Chapter review

Fitzgerald PMHNP board review. ch17. Prescribing in the Older Adult: Doing More by Doing Less. This is drive 1 of 4. When I say Pause. Answer. wait, then I will give the answer. New section. Aging PK/PD changes that change psychotropic choice and dose. Topic. Pharmacokinetic Alterations: Fat and Water Distribution. FITZGERALD CH17 — Prescribing in the Older Adult: Doing More by Doing Less. Aging PK/PD changes that change psychotropic choice and dose. Pharmacokinetic Alterations: Fat and Water Distribution. Bottom Line. - Total body water decreases by 10% to 15% in older adults, while total body fat increases by 20% to 40%. - Hydrophilic (water-soluble) psychotropics like **lithium** distribute into a smaller volume of distribution, producing higher peak serum concentrations and elevated toxicity risk at standard adult doses. - Lipophilic (fat-soluble) psychotropics like **diazepam**, **chlordiazepoxide**, and long-acting antipsychotics distribute into an expanded fat mass, significantly increasing their volume of distribution. - An increased volume of distribution for lipophilic drugs prolongs their elimination half-life, leading to drug accumulation, daytime somnolence, cognitive slowing, ataxia, and falls. - Serum albumin levels often decrease in frail older adults, reducing protein binding for highly bound drugs like **valproate** and increasing the active free drug concentration. - Always follow the clinical rule to start low and go slow, initiating lipophilic and hydrophilic psychotropics at 50% of the standard young adult starting dose while titrating to therapeutic targets. Spoken Teaching: Fat and Water Distribution Dynamics. As the human body ages, physiological composition undergoes a predictable shift characterized by a loss of lean muscle mass and total body water, accompanied by a relative increase in total body fat. These structural changes fundamentally alter drug distribution, which is the movement of a absorbed drug throughout body fluids and tissues. For water-soluble or hydrophilic medications, the primary distribution space is total body water. Because an older adult has significantly less total body water, a standard dose of a hydrophilic drug distributes into a smaller fluid compartment. This restriction leads to a higher initial serum concentration. **Lithium** is the classic high-yield board example of a hydrophilic psychotropic. When initiating **lithium** in an older adult, the reduced volume of distribution, combined with age-related declines in estimated glomerular filtration rate below 60 mL/min, causes rapid spikes in serum lithium levels. A dose that produces a therapeutic level of 0.8 mEq/L in a 30-year-old can easily precipitate neurotoxicity, delirium, coarse tremors, and ataxia in a 75-year-old. For fat-soluble or lipophilic medications, the clinical challenge is the exact opposite. Most psychotropic medications, including benzodiazepines, tricyclic antidepressants, and second-generation antipsychotics, are highly lipophilic. Increased adipose tissue in older adults acts as a massive tissue reservoir. Lipophilic molecules rapidly leave the bloodstream and dissolve into fat stores. This vast expansion in the volume of distribution means that while peak plasma levels may appear lower initially, the drug remains sequestered in fat tissue for an extended period. As plasma concentrations eventually drop, the drug slowly leaches back out of adipose storage into the circulation. This reservoir effect dramatically extends the elimination half-life of lipophilic agents. A classic board scenario involves long-acting lipophilic benzodiazepines like **diazepam** or **chlordiazepoxide**. In a young adult, **diazepam** has an elimination half-life of 20 to 50 hours. In an 80-year-old adult, that same drug's half-life can stretch beyond 90 to 120 hours. Daily dosing causes severe tissue accumulation over several days or weeks. The patient does not experience simple anxiety relief; instead, they develop drug-induced delirium, psychomotor slowing, daytime sedation, gait instability, and hip fractures. Protein binding further modifies distribution. Many psychotropics bind tightly to serum albumin. In healthy community-dwelling older adults, albumin levels remain relatively stable, but in malnourished, chronically ill, or institutionalized older adults, serum albumin drops. With fewer albumin binding sites available, a higher percentage of the drug remains unbound or free. Because only free drug can cross the blood-brain barrier and exert pharmacological effects or toxicity, drugs like **valproate** or **diazepam** can produce toxic clinical effects even when total serum drug levels fall within the normal laboratory reference range. Signposts and Board Pearls. First-line. When a benzodiazepine is clinically required in an older adult, select short-acting agents that undergo direct glucuronidation and have lower lipid solubility, specifically **lorazepam**, **oxazepam**, or **temazepam** (remembered by the mnemonic LOT). These agents do not accumulate in fat tissue to the same extent and do not depend on declining hepatic CYP450 phase I oxidation. Safety Alert. **Lithium** toxicity occurs at lower serum concentrations in older adults due to reduced total body water and decreased renal clearance. Always obtain baseline renal function (eGFR and serum creatinine) before starting **lithium**, start at low doses such as 150 mg to 300 mg daily, and maintain target geriatric serum levels between 0.4 and 0.6 mEq/L rather than standard adult targets. Board Trap. Questions often describe an older adult taking a lipophilic psychotropic who presents with new confusion, slurred speech, and frequent falls. Test-writers design distractors that prompt you to order neuroimaging for stroke or diagnose Alzheimer disease. The board trap is failing to recognize drug accumulation from an expanded volume of distribution. The correct initial action is to review the medication list and taper or discontinue the accumulating lipophilic agent. Sample Practice Questions. Question 1. An 81-year-old female is brought to the clinic by her daughter due to progressive confusion, excessive daytime drowsiness, and two near-falls over the past week. Review of records shows she was prescribed **diazepam** 5 mg twice daily for generalized anxiety three weeks ago. Her physical exam demonstrates mild ataxia but no focal neurological deficits. What age-related pharmacokinetic change is primarily responsible for her symptoms? A. Increased total body water leading to accelerated renal clearance B. Decreased total body fat leading to a reduced volume of distribution C. Increased total body fat leading to an increased volume of distribution and prolonged elimination half-life D. Increased serum albumin concentration leading to excessive protein binding Pause. Answer: C. Why it is correct: Older adults experience an age-related increase in total body fat and a decrease in total body water. Highly lipophilic medications like **diazepam** distribute extensively into expanded adipose tissue, markedly increasing their volume of distribution. This sequesters the drug and significantly prolongs its elimination half-life, causing systemic accumulation, prolonged CNS depression, confusion, ataxia, and elevated fall risk. Why the other choices are wrong: - A: Total body water decreases with age, not increases, and water volume primary impacts hydrophilic rather than lipophilic drug distribution. - B: Total body fat increases with aging, which expands rather than reduces the volume of distribution for lipophilic drugs. - D: Serum albumin concentrations decrease or remain unchanged in older adults; an increase in albumin would decrease free active drug fractions rather than increase them. Test-taking pearl: Lipophilic psychotropics in older adults accumulate in expanded adipose tissue, dramatically extending elimination half-life and causing toxicity that mimics neurocognitive decline. Question 2. A 76-year-old male with bipolar I disorder is evaluated for maintenance therapy. His baseline laboratory work reveals an eGFR of 52 mL/min and normal liver function tests. The PMHNP considers initiating **lithium**. When planning therapy, how does the patient's age-related change in body composition influence **lithium** pharmacokinetics? A. Decreased total body water reduces the volume of distribution, causing higher peak serum levels. B. Increased total body fat expands the volume of distribution, delaying therapeutic onset. C. Decreased total body fat accelerates hepatic metabolism via CYP3A4 pathways. D. Increased total body water expands the volume of distribution, requiring higher starting doses. Pause. Answer: A. Why it is correct: **Lithium** is a hydrophilic (water-soluble) ion that distributes exclusively in total body water. Because total body water decreases with advancing age, the volume of distribution for **lithium** is significantly reduced. Consequently, standard doses produce higher peak serum concentrations, increasing the risk of acute neurotoxicity and renal impairment unless lower starting doses are used. Why the other choices are wrong: - B: **Lithium** is not lipophilic and does not distribute into adipose tissue, so body fat changes do not alter its distribution volume. - C: **Lithium** is not metabolized by hepatic CYP450 enzymes; it is excreted unchanged by the kidneys. - D: Total body water decreases rather than increases with age, which shrinks the volume of distribution and necessitates lower, not higher, starting doses. Test-taking pearl: Hydrophilic drugs like **lithium** distribute into smaller fluid volumes in older adults, producing higher serum concentrations per milligram given and requiring lower starting doses. Next. Topic. Renal Function: eGFR vs. Serum Creatinine. Bottom Line Summary. * **Serum creatinine** remains deceptively normal in older adults due to age-related loss of muscle mass, masking a renal function decline of up to 30 percent or more. * **eGFR** (estimated glomerular filtration rate) is the gold standard metric for evaluating renal clearance and driving psychotropic dosing decisions in geriatric patients. * **eGFR greater than 60 mL/min** indicates adequate renal clearance where most psychotropics require no dosage adjustment. * **eGFR less than 60 mL/min** defines moderate renal impairment that requires dose reduction or drug switching for renally cleared psychotropics, including **lithium**, **gabapentin**, and **paliperidone**. * **eGFR less than 30 mL/min** represents severe renal impairment requiring significant dose decreases or complete avoidance of renally excreted psychotropics. * **Lithium** toxicity risk increases dramatically in older adults when renal clearance drops, requiring frequent lab monitoring of eGFR and serum drug levels. High-Yield Concept Review. Renal Assessment in Geriatric Psychopharmacology. Age-related physiological changes significantly alter pharmacokinetics in older adults. Decreased renal blood flow, reduced glomerular filtration, and loss of functional nephrons decrease drug excretion. Serum creatinine is produced by muscle breakdown. Because older adults experience age-related sarcopenia, serum creatinine production drops. As a result, an older adult can have a normal serum creatinine level despite a 30 percent reduction in actual renal clearance [1, 2]. Dosing Thresholds by eGFR Level. * **eGFR greater than 60 mL/min**: Standard psychotropic dosing is generally safe source 3. * **eGFR 30 to 50 mL/min**: Moderate clearance reduction [4, 5]. Reduce starting doses of renally cleared medications by 25 to 50 percent or select hepatically metabolized alternatives. * **eGFR less than 30 mL/min**: Severe clearance reduction. Avoid **lithium** if possible, or use extreme caution with reduced doses and frequent blood level monitoring [4, 5]. Compare and Distinguish: eGFR vs. Serum Creatinine. Serum Creatinine * **Fast mental label**: Deceptive muscle breakdown marker source 1. * **Geriatric limitation**: Normal values mask significant renal impairment due to low muscle mass [1, 2]. * **Boards are testing**: Why you should never rely on serum creatinine alone in older adults [1, 2]. eGFR (Estimated Glomerular Filtration Rate) * **Fast mental label**: True renal clearance metric [2, 6]. * **Geriatric value**: Accurately reflects functional nephron clearance regardless of muscle mass source 2. * **Boards are testing**: The primary lab value used to adjust renally excreted psychotropics [3, 4]. Exam Signposts. Safety Alert. Relying solely on serum creatinine in an older adult can lead to severe psychotropic toxicity source 1. Medications like **lithium** accumulate rapidly when renal clearance declines, causing tremors, confusion, ataxia, seizures, and neurotoxicity even when serum creatinine appears normal source 4. Board Trap. Test writers frequently present an elderly patient with a normal serum creatinine of 0.8 mg/dL alongside an **eGFR** of 45 mL/min [1, 2]. The trap choice advises standard adult dosing of **lithium** based on the normal creatinine source 1. The correct board decision requires dosing adjustments based on the decreased **eGFR** [4, 5]. First-Line Approach. Always evaluate **eGFR** before initiating or titrating renally excreted psychotropic medications in geriatric patients [2, 3]. Sample Practice Question. Question 1. A 76-year-old woman with a history of bipolar disorder presents for a medication review. Her laboratory results show a serum creatinine of 0.9 mg/dL and an eGFR of 42 mL/min. Which of the following is the most appropriate PMHNP intervention regarding her **lithium** therapy? A) Maintain standard adult lithium dosing because her serum creatinine is normal. B) Increase the lithium dose to achieve rapid therapeutic stabilization. C) Reduce the lithium dose or switch to an alternative agent due to reduced eGFR. D) Discontinue all laboratory monitoring since her serum creatinine indicates normal renal function. Pause. **Answer**: C **Why it is correct**: An eGFR of 42 mL/min indicates moderate renal impairment requiring dose reduction or drug switching for renally cleared medications like **lithium** [4, 5]. Normal serum creatinine in older adults is misleading due to reduced muscle mass [1, 2]. **Why the other choices are wrong**: * **A**: Fails because normal serum creatinine masks reduced renal clearance in older adults with decreased muscle mass [1, 2]. * **B**: Fails because increasing the dose in moderate renal impairment causes severe drug accumulation and **lithium** toxicity source 4. * **D**: Fails because eGFR reveals decreased renal function, requiring ongoing monitoring rather than stopping lab checks [2, 4]. **Test-Taking Pearl**: In older adults, always check eGFR rather than serum creatinine to evaluate renal clearance before prescribing renally eliminated psychotropics [2, 3]. 💡 **Next Study Step**: Would you like to review geriatric hepatic changes and the CYP450 isoenzyme considerations for older adults next? Next. Topic. Liver Metabolism: CYP450 Enzyme Changes. Bottom Line Summary. - **Hepatic blood flow** decreases by 20% to 50% in older adults, while overall liver mass decreases by 20% to 40%. - **Phase I metabolism** involving CYP450 oxidation, reduction, and hydroxylation decreases significantly with age, prolonging drug elimination half-lives and raising toxicity risks. - **Phase II metabolism** involving glucuronidation, acetylation, and sulfation remains largely preserved in normal aging. - **LOT benzodiazepines** (**lorazepam**, **oxazepam**, **temazepam**) undergo Phase II glucuronidation directly and bypass Phase I CYP450 oxidation, making them preferred when benzodiazepine therapy is unavoidable. - **CYP2D6 inhibition** by **fluoxetine** and **paroxetine** blocks the breakdown of co-administered substrates like **metoprolol**, causing severe bradycardia, hypotension, and falls. - **First-pass hepatic extraction** is reduced in older adults, which increases the oral bioavailability and peak plasma concentrations of highly extracted psychotropics. - **Prescribing strategy** requires starting at 25% to 50% of standard adult starting doses and titrating slowly while monitoring for polypharmacy interactions. High-Yield Concepts and Signposts. Aging Liver Physiology. - **Hepatic mass**: Decreases by 20% to 40% in older adults, reducing overall metabolic capacity. - **Hepatic blood flow**: Decreases by 20% to 50%, reducing first-pass clearance and increasing systemic bioavailability. - **Serum liver enzymes**: AST, ALT, and alkaline phosphatase remain in normal ranges in healthy aging; elevations signal primary liver pathology rather than normal age-related changes. Phase I vs Phase II Liver Metabolism. Phase I Metabolism (Oxidation) - **Mechanism**: Utilizes CYP450 isoenzymes for oxidation, reduction, hydroxylation, and demethylation. - **Aging effect**: Significantly reduced due to decreases in liver mass, perfusion, and enzyme activity. - **Clinical impact**: Slower drug clearance, prolonged elimination half-life, and drug accumulation. - **Affected drugs**: **diazepam**, **alprazolam**, **chlordiazepoxide**, **flurazepam**, tertiary TCAs, and **fluoxetine**. Phase II Metabolism (Conjugation) - **Mechanism**: Converts drugs into water-soluble metabolites via glucuronidation, acetylation, and sulfation. - **Aging effect**: Preserved and minimally altered by normal aging. - **Clinical impact**: Predictable clearance without significant accumulation. - **Preferred drugs**: **lorazepam**, **oxazepam**, and **temazepam** (the LOT benzodiazepines). Signposts. - **Safety alert**: **fluoxetine** and **paroxetine** are potent CYP2D6 inhibitors. Co-prescribing them with CYP2D6 substrates like **metoprolol**, **carvedilol**, or **risperidone** blocks substrate clearance, causing elevated drug levels, severe bradycardia, profound hypotension, and falls. - **Safety alert**: Long-acting benzodiazepines cleared by Phase I oxidation (**diazepam**, **chlordiazepoxide**) accumulate in geriatric adipose tissue, causing prolonged sedation, ataxia, confusion, and hip fractures. - **Board trap**: Selecting **diazepam** or **alprazolam** for an elderly patient who requires short-term anxiolysis. Boards expect you to select **lorazepam**, **oxazepam**, or **temazepam** because they bypass Phase I oxidation. - **Board trap**: Assuming normal AST and ALT levels indicate youthful hepatic drug clearance in an older adult. Liver enzymes measure acute cellular injury, not functional metabolic clearance rate. - **First-line**: For depression in older adults, choose SSRIs with minimal CYP450 inhibition such as **sertraline** or **escitalopram** (or **citalopram** with a maximum dose of 20 mg daily to avoid QTc prolongation). Avoid **fluoxetine** due to its long half-life and **paroxetine** due to anticholinergic effects and CYP2D6 inhibition. Compare and Distinguish. Phase I Oxidation vs Phase II Conjugation - **Think**: Phase I decreases with age; Phase II is preserved. - **Priority**: Choose Phase II cleared medications to prevent drug accumulation in older adults. - **Boards are testing**: Recognition that LOT benzodiazepines (**lorazepam**, **oxazepam**, **temazepam**) bypass age-related CYP450 oxidation decline. - **Mini example**: An 82-year-old patient needs short-term anxiolysis. Select **lorazepam** over **diazepam** because **lorazepam** undergoes Phase II glucuronidation. CYP2D6 Inhibitors (**fluoxetine**, **paroxetine**) vs Low CYP450 Inhibitors (**sertraline**, **escitalopram**) - **Think**: High CYP450 inhibition causes severe drug interactions; low CYP450 inhibition is safe in polypharmacy. - **Priority**: Avoid **fluoxetine** and **paroxetine** in older adults taking cardiac or psychotropic co-medications. - **Boards are testing**: Selecting SSRIs based on drug interaction profiles in geriatric polypharmacy. - **Mini example**: A 76-year-old taking **metoprolol** develops major depression. Choose **sertraline** instead of **fluoxetine** to prevent CYP2D6 inhibition and severe bradycardia. Sample Board Practice Questions. Question 1. A 78-year-old male with a history of hypertension and mild cognitive impairment requires short-term pharmacological management for acute anxiety. He has age-related declines in hepatic Phase I oxidation. Which medication is most appropriate because its clearance relies on Phase II glucuronidation? - A. **diazepam** - B. **lorazepam** - C. **alprazolam** - D. **chlordiazepoxide** Quick Answer. **lorazepam** is the best choice because it undergoes Phase II glucuronidation, which remains intact in older adults. Key Clue. The phrase "declines in hepatic Phase I oxidation" indicates the need for a Phase II conjugated benzodiazepine. Best Answer. B. **lorazepam** Why It Is Correct. **lorazepam**, along with **oxazepam** and **temazepam**, is cleared exclusively through Phase II hepatic glucuronidation. Phase II conjugation pathways are preserved in aging, preventing drug accumulation, excessive sedation, and ataxia. Why the Other Choices Are Wrong. - A. **diazepam** undergoes Phase I CYP2C19 and CYP3A4 oxidation, generating active long-acting metabolites that accumulate and cause falls. - C. **alprazolam** requires Phase I CYP3A4 oxidation, which is impaired in older adults, leading to prolonged elimination half-life and toxicity. - D. **chlordiazepoxide** is a long-acting benzodiazepine cleared by Phase I oxidation that accumulates in geriatric fat tissue and carries a high risk of delirium. Test-Taking Pearl. Remember the LOT mnemonic (**lorazepam**, **oxazepam**, **temazepam**) for benzodiazepines that bypass Phase I oxidation and are safer in geriatric patients. Concept Tested. Geriatric hepatic metabolism and Phase II glucuronidation. Question 2. An 81-year-old female taking **metoprolol** for hypertension is started on **fluoxetine** 20 mg daily for major depressive disorder. Three weeks later, she presents to the emergency department after a fall. Vital signs reveal a heart rate of 44 beats per minute and a blood pressure of 86/52 mmHg. Which pharmacokinetic mechanism explains this clinical presentation? - A. **fluoxetine** induces CYP2D6, lowering **metoprolol** blood concentrations. - B. **fluoxetine** potent CYP2D6 inhibition blocks **metoprolol** clearance, causing toxicity. - C. **fluoxetine** displaces **metoprolol** from Phase II conjugation pathways in the kidney. - D. Age-related increases in hepatic blood flow accelerate **metoprolol** absorption. Quick Answer. **fluoxetine** inhibits CYP2D6, blocking the breakdown of **metoprolol** and causing severe bradycardia and hypotension. Key Clue. The combination of **fluoxetine** and **metoprolol** resulting in bradycardia and hypotension indicates CYP2D6 inhibition. Best Answer. B. **fluoxetine** potent CYP2D6 inhibition blocks **metoprolol** clearance, causing toxicity. Why It Is Correct. **fluoxetine** is a potent inhibitor of the CYP2D6 isoenzyme. **metoprolol** is a substrate cleared by CYP2D6. Inhibiting CYP2D6 prevents **metoprolol** metabolism, causing drug accumulation, profound bradycardia, hypotension, and subsequent falls. Why the Other Choices Are Wrong. - A. **fluoxetine** inhibits CYP2D6 rather than inducing it; induction would decrease drug levels rather than causing toxicity. - C. **metoprolol** is cleared by hepatic Phase I CYP2D6 oxidation rather than renal Phase II conjugation. - D. Aging causes a decrease in hepatic blood flow of 20% to 50%, not an increase, and hepatic flow does not directly alter absorption. Test-Taking Pearl. Avoid **fluoxetine** and **paroxetine** in older adults taking cardiovascular medications due to strong CYP2D6 inhibition. Concept Tested. CYP450 drug-drug interactions in geriatric polypharmacy. Active Recall Checkpoints. 1. What percentage decrease in hepatic blood flow and liver mass occurs in normal aging? 2. Which liver metabolic pathway decreases significantly with age: Phase I oxidation or Phase II conjugation? 3. What three benzodiazepines make up the LOT group that bypasses Phase I oxidation? 4. Why does reduced first-pass hepatic extraction increase systemic drug exposure in older adults? 5. Which two SSRIs are potent CYP2D6 inhibitors that should generally be avoided in geriatric polypharmacy? Next Study Step. Study renal clearance changes in older adults, specifically evaluating estimated glomerular filtration rate versus serum creatinine and lithium dosing rules. - **Why this is the best next step**: Renal elimination works together with hepatic metabolism to determine total drug clearance in geriatric psychopharmacology. - **What knowledge gap it closes**: Prevents confusing liver metabolism changes with renal clearance mechanisms when adjusting psychotropic doses. - **What confusion it helps prevent on boards**: Clarifies why serum creatinine can appear normal in an elderly patient with significant renal impairment due to age-related loss of muscle mass. Next. Topic. Practice Question: Best Lab for Renal Assessment. Bottom Line Summary. * **eGFR** is the single most accurate lab metric for evaluating renal clearance in older adults. * **Serum creatinine** alone is deceptive in elderly patients because age-related loss of muscle mass reduces creatinine production, masking up to a 30% reduction in renal filtration. * An **eGFR** greater than 60 mL/min indicates adequate renal clearance for standard psychotropic dosing. * An **eGFR** below 60 mL/min requires dosage reduction, extended dosing intervals, or selecting non-renally cleared alternatives. * **Lithium** is eliminated almost entirely unchanged by the kidneys, making baseline and routine **eGFR** monitoring essential. * Other renally cleared psychotropics requiring renal dose adjustments in aging include **gabapentin**, **pregabalin**, **topiramate**, and **paliperidone**. * Dehydration, nonsteroidal anti-inflammatory drugs, and ACE inhibitors further impair renal perfusion, rapidly elevating serum levels of renally cleared drugs. High-Yield Concept Review: Geriatric Renal Assessment. Age-related physiological changes significantly alter the pharmacokinetics of psychotropic medications. Glomerular filtration rate declines progressively with age, reducing the clearance of renally excreted drugs. Serum Creatinine versus eGFR. * **Serum creatinine**: Serum creatinine is a breakdown product of skeletal muscle. Because older adults experience sarcopenia and decreased muscle mass, baseline creatinine production is reduced. Consequently, serum creatinine can remain within the normal laboratory reference range even when kidney function has dropped significantly. * **eGFR**: Estimated glomerular filtration rate incorporates age, sex, and serum creatinine to estimate actual renal clearance. It provides the true measure of functional nephron capacity. Clinical Signposts for Boards. * **First-line**: Evaluate **eGFR** as the primary lab value when assessing renal function prior to initiating renally cleared psychotropics in older adults. * **Board trap**: Assuming normal renal function based solely on a normal **serum creatinine** level in an elderly patient. Test writers use normal serum creatinine values to trick candidates into prescribing full adult doses of renally cleared medications. * **Safety alert**: Imppaired renal clearance of **lithium** leads to drug accumulation and severe **lithium toxicity**. Watch for red-flag signs including coarse hand tremors, ataxia, dysarthria, confusion, and seizures. Board Practice Question. Question 1. Question: A 72-year-old male with **bipolar I disorder** is evaluated for mood stabilizer initiation. His laboratory report shows a serum creatinine of 0.9 mg/dL. Which lab value provides the most accurate assessment of renal clearance in this older adult before prescribing **lithium**? * A. Serum creatinine * B. Blood urea nitrogen * C. Estimated glomerular filtration rate * D. Urine specific gravity Pause. Answer: C. Why it is correct: Estimated glomerular filtration rate is the gold standard lab metric for evaluating renal function in older adults. Sarcopenia and loss of muscle mass in aging decrease creatinine production, maintaining normal serum creatinine levels even when renal filtration is significantly reduced. Why the other choices are wrong: * A. Serum creatinine alone misleads clinicians in geriatric patients because reduced muscle mass masks underlying renal impairment. * B. Blood urea nitrogen fluctuates with hydration status, dietary protein intake, and gastrointestinal bleeding, making it unreliable for measuring renal clearance. * D. Urine specific gravity evaluates urine concentration and hydration state rather than glomerular filtration capacity. Test-taking pearl: Always look for **eGFR** rather than **serum creatinine** when assessing renal clearance in older adults on board exams. Concept tested: Geriatric renal assessment and **eGFR** interpretation. Active Recall Checkpoints. * What physiological age-related change causes **serum creatinine** to remain normal despite decreased kidney function? * What **eGFR** threshold indicates the need for renal dosage adjustments or drug switching? * Which mood stabilizer is excreted unchanged by the kidneys and requires strict **eGFR** monitoring? * Which common over-the-counter pain medications decrease renal blood flow and elevate **lithium** levels? * Name two non-lithium psychotropics that require renal dose titration when **eGFR** is reduced. Next Study Step. Proceed to the next sub-topic in Chapter 17: Deprescribing and 'doing more by doing less' rules in geriatric psychopharmacology, focusing on the Beers Criteria and anticholinergic burden. Next. New section. Deprescribing and 'doing more by doing less' rules from this chapter. Topic. Deprescribing Strategy: Low Hanging Fruit. Fitzgerald Chapter 17: Prescribing in the Older Adult. Note: Fitzgerald Chapter 17 transcript is not explicitly present as a standalone workbook scan in this notebook, which covers Chapters 1 through 16. Content for this leaf is grounded strictly in matching Fitzgerald geriatric review sources in this notebook, including Chapter 14 (Older Adults), Chapter 2 (Special Topics in Psychiatric Practice), the 2019 AGS Beers Criteria, and the Prescribing in Older Adults brief lecture. Bottom Line Summary. - Deprescribing low hanging fruit targets high-risk, low-benefit medications in patients age **65 and older**, specifically **benzodiazepines**, **sedative-hypnotics**, and **anticholinergics**. - **Beers Criteria** explicitly identifies strong **anticholinergics** such as diphenhydramine, hydroxyzine, and tertiary TCAs as high risk for inducing delirium, cognitive decline, constipation, and urinary retention. - **eGFR** below **60 mL/min** requires renal dosage adjustments or drug switches for medications like **lithium**. Serum creatinine alone underestimates renal dysfunction due to age-related loss of muscle mass. - Antipsychotics carry an **FDA Black Box Warning** for increased mortality in elderly patients with dementia-related psychosis, primarily from cardiovascular events or infectious causes like pneumonia. - Polypharmacy, defined as taking **5 or more** daily medications, significantly increases the risk of prescribing cascades, drug interactions, and fall-related fractures. - Deprescribing **benzodiazepines** requires a gradual dose reduction over weeks to months to prevent acute withdrawal symptoms, seizures, and severe rebound hyperarousal. - Non-pharmacological behavioral modifications and environmental adaptations are **first-line** for sleep disturbances and behavioral symptoms of dementia prior to considering psychotropics. High-Yield Concept Map: Deprescribing Low Hanging Fruit. What It Is. Deprescribing low hanging fruit refers to the systematic identification and discontinuation of easily recognizable, high-risk, low-benefit medications in older adults. It focuses on drugs listed on the **Beers Criteria** that lack strong clinical indications and present high potential for severe adverse events. Target Medication Classes. - **Benzodiazepines** and **Z-drugs** (zolpidem, zaleplon, eszopiclone): High risk for motor impairment, ataxia, falls, fractures, delirium, and severe cognitive decline. - **Anticholinergics** (diphenhydramine, hydroxyzine, amitriptyline, benztropine, oxybutynin): High anticholinergic burden leading to acute confusion, memory disruption, dry mouth, constipation, and urinary retention. - **Antipsychotics** used for non-emergent behavioral management in dementia: Elevated mortality risk and metabolic or extrapyramidal adverse effects. - **Duplicate Therapies**: Co-prescribing multiple agents within the same drug class without clinical rationale. Priority Clinical Rules. - **First-line**: Implement non-pharmacological sleep hygiene or behavioral interventions before initiating any psychotropic medication in older adults. - **Safety alert**: Antipsychotic administration in elderly patients with dementia-related psychosis carries an **FDA Black Box Warning** for increased mortality. - **Safety alert**: Anticholinergic toxicity can mimic worsening dementia or acute delirium. Always audit the medication list for OTC anticholinergics before ordering new psychiatric workups. - **Board trap**: Relying solely on serum creatinine to assess renal function in an elderly patient. Reduced muscle mass keeps serum creatinine deceptively low despite significant renal impairment. Always utilize **eGFR** or calculated creatinine clearance. Compare and Distinguish. Benzodiazepines vs SSRIs in Older Adults. - Think Benzodiazepines: High-risk low hanging fruit that causes ataxia, cognitive impairment, dependence, and fall fractures. Avoid for insomnia and chronic anxiety in older adults. - Think SSRIs: Preferred first-line agents for anxiety or depression in older adults (sertraline, escitalopram). Monitor for hyponatremia and SIADH. - Priority: Discontinue or taper benzodiazepines while initiating safer non-anticholinergic agents if chronic treatment is indicated. Serum Creatinine vs eGFR in Geriatric Dosing. - Think Serum Creatinine: Inaccurate standalone indicator of renal function in older adults due to decreased muscle mass masking renal decline. - Think eGFR: The gold standard metric for assessing geriatric renal clearance. - Priority: Adjust doses or switch renally cleared psychotropics when **eGFR** falls below **60 mL/min**. Anticholinergic Delirium vs Primary Neurocognitive Disorder. - Think Anticholinergic Delirium: Acute onset of confusion, disorientation, dry mucous membranes, and urinary retention following medication changes or OTC antihistamine use. - Think Primary Neurocognitive Disorder: Gradual, progressive decline in cognitive domains over months to years without acute physiological toxidrome features. - Priority: Deprescribe the offending anticholinergic agent immediately before diagnosing primary cognitive decline. Board-Style Practice Questions. Question 1. An 81-year-old female living in an assisted living facility is evaluated for worsening memory loss and acute urinary retention over the past ten days. Her medical history includes mild cognitive impairment and osteoarthritis. A review of her home medications reveals she recently began taking over-the-counter diphenhydramine 25 mg at bedtime for insomnia. Physical examination reveals dry mucous membranes and lower abdominal distension. Which action represents the PMHNP's priority intervention? A) Order a non-contrast CT scan of the head B) Discontinue diphenhydramine and provide sleep hygiene education C) Initiate donepezil 5 mg daily for Alzheimer's disease D) Prescribe zolpidem 5 mg at bedtime for sleep maintenance Pause. Answer: B Why It Is Correct: Diphenhydramine is a potent anticholinergic medication highlighted on the **Beers Criteria** as a high-risk low hanging fruit agent that should be avoided in older adults. It causes acute cognitive impairment, delirium, dry mouth, and urinary retention. Deprescribing the offending anticholinergic medication and initiating non-pharmacological sleep hygiene is the **first-line** intervention. Why the Other Choices Are Wrong: - A: Ordering neuroimaging is premature before addressing a clear drug-induced anticholinergic etiology. - C: Initiating a cholinesterase inhibitor is inappropriate while the patient is actively experiencing anticholinergic toxicity from diphenhydramine. - D: Prescribing zolpidem replaces one high-risk **Beers Criteria** medication with another non-benzodiazepine hypnotic that carries significant risks of falls, delirium, and motor impairment. Question 2. A 76-year-old male with stable major depressive disorder is being considered for lithium therapy due to inadequate response to prior antidepressant trials. Laboratory evaluation reveals a serum creatinine of 0.9 mg/dL. His estimated glomerular filtration rate (eGFR) is calculated at 48 mL/min. Which prescribing decision is most appropriate for the PMHNP? A) Initiate standard adult lithium dosing because serum creatinine is within normal limits B) Adjust the lithium dosage downward and monitor serum lithium levels and eGFR closely C) Avoid renal dose adjustments since age-related serum creatinine changes are expected D) Discontinue all psychiatric medications immediately due to acute renal failure Pause. Answer: B Why It Is Correct: An **eGFR** below **60 mL/min** indicates reduced renal clearance, requiring lower starting doses and vigilant monitoring of lithium levels and renal function. Serum creatinine alone underestimates renal dysfunction in older adults due to age-related loss of muscle mass. Why the Other Choices Are Wrong: - A: Standard adult dosing in the presence of an eGFR of 48 mL/min risks severe lithium accumulation and toxicity. - C: Failing to adjust dosage based on eGFR demonstrates a lack of awareness regarding geriatric pharmacokinetics and toxicity risks. - D: An eGFR of 48 mL/min represents mild-to-moderate chronic reduction in renal clearance, not acute renal failure requiring abrupt cessation of all essential psychiatric care. Question 3. An 84-year-old female with major neurocognitive disorder due to Alzheimer's disease exhibits mild verbal agitation during late evening hours at her memory care facility. She does not display aggressive behaviors, hallucination, or distress, and her physical assessment and laboratory workup are unremarkable. The facility nurse requests a prescription for quetiapine. What is the PMHNP's most appropriate response? A) Prescribe quetiapine 25 mg daily at bedtime B) Recommend non-pharmacological environmental modifications and individualized evening routines C) Prescribe haloperidol 2 mg intramuscularly for acute agitation D) Prescribe lorazepam 1 mg twice daily as needed for anxiety Pause. Answer: B Why It Is Correct: Non-pharmacological strategies are **first-line** for managing non-emergent behavioral symptoms of dementia. Antipsychotics carry an **FDA Black Box Warning** for increased mortality in elderly patients with dementia-related psychosis and should only be considered when non-pharmacological approaches fail and behaviors cause severe distress or safety risks. Why the Other Choices Are Wrong: - A: Prescribing quetiapine for mild non-dangerous agitation violates safety guidelines and exposes the patient to black box mortality risks without clear justification. - C: High-potency typical antipsychotics like haloperidol carry high risks of extrapyramidal symptoms and mortality in older adults with dementia. - D: Benzodiazepines like lorazepam are **Beers Criteria** medications that increase fall risk, ataxia, and paradoxical disinhibition in patients with dementia. Question 4. A PMHNP is reviewing the medication profile of an 80-year-old male presenting for an initial outpatient visit. The patient takes alprazolam 1 mg three times daily, clonazepam 1 mg at bedtime, sertraline 100 mg daily, and hydroxyzine 25 mg as needed for anxiety. The patient reports frequent near-falls and daytime drowsiness. What is the primary deprescribing objective for this patient? A) Abruptly stop alprazolam and clonazepam today B) Develop a structured, gradual tapering schedule to systematically discontinue the benzodiazepines and hydroxyzine C) Increase sertraline to 200 mg daily before making any medication changes D) Replace hydroxyzine with diphenhydramine for nighttime sedating effects Pause. Answer: B Why It Is Correct: The patient is experiencing significant polypharmacy and anticholinergic/sedative toxicity from duplicate benzodiazepines and hydroxyzine, leading to daytime drowsiness and near-falls. Deprescribing low hanging fruit requires systematically tapering benzodiazepines slowly to avoid withdrawal while discontinuing high-risk anticholinergics. Why the Other Choices Are Wrong: - A: Abrupt cessation of chronic benzodiazepines can trigger life-threatening withdrawal seizures, delirium, and severe rebound hyperarousal. - C: Increasing the sertraline dose does not address the immediate safety risk posed by sedatives and anticholinergics. - D: Replacing hydroxyzine with diphenhydramine replaces one potent anticholinergic with another, failing to reduce the patient's anticholinergic burden or fall risk. Next. End of this drive.