Principles in Geriatric & Pediatric Pharmacology Flashcards
How do the pharmacodynamics of drugs change as you age?
The pharmacodynamic actions of drugs at receptor sites of action DO NOT differ substantially across age groups, i.e., plasma drug levels [Cpss (avg)] necessary for therapeutic effects are equivalent and thus dosage adjustments beyond those necessary for age-related size differences (mg/kg basis) are NOT generally necessary (although some important exceptions exist
How do the pharmacokinetics of drugs change as you age?
The physiological factors relevant to the pharmacokinetic disposition of drugs DO change substantially with development and aging, as necessarily will the metabolism and excretion [CL] of said drugs.
Recognition of these changes is essential for the proper adjustment of dosage regimens [MD (maintenance dose) and tau (dosage interval)] in order to avoid underdosage or overdosage of the very young and very old patient populations.
Rate of absorption (time to peak) may be changed with aging, but extent of absorption (i.e., bioavailability) usually not changed much with most medication
Is absorption different in kids?
By 1 year of age differences between adults and children are not substantial.
How do loading doses of drug change with age?
They don’t
Volume of Distribution: Body proportions and fat distribution change with age, but the effect of these changes on volumes of distribution are relatively insignificant for most drugs. Thus, loading doses of drugs change little with age.
How is hepatic metabolism different for pediatric pts?
Hepatic metabolism matures as a function of postnatal age and is highly variable
Hepatically eliminated drugs have clearances that vary more widely in children than in adults
Hepatic metabolism at birth is poor relative to adults, but rates of development of individual metabolic pathways to adult or greater than adult capacities are variable and unpredictable.
Renal excretion in kids
Renal clearance of drugs is more predictable in children and less interindividually variable. In general, renally excreted drugs are more rapidly cleared in children than in adults.
How are maintenance doses different in children?
Maintenance doses of drugs may change dramatically with age.
In general, drugs are cleared more rapidly in children (i.e., school age through puberty) than in adults and maintenance doses (calculated on mg/kg/day basis) are often higher than encountered in adults.
Drug Dosing and Administration for pediatric patients
Medication dosing for infants and children should be based on weight (mg/kg) or body surface area (mg/m2).
NOTE: In general, even for very large children, doses should not exceed the maximum adult dose.
Always administer oral liquid medications via a calibrated medication syringe, dropper, or cup. A kitchen teaspoon can range from 2 ml to 10 ml in volume and result in significant over- or underdosage.
Never mix medications in a bottle of milk or formula. Failure to consume entire bottle would result in failure to deliver entire dose.
Use caution with medication dosage forms. Example: acetaminophen infant drops (80 mg/0.8 ml) vs acetaminophen children’s suspension (160 mg/5 ml)
Drug Reactions Specific to Children
Anti-inflammatory corticosteroids: potent inhibitors of growth
CNS stimulants utilized in ADHD: may have modest effects of decreased growth
Tetracyclines: Incorporated into calcifying bone, cartilage, and teeth. Staining is not permanent in tissues that are remodeled (bone and cartilage) but is permanent in teeth which are not remodeled.
Salicylates: contraindicated because of Reyes Syndrome (fatty liver with acute encephalopathy) through an incompletely understood interaction with common childhood viral infections (especially chicken pox and influenza)
Barbiturates: can impair intellectual development
Changes in volume of distribution associated with aging
Body composition changes associated with aging, in general, are a relative decrease in total body water and lean body mass and a relative increase in adipose tissue.
Changes in volume of distribution (Vd) include:
Decrease in Vd for relatively water soluble drugs resulting in higher plasma concentrations if normal adult doses are given (e.g., digoxin, aminoglycoside antibiotics, lithium)
Increase in Vd for relatively lipid soluble drugs resulting in prolonged elimination (increased half-life) and drug accumulation (e.g., chlordiazepoxide, diazepam)
Changes in Vd associated with aging may require dosage adjustments to prevent toxicity in the elderly
How is hepatic metabolism different for geriatric pts?
In general, decrease in hepatic blood flow and decreased enzymatic activity
No adequate marker exists to determine hepatic drug metabolizing capacity and necessary dosage adjustments are difficult to determine. Thus, titration of doses to achieve desired response is important.
If a choice exists among agents in a therapeutic class between those metabolized via phase I pathways and those metabolized by phase II pathways, those drugs undergoing phase II metabolism will be more reliably eliminated in the elderly (e.g., lorazepam or oxazepam are preferred over diazepam / chlordiazepoxide).
Renal excretion in the elderly
In general, decreased GFR
Renal dosing (i.e., dosage adjustments based on CrCl) should be routinely considered in elderly patients receiving drugs that are primarily eliminated by the kidney to prevent toxic accumulations
Preventing Adverse Drug Events in the Elderly – Screening Tools
The “Beers List”: defines explicit criteria for determining potentially inappropriate medication use in the elderly (> 65 years old). Drugs are categorized as medications to avoid or to use within dose and duration ranges in the elderly OR medications to avoid in elderly patients with specific concomitant diseases
The STOPP (Screening Tool of Older Person’s potentially inappropriate Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment) criteria address some of the concerns with the beers list. These lists can be used to identify red flags that might require intervention, not as the final word on medication inappropriateness.
Drug-Induced Functional Impairments in mobility to consider in the elderly (supporting structure, movement disorders, balance, falls)
Supporting structure (arthralgias, myopathies, osteoporosis): worsened by corticosteroids, phenytoin, heparin, decrease vitamin D intake
Movement disorders (extrapyramidal disorders): worsened by antipsychotic agents, metoclopramide (block of dopamine receptors)
Balance:
-Tinnitus, vertigo: worsened by aspirin, aminoglycosides, ethacrynic acid
- Hypotension: worsened by beta-blockers, calcium channel blockers, diuretics, vasodilators, antidepressants
- Psychomotor retardation: worsened by benzodiazepines, antihistamines, antipsychotic agents, antidepressants
Falls: One-third of persons 65 years old who live in the community fall each year; leading cause of non-fatal injuries and hospital admissions
- Psychotropic medications double the risk of falls – benzodiazepines are most problematic, esp. longer-acting agents and higher doses. “Z” drugs (zolpidem) are safer choices for treatment of insomnia in elderly.
- Tricyclic antidepressants and meperidine-methadone also increase fall risk
Drug-induced incontinence problems to consider in the elderly
Overflow (from urinary retention):
- Worsened by anticholinergic agents, agents with anticholinergic side effects (tricyclic antidepressants, antihistamines, typical antipsychotic agents), smooth muscle relaxants, α -adrenergic agonists.
- Treated with: α-adrenergic antagonists [tamsulosin]
Stress (from urethral sphincter insufficiency unmasked by coughing, sneezing, lifting):
-Worsened by α-adrenergic antagonists (prazosin, doxazosin).
Urge (from detrusor hyperreflexia with sphincter dysfunction):
- Worsened by cholinergic drugs, diuretics
- Treated with: antimuscarinic agents [tolterodine]
Can be secondary to oversedation with sedatives or hypnotics
