredictable

• GI enzymes may be immature/inadequate

• Normal flora vary in breast v. formula-fed babies

Consideration for topical application in children and adolescents?

Skin is thinner → drugs more readily absorbed (monitor for toxicity)

Factors affecting drug distribution? (3)

• Body fluid & tissue composition

• Protein-binding capability

• Effectiveness of barriers to drug transport

How does fluid composition in neonates/infants affect drug concentrations?

75% water → greater volume to distribute water → lower drug concentrations

How does protein concentrations affect distribution in neonates/infants?

Decreased protein concentrations → higher levels unbound drug and increased toxicity risk

Role of the BBB in infants/neonates?

BBB relatively immature → drugs pass easily into CNS → toxicity risk

Where does metabolism primarily occur in neonates/infants? Consideration?

Primarily in liver (small kidney/lungs role) → consider hepatic blood flow & drug-metabolizing enzymes

What does excretion primarily occur in neonates/infants? Consideration?

Primarily renal but GFR in neonates is roughly 30% of what adults have → monitor renal function + drug effectiveness

Consideration for chronological v. developmental age?

Developmental age → ability to understand drug process, reason, & need to cooperate

Factors of family-centered care to promote? (2)

• Allow family to assist in drug administration when possible & safe

• Teach family to help identify therapeutic & adverse effects (know patient best)

Define principle of Atraumatic Care

Eliminate/minimize distress experienced by children + families

Atraumatic care measures? (4)

1. Decrease separation from family

2. Identify patient/family stressors

3. Decrease pain (topical anesthetics)

4. Maintain collaborative partnership

Physical pharmacology considerations for adolescents? (4)

• Height-to-weight proportions & BSA

• Secondary sex characteristics

• Physical maturity

• BMR (increased BMR → increased sleep required)

Cognitive pharmacology considerations for adolescents? (2)

• Move from concrete to abstract thinking → more questions

• Development of decision-making skills → give autonomy

Emotional pharmacology considerations for adolescents? (4)

• More risk taking and peer influence

• Risky behaviors (alcohol/tobacco/drugs) → potential interactions

• Confidentiality with family/caregivers

• Increased self-care responsibilities → autonomy for med admin

Key takeaways for adolescent pharmacology? (2)

• Monitor for Therapeutic effect + Adverse reactions

• Dosing based on weight/BSA, age, organ function, health, & route

Dosing consideration for older adults?

Start low & go slow

Physiologic change with total body water + lean mass in adults?

TBW & lean mass reduced → increased body fat

Changes in kidneys with older adults? And the liver?

Reduced kidney mass & blood flow → reduced GFR → reduced clearance of drugs by kidneys; Liver → reduced size + blood flow → reduced clearance

Incidence of adverse effects in older adults + examples? (4)

Higher incidence

• BP meds → orthostatic hypotension

• Diuretics → volume depletion + electrolyte imbalances

• Antidiabetics → altered glycemic response

• NSAIDs → GI irritated

Factors affecting absorption in older adults? (4)

• Decreased smell bowel surface area

• Slowed gastric emptying

• Reduced gastric blood flow & gastric acid production

• Swallowing difficulties & poor nutrition

How does muscle & fat effect drug distribution in older adults?

Decline in muscle → 20-40% fat increase → liquid soluble drugs greater volume of distribution, storage, reduced elimination, & prolonged period of action

How does total body water effect drug distribution in older adults?

10-15% reduction in TBW + 10% albumin reduction → decreased protein binding & increased free dug → increased toxicity risk

Key drug metabolism changes in older adults?

Decreased hepatic first-pass → prolonged half-life → increased drug levels & toxicity; monitor liver enzymes (decreased activity)

Key drug excretion changes in older adults?

Decreased renal size/volume → prolonged half-life → elevated drug levels

Key CV & CNS receptor change in older adults + outcome?

Decreased number of receptors → reduced response to beta-blockers & beta2 agonists

Key blood-brain barrier change in older adults?

Reduced blood flow to brain → more permeable BBB → increased CNS side effects

Key compensatory reflex change in older adults + outcome?

Compensatory reflexes decline → orthostatic hypotension & falls

Key risk factors for polypharmacy? (3)

• Female sex

• Use of herbal therapies & OTC meds

• Increased number of hospitalizations & care transitions

Key consequence of polypharmacy?

Geriatric syndromes → cognitive impairment, falls, urinary incontinence, p injuries, weight loss

Define Beer’s criteria

Evidence-based information to guide decision-making for drug therapy in older adults

Key exception for Beer’s criteria?

Does NOT apply to hospice or end-of-life care situations

Key examples of Beer’s criteria meds? (3)

• Diphenhydramine → CNS effects

• Ibuprofen

• Ketorolac (IV NSAID) → GI issues

How common are ADEs in older adults?

Older adults 7x more likely to be hospitalized due to ADEs

Most common ADE causing meds for older adults? (5)

• Blood thinners (bleeds)

• Diabetes meds (hypoglycemia)

• Seizure meds (many interactions)

• Cardiac meds (ortho hypotension)

• Pain control meds (sedation)

5 types of ADEs?

• Adverse drug reactions

• Med errors

• Therapeutic failures (i.e. underdosing)

• Adverse withdrawal events

• Overdoses

Key risk factors for ADEs? (4)

• Frailty

• Comorbidities

• Polypharmacy

• Cognitive issues

Most common cause for lack of drug adherence in older adults? + Outcome?

Fail to ask questions → lack of understanding and precise following → underdosing or overdosing