Geriatric Medication/Getting older and Medicine – Wikibooks, open books for an open world
Chapter 2: Getting older and Medicine
- Describe the pharmacokinetic and pharmacodynamic adjustments that happen with getting older and the affect of those adjustments on drug prescribing
- Outline and focus on polypharmacy within the aged together with hostile drug reactions, inappropriate use of medicines, drug-drug interactions, and drug-disease interactions
- Focus on medication that are contraindicated within the geriatric inhabitants and establish key issues in prescribing drugs that are generally used within the therapy of widespread medical circumstances and psychiatric sicknesses
- Outline polypharmacy and establish the traits and circumstances that place geriatric sufferers susceptible to polypharmacy and prescribing cascades
- Make the most of renal operate to find out protected drug dosing
- Perceive the impact of NSAIDs on renal operate
- Perceive the dangers and obvious advantages related to dietary supplements
- Be capable of stage persistent kidney illness primarily based on glomerular filtration price (GFR) and creatinine clearance (CrCl)
- Determine potentially-inappropriate drugs per the rules of Beers standards, START standards, and STOPP standards
- Describe the pharmacology/psychopharmacology and acceptable/inappropriate use of psychiatric drugs, particularly for dementia, agitation, melancholy, and anxiousness
- Determine widespread drugs used/misused within the aged with particular emphasis on antihypertensives, antipsychotics, benzodiazepines, NSAIDs, and digoxin
- Acknowledge penalties of polypharmacy within the aged
Minimizing Adversarial Drug Occasions
Geriatric sufferers typically have a number of persistent medical circumstances and are, subsequently, prescribed quite a few drugs for medical administration. Each time attainable, non-pharmacologic interventions needs to be used previous to the initiation of medicines.
A drug is outlined as any administered substance that alters regular bodily operate. An hostile drug occasion is any noxious, unintended, and undesired impact of a drug which happens at doses used for prophylaxis, prognosis, or remedy. Polypharmacy is a sample of extreme and inappropriate use of prescription and non-prescription drugs; greater than 5 drugs is taken into account polypharmacy.
Dangers for hostile drug occasions embody:
- 6 or extra concurrent persistent medical circumstances
- 12 or extra treatment doses per day
- 5 or extra prescribed or non-prescribed drugs
- prior hostile drug occasions
- low physique weight or BMI
- age over 80
- creatinine clearance lower than 50 mL/min
Over 35% of geriatric sufferers have hostile drug occasions yearly, and over 50% of those occasions are preventable and predictable. As much as one-third of hospital admissions may be attributed to hostile drug occasions.
Drug-drug interactions are the scientific response of combos of medicine that differ from anticipated results in comparison with if the medication are administered individually; that’s, how medication work together with different medication. Drug-drug interactions enhance with rising variety of medication, are mostly seen between cardiovascular and psychotropic medication, and embody confusion, hypotension, and renal failure.
Examples of drug-drug interactions embody:
- Warfarin plus NSAIDs or antibiotics can result in elevated INR values
- ACE (angiotensin changing enzyme) inhibitors plus potassium dietary supplements, spironolactone, or NSAIDs can enhance the chance of hyperkalemia
- Digoxin plus amiodarone results in elevated digoxin ranges resulting from amiodarone inhibiting the cytochrome P450 system
- Digoxin plus verapamil contributes to an elevated threat of coronary heart block
- Antipsychotic brokers with or with out fluoroquinolones can enhance the QT interval and likewise be related to sudden demise
- Clopidogrel plus proton-pump inhibitors has been proven to extend incidence of cardiovascular occasions (comparable to MI, CVA, and so forth.)
Prescribing cascades happen when uncomfortable side effects of medicine are misdiagnosed as signs of one other drawback, leading to additional prescriptions and additional uncomfortable side effects together with unanticipated drug interactions, which can result in additional misdiagnosis and additional signs.
|Instance: Prescribing cascades|
|A affected person with coronary artery illness, persistent ache, and main depressive dysfunction could also be prescribed isosorbide mononitrate (a vasodilator that metabolizes to nitric oxide) and pregabalin (a ache treatment that inhibits voltage-dependent calcium channels). Each isosorbide and pregabalin could cause orthostatic hypotension (low blood stress with altering positions) and headache. These signs could also be interpreted as new signs, relatively than uncomfortable side effects of the prescribed drugs, and new drugs comparable to sumatriptan (a serotonin receptor agonist used for the therapy of complications) and fludrocortisone (a mineralocorticoid with actions just like aldosterone utilized in individuals with adrenal insufficiency and related hypotension). Corticosteroids are related to decrease extremity edema, amongst different uncomfortable side effects, which can result in the prescribing of furosemide (a loop diuretic), which can additional contribute to orthostatic hypotension and complications. These signs could even result in the prescribing of further drugs to handle these signs.|
Non-steroidal anti-inflammatory medication (NSAIDs) can result in dyspepsia, elevated blood stress, and peripheral edema. By inhibiting prostaglandin synthesis, NSAIDs could cause dyspepsia. Elevated blood pressures happen because of afferent vasoconstriction within the glomerulus of the nephron, resulting in elevated renin secretion, in the end resulting in elevated angiotensin manufacturing and vasoconstriction. Peripheral edema happens because of elevated sodium reabsorption because of inhibiting prostaglandin synthesis. With the looks of those new signs, physicians could also be tempted to prescribe omeprazole (for dyspepsia signs), lisinopril (for elevated blood stress), and furosemide (for peripheral edema).
To summarize, the results of NSAIDs on renal operate embody:
- Afferent arterioles are constricted
- Efferent arterioles are dilated
- Decreased filtration fraction
- Juxtaglomerular equipment senses decreased filtration fraction and triggers renin launch and fluid-retaining mechanisms
- Elevated angiotensin synthesis causes hypertension
Corticosteroids can result in hyperglycemia (stimulating hepatic gluconeogenesis), elevated blood pressures (resulting from mineralocorticoid results mimicking aldosterone), and dyspepsia (resulting from inhibition of prostaglandin synthesis). Due to this fact, physicians could prescribe glucose-lowering drugs, anti-hypertensives, and proton-pump inhibitors to deal with these uncomfortable side effects.
Calcium-channel blockers, comparable to amlodipine, trigger peripheral edema (resulting from vasodilation of blood vessels, permitting third-spacing of fluid), urinary incontinence (resulting from decreased clean muscle contractility within the bladder), psychosis (resulting from interference with temper regulation), parkinsonism (reversible with stopping the drug, mechanism unclear), and hypotension (resulting from extreme vasodilation). Physicians could really feel compelled to prescribe drugs, respectively, comparable to furosemide, oxybutynin (an anticholinergic treatment), risperidone (an anti-dopaminergic treatment), carbidopa/levodopa (to extend dopamine availability within the mind), and midodrine (for hypotension).
Drug-disease interactions are vital to contemplate as a result of medication which can be useful in a single illness could also be dangerous in one other dysfunction. For instance, a affected person could also be prescribed a beta blocker for a cardiac illness. Whereas this can be useful in reducing blood stress or coronary heart price, it might probably worsen reactive airway illness (i.e. bronchial asthma) signs and likewise make it tougher for diabetics to sense hypoglycemia. Additionally, beta blockers could cause or worsen melancholy signs. Particular drug-disease interactions embody weight problems, ascites, dementia, renal illness, and liver illness. Weight problems alters the amount of distribution of lipophilic medication. Ascites alters the amount of distribution of hydrophilic medication. Renal illness and liver illness scale back the non-renal clearance and alter bioavailability of medicine predominantly metabolized by the liver and gut.
Examples of drug-disease interactions embody:
- Congestive coronary heart failure interactions with NSAIDs, thiazolidinediones, and sodium-containing drugs can all result in elevated fluid retention
- Peptic ulcer illness interactions with NSAIDs, high-dose aspirin trigger inhibition of prostaglandin synthesis and worsen peptic ulcer illness and elevated threat of GI bleeding
- COPD interactions with long-term benzodiazepines have elevated threat of confusion and respiratory melancholy
- Diabetes mellitus interactions with long-acting sulfonylureas could cause hypoglycemia
- Hypertension interactions with pseudoephedrine and amphetamines can exacerbate elevated blood pressures
- Cognitive impairment interactions with anticholinergics, antispasmodics, muscle relaxants, and CNS stimulants can all result in elevated confusion
- Urinary incontinence interactions with anticholinergic results resulting in urinary retention
- Parkinson’s illness interactions with dopamine antagonists and metoclopramide could cause parkinsonism and tardive dyskinesias in addition to exacerbate Parkinson’s illness signs (i.e. tremors)
- Falls/Syncope interactions with tricyclic antidepressants and benzodiazepines enhance threat of the identical
- Power constipation interactions with calcium-channel blockers, anticholinergics, and tricyclic antidepressants result in worsening of constipation
Dietary supplements embody nutritional vitamins, minerals, herbs, and different pure merchandise. Dietary supplements are usually not topic to growth and approval processes by the Meals and Drug Administration (FDA). Some dietary supplements can play an vital function in well being. For instance, calcium and vitamin D dietary supplements are helpful for bone well being and are sometimes prescribed for sufferers with osteoporosis. Different dietary supplements haven’t been studied extensively nor has their perceived profit been confirmed by analysis. Dietary supplements can also contribute to hostile drug occasions.
Widespread dietary supplements with uncomfortable side effects that should be thought-about in geriatric sufferers are:
- Gingko biloba: Obvious advantages are to enhance blood circulation, oxygenation, and reminiscence and application. Uncomfortable side effects embody rising bleeding threat, significantly in sufferers taking aspirin or warfarin.
- Noticed palmetto: Obvious advantages for enlarged prostate and urinary issues. Uncomfortable side effects embody interference with different hormonal therapies.
- St. John’s wort: Obvious advantages are for mild-to-moderate melancholy signs, anxiousness signs, or insomnia signs. Uncomfortable side effects embody interplay with different medication comparable to sedatives, verapamil, warfarin, and selective-serotonin re-uptake inhibitors (SSRIs)
- Garlic: Obvious advantages are for reducing ldl cholesterol. Uncomfortable side effects embody interactions with different medication.
By illustrating the potential catastrophes related to prescribing cascades, it’s important for physicians to determine the proper prognosis for which a drugs is being prescribed, decide if pharmacologic therapy is critical, think about drug-drug interactions, and stopping or lowering the dose of the newest causative agent.
A often used phrase by geriatricians (and members of different specialties) is to “begin low and go gradual” when prescribing a brand new treatment, significantly to a geriatric affected person, and to contemplate gradual dose reductions of medicines in an effort to scale back uncomfortable side effects and hostile drug occasions. One other contributing issue to prescribing cascades and polypharmacy is physicians (i.e. the first care doctor and any specialists) who don’t talk with one another. Frail older adults typically have decreased levels of cholesterol. As such, lipid-lowering drugs shouldn’t be prescribed to sufferers with a restricted life expectancy as additionally they contribute to polypharmacy.
Getting older and Pharmacology
Age-related organic and physiological adjustments should be thought-about for older adults when prescribing drugs. Pharmacodynamics and pharmacokinetics are topic to age-related adjustments.
Pharmacokinetics is the department of pharmacology that offers with the motion of medicine all through the physique and metabolism; particularly, age-related adjustments can have an effect on absorption, first-pass results, distribution, metabolism, elimination (used interchangeably with excretion), and clearance.
With regard to absorption, the motion of a drug from the location of administration to the blood, decreases in absorptive floor splanchnic blood movement, will increase in gastric pH, and slowed gastrointestinal motility are points that should be thought-about. The most typical strategies of administration of medicine are orally (PO, which means per os in Latin, or “by means of the opening”), intravenously (IV), intramuscularly (IM), or subcutaneously (SQ) in adipose tissue just below the pores and skin. There isn’t any vital change in absorption related to regular getting older, although there could also be a delay in time wanted to see an impact because of the quantity and sort of medicines taken.
Distribution describes the reversible switch of a drug from one location to a different (comparable to from the gastrointestinal tract to the systemic circulation). With getting older, there’s a lower in lean physique mass and serum albumin (the foremost drug-binding protein), elevated adipose tissue, and altered protein binding affecting the quantity of distribution (VD). Water-soluble medication turn out to be extra concentrated within the serum in consequence; fat-soluble medication can have longer half lives (comparable to benzodiazepines, for instance).
With respect to the first cross impact (the discount within the focus of a drug earlier than it reaches the systemic circulation) and metabolism, the enzymatic breakdown and biotransformation of medicine, decreases in hepatic blood movement, enzyme exercise, and enzyme inducibility needs to be thought-about. Part 1 metabolism (i.e. oxidation) is inhibited within the cytochrome P450 system (and its subsets comparable to CYP3A and CYP2D6) by drugs comparable to amiodarone, SSRIs, and fluoroquinolones and induced by anti-epileptic medication comparable to phenytoin.
Consideration of elimination, or the excretion of a drug, adjustments in renal operate, described within the coming pages, performs a major function in pharmacokinetics. It’s very often tough to foretell for people how every of those processes is affected, however basic ideas may be utilized on this dialogue. Renal operate decreases by roughly 1% per 12 months after age 40.
Pharmacodynamics is the department of pharmacology involved with the results of medicine and their mechanism of motion; age-related considerations embody therapeutic dosing and results and uncomfortable side effects. Pharmacodynamic issues embody:
- Blunted baroreceptor reflexes resulting from orthostatic hypotension resulting in an elevated threat of syncope and falls
- Decreased beta adrenoreceptor responsiveness
- Decreased dopaminergic receptors within the central nervous system (i.e. seeing parkinsonism with haloperidol)
- Elevated inhibitory results of warfarin
- Elevated sensitivity to the anticholinergic results of medicine that contributes to elevated threat of delirium and urinary retention
- Elevated central nervous system impact of benzodiazepines, opioids, and psychotropics will contribute to elevated threat of falls, confusion, and delirium
Renal clearance performs a task in drug metabolism. Each glomerular filtration price (GFR) and creatinine clearance (CrCl) are measurements of kidney operate. Although related, these two portions needs to be handled distinctly. GFR and CrCl are usually not equivalent portions! Decreased muscle mass (i.e. sarcopenia) in geriatric sufferers decreases serum creatinine.
Creatinine clearance may be calculated utilizing the Cockcroft-Gault equation:
Glomerular filtration price (GFR) is calculated utilizing a fancy equation often called the MDRD equation (Modification of Diet in Renal Disease). This equation considers intercourse, race (African-American vs. non-African-American), age, and serum creatinine; this won’t be lined right here. The estimated GFR (or eGFR) is commonly offered on laboratory research comparable to a Primary Metabolic Panel (BMP) or Renal Operate Panel (RFP).
Power kidney illness is staged by GFR ranges for no less than 3 months. In any other case, decreased GFR and elevated creatinine are attributable to acute kidney harm which ought to resolve in a brief time period. Power kidney illness (CKD) is commonly related to long-standing hypertension and may be extra accurately described as hypertensive kidney illness.
To categorise the extent of persistent kidney illness, GFR is used:
- CKD stage 1 happens when GFR is bigger than 90
- CKD stage 2 happens when GFR is between 60-90
- CKD stage 3 happens when GFR is between 30-60 (This may be cut up into 3A/3B, however this isn’t thought-about on this dialogue.)
- CKD stage 4 happens when GFR is between 15-30
- CKD stage 5 (end-stage renal illness) happens when GFR is lower than 15
Power kidney ailments stage 1 and a pair of are usually not mandatory to contemplate in geriatric sufferers. A majority of sufferers over the age of 65 have persistent kidney illness stage 3 or past. Power kidney illness stage 5 is synonymous with end-stage renal illness (ESRD) which can finally require hemodialysis, peritoneal dialysis, or renal transplantation. Nevertheless, the choice to proceed with both peritoneal dialysis or hemodialysis needs to be in alignment with the affected person’s wishes and preferences. Hemoglobin ranges are additionally diminished because of decreased erythropoietin manufacturing. This will likely be mentioned in additional element in subsequent chapters. Anticipated signs embody fatigue and shortness of breath secondary to anemia (particularly, anemia of persistent illness, or, extra particularly, anemia of persistent kidney illness).
There are three sources geriatricians generally seek the advice of when deciding to prescribe new drugs. These sources embody:
- American Geriatrics Society Beers Standards for Doubtlessly Inappropriate Treatment Use in Older Adults – Beers listing
- START standards (Screening Instrument to Alert medical doctors to Proper Remedy)
- STOPP standards (Screening Instrument of Older Particular person’s Prescriptions)
These sources shouldn’t be memorized however relatively understood when it comes to the appropriateness of prescribing drugs. Doubtlessly inappropriate doesn’t imply don’t use; it means use with warning and search for alternate options every time attainable resulting from concern about uncomfortable side effects.
Some examples of doubtless inappropriate drugs embody:
- Muscle relaxants: carisoprodol, cyclobenzaprine, and metaxalone
- Sedatives/Anxiolytics/Hypnotics: benzodiazepines comparable to alprazolam, diazepam, and chlordiazepoxide
- Anti-depressants: amitriptyline
- Anti-histamines: diphenhydramine, hydroxyzine, promethazine (all first technology)
- Anti-hypertensives: nifedipine
- Anti-cholinergics: oxybutynin, dicyclomine, and hyoscyamine
- Analgesics: NSAIDs, opioids
- Others: barbiturates, nitrofurantoin (if CrCl < 30)
To Prescribe or To not Prescribe?
Think about the next drugs:
- Proton-pump inhibitors: if required longer than six weeks, needs to be referred to gastroenterology for additional workup
- Benzodiazepines: use solely within the short-term if attainable; use short-acting benzodiazepines comparable to alprazolam or lorazepam versus diazepam when attainable
- Tricyclic antidepressants: have anti-cholinergic properties, don’t use for melancholy if SSRIs are an choice
- Anti-psychotics: not accepted for Alzheimer’s illness however are often used for agitation (will focus on in additional element in Chapter 5)
- Sedatives/Hypnotics: trazodone solely; keep away from zolpidem
- Beta-blockers: solely in cardiac ailments, keep away from in COPD
- Ache drugs: tramadol precipitates seizures; opioids trigger constipation and confusion
- NSAIDs: enhance renal points and fluid retention
- Digoxin: maintain at sub-therapeutic ranges to forestall toxicity for sufferers with cardiac arrhythmias
- Oxybutynin: anticholinergic results
- Stool softeners: all the time prescribe with opioid ache drugs (will focus on in additional element in Chapter 12); prescribe on this order till effectiveness is achieved:
- senna/docusate (collectively)
- Tamsulosin/Finasteride: tamsulosin works instantly however could cause orthostatic hypotension; finasteride takes about 6 months to work
- Megesterol: could cause deep venous thromboses (DVTs; i.e. blood clots within the decrease extremities); use mirtazapine for urge for food stimulation first
- Aromatase inhibitors: could cause DVTs (i.e. tamoxifen)
- Statins: require no less than 2 years for main prevention and 5 years for secondary prevention of heart problems; can discontinue in sufferers with restricted life expectancy
- Diabetes drugs Chapter 11:
- Sulfonylureas: precipitate hypoglycemia
- Thiazolidinediones: CHF/fluid retention
- DPP4-inhibitors: CHF/fluid restriction
- Metformin and sitagliptin are acceptable (no metformin if serum Cr > 1.5 mg/dL)
1. An 86-year-old male is hospitalized following a left hip fracture after a fall. She undergoes an elective left hip open discount with inner fixation and placement of an extended cephalomedullary nail. On post-operative day 2, she complains of stomach ache that she attributes to not having a bowel motion because the process. Her very important indicators and bodily examination are unremarkable. Rectal examination reveals an absence of fecal impaction. Belly X-ray reveals a big bowel burden however no proof of ileus. Which of the next treatment(s) is first line for the therapy of this affected person?
E. Senna and docusate
2. Which antibiotic for the therapy of urinary tract infections is taken into account probably inappropriate primarily based on the Beers listing of doubtless inappropriate drugs?
3. Which of the next doesn’t have an effect on the calculation of the creatinine clearance in keeping with the Cockcroft-Gault equation?
D. Serum creatinine
E. Glomerular filtration price
4. How do non-steroidal anti-inflammatory drugs (NSAIDs) have an effect on renal blood movement?
A. NSAIDs trigger vasodilation of the efferent arteriole.
B. NSAIDs trigger vasoconstriction of the efferent arteriole.
C. NSAIDs trigger vasodilation of the afferent arteriole.
D. NSAIDs trigger vasoconstriction of the afferent arteriole.
E. NSAIDs haven’t any impact on renal blood movement.
5. A 76-year-old male presents to his main care doctor on the urging of his son for analysis of frequent falls. He notes that he has been falling often. The falls are occurring always of the day. He notes that he feels dizzy generally instantly upon standing up. He has not been began on any new drugs lately. He denies any head harm or lack of consciousness. He states that the signs started roughly 4 months in the past. His drugs embody amlodipine 5 mg 1 tab day by day, hydrochlorothiazide 12.5 mg 1 tab day by day, lisinopril 2.5 mg 1 tab day by day and metformin 500 mg 1 tab with breakfast and dinner. His very important indicators present a blood stress of 130/80 seated, which drops to 100/68 upon standing; coronary heart price of 75 seated which elevated to 90 standing; temperature of 98.8 F, respiratory price of 18, and oxygen saturation of 97%. His bodily examination is notable for bruises at gentle phases of resolving throughout his physique together with on his head, chest, arms, again, and legs. His neurologic examination is unremarkable. He does present +2 bilateral decrease extremity edema. The rest of the bodily examination is unremarkable. Which of the next drugs could be most acceptable to cease right now?
E. No drugs needs to be stopped right now
6. Which of the next drugs is probably inappropriate?
A. A 78-year-old male with end-stage renal illness on lisinopril
B. A 99-year-old feminine with hyperlipidemia and no different cardiovascular or peripheral vascular illness on atorvastatin
C. An 85-year previous male with peptic ulcer illness and a historical past of higher GI bleeds on omeprazole
D. A 79-year-old feminine with grownup failure to thrive syndrome on mirtazapine
E. An 86-year-old feminine with a coronary artery illness, historical past of NSTEMI, and atrial fibrillation who’s on hospice on aspirin 325 mg day by day
Solutions to Evaluate Questions