geriatric and pediatric pharm Flashcards
define age ranges for premature, neonatal, infants, children, adolescents, geriatric
Premature: born before 37 weeks gestational age. Neonatal: 1 day-1 month. Infants: 1 month-1 year. Pediatric - children 1-11 years. Adolescent: 12-16 years. Geriatric: > 65 years
pediatric absorption
By 1 year of age, adult-child differences NOT substantial
pediatric volume of distribution
Body proportions and fat distribution change with age, but effect on Vd for most drugs is relatively minor. Loading doses change little
pediatric hepatic metabolism- list phase 1 pathways and when they reach adult levels
CYP1A2: 4-5 months. CYP2C9: teens (<30% at birth). CYP2D6: 10 years (no activity at birth). CYP3A4: 1 year (30-75% at birth).
List substrates for CYP1A2, CYP2C9, CYP2D6 and CYP3A4
CYP1A2: caffeine, theophylline. CYP2C9: NSAIDS, Warfarin. CYP2D6: antidepressants, opioid analgesics. CYP3A4: statins, calcium channel blockers
pediatric hepatic metabolism- list phase 2 pathways and when they reach adult levels
- sulfate and glycine conjugation- at birth. 2. acetylation- 2 yrs. 3. glucuronide conjugation- 2-3 yrs (0-25% at birth). This is the cause of grey baby syndrome with chloramphenicol
pediatric renal function maturation
Adult level functioning is achieved by 5 months for renal blood flow, 6 months for tubular sec and 3 years for GFR
compare renal vs hepatic clearance of drugs in children
renal clearance is more predictable and renally excreted drugs are cleared more rapidly. Hepatic elimination varies widely in children
pediatric maintenancedoses
Drugs are cleared more rapidly in children (in general), whether eliminated via renal or hepatic processes. Maintenance doses (calculated on a mg/kg/day basis) are often higher than encountered in adults
pediatric therapeutic levels of drugs (Cp)
Therapeutic levels of drugs (Cp) in children same as adults. Calculated based on weight
drugs that affect growth in kids
Most psychoactive agents have modest effects on growth. Anti-inflammatory corticosteroids (including topical agents) are potent inhibitors of growth
drugs that affect intellectual development in kids
barbiturates
side effects of tetracyclines in kids
are incorporated into growing bone and teeth and are contraindicated in children and in pregnancy
Aspirin side effects in kids
not recommended for use in children prior to puberty because of risk for hepatic dysfunction: Reyes syndrome- fatty liver with acute encephalopathy. Aspirin interaction with chicken pox and influenza
List drugs that have potential for life threatening sx in young children
Benzonatate, iron, antidepressants, antipsychotics, antimalarials, antiarrythmics, Ca channel blockers, sulfonylurea hypoglycemics, opioids, acetaminophen, diphenhydramine
geriatric changes in absorption
Rate of absorption changes slightly but extent of absorption (bioavailability) is unchanged. increased gastric pH, decreased absorptive surface, splanchnc blood flow, GI motility and gastric emptying rate
geriatric changes in distribution
decreased cardiac output, hepatic/ renal blood flow, body fat (changes volume of distribution), total body water, relative tissue perfusion and albumin
geriatric changes in metabolism
decreased liver mass, hepatic blood flow and enzyme activity (changes clearance rate)
geriatric changes in excretion
decreased renal blood flow, decreased GFR (changes clearance), tubular secretion and renal mass
how does decreased gastric acid affect drug absorption in geriatrics
- Decrease in absorption of weak acid drugs (e.g., warfarin, penicillin). 2. Increase in absorption of weak base drugs (e.g., TCADs, benzodiazepines, opioid analgesics, anticonvulsants). 3. Inappropriate (early) release of enteric-coated drugs (e.g., aspirin)
List disease which may affect absorption
CHF: slowed or reduced absorption. Gastroparesis: decreased gastric emptying and GI motility
list drugs/ drug properties which may affect absorption
- drugs that decrease gastric emptying/ motility- anticholinergics like diphenhydramine and TCADs. 2. drugs that increase gastric emptying/ motility- metoclopramide, cisapride, stimulant laxatives. 3. drugs that decrease absorption by interacting in the guy- ie. cholestyramine binds warfarin
drugs which have a decreased Vd in geriatrics
Water soluble drugs will have decreased Vd due to decreased total body water. This increases plasma concentrations of these drugs. Ie. digoxin, aminoglycosides, lithium. This may lower the loading dose
drugs which have an increased Vd in geriatrics
lipid soluble drugs have increased Vd due to increased body fat. This causes slower elimination, increased half life and drug accumulation. Ie. Chlordiazepoxide and diazepam. May require lower maintenance dose
How do geriatric serum albumin levels affect distribution
decreased albumin Can result in increase in free (active) drug concentrations of highly protein bound drugs like phenytoin, phenobarbital, warfarin and diazepam.
describe drug metabolism in general
lipophilic drug undergoes phase 1 enzyme action (CYP450) to form hydrophilic less active compound. This then undergoes phase II glucuronidation or conjugation to form highly water soluble, inactive substrate
how do phase I and phase II reactions change in geriatrics
Phase I reactions (oxidation, reduction, hydrolysis) decrease with age in 30-35% of elderly patients. Drugs like chlordiazepoxide and diazepam will have an increased plasma half life. Phase II reactions (conjugation, glucuronidation) are minimally affected by aging. This includes lorazepam, oxazepam, temazepam
Which benzodiazepams are preferred in elderly
Lorazepam / oxazepam are preferred over diazepam / chlordiazepoxide due to their phase II metabolism
Dosing of renally excreted drugs in geriatrics
Drugs eliminated primarily by the kidneys will accumulate in the presence of renal impairment. Use renal dosing based on creatinine clearance
equation for creatinine clearance
[(140-age) x (Kg) x 0.85 (females)] / (serum creatinine x 72)
Beers criteria
Addresses inappropriate drugs regardless of diagnosis- conditions OR drug use in certain diagnosis-condition for elderly patients.
Worst drugs from the Beers criteria
amitriptyline, diazepam, doxepin
Beers criteria- drugs to avoid in HTN
pseudoephedrine, methylphenidate
Beers criteria- drugs to avoid syncope or falls
benzos, TCADs
List drugs that worsen arthralgias, myopathies and osteoporosis
Worsened by corticosteroids, phenytoin, heparin-warfarin, decreased vitamin D intake
list drugs that worsen movement disorders
Worsened by dopamine receptor blockers: antipsychotic agents, metoclopramide
list drugs that worsen tinnitus and vertigo
Worsened by aspirin, aminoglycosides, ethacrynic acid
list drugs that worsen hypotension
Worsened by beta-blockers, calcium channel blockers, diuretics, vasodilators, antidepressants
list drugs that worsen psychomotor retardation
Worsened by benzodiazepines, antihistamines, antipsychotic agents, antidepressants
receptors involved in urination
GO: stimulate Muscarinic receptors (bladder and neck), block alpha 1 receptors (trigone). Stop: block M or stimulate alpha1, Beta2 or 3 (bladder)
list drugs that worsen urinary retention and overflow
Worsened by anticholinergic agents, agents with anticholinergic side effects (tricyclic antidepressants, antihistamines, typical antipsychotic agents), smooth muscle relaxants, a -adrenergic agonists. Treated with tamsulosin (flomax), a alpha-adrenergic antagonist
List drugs that worsen stress incontinence
a-adrenergic antagonists (prazosin, doxazosin)
list drugs that worsen urge incontinence due to detrusor hyperreflexia (overactive bladder)
Worsened by cholinergic drugs for dementia (AChEIs), diuretics. Treated with: antimuscarinic agents [tolterodine]
List drugs that worsen constipation
Worsened by opioid analgesics, antimuscarinic agents, 1st gen antihistamines (esp. diphenhydramine), CCBs- verapamil
List drugs that cause metabolic alterations leading to mental state dysfunction
Metabolic alterations with beta-blockers, corticosteroids, diuretics, sulfonylureas
list drugs that cause cognitive impairment
opioid analgesics, cimetidine, propranolol, antipsychotic agents, anticonvulsants, BDZs
list drugs that cause behavioral toxicity
anticholinergics, cimetidine, l-dopa, digoxin, opioid analgesics, β-blockers, corticosteroids
