Population Specific Pharmacology

Discussion (article)

(article) . Previously, as many as 40% of older adults received one or more medications on this list, depending on the care setting.29-3 The medications that have a high risk of toxicity and adverse effects in older adults and limited effectiveness, and all medications in Table 2 (Independent of Diagnosis or Condition) should be avoided in favor of an alternative safer medication or a nondrug approach. The drug-disease or -syndrome interactions summarized in Table 3 are particularly important in the care of older adults because they often take multiple medications for multiple comorbidities. Their occurrence may have greater consequences in older adults because of age-related decline in physiological reserve. Recent studies in which drug-disease interactions have been shown to be important risk factors for ADEs highlight their importance.32 There may be cases in which the healthcare provider determines that a drug on the list is the only reasonable alternative (e.g., end-of-life or palliative care).

results (article)

(article) 34 potentially inappropriate medications and classes to avoid in older adults. Notable new additions include megestrol, glyburide, and sliding-scale insulin. Table 3 summarizes potentially inappropriate medications and classes to avoid in older adults with certain diseases and syndromes that the drugs listed can exacerbate. Notable new inclusions are thiazolidinediones or glitazones with heart failure, acetylcholinesterase inhibitors with history of syncope, and selective serotonin reuptake inhibitors with falls and fractures. Table 4 lists medications to be used with caution in older adults. Fourteen medications and classes were categorized. Two of these involve recently marketed antithrombotics for which early evidence suggests caution for use in adults aged 75 and older.

Cardiovascular (article)

(article) Alpha1 blockers Doxazosin Prazosin Terazosin High risk of orthostatic hypotension; not recommended as routine treatment for hypertension; alternative agents have superior risk/benefit profile Avoid use as an antihypertensive Moderate evidence Strong reco Alpha agonists, central Clonidine Guanabenz* Guanfacine* Methyldopa* Reserpine (> 0.1 mg/d)* High risk of adverse CNS effects; may cause bradycardia and orthostatic hypotension; not recommended as routine treatment for hypertension Avoid clonidine as a first-line antihypertensive. Avoid others as listed Lowevidence Strong reco

Antiarrhythmic drugs (Class Ia, Ic, III) (article)

(article) Amiodarone Dofetilide Dronedarone Flecainide Ibutilide Procainamide Propafenone Quinidine Sotalol Data suggest that rate control yields better balance of benefits and harms than rhythm control for most older adults. Amiodarone is associated with multiple toxicities, including thyroid disease, pulmonary disorders, and QT- interval prolongation Avoid antiarrhythmic drugs as first-line treatment of atrial fibrillation High evidence Strong reco

Medications Moved to Another Category or Modified Since 2003 Beers Criteria (article)

(article) Amphetamines (excluding methylphenidate hydrochloride and anorexics) Fluoxetine, citalopram, fluvoxamine, paroxetine, and sertraline with syndrome of inappropriate antidiuretic hormone secretion All barbiturates (except phenobarbital) except when used to control seizures Olanzapine with obesity Naproxen, oxaprozin, and piroxicam Vasodilators with syncope Nitrofurantoin Non-cyclooxygenase selective nonsteroidal anti-inflammatory drugs (excludes topical) Oral short-acting dipyridamole; does not apply to the extended-release combination with aspirin Oxybutynin Reserpine in doses >0.25 mg

Antiparkinson agents (article)

(article) Benztropine (oral) Trihexyphenidyl Not recommended for prevention of extrapyramidal symptoms with antipsychotics; more-effective agents available for treatment of Parkinson disease Avoid Moderate evidence Strong reco

Sulfonylureas, long duration (articles)

(article) Chlorpropamide Glyburide Chlorpropamide: prolonged half-life in older adults; can cause prolonged hypoglycemia; causes syndrome of inappropriate antidiuretic hormone secretion. Glyburide: greater risk of severe prolonged hypoglycemia in older adults Avoid High Strong

Table 6. Medications Removed Since 2003 Beers Criteria Independent of Diagnoses Considering Diagnoses (article)

(article) Cimetidine (H2 antihistamines added as a class; see Table 7) Antispasmodics and muscle relaxants; CNS stimulants: dextroamphetamine, methylphenidate, methamphetamine, pemoline, with cognitive impairment Cyclandelate CNS stimulants: dextroamphetamine, methylphenidate, methamphetamine, pemoline, and fluoxetine with anorexia and malnutrition Daily fluoxetine Clopidogrel with blood clotting disorders or receiving anticoagulant therapy Ferrous sulfate >325 mg/d Guanethidine with depression Guanadrel High-sodium content drugs with heart failure Guanethidine Monoamine oxidase inhibitors with insomnia Halazepam Oxybutynin and tolterodine with bladder outlet obstruction Long-term use of stimulant laxatives: bisacodyl, cascara sagrada, and neoloid except in the presence of opiate analgesic use Pseudoephedrine and diet pills with hypertension Mesoridazine Tacrine with Parkinson's disease Propoxyphene and combination products Tripelennamine

Desiccated thyroid (article)

(article) Concerns about cardiac effects; safer alternatives available Avoid Low evidence Strong reco

Antithrombotics (article)

(article) Dipyridamole, oral short acting* (does not apply to extendedrelease combination with aspirin) May cause orthostatic hypotension; more-effective alternatives available; intravenous form acceptable for use in cardiac stress testing Avoid Moderate evidence Strong reco

Growth hormone (article)

(article) Effect on body composition is small and associated with edema, arthralgia, carpal tunnel syndrome, gynecomastia, impaired fasting glucose Avoid, except as hormone replacement after pituitary gland removal High evidence Strong reco

Nonbenzodiazepine hypnotics (article)

(article) Eszopiclone Zolpidem Zaleplon Benzodiazepine-receptor agonists that have adverse events similar to those of benzodiazepines in older adults (e.g., delirium, falls, fractures); minimal improvement in sleep latency and duration Avoid chronic use (> 90 days) Moderate evidence Strong reco

Estrogens with or without progestins (article)

(article) Evidence of carcinogenic potential (breast and endometrium); lack of cardioprotective effect and cognitive protection in older women Evidence that vaginal estrogens for treatment of vaginal dryness is safe and effective in women with breast cancer, especially at dosages of estradiol < 25 lg twice weekly Avoid oral and topical patch. Topical vaginal cream: acceptable to use low-dose intravaginal estrogen for the management of dyspareunia, lower urinary tract infections, and other vaginal symptoms Oral and patch: high evideence Topical: moderate evidence Oral and patch: strong reco Topical: weak reco

Anticholinergics (excludes TCAs) (article)

(article) First-generation antihistamines (as single agent or as part of combination products) Brompheniramine Carbinoxamine Chlorpheniramine Clemastine Cyproheptadine Dexbrompheniramine Dexchlorpheniramine Diphenhydramine (oral) Doxylamine Hydroxyzine Promethazine Triprolidine Highly anticholinergic; clearance reduced with advanced age, and tolerance develops when used as hypnotic; greater risk of confusion, dry mouth, constipation, and other anticholinergic effects and toxicity. Use of diphenhydramine in special situations such as acute treatment of severe allergic reaction may be appropriate Avoid Hydroxyzine and promethazine: high evidence All others: moderate Strong Reco

Meprobamate (article)

(article) High rate of physical dependence; very sedating Avoid Moderate evidence Strong reco

Spironolactone > 25 mg/d (article)

(article) In heart failure, the risk of hyperkalemia is higher in older adults especially if taking > 25 mg/d or taking concomitant NSAID, angiotensin converting-enzyme inhibitor, angiotensin receptor blocker, or potassium supplement Avoid in patients with heart failure or with a CrCl < 30 mL/min Moderate evidence Strong reco

Antipsychotics, first (conventional) and second (atypical) generation (see Table 8 for full list) (article)

(article) Increased risk of cerebrovascular accident (stroke) and mortality in persons with dementia Avoid use for behavioral problems of dementia unless nonpharmacological options have failed and patient is threat to self or others Moderate evidence Strong reco

Ergot mesylates* Isoxsuprine* (article)

(article) Lack of efficacy Avoid High evidence Strong reco

Megestrol (article)

(article) Minimal effect on weight; increases risk of thrombotic events and possibly death in older adults Avoid Moderate evidence Strong reco

Anti-infective (article)

(article) Nitrofurantoin Potential for pulmonary toxicity; safer alternatives available; lack of efficacy in patients with CrCl < 60 mL/min due to inadequate drug concentration in the urine Avoid for long-term suppression; avoid in patients with CrCl < 60 mL/min Moderate evidence Strong reco

Ticlopidine (article)

(article) Safer effective alternatives available Avoid Moderate evidence Strong reco

intent of criteria - beers (article)

(article) The 2012 AGS Beers Criteria are intended for use in all ambulatory and institutional settings of care for populations aged 65 and older in the United States. The primary target audience is the practicing clinician. Researchers, pharmacy benefit managers, regulators, and policy-makers also use the criteria widely. The intentions of the criteria include improving the selection of prescription drugs by clinicians and patients, evaluating patterns of drug use within populations, educating clinicians and patients on proper drug usage, and evaluating health-outcome, quality of care, cost, and utilization data.

Chloral hydrate* (article)

(article) Tolerance occurs within 10 days, and risks outweigh benefits in light of overdose with doses only 3 times the recommended dose Avoid Low evidence Strong reco

Central nervous system (article) a. Chronic seizures or epilepsy b. Delirium c. Dementia and cognitive impairment d. History of falls or fractures e. Insomnia f. Parkinson's disease

(article) a. Bupropion Chlorpromazine Clozapine Maprotiline Olanzapine Thioridazine Thiothixene Tramadol Lowers seizure threshold; may be acceptable in patients with well-controlled seizures in whom alternative agents have not been effective Avoid Moderate Strong b. All TCAs Anticholinergics (see Table 9 for full list) Benzodiazepines Chlorpromazine Corticosteroids H2-receptor antagonist Meperidine Sedative hypnotics Thioridazine Avoid in older adults with or at high risk of delirium because of inducing or worsening delirium in older adults; if discontinuing drugs used chronically, taper to avoid withdrawal symptoms Avoid Moderate Strong c. Anticholinergics (see Table 9 for full list) Benzodiazepines H2-receptor antagonists Zolpidem Antipsychotics, chronic and as-needed use Avoid because of adverse CNS effects. Avoid antipsychotics for behavioral problems of dementia unless nonpharmacological options have failed, and patient is a threat to themselves or others. Antipsychotics are associated with an increased risk of cerebrovascular accident (stroke) and mortality in persons with dementia Avoid High Strong d. Anticonvulsants Antipsychotics Benzodiazepines Nonbenzodiazepine hypnotics Eszopiclone Zaleplon Zolpidem TCAs and selective serotonin reuptake inhibitors Ability to produce ataxia, impaired psychomotor function, syncope, and additional falls; shorter-acting benzodiazepines are not safer than long-acting ones Avoid unless safer alternatives are not available; avoid anticonvulsants except for seizure disorders High Strong e. Oral decongestants Pseudoephedrine Phenylephrine Stimulants Amphetamine Methylphenidate Pemoline Theobromines Theophylline Caffeine CNS stimulant effects Avoid Moderate Strong f. All antipsychotics (see Table 8 for full list, except for quetiapine and clozapine) Antiemetics Metoclopramide Prochlorperazine Promethazine Dopamine receptor antagonists with potential to worsen parkinsonian symptoms. Quetiapine and clozapine appear to be less likely to precipitate worsening of Parkinson's disease Avoid Moderate Strong

Disopyramide* (article)

(article) potent negative inotrope and therefore may induce heart failure in older adults; strongly anticholinergic; other antiarrhythmic drugs preferred Avoid Low evidence Strong reco

Insulin (article)

(article) sliding scale Higher risk of hypoglycemia without improvement in hyperglycemia management regardless of care setting Avoid Moderate evidence Strong reco

Antispasmodics (article)

(article) Belladonna alkaloids Clidinium-chlordiazepoxide Dicyclomine Hyoscyamine Propantheline Scopolamine Highly anticholinergic, uncertain effectiveness Avoid except in short-term palliative care to decrease oral secretions Moderate evidence Strong Reco

Endocrine (article)

(article) Androgens Methyltestosterone* Testosterone Potential for cardiac problems and contraindicated in men with prostate cancer Avoid unless indicated for moderate to severe hypogonadism Moderate evidence Weak reco

Digoxin > 0.125 mg/d (article)

(article) In heart failure, higher dosages associated with no additional benefit and may increase risk of toxicity; slow renal clearance may lead to risk of toxic effects Avoid Moderate evidence Strong reco

Nifedipine, immediate release* (article)

(article) Potential for hypotension; risk of precipitating myocardial ischemia Avoid High evidence Strong reco

Benzodiazepines (article)

(article) Short and intermediate acting: Alprazolam Estazolam Lorazepam Oxazepam Temazepam Triazolam Long acting: Clorazepate Chlordiazepoxide Chlordiazepoxide-amitriptyline Clidinium-chlordiazepoxide Clonazepam Diazepam Flurazepam Quazepam Older adults have increased sensitivity to benzodiazepines and slower metabolism of long-acting agents. In general, all benzodiazepines increase risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents in older adults May be appropriate for seizure disorders, rapid eye movement sleep disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, periprocedural anesthesia, end-of-life care Avoid benzodiazepines (any type) for treatment of insomnia, agitation, or delirium High Strong

Beers Intro (article)

(article) https://nnotes5.nursing.sunysb.edu/LMS/Resources.nsf/Attachment/2BBE2431D4D1F95C85257A4A001C7983/$FILE/2012BeersCriteria_JAGS.pdf Estimates from past studies in ambulatory and longterm care settings found that 27% of adverse drug events (ADEs) in primary care and 42% of ADEs in long-term care were preventable, with most problems occurring at the ordering and monitoring stages of care.1,2 In a study of the 2000/2001 Medical Expenditure Panel Survey, the total estimated healthcare expenditures related to the use of potentially inappropriate medications (PIMs) was $7.2 billion.3 Explicit criteria can identify high-risk drugs using a list of PIMs that have been identi- fied through expert panel review as having an unfavorable balance of risks and benefits by themselves and considering alternative treatments available. A list of PIMs was developed and published by Beers and colleagues for nursing home residents in 1991 and subsequently expanded and revised in 1997 and 2003 to include all settings of geriatric care.4-6 Implicit criteria may include factors such as therapeutic duplication and drug-drug interactions. PIMs determined by explicit criteria (Beers Criteria) have also recently been found to identify other aspects of inappropriate medication use identified by implicit criteria.7 research has shown that a number of PIMs have limited effectiveness in older adults and are associated with serious problems such as delirium, gastrointestinal bleeding, falls, and fracture.8, a "less-is-more approach" is often the best way to improve health outcomes in older adults.15 9 PIMs now form an integral part of policy and practice in the Centers for Medicare and Medicaid Services (CMS) regulations and are used in Medicare Part D. They are also used as a quality measure in the National Committee for Quality Assurance (NCQA) Healthcare Effectiveness Data and Information Set (HEDIS). Several stakeholders, including CMS, NCQA, and the Pharmacy Quality Alliance (PQA) have identified the Beers Criteria as an important quality measure. e incorporating Beers Criteria PIMs into electronic health records as an aid to real-time e-prescribing.19 , this update will categorize PIMs into two broad groups: medications to avoid in older adults regardless of diseases or conditions and medications considered potentially inappropriate when used in older adults with certain diseases or syndromes. A third group, medications that should be used with caution, has been added.

fluids and electrolytes (book)

(book) Fluid and electrolyte homeostatic mechanism is decreased in the geriatric population. the elderly experience more severe dehydration with equal amounts of fluid loss compared with younger adults. the multitude of factors involved include decreased thirst and cardiovascular reflexes, decreased fluid intake and decreased ability of the kidneys to concentrate urine, increased atrial natriuretic peptide, decreased aldosterone response to hyperkalemia and decreased response to antidiuretic hormone. the result is an increased incidence of hyponatremia, hyperkalemia and prerenal azotemia especially when the older adult is taking a diuretic like hydrochlorthiazide and furosemide. angiotensin converting enzyme inhibitors have an increased potential to cause hyperkalemia and acute renal failure in older adults thus these agents need to be started with low doses titrated slowly and monitored frequently

Pharmacokinetics: Excretion (ppt)

(ppt) At birth, kidney function is decreased, GFR matures first, then tubular secretion, and lastly tubular reabsorption GFR at birth is 2-4 ml/min/m2; 0.5% of an adult level After the first week of life, a significant increase in GFR is seen.This explains why recommended doses change after 7 days of life At 1 year, GFR reaches 70 ml/min/m2 GFR increases with age, peaking at 3 to 12 years of age, after which there is a decline to appropriate adult value. premature neonates- reduction in GFR effects renal drug clearance thereby necessitating longer dosing interval for renally cleared medication such as vancomycin, to prevent accumulation. (similar occurrence in child with cystic fibrosis) ex. vancomycin is often given every 18 to 24 hours in a low birth weight premature neonate, every six hours in children with normal renal function. *the schwartz equation is a common method of estimating pediatric GFR from infancy. *urine output is also a parameter used to assess renal function in pediatric patients- urine output more than 1 to 2 mL per kilogram per hour considered normal.

Strategies to prevent adverse drug reaction in older adults (ppt)

(ppt) -evaluating comorbidities frailty and cognitive function -identifying caregivers to take responsibility for medication management -evaluating renal function and adjusting doses appropriately -monitoring drug effects -recognizing that clinical signs or symptoms can be an ADR -minimizing number of medications prescribed -adapting treatment to patients life expectancy -realizing that self medication and nonadherence are common and can induce ADRs **Communication!!!! -renal function is important -always calc GFR, make sure drug is approp for patient before prescribing, takes 10 seconds -potassium became 8, emergency dialysis, creatinine was 12 - could have been avoided -Pepcid AC - feeling fine, no evidence espohageal erosion, stomach is fine, they feel good, get them off Pepcid, take the pill away **If they don't have to be on 12 meds, get them off -its our job to keep you alive for 10 years -when they get to 90, tired of taking these pills, do you wanna live to 100? No I don't, okay lets take away your statin then, its not that important at 90.

Age Matters (ppt)

(ppt) AGE Neonate: Birth to 28 days (4 weeks) of life Infant: 29 days to less than 12 months Child: One year to twelve years of age Adolescents: Thirteen to seventeen years of age

Outcomes of Over-Prescribing (ppt)

(ppt) Adverse drug events (ADEs)/ reactions Drug interactions Duplication of drug therapy* Decreased quality of life Unnecessary cost - don't have a lot of money Medication non-adherence - can't afford Leads to death -how many times have you in your career have you seen a patient on ACE and ARB together, two beta blockers, amoxicillin and penicillin -avoid a pill for every ill -avoid a pill to treat side effects from a pill -don't give another pill for nausea if med makes patient nauseous

Route and Timing (ppt)

(ppt) Avoid painful intramuscular injections Oral medications may have flavors added = sugar, giving child extra sugar within medication, what if they are type 1 diabetic. (use of corticosteroid) Whenever possible, avoid medications that need to be administered during school hours. If it is a problem, needs to be admin during school, need to provide the patient with a note for the school nurse, plus an extra dose of med just to be kept at school. Teaching patient or school nurses - get a prescription pad and pwrite a note describing exactly what the child is to take and says "during school hours" it must say that. Also give a separate supply to be kept at school Complicated with antibiotics and inhalers. Need to keep inhaler at school, $100 on just two inhalers. *consider the dosage form availability and a child's ability to swallow a solid dosage form. *can be mixed with pudding, fruit flavored gelatin, chocolate syrup, applesauce or other fruit Purée immediately before administration of individual doses. honey, may contain spores of clostridium botulism- not given if younger than 1yr.

Beer's List (ppt)

(ppt) Beers List will note the drug... Alprazolam: increased sensitivity to benzodiazepines. Increased risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents in older adults Amiodarone: data suggest that rate control yields better balance of benefits and harms than rhythm control for most older adults Amitriptyline: highly anticholinergic, sedating, and cause orthostatic hypotension Aspirin: >325mg/d increases risk of GI bleeding and peptic ulcer disease in high-risk groups, including those aged >75 or taking corticosteroids or anticoagulants

Pharmacokinetics: Distribution (ppt)

(ppt) Body Water: Neonates are 85% body water compared to 55% in adults- need higher doses by weight (milligram per kilogram) than older children and adolescents to achieve the same therapeutics serum concentration. Extracellular fluid and total body water per kg of body weight are increased in neonates and infants, resulting In higher Vd for water-soluble drugs, this decreases with age Percutaneous: Total body fat is 1% in a 29 week neonate Total body fat is 15% in a full term baby Total body fat is 20-25% in a 2 yo toddler Fat content tends to increase between 5-10 years followed by a decrease through age 17 *Vd is increased for drugs that are highly lipid soluble Neonates and infants have lower serum albumin- highly protein-bound drugs such as sulfamethoxazole trimethoprim (Bactrim) are not typically used r/t concern for bilirubin displacement and risk of kernicterus from bilirubin encephalopathy. Immature blood brain barrier: vancomycin or phenobarbital may also reach higher concentrations in the central nervous system of neonates.

Weight Calculation (ppt)

(ppt) Calculation of body weight in the overweight child may result in higher doses being administered than necessary **In these type of cases, dose the child at the ideal weight related to age and height Body surface area estimates are more accurate for calculation of pediatric doses than the ideal body weight BSA is based on height and weight The Dubois & Dubois formula Use of "body surface area" BSA- usually only seen in antivirals (acyclovir) and chemotherapy

Select the Appropriate Dose (ppt)

(ppt) Check if there is any underlying diseases before prescribing a drug for presenting symptom/disease process. This is important to know how the present disease may influence the pharmacokinetics of a drug that you are going to give for the presenting disease CHILDREN ARE NOT MINI-ADULTS! Utilization of an adult drug guide is NOT an option need peds guide. -Harriet lane book - number one reco from pediatric practitioner colleages, age related guide Prescribe regiments based on child's routine **Do NOT prescribe in VOLUME! ex. For a 15 month old child, you want to prescribe Amoxicillin for otitis media: The child is 22 lbs (9.97kg) AAP recommended dose is 45 mg/kg in divided doses every 12 hours 10kg. 45mg x 10 kg = 450 mg 450 mg/bid = 225 per dose Amoxicillin 250 mg/5mL - might not have formulation **When writing Rx can just put: Sig: amoxicillin 4.5mL PO q12h x 10 days (or) Sig: amoxicillin 225mg oral twice daily x 10 days **The pharmacist can figure out the volume and the concentration** -if child goes to school, prescribe a drug twice a day that doesn't interfere with child schooling, so they don't have to bring the drug to school and have medication there as well as at home -always in mg, prescribe what you want, let pharmacist prescribe the volume and concentration

Pharmacokinetics:Volume of Distribution (ppt)

(ppt) Decreased cardiac output/circulation changes May delay onset or extend effect of medications Decrease of lean body mass/increase of fatty tissue where medications are stored -Prolong medication's action -Increase sensitivity -Increase toxic effects Higher plasma levels/more erratic distribution ex. Dilantin - older adults, prolong the meds action, increase sensitivity, increase toxic effects -Lean body mass can decrease by as much as 12-19% through loss of skeletal muscle in the elderly. -Total body water deceases by about 10-15% by age 80. -Decreased body water -> decrease VD for hydrophilic drug ex. ethanol/lithium/aspirin= higher plasma concentration- greater toxic risk -decreased lean body mass -> decrease VD for drugs that bind to muscle ex. digoxin= higher plasma concentration- greater risk of overdose. -increased fat stores -> increased VD for lipophilic drugs ex. diazepam trazodone= higher tissue concentration- prolongs half life/duration of action -decreased plasma protein (albumin) -> increased percent of unbound or free drug (active) ex. diazepam, valproic acid phenytoin, warfarin= increase in free floating/unbound drug- greater toxic risk. -increased plasma protein (a1-acid glycoprotein) -> decreased percent of unbound or free drug (active) ex quinidine propanolol erythromycin and amitriptyline (VD - volume distribution)

Pharmacokinetics: Absorption Peds (ppt)

(ppt) Gastrointestinal: PH: Gastric acid output maturity is related to postnatal age; approaches adult values by 3 months of age. increased serum concentration of weak bases and acid-labile medication (penicillin) and decreased serum concentrations of weak acid medication (phenobarbital) GI motility: Neonates have a delay in gastric emptying time; adult values are reached at 6-8 months of age. (increase drug absorption)-further delayed in gastroesophageal reflux, respiratory distress syndrome and congenital heart disease GI contents: Develops rapidly within the first year of life; underdeveloped flora can increase absorption of drugs (digoxin) Percutaneous: Absorption is increased in the newborn due to immature epidermal barrier and increased skin hydration during the first 2 weeks of life **Increased surface area to weight ratio increases percutaneous absorption ***Hence, application of topical medications should be limited to the smallest amount possible*** (Can lead to high serum concentrations of topically applied drugs Lidocaine, corticosteroids, chlorhexidine) Intramuscular: Absorption in premature and full-term infants can be erratic due to variable perfusion, poor muscle contractions, and decreased muscle mass compared with older patients *IM can be painful- Reserved when other routes are not available (Ie. IV) Rectal: Can be erratic and not commonly recommended if other routes are available (ie. Oral) *This route is useful in cases of severe nausea and vomiting or seizure activity for medications that undergo extensive first pass metabolism- in this case, bioavalibility increases as the blood supply bypasses the liver from the lower rectum directly into the inferior vena cava (the drug is not reduced by the liver so more drug is circulating in the blood). Generally- **If you can give it in the gut, give it in the gut! For everyone**

Pharmacokinetics:Metabolism (ppt)

(ppt) Metabolic clearance of drugs by the liver may be ↓ due to: Decreased hepatic blood flow (increase half-life) -Decreased liver size and mass -General health & nutritional status - are they eating enough cal? Protein? For the drug to bind to (hypoalbuminemia). * frail elderly have a more diminished drug metabolism than those with healthy body weight. -Use of alcohol, other medications, polypharmacy -Long term exposure to environmental toxins/ pollutants Lower serum protein levels -Loss of protein binding Other factors that affect metabolism: -Gender -Comorbid conditions -Smoking -Diet -Drug to drug interactions -Race -Frailty **Drugs that have high extraction ratio have significant first pass metabolism resulting in higher bioavailability for older adults. (propranolol, levodopa, statins, morphine)

Response and Therapeutic Dose Monitoring (ppt)

(ppt) Monitor pharmacokinetic aspects Check for any possible alterations in pharmacokinetics of a treated drug Monitor the plasma concentration if a drug or age related adverse effects are observed

Pharmacokinetics: Metabolism (ppt)

(ppt) Neonates have decreased activity of many enzyme pathways, that is why drug dosages are decreased for neonates CYP450 activity is 50% of adult levels Decreased hydroxylation activity leads to decreased metabolism of phenobarbital, phenytoin, lidocaine Children have increased hepatic enzyme activity between 2-4 years of age which may be related to increased liver size compared to total body weight. Doses are increased during this time for theophylline, phenytoin, and phenobarbital.

Child vs Adult (ppt)

(ppt) Pediatric doses are often based on body weight Ie. Mg/Kg/Dose Adult doses are usually uniformed Mg/Day Mg/dose Pediatric doses may exceed adult doses by body weight for certain medications due to differences in pharmacokinetics and pharmacodynamics Hence, the use of pediatric drug dosing guides is recommended. *phenobarbital is commonly used for treatment of neonatal seizures but seldom used for seizure treatment in adults due to differences in seizure ideology. there are some commonalities between pediatric and adult patients such as therapeutic serum drug concentrations required to treat certain diseases. for example gentamicin for bacteremia. *drug therapy for a pediatric patient depends on a number of specific factors such as age, weight, height, disease, comorbidities, developmental pharmacokinetics, and available drug dosage forms.

Pharmacokinetics: Absorption (ppt)

(ppt) Rate of absorption may be delayed -Lower peak concentration -Delayed time to peak concentration Overall amount absorbed (bioavailability) is unchanged For drugs with extensive first-pass metabolism, bioavailability may increase because less drug is extracted by the liver -Decreased liver mass/size -Decreased liver blood flow -Decreased esophageal motility -Capsules more difficult to swallow Loss of subcutaneous fat -Increased rate of absorption of topical medications Enteric coated drugs, delayed absorption - red (Uniquely release) and blue (in-spike-out) decreases in overall surface of the intestinal epithilium and gastric acid secretion and splanchnic blood flow, peristalsis is weaker and gastric emptying is delayed. These changes slow absorption in the stomach especially for enteric-coated and delayed release preparations. **Delays in absorption may lead to a longer time required to achieve peak drug effects** BUT IT DOES NOT significantly alter the amount of drug absorbed, and drug movement from the G.I. tract into the circulation is not meaningfully changed. **Decreased absorption of B12, calcium, and Iron. **Intramuscular injections should generally be avoided in the elderly due to unpredictable drug absorption.

Polypharmacy (ppt)

(ppt) Risks of problems: -Medication errors Wrong drug, time, route, drug to drug interactions -Adverse effects from each drug Polypharmacy primary reason for adverse reactions -Adverse interactions between drugs *Balance between overprescribing and underprescribing -Correct drug -Correct dose -Targets appropriate condition -Is appropriate for the patient common use of dietary supplements and herbal products in this population adds to the polypharmacy. *one apparent cause is a patient receiving multiple medications from different providers who treat the patients comorbidity without coordinated care. medication reconciliation after thorough medication review is very important!!

First Pass (ppt)

(ppt) -metabolism -The term used for the hepatic metabolism of a drug when it is absorbed from the gut and delivered to the liver via the portal circulation. -The greater the first-pass effect, the less the agent will reach the systemic circulation when the agent is administered orally. -After the absorption, the drug goes directly into the liver via the portal vein. Then the liver, the hepatic enzymes act on the drug, reducing the amount of active drug reaching the body system and decreasing the amount available to that body. -??? % of Med reaching systemic circulation after the first pass through the liver is referred to the drug's bioavailability. -100mg of a dose, goes into body through stomach into small bowel, now we have 70% of the dose reaching the portal vein, goes into liver, hepatic enzymes metabolize it **only 15mg enters the systemic circulation.

Weight Matters (ppt)

(ppt) Check the weight Confirm weight is appropriate for the age Check if the weight is relative to age I.E cerebral palsy - under weight of the child Check if the drug is dosed based on body surface area. **Always weigh the infant/child PRIOR to prescribing treatment. Most drugs are not based on BSA, only time is if patient is on acyclovir or chemotherapy in acute care, not seen often in primary care setting

Estimating the GFR (ppt)

(ppt) Creatinine clearance is used to estimate glomerular rate Serum creatinine alone is not accurate in the elderly -lean body mass lower creatinine production, it fools you - decreases glomerular filtration rate **Serum creatinine stays in normal range, masking change in creatinine clearance (know this)** Estimate using the Cockroft-Gault equation: {(140 - Age) x wt (kg) / (Plasma Creatinine * 72) } x F Where F = 1 if male, and 0.85 if female Normal creatinine men is 0.7-1.3 MG/DL normal creatinine clearance in men 100-135 ML/minute normal creatinine women 0.6-1.1 MG/DL normal creatinine clearance 85-125 ML/minute How we eliminate the drug Know formula - don't memorize it **Cockroft-Gault equation is the equation we use to calculate the creatinine clearance You'll know looking at GFR and CC, look at drug, if the renal elimination/impairment is this (GFR 30-60%) reduce that med by 50% *Download the app in epocrates, google calculating GFR

Adverse Drug Effects (ppt)

(ppt) Responsible for @ 35% of hospital admissions of geriatric patients More than 95% of ADEs in this population are predictable and approximately 50% are considered preventable American Geriatric Society - to prevent drug reactions Beers List - look it over (Beers Criteria for Potentially Inappropriate Medication Use in Older Adults) Could get a day off, if 1/3 of unit not there -do not memorize Beers list, changes every couple years, whats it about what is it saying Four predictors for severe ADRs experienced by the elderly: a) use of certain medications including diuretics NSAIDs, antiplatelet medication and digoxin b) the number of drugs taken C) age D) comorbidites. *particular caution must be taken when prescribing drugs that alter cognition in the elderly including antiarrhythmics, antidepressant, anti-emetics, anti-histamine, anti-Parkinson, antipsychotics, benzodiazepines, digoxin, histamine-two receptor antagonist, NSAIDs, opioids, and skeletal muscle relaxants. ** Can increase risk for falls: comprehensive fall prevention strategies should include medication simplification and modification to prevent or resolve ADRs

Drugs dependent on Renal Function (ppt)

(ppt) acetazolamide, acyclovir, allopurinol, amantadine, amiloride, aminoglycosides, amphotericin B, atenolol, aztreonam, captopril, cephalosporins (most), clonidine, colistimethate, digoxin, enalapril, flucanazole, fluoroquinolones (most), furosemide, H2 blockers (most), impenem, lisinopril, lithium, methotrexate, metoclopramide, nadolol, phenopyridine, penicillins (most), procainamide, pyridostigmine, spironolactone, sulfamethoxazole, thiazides, trimethoprim and vancomycin. *Drugs that are truly really dependent: captopril, lisonpril, penicilin, nadolol, lasix, h2 blockers. **Important to know if patient can actually take it

Pediatric age groups age terminology and weight classification (ppt)

(ppt) p. 20 -neonate - less than or equal to 28 days (4 weeks) of life -infant - 29 days to less than 12 months -child - 1 to 12 years -adolescent - 13-17 years (most common definition) -gestational age GA - age from date of mothers first day of last menstrual period to date of birth -full term describes infant born at 37 weeks gestation or greater -premature describes infants born before 37 weeks gestation -small for GA neonates with birth weights the below the 10th percentile among neonates of the same GA -large for GA neonates with birth weight above the 90th percentile among neonates of the same GA -chronological or postnatal age - age from birth to present measured in days weeks months or years -corrected or adjusted age - may be used describe the age of a premature child up to three years of age corrected age = chronicological age in months - [(40 -GA at births in weeks) x 1month/4 weeks], for example if a former 29 week GA child is now 10 months old chronologically his corrected age is approximately seven months. 10 months -[(40 - 29 weeks) x 1 month / four weeks] equals 7.25 months **have to convert** "weeks" to "months" there are 4 wks in 1 month. 40wks-29wks= 11wks (convert to mths)= 2.75mths. then do 10mths - 2.75mths = 7.25mths* - LBW infant - premature infant with birth weight between 1500 grams and 2500 grams -VLBW infant- premature infant with birth weight 1000 g to less than 1500 g -ELBW infant - premature infant with less than 1000g

Helpful tips for medication administration for selected dosage forms (ppt)

(ppt) pg 27 opthalmic drops or ointment - wash hands thoroughly prior to administration, position child laying down in supine position, avoid contact of applicator tip to surfaces including the eye, drop should be placed in the pocket of the lower eyelid, ointment strip should be placed on the pocket of the lower eyelid -otic drops - wash hands thoroughly prior to administration, position child laying down in a prone position, tilt head to expose treated ear, gently pull outer ear outward then due to age dependent change in angle of eustachian tube: if child less than three years of age gently pull down ward and back apply drops, if child is more than three years of age gently pull upward and back, apply drops -Nasal drops: wash hands thoroughly prior to administration, position child laying down in supine position, slightly tilt head back, place drops in nostrils, remain in position for appropriate distribution of medication -rectal suppository: similar to adult administration, challenging route for administration for younger patients, less than three years, a smaller finger e.g. pinky finger should be used to insert suppository - metered dose inhalers: use a spacer, for younger children use one with a mask, be sure the mask is secured/placed closely up against the child's face avoiding gaps between face and mask and creating a Seal to ensure medication delivery, child should take slow breaths in with each dose, wait at least one minute between doses

Pharmacokinetics:Elimination (ppt)

**the Clinically most important pharmacokinetic change in the elderly is the decrease in Renal drug elimination** Half-life: Time for serum concentration of drug to decline by 50% (expressed in hours) Clearance: Volume of serum from which the drug is removed per unit of time (mL/min or L/hr) Reduced elimination: drug accumulation and toxicity Effects of aging: -Decreased kidney size -Decreased renal blood flow -Decreased number of functional nephrons -Decreased tubular secretion Result: glomerular filtration rate (GFR) decrease after 40yrs age ** these changes cause prolonged drug half-life, increased serum drug level, and increased potential for adverse drug reactions (ADRs)-closely monitor/serum concentrations and make appropriate adjustments especially for renal eliminated drugs with a narrow therapeutic index (digoxin) *Once we get the drug absorbed, we metabolize the drug we need to get rid of the drug. Every drug will have a half life *Benadryl 12-15 hour, 50% of the drug is released in 12-15 hrs serum creatinine may remain fairly unchanged and remain within normal limits despite kidney function= creatinine clearance should be calculated when starting or adjusting pharmacotherapy in older adults.

Metabolism (book)

Drug metabolism is affected by age, acute and chronic diseases and drug to drug interactions. The liver is the primary site of drug metabolism, which undergoes changes with age. Though the decline is not consistent, older patients have decreased metabolism of many drugs. liver mass is reduced by 20% to 30% with advanced age and hepatic bloodflow is decreased by as much as 40%. these changes can drastically reduce the amount of drug delivered to the liver per unit of time, reduce its metabolism and increase the half-life. metabolic clearance of some drugs is decreased by 20 to 40% (e.g. amiodarone amitriptyline warfarin and verapamil) but it is unchanged for drugs with a low hepatic extraction. Drugs that have high extraction ratio have significant first pass metabolism resulting in higher bioavailability for older adults. for example, the effect of morphine is increased due to a decrease in clearance by around 33%. similar increases in bioavailability can be seen with propanolol, levodopa and statins. thus older patients may experience a similar clinical response to that of Younger patients using lower doses of these medications. the effect of aging on liver enzymes (cytochrome P450 system - CYP 450) may lead to a decreased elimination rate of drugs that undergo oxidative phase 1 metabolism, but this is controversial. originally, it was that the CYP 450 system was impaired in the elderly leading to decreased drug clearance and increased serum half life but studies have not consistently confirmed this. thus variations in the CYP 450 activity may not be due to aging but to lifestyle e.g. smoking illness or drug interactions. a patients nutritional status play a role in drug metabolism as well. frail elderly have a more diminished drug metabolism than those with healthy body weight. aging does not affect drugs that undergo the phase 2 hepatic metabolism known as conjugation or glucuronidation, but conjugation is reduced with frailty. temazepam and lorazepam are examples of drugs that undergo phase II metabolism

Underprescribing (ppt)

Many reasons including belief that treatment of primary problem is enough intervention, cost, concerns of non-adherence, fear of adverse effects and associated liability, starting low and failing to increase to an appropriate dose, skepticism regarding secondary prevention benefits or ageism. anticoagulation in patients with atrial fibrillation - providers may be overly concerned with risk of bleeding or the risk of falls if anticoagulated -malignant and nonmalignant pain complaints - providers are often hesitant to prescribe opioids due to possible cognitive and bowel side effects, concerns about addiction, patients may often be hesitant to take opioids -antihypertensive therapy - providers may underestimate the benefits on stroke and cardiovascular events and/or fail to add the second or third medication needed to retain control -beta blocker treatment in heart failure - providers are concerned about complications in high-risk patients despite the substantial evidence of mortality reduction/benefit -Statin treatment for hyperlipidemia - providers may underestimate benefit or have high concern for adverse events - treatment of osteopenia/osteoporosis in men and women at risk of fractures - providers often fail to screen for bone mineral density and are therefore unaware to offer treatment Anticoag - good example - giving med expecting INR to be at such, concerned around about risk of bleeding, fall and hit their head -prescribe appropriately **Underprescribing can be avoided by using clinical assessment strategies and improving adherence support and liberalizing financial coverage of drugs.

Pain a. Meperidine b. Non-COX-selective NSAIDs, oral c. Indomethacin d. Pentazocine* e. Skeletal muscle relaxants

a. Not an effective oral analgesic in dosages commonly used; may cause neurotoxicity; safer alternatives available Avoid High evidence Strong reco b. Aspirin > 325 mg/d Diclofenac Diflunisal Etodolac Fenoprofen Ibuprofen Ketoprofen Meclofenamate Mefenamic acid Meloxicam Nabumetone Naproxen Oxaprozin Piroxicam Sulindac Tolmetin Increases risk of GI bleeding and peptic ulcer disease in high-risk groups, including those aged > 75 or taking oral or parenteral corticosteroids, anticoagulants, or antiplatelet agents. Use of proton pump inhibitor or misoprostol reduces but does not eliminate risk. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months and in approximately 2-4% of patients treated for 1 year. These trends continue with longer duration of use Avoid chronic use unless other alternatives are not effective and patient can take gastroprotective agent (proton pump inhibitor or misoprostol) Moderate evidence Strong reco c. Ketorolac, includes parenteral Increases risk of GI bleeding and peptic ulcer disease in high-risk groups. (See above Non-COX selective NSAIDs.) Of all the NSAIDs, indomethacin has most adverse effects Avoid Indomethacin: moderate evidence Ketorolac: high Strong reco d. Opioid analgesic that causes CNS adverse effects, including confusion and hallucinations, more commonly than other narcotic drugs; is also a mixed agonist and antagonist; safer alternatives available Avoid Low evidence Strong reco e. Carisoprodol Chlorzoxazone Cyclobenzaprine Metaxalone Methocarbamol Orphenadrine Most muscle relaxants are poorly tolerated by older adults because of anticholinergic adverse effects, sedation, risk of fracture; effectiveness at dosages tolerated by older adults is questionable Avoid Moderate evidence Strong reco

Gastrointestinal (article) a. Chronic constipation b. History of gastric or duodenal ulcers

a. Oral antimuscarinics for urinary incontinence Darifenacin Fesoterodine Oxybutynin (oral) Solifenacin Tolterodine Trospium Nondihydropyridine CCB Diltiazem Verapamil First-generation antihistamines as single agent or part of combination products Brompheniramine (various) Carbinoxamine Chlorpheniramine Clemastine (various) Cyproheptadine Dexbrompheniramine Dexchlorpheniramine (various) Diphenhydramine Doxylamine Hydroxyzine Promethazine Triprolidine Anticholinergics and antispasmodics (see Table 9 for full list of drugs with strong anticholinergic properties) Antipsychotics Belladonna alkaloids Clidinium-chlordiazepoxide Dicyclomine Hyoscyamine Propantheline Scopolamine Tertiary TCAs (amitriptyline, clomipramine, doxepin, imipramine, and trimipramine) Can worsen constipation; agents for urinary incontinence: antimuscarinics overall differ in incidence of constipation; response variable; consider alternative agent if constipation develops Avoid unless no other alternatives For urinary incontinence: high All others: Moderate to low Weak b. Aspirin (>325 mg/d) Non-COX-2 selective NSAIDs May exacerbate existing ulcers or cause new or additional ulcers Avoid unless other alternatives are not effective and patient can take gastroprotective agent (proton pump inhibitor or misoprostol) Moderate Strong

Table 4. 2012 American Geriatrics Society Beers Criteria for Potentially Inappropriate Medications to Be Used with Caution in Older Adults (article) a. Aspirin b. Dabigatran c. Prasugrel d. Antipsychotics e. Vasodilators

a. for primary prevention of cardiac events Lack of evidence of benefit versus risk in individuals aged 80 Use with caution in adults aged 80 Low Weak b. Greater risk of bleeding than with warfarin in adults aged 75; lack of evidence for efficacy and safety in individuals with CrCl < 30 mL/min Use with caution in adults aged 75 or if CrCl < 30 mL/ min Moderate Weak c. Greater risk of bleeding in older adults; risk may be offset by benefit in highest-risk older adults (e.g., with prior myocardial infarction or diabetes mellitus) Use with caution in adults aged 75 Moderate Weak d. Carbamazepine Carboplatin Cisplatin Mirtazapine Serotonin-norepinephrine reuptake inhibitor Selective serotonin reuptake inhibitor Tricyclic antidepressants Vincristine May exacerbate or cause syndrome of inappropriate antidiuretic hormone secretion or hyponatremia; need to monitor sodium level closely when starting or changing dosages in older adults due to increased risk Use with caution Moderate Strong e. May exacerbate episodes of syncope in individuals with history of syncope Use with caution Moderate Weak

Adverse Drug Reactions (book)

book ADR is defined by the world health organization as a reaction that is noxious and unintended which occurs at dosages normally used in humans for prophylaxis diagnosis or therapy. ADRs increase with polypharmacy use and are the most frequently occurring drug related problem among elderly nursing home residents. the yearly occurrence in outpatient older adults is 5% to 33%. Seven predictors of ADRs in older adults have been identified as a) taking more than four medications b) more than 14 day hospital stay c) having more than four active medical problems d) general medical unit admission versus geriatric ward E) alcohol use history F) lower mini mental state examination score confusion dementia g) 2 to 4 new medications added during hospitalization. Similarly there are four predictors for severe ADRs experienced by the elderly: a) use of certain medications including diuretics NSAIDs, antiplatelet medication and digoxin b) the number of drugs taken C) age D) comorbidites. particular caution must be taken when prescribing drugs that alter cognition in the elderly including antiarrhythmics, antidepressant, anti-emetics, anti-histamine, anti-Parkinson, antipsychotics, benzodiazepines, digoxin, histamine-two receptor antagonist, NSAIDs, opioids, and skeletal muscle relaxants. one of the most damaging ADRs that frequently occur in older adults is medication related falls. falls are associated with a poor prognosis ranging from premature institutionalization to early death and polypharmacy is A risk factor. a systematic review concluded that psychotropic medications including benzodiazepines, antidepressants and antipsychotic have a strong association with increased risk of falls while antiepileptics and antihypertensive have a weak association. comprehensive fall prevention strategies should include medication simplification and modification to prevent or resolve ADRs

Medication Nonadherence (book)

book America's other drug problem is The term given to medication nonadherence by the national Council on patient information and education. non adherence to chronic medications is prevalent and escalates healthcare costs associated with worsening disease and increased hospitalization. medication adherence describes a patient's medication taking behavior, generally defined as the extent to which one adheres to an agreed regimen derived from collaboration with their healthcare provider. older adults are at greater risk for medication non adherence due to the high prevalence of multi morbidities, cognitive deficit, polypharmacy and financial barriers. numerous barriers to optimal medication adherence exist and include: patient's lack of understanding, providers failure to educate, polypharmacy leading to complex regimen and inconvenience, treatment of asymptomatic conditions, such as hypertension and dyslipidemia and cost of medications. following is a list of six "how" questions to ask when assessing medication adherence: how do you take your medicines? how do you organize your medicines to help you remember to take them? how do you schedule your meals and medicine times? how do you pay for your medicine? how do you think the medicine are working for your conditions? how many times in the last week or month have you missed your medicine? although no single intervention has found to improve adherence consistently, patient centered multi-component interventions such as combining education, convenience and regular follow-up have resulted in a positive impact on medication adherence and associated health outcomes. future research needs to include adherence studies evaluating belief related variables such as personal and cultural beliefs in larger and more ethnically diverse samples of older population

glucose metabolism (book)

book An inverse relationship between glucose tolerance and age has been reported. this is likely due to reduced insulin secretion and sensitivity (greater insulin resistance). consequently, the incidences of hypoglycemia are increased when using sulfonylureas, like glyburide and glipizide, from age-related impairment to counterregulate the hypoglycemic response. due to an impaired autonomic nervous system, elderly patients may not distinguish symptoms of hypoglycemia such as sweating, palpitations or tremors. they do experience neurological symptoms of syncope, ataxia, confusion or seizures

Off Label Medication Use (book)

book Currently there is a lack of pediatric dosing, safety and efficacy information for more than 75% of drugs approved in adults. off label use of medications occur in both outpatient and inpatient settings. off label use of medications is the use of a drug outside of its approved label indication. this includes the use of a medication in the treatment of illness that is not listed on the manufacturers package insert, use outside the licensed age range, dosing outside those recommended, or use of a different route of administration. it is appropriate to use a drug off label when no alternatives are available, however, clinicians should refer to published studies and case reports for availability, safety and efficacy and dosing information. FDA regulatory changes such as an extended patent exclusivity, provide incentives for a pharmaceutical manufacturer to market new drugs for pediatric patients, however, such incentives are not available for generic drugs.

Routes of Administration and Drug Formulation (book)

book Depending on age, disease and disease severity different routes of administration maybe considered. the rectal route of administration is reserved for cases where oral administration is not possible and IV reroute is not necessary. topical administration is often used for treatment of dermatological ailments. transdermal routes are often not recommend unless it is an approved indication such as the methylphenidate transdermal patch for treatment of attention deficit hyper activity disorder. the injectable route of initiation is used in patients with severe illnesses or when other routes in a ministration or not possible as done with adult patients. IV compatibility and access should be evaluated when giving parenteral medications. dilution of parenteral medications may be necessary to measure smaller doses for neonates. however a higher concentration of parenteral medication maybe necessary for patients with fluid restriction such as premature infants and patients with cardiac anomalies and/or renal disease. appropriate stability and diluent selection data should be obtained from the literature. When oral drug therapy is needed one must also consider the dosage form availability and a child's ability to swallow a solid dosage form. children younger than six are often not able to swallow oral tablets or capsules and may require oral liquid formulation. not all oral medication especially those that are approved for use in infants and children have a commercially available liquid dosage form. use of a liquid dosage formulation compounded from a solid oral dosage form is an option when they're available. factors such as drug stability, suspended daily dose, uniformity and palatability should be considered when compounding a liquid formulation. commonly used suspending agents include methylcellulose and carboxymethylcellulose eg ora-plus. palatability of a liquid formulation can be enhanced by using simple syrup or ora-sweet. if no dietary contraindication or interactions exist, doses can be mixed with food items such as pudding, fruit flavored gelatin, chocolate syrup, applesauce or other fruit Purée immediately before administration of individual doses. honey, although capable of masking unpleasant taste of medication may contain spores of clostridium botulism and should not be given to infants younger than one years old due to increased risk for developing botulism. most hospitals caring for pediatric patients compound formulations in their inpatient pharmacy. limited accessibility to compounded oral liquids in a community pharmacy poses greater challenges. a list of community pharmacy with compounding capabilities should be maintained and provided to the parents and caregivers before discharge from the hospital.

Effects of Pharmacokinetics and Pharmacodynamic Differences on Drug Therapy (book)

book Drug selection strategy may be similar or different depending on age or disease state as a result of differences in pathophysiology of certain diseases and pharmacokinetics and pharmacodynamics parameters among pediatric and adult patients. it is noteworthy that pediatric patients may require the use of different medications from those used in adults affected by certain diseases. for example phenobarbital is commonly used for treatment of neonatal seizures but seldom used for seizure treatment in adults due to differences in seizure ideology and availablity of extensive data regarding it's use in neonates compared with newer anti epileptic medications. there also exist commonalities between pediatric and adult patients such as therapeutic serum drug concentrations required to treat certain diseases. for example gentamicin peak and trough serum concentration needed for bacteremia treatment are the same in children and adults. appropriate selection and dosing of drug therapy for a pediatric patient depends on a number of specific factors such as age, weight, height, disease, comorbidities, developmental pharmacokinetics, and available drug dosage forms. pediatric drug doses are often calculated based on body weight like milligrams per kilogram per dose compared with uniform dosing like milligrams per day or milligrams per dose for adult patients. best accurate weight should be available when prescribing or dispensing medications for this patient population. pediatric doses may exceed adult doses by body weight for certain medications due to differences in pharmacokinetics and pharmacodynamics. hence the use of the pediatric drug dosing guide is recommended. due to multiple differences, including age-dependent development of organ function in pediatric patients, the pharmacokinetics, efficacy and safety of drugs often differ between pediatric and adult patients doses. pediatric dosing cannot be calculated based on a single factor of difference. equations proposed to estimate pediatric doses based on adjusted age or weight such as Clarks, Frieds or Youngs rule should not be routinely used to calculate pediatric doses because they account for only one factor of difference e.g. age or weight and they lack integration of the effect of growth and development on drug pharmacokinetics and pharmacodynamics in this population. for off label medication dosing when no alternative treatment is available in limited dosage guidelines have been published. clinicians may estimate a pediatric dose based on body surface area ratio. a proper pediatric dose equals adult dose times BSA in meters squared divided by 1.73 m². limitations for this dose estimating approach include the need for the patient to be of normal height and weight for age and lack of incorporation of exact pharmacokinetic differences regarding each medication

Metabolism Pediatrics (book)

book Hepatic drug metabolism is slower at birth in full-term infants compared with adolescents and adults with further delay in premature neonates. phase 1 reactions and enzymes, such as oxidation and alcohol dehydrogenase, are impaired in premature neonates and infants and do not fully develop until later childhood or adolescence. accordingly, the use of products containing ethanol or propylene glycol can result in increased toxicities including respiratory depression, hyperosmolarity, metabolic acidosis and seizures, thus should be avoided in neonates and infants. age at which cytochrome P450 isoenzymes like CYP 3A4, CYP2C19, activity reaches adult values varies depending on the iso Enzyme, with delayed development in premature infants. increased dose requirements by body weight for some hepatically metabolized medications like phenytoin and valproic acid in young children like ages 2 to 4 is theorized due to an increase liver mass to body mass ratio. this increasing metabolism slows to adult levels as the child grows through puberty into adulthood. among phase 2 reactions, sulfate conjugation by sulfotransferases is well developed at birth in term infants. glucuronidation by the uridine diphosphate glucuronosyltransferases, in contrast, is immature in neonates and infants reaching adult values at 2 to 4 years of age. in neonates, this deficiency results in adverse effects including cyanosis, ash gray color of the skin, limp body tone and hypotension also known as gray baby syndrome with the use of chloramphenicol. products containing benzyl alcohol or benzoic acid should be avoided in neonates due to immature glycine conjugation resulting in accumulation of benzoic acid. this accumulation can lead to gasping syndrome which includes respiratory depression, metabolic acidosis, hypotension, seizures or convulsions and gasping respirations. acetylation via N-acetyltransferase reaches adult maturation at around one year of life, however, overall activity is dependent on genotypic variability

Age Related Changes (book)

book In basic terms, pharmacokinetics is what the body does to the drug and pharmacodynamics is what the drug does to the body. All four components of pharmacokinetics: absorption, distribution, metabolism and excretion are affected by aging. The most clinically important and consistent is the reduction of renal elimination of drugs. As people age, they can become more frail and are more likely to experience altered and variable drug pharmacokinetics and pharmacodynamics. Even though this alteration is influenced more by patient's clinical state than their chronological age, the older patient is more likely to be malnourished and suffering from diseases that affect pharmacokinetics and pharmacodynamics. Clinicians have the responsibility to use pharmacokinetics and pharmacodynamic principles to improve the care of older patient and avoid adverse effects of pharmacotherapy.

Volume of Distribution (book)

book In pediatric patients, apparent volume of distribution is normalized based on body weight and expressed as L/kilogram. extracellular fluid and total body water per kilogram of body weight are increased in neonates and infants, resulting in a higher VD for water-soluble drugs such as aminoglycosides and decreases with age. therefore neonates and infants often require higher doses by weight (milligram per kilogram) than older children and adolescents to achieve the same therapeutics serum concentration. the use of the extracorporal membrane oxygenation (ECMO) can further affect VD of medications in patients due to the added volume from the circuit and potential fluid changes like edema while on the circuit. thus, the use of additional close clinical and, when available, therapeutic drug monitoring is recommended for those patients requiring ECMO. neonates and infants have a lower normal range for serum albumin (2 to 4 g per DL, 20 to 40 g per liter) reaching aduly levels after one year of age. highly protein-bound drugs such as sulfamethoxazole trimethoprim (Bactrim) are not typically used in neonates due to theoretical concern for bilirubin displacement. this displacement may result in a complication known as kernicterus from bilirubin encephalopathy. although neonates have lower body adipose composition compared with older children and adults, their overall VD for many lipid soluble drugs like lorazepam is similar to infants and adults. some medication like vancomycin or phenobarbital may also reach higher concentrations in the central nervous system of neonates due to an immature blood brain barrier

Inappropriate Prescribing (book)

book Inappropriate prescribing is defined as prescribing medications that cause a significant risk of adverse events when there is an effective and safer alternative. the incidence of prescribing potentially inappropriate drugs to elderly patients has been reported to be 12% in those living in the community and 40% in nursing home residents. a systematic review in 2012 reported that the median rate of an appropriate medication prescribing among elderly patients in the primary care setting was 19.6%. at times medications are continued long after the initial indication has resolved. the clinician prescribing for older adults must understand the rate of adverse reactions and drug to drug interactions, the evidence available for using a specific medication and patient use of over-the-counter, OTC medications and herbal supplements. screening tools have been developed to help the clinician identify potentially inappropriate medications in older adults. the most utilized is the beers criteria. first developed in 1991, the current beers criteria include 53 medications or medication classes that are potentially inappropriate in elderly patients listed in three categories: a) medications that should be avoided regardless of disease/condition b) potentially inappropriate medications when used in older adults with certain diseases/syndrome c) medications to use with caution. common medications referred to in the beers criteria are as follows: 1) tertiary tricyclic antidepressants (TCAs) like amitriptyline - strong anti-cholinergic and sedated properties 2) benzodiazepines including diazepam - increased risk of falls and fractures and cognitive impairment 3) first generation antihistamines like diphenhydramine - confusion and fall risk with prolonged affect 4) nonsteroidal anti-inflammatory drugs (NSAIDs) - increased risk of G.I. bleeding, exacerbate heart failure and cause kidney injury. examples of drug/disease combinations reported as potentially inappropriate: - anticholinergic drugs in patients with bladder outlet obstruction or benign prostatic hyperplasia, -metoclopramide and antipsychotics in patients with Parkinson's disease and antipsychotics in patients with dementia -benzodiazepines, anticholinergics, anti-spasmodics and muscle relaxers with cognitive impairment. practical strategies for appropriate medication prescribing include establishing a partnership with patients and caregivers to enable them to understand and self monitor their medication effects. provider should perform drug to drug and drug to disease interaction screening using time-limited trials to evaluate the benefits and risks of new regimens and trial of medications to assess need

Distribution (book)

book Mean physiological changes that affect distribution of drugs in older adults are changes in body fat and water and in protein binding. Lean body mass can decrease by 12% to 19% through loss of skeletal muscle in the elderly. Thus blood levels of drugs primarily distributed in muscle increase (e.g. digoxin), presenting a risk for overdose. While lean muscle mass decreases, adipose tissue can increase with aging by 18% to 36% in men and 33% to 45% in women. Therefore, fat soluble drugs (e.g. diazepam, amiodarone and verapamil) have increased volume of distribution (VD) leading to higher tissue concentration and prolonged duration of action. Greater VD levels leads to increased half life and time required to reach steady-state serum concentration. Total body water decreases by 10% to 15% by age 80. This lowers VD of hydrophillic drugs (e.g. aspirin lithium and ethanol) leading to higher plasma drug concentration than in younger adults when equal doses are used. Toxic drug affects may be enhanced when dehydration occurs and when the extracellular space is reduced by diuretic use. Likewise, plasma albumin concentration decreases by 10% to 20%, although disease and malnutrition contribute more to this decrease then age alone. In patients with an acute illness, rapid decreases in serum albumin can increase drug effects. Examples of highly protein-bound drugs include warfarin, phenytoin and diazepam. For most chronic medication these changes are not clinically important because although the changes affect peak level of the single-dose mean, serum concentrations at steady-state are not altered unless clearance is affected. For highly protein-bound drugs with narrow therapeutic indices (e.g. phenytoin), however, it is important to appropriately interpret serum drug levels in light of the older patients albumin status. In a malnourished patient with hypoalbuminemia, a higher percentage of the total drug levels consists of free drug than in a patient with normal serum albumin. If a hypoalbuminemia patient has a low total phenytoin level and the phenytoin dose is increased, the free phenytoin concentration may rise to a toxic level.

absorption (book)

book Multiple changes occur throughout the G.I. tract with aging but little evidence indicates that drug absorption is significantly altered. The changes include decreases in overall surface of the intestinal epithilium and gastric acid secretion and splanchnic blood flow. Peristalsis is weaker and gastric emptying is delayed. These changes slow absorption in the stomach especially for enteric-coated and delayed release preparations. Delays in absorption may lead to a longer time required to achieve peak drug effects but it does not significantly alter the amount of drug absorbed, and drug movement from the G.I. tract into the circulation is not meaningfully changed. However, relative achlorhydria can decrease the absorption of nutrients which is vitamin B 12, calcium and iron. Aging facilitates atrophy of the epidermis and dermis with a reduction in barrier function of the skin. Tissue blood perfusion is reduced leading to decreased or variable rates of transdermal subcutaneous and intramuscular drug absorption. Therefore, intramuscular injections should generally be avoided in the elderly due to unpredictable drug absorption. Additionally because saliva production decreases with age, medications that need to be absorbed rapidly by the buccal mucosa are absorbed at a lower rate. Yet for most drugs, absorption is not significantly altered in older patients and the changes described are clinically inconsequential.

Anticoagulants (book)

book Older people are more sensitive to anticoagulant drug affects compared to younger people. when similar plasma concentrations of warfarin are attained there is greater inhibition of vitamin K dependent clotting factors in older patients than in younger counterparts. overall ,the risk of bleeding is increased in the elderly and when over-anticoagulated, the likelihood of morbidity and mortality is higher. this is further complicated by the presence of polypharmacy, drug-drug interactions, non-adherence, and acute illness. close monitoring of the international normalized ratio (INR), and appropriate use is paramount. in contrast there's no association between age and response to heparin.

Central Nervous System (book)

book Overall geriatric patients exhibit a greater sensitivity to the effects of drugs that gain access to the CNS. in most cases, lower doses result in adequate response and higher incidence of adverse effects may be seen with standard and high doses. for example, lower doses of opioids provide sufficient pain relief for older patients, where as conventional doses can cause over sedation and respiratory depression. the blood brain barrier becomes more permeable as people age thus more medications can cross the barrier and cause CNS adverse effects. examples of problematic medications include benzodiazepines, antidepressants, neuroleptics and anti-histamines. there is a decrease in the number of cholinergic neurons as well as nicotinic and the muscarinic receptors, decreased choline uptake from the periphery and increased acetylcholinesterase. the elderly have a decreased ability to compensate for these imbalances of the neurotransmitters, which can lead to movement and memory disorders. older adults have an increased number of dopamine type 2 receptors making them more susceptible to delirium from anticholinergic and dopiminergic medications. at the same time they have a reduced number of dopamine and dopaminergic neurons in the substantial nigra of the brain resulting in higher incidence of extrapyramidal symptoms from antidopaminergic medication e.g. antipsychotics

Common Errors in Pediatric Drug Therapy (book)

book Pediatric drug therapy begins with identification of possible sources. the error rates for medication is as high as one in 6.4 orders among hospitalized pediatric patients. off label use of medication increases risk of medication error and has been attributed to the difference in frequency of errors compared with adults. one of the most common reasons for medication errors in the specialized population is incorrect dosing such as calculation errors. medication errors among pediatric patients are possible due to differences in dose calculation and preparation. it is important to identify potential errors thus **careful review of orders, calculations, dispensing, and administration drug therapy to infants and children. it is crucial to verify accurate weight, height and age for dosing calculations and dispensing of prescriptions because pediatric patients are vulnerable population for medication errors. consistent units of measurement and reporting patient variables such as weight kilograms and height centimeters should be used. dosing units such as milligram per kilogram micrograms per kilogram mEq per kilogram MMOL per kilogram or units per kilogram should also be used accurately. **given the age related differences in metabolism of additives such as propylene glycol and benzyl alcohol, careful consideration should be given to the active and inactive ingredients when selecting a formulation. Decimal errors including trailing zeros like 1.0 mg misread as 10 mg and missing leading zeros like .5 mg misread as 5 mg in drug dosing or body weight documentation are possible resulting in several fold overdosing. strength or concentration of drug should also be clearly communicated by the clinician and prescription orders. similarly labels that look alike may lead to drug therapy errors like mistaking a vile of heparin for insulin. dosing errors of combination drugs can be prevented by using the right component for those calculation like dose of Bactrim is calculated based on the trimethoprim component. Use of standardized concentrations and programmable infusion pumps such a smart pumps with built-in libraries is encouraged to minimize errors with fragile medication especially those for continuous infusion such as inotropes. computer physician order entry systems and barcoding technology with ability for dose range checks by weight for pediatric medication orders and accurate matching of correct order medication to a patient respectively have decreased medication errors. Prevention of medication errors is a joint effort between healthcare professionals and patients and patient's parents.caregivers. obtaining a complete medication history including over-the-counter and complementary and alternative medications, simplification of medication regimen, clinician awareness for potential errors, and appropriate patient parent caregiver education on measurement and administration of medications are essential in preventing medication errors.

Drug-related problems (book)

book Polypharmacy complicates elderly health status particularly inappropriate medications that lead to drug related problems. it is reported that 20% of hospitalizations in older adults are due to medication related problems including non-adherence and ADRs. studies also indicate that 14% to 40% of the frail elderly are prescribed at least one inappropriate drug and unnecessary medication use was detected in 44% of older veterans at the time of hospital discharge. a decision tree model estimates the overall cost of drug-related morbidity and mortality in 2000 was greater than $177.4 billion with $121.5 billion (almost 70%) for hospital admissions and $32.8 billion (18%) for long-term care admission. Collaboration among interprofessional providers and older patients can ensure appropriate therapy, minimize adverse drug events and maximize medication adherence.

Polypharmacy (book)

book Polypharmacy is defined as taking multiple medications concurrently (4-9 medications or more have been used as criteria in studies). polypharmacy is prevalent in older adults who composed 14% of the US population but receive 36.5% of all prescription drugs. an estimated 50% of the community dwelling elderly take five or more medication and 12% of them take 10 or more . also common use of dietary supplements and herbal products in this population adds to the polypharmacy. in nursing home settings, patients receive nine or more chronic medications increased from 17% in 1997 to 27% in 2000. among various reasons for polypharmacy, an apparent one is a patient receiving multiple medications from different providers who treat the patients comorbidity without coordinated care. thus medication reconciliation becomes increasingly important as the aging population continues to grow. a review analyzing studies aimed at reducing polypharmacy in elderly emphasized complete evaluation of all medications by healthcare providers at each patient visit to prevent inappropriate polypharmacy. Efforts should be made to reduce polypharmacy by discontinuing any medication without indication. however clinicians should also understand that appropriate polypharmacy is indicated for older adults who have multiple diseases and support should be provided for optimal adherence. drug related problems associated with polypharmacy can be identified by performing a comprehensive medical review

Geriatric Education (book)

book Poor adherence in the geriatric age group could be related to inadequate patient education. ask me three cues the patient to ask three important questions of their provider to improve health literacy. 1. what is my main problem? 2. what do I need to do? 3. why is it important for me to do this? the provider can assess patient grasp of medication instructions by asking the patient to repeat instructions initially and then again in three minutes (teach back method). consideration of geriatric patients vision hearing swallowing cognition motor impairment education and health literacy during counseling and education can lead to enhanced medication adherence. specific drug formulation such as metered dose inhalers, opthalmic/otic drops, and subcutenous injections will require detailed education and practice. more time needs to be spent on advising the patient and/or care givers of potential ADRs and when to notify the provider about ADRS also.

Cardiovascular System (book)

book decreased homeostatic mechanism in older adults increase their susceptibility to orthostatic hypotension when taking drugs that affect the cardiovascular system and lower the arterial blood pressure. this is explained by a decrease in arterial compliance and baroreceptor reflex response which limits their ability to compensate quickly for postural changes in blood pressure. it has been estimated that 5% to 33% of the elderly experience drug-induced orthostasis. examples other than typical antihypertensives that have a higher likelihood of causing orthostatic hypertension in geriatric patients are tricyclic antidepressants, antipsychotics, loop diuretics, direct vasodilators, and opioids. older patients have a decreased beta adrenergic receptor function and they are less sensitive to beta agonist and beta adrenergic antagonist effects in the cardiovascular system and possibly in the lungs but their response to alpha agonist and antagonist is unchanged. increased hypotensive and heart rate response to a lesser degree to calcium channel blocker's (e.g. verapamil) are reported. increased risk of developing drug-induced QT prolongation and torsades de pointes is also present. therefore clinicians may start at low doses and titrate slowly, closely monitoring the patient for any adverse effects

Elimination (book)

book p. 10 the Clinically most important pharmacokinetic change in the elderly is the decrease in Renal drug elimination. as people age, Renal blood flow, renal mass, glomerular filtration rate, filtration fraction, and tubular secretion decrease after age 40. there is a decrease in the number of functional glomeruli and renal blood flow declines by approximately 1% yearly. From age 25 to 85 years, average renal clearance declines by as much as 50% and is independent of the effects of the disease. still the impact of age on renal function is variable and not always linear. longitudinal studies have suggested that a percentage up to 33% of older adults do not experience this age-related decline in renal function. Clinically significant effects of decreased renal clearance include prolonged drug half-life, increased serum drug level and increased potential for adverse drug reactions (ADRs). special attention should be given to renal eliminated drugs with a narrow therapeutic index (e.g. digoxin and aminoglycosides). monitoring serum concentration and making appropriate dose adjustments for these agents can prevent serious ADRs resulting from drug accumulation. it is important to know that despite a dramatic decrease in renal function (creatinine clearance) with aging, serum creatinine may remain fairly unchanged and remain within normal limits. this is because elderly patients especially the frail elderly have decreased muscle mass resulting in less creatinine production for input into circulation. because chronic kidney disease can be overlooked the clinician focuses only on the serum creatinine value, and overdose and AGRs can occur. thus creatinine clearance should be calculated when starting or adjusting pharmacotherapy in older adults. Clearance measure using 24 hour urine collection is impractical, costly and often done inaccurately. the Cockroft Gault equation is the most widely used formula for estimating renal function and adjusting drug doses. creatinine clearance = ((140 - age) x Weight in kilograms / serum creatinine x 72) × 0.85 if female when serum creatinine is expressed in mg/dL. CrCl (mls per minute) = ((140-age)×1.23 times BW / Scr) x 0.85 if woman when Serum creatinine is expressed in umol/L and converted to units of milliliters per second by multiplying by 0.167. This equation is also used by drug manufacturers to determine Renal dosing guidelines. the cockcroft-gault equation provided the best balance between predictive ability and bias in a study that compared it with the modification of diet and renal disease (MDRD )and Jelliffe bedside clearance equations. understand that the predictive formula can significantly overestimate actual renal function in chronically ill debilitated older patients

Elimination Pediatrics (book)

book p 24 Nephrogenosis is complete at approximately 36 weeks gestation thus premature neonatal and infants have compromised glomerular and tubular function that may correlate with the glomerular fultration rate. this reduction in GFR effects renal drug clearance thereby necessitating longer dosing interval for renally cleared medication such as vancomycin, to prevent accumulation. GFR increases with age and exceeds adult values an early childhood after which there is a gradual decline to approximate adult values during adolescence. for example vancomycin is often given every 18 to 24 hours in a low birth weight premature neonate, every six hours in children with normal renal function, and every 8-12 hours in adult patients with normal renal function. children with cystic fibrosis also present with greater renal clearance of drugs such as aminoglycoside compared with children without the disease requiring higher dosage by weight and more frequent dosing intervals. pediatric GFR also referred to as creatinine clearance informally by clinicians is normalized due to variable body size (ml/min/ 1.73 m2). The Cockroft Gault, Jelliffe, or modification of diet and renal disease (MDRV) equations for estimated GFR in adults should not be used for evaluating patients younger than 18 years. the schwartz equation is a common method of estimating pediatric GFR from infancy. after 21 years of age this equation uses patient length in centimeters, serum creatinine (milligrams per DL or umol/L times 0.0113) and a constant, K, which depends on the age including LBW status for infants, for all patients and also gender for all for those older than 12 years. there's also a simplified version of this equation validated for ages one through 16 years old commonly referred to as the bedside schwartz equation. estimated GFR = .413 x height inches centimeters / CM creatinine milligrams per DL or estimated GFR = 36.5 x height inches centimeters / serum creatinine in umol/L GFR = KL / SCR low birth weight/less than one year k is .33 full-term/less than one year K is .45 1 to 12 years K is .55 13 to 21 in a female. 55 13-21 in male is .70 K is proportionally constant L is length in centimeter SCR equals serum creatinine in milligrams per DL GFR estimated glomerular filtration rate or creatinine clearance in ml per min per 1.73m2 because serum creatinine is a crude marker of GFR the Schwartz equation as with other estimation calculations carries limitations including the potential for overestimating GFR in patients with moderate to severe renal insufficiency. urine output is also a parameter used to assess renal function in pediatric patients with a urine output more than 1 to 2 mL per kilogram per hour considered normal.

Pharmacodynamic Changes (book)

pharmacodynamics refers to the actions of a drug at its target site and the body's response to that drug. in general, the pharmacodynamic changes that occur in the elderly tend to increase their sensitivity to drug effects. most pharmacodynamic changes in the elderly are associated with a progressive reduction in homeostatic mechanisms and changes in receptor properties. Although the end result of these changes is an increased sensitivity to the effects of many drugs, a decrease in response can also occur. the changes in the receptor site include alterations in binding affinity of the drug, number or density of active receptors of the target organ, structural features and post receptor effects (biochemical processes/signal transmission). these include receptors in the adrenergic, cholinergic, and dopaminergic systems as well as y-aminobutyric acid (GABA) and opioid receptors

Central Nervous System (article)

Tertiary TCAs, alone or in combination: Amitriptyline Chlordiazepoxide-amitriptyline Clomipramine Doxepin > 6 mg/d Imipramine Perphenazine-amitriptyline Trimipramine Highly anticholinergic, sedating, and cause orthostatic hypotension; safety profile of low-dose doxepin ( 6 mg/d) is comparable with that of placebo Avoid High evidence Strong reco

Thioridazine Mesoridazine (article)

(Article) Highly anticholinergic and risk of QT-interval prolongation Avoid Moderate evidence Strong reco

Cardiovascular potentially inappropriate (article) a. Heart failure b. Syncope

(article) a. NSAIDs and COX-2 inhibitors Nondihydropyridine CCBs (avoid only for systolic heart failure) Diltiazem Verapamil Pioglitazone, rosiglitazone Cilostazol Dronedarone Potential to promote fluid retention and exacerbate heart failure Avoid NSAIDs: moderate CCBs: moderate Thiazolidinediones (glitazones): high Cilostazol: low Dronedarone: moderate Strong b. AChEIs Peripheral alpha blockers Doxazosin Prazosin Terazosin Tertiary TCAs Chlorpromazine, thioridazine, and olanzapine Increases risk of orthostatic hypotension or bradycardia Avoid Alpha blockers: high TCAs, AChEIs, and antipsychotics: moderate AChEIs and TCAs: strong Alpha blockers and antipsychotics: weak

Barbiturates (article)

(article) Amobarbital* Butabarbital* Butalbital Mephobarbital* Pentobarbital* Phenobarbital Secobarbital* High rate of physical dependence; tolerance to sleep benefits; risk of overdose at low dosages Avoid High evidence Strong reco

Dronedarone (article)

(article) Worse outcomes have been reported in patients taking dronedarone who have permanent atrial fibrillation or heart failure. In general, rate control is preferred over rhythm control for atrial fibrillation Avoid in patients with permanent atrial fibrillation or heart failure Moderate evidence Strong reco

Medication Nonadherence (ppt)

-three or more chronic medical condition -significant cognitive or physical impairments -living alone in the community -five or more chronic medications -recent hospital discharge -three times or more per day dosing of 12 or more medication doses per day -caregiver reliance -low health literacy -four or more medication changes in the past 12 months -medication cost, -history of medication non adherence -three or more prescribers -taking a med 3x a day or more -someone has problem remembering to take vitamins, let alone 3 times a day -3 or more prescribers involved someone has to take control, primary care provider, you say what are we doing, lets talk about it -med cost? - brand name, can they use/tolerate generic, is there a reason why they want brand name **numerous barriers to optimal medication adherence exist and include: patient's lack of understanding, providers failure to educate, polypharmacy leading to complex regimen and inconvenience, treatment of asymptomatic conditions, such as hypertension and dyslipidemia and cost of medications. **Education, convenience and regular follow-up

Geriatric changes 1. cardiac 2. CNS 3. Fluids an Electrolytes 4. glucose metabolism 5. anticoagulants

1. increase susceptibility to orthostatic hypotension when taking drugs that affect the cardiovascular system and lower the arterial blood pressure. May start at low doses and titrate slowly, closely monitoring the patient for any adverse effects. 2. sensitive to drugs that gain access to CNS- lower doses result in adequate response and higher incidence of adverse effects may be seen with standard and high doses. susceptible to movement and memory disorders, delirium, higher incidents of extra-pyramidal symptoms. The blood brain barrier becomes more permeable-medications can cross more easily. 3. Fluid and electrolyte homeostatic mechanism is decreased in the geriatric population. the elderly experience more severe dehydration, increased incidence of hyponatremia, hyperkalemia and prerenal azotemia especially when the older adult is taking a diuretic. increased potential to cause hyperkalemia and acute renal failure in older adults- agents need to be started with low doses titrated slowly and monitored frequently. 4. Incidences of hypoglycemia are increased when using sulfonylureas. Impaired autonomic nervous system, elderly patients may not distinguish symptoms of hypoglycemia such as sweating, palpitations or tremors. they do experience neurological symptoms of syncope, ataxia, confusion or seizures. 5. More sensitive to effects and also higher bleeding risk. issues r/t polypharmacy, non-adherence, acute illness. close monitoring of the international normalized ratio (INR), and appropriate use is paramount. in contrast there's no association between age and response to heparin.

Most Common Medications Associated with ADEs (ppt)

Opioid analgesics NSAIDs Anticholinergics Benzodiazepines Also: CV agents, CNS agents, & Musculoskeletal agents Not saying don't give them their anti-hypertensives, need to educate!, you may have orthostatic hypotension, when you get out of bed really quick in the morning, after you take BP med if you get up really quickly from chair you may become dizzy -flexiril, back spasms, muscle relaxer, musculoskeletal agents - get 40's and 50's, healthy, melt into couch or bed, think about older population for that

Undermedication (book)

Much has been written about the consequences of overmedication and polypharmacy in the elderly, however, underutilization of medication is just as harmful resulting in reduced functioning at increased morbidity and mortality. there are instances when a drug is truly contraindicated when a lower dose is indicated or when prognosis dictates withholding therapy. outside of those scenarios many elders do not receive therapeutic interventions that would provide benefit. this occurs for many reasons including belief that treatment of primary problem is enough intervention, cost, concerns of non-adherence, fear of adverse effects and associated liability, starting low and failing to increase to an appropriate dose, skepticism regarding secondary prevention benefits or ageism. A study found under prescribing in 64% of older patients and those on more than eight medications at the highest risk. interestingly, the lack of proven beneficial therapy did not depend on age, race, sex, comorbidity, cognitive status and dependence, and activities of daily living. a clinical assessment to weigh the potential benefit verse harm of the older patients complete medication regimen is required. once obvious contraindications have been dismissed, the patient's goals and preferences, prognosis and time to therapeutic benefit should be taken into consideration to determine whether the pharmacotherapy meets treatment goals. Underprescribing can be avoided by using clinical assessment strategies and improving adherence support and liberalizing financial coverage of drugs

Kidney and urinary tract (article) a. Chronic kidney disease Stages b. Urinary incontinence (all types) in women c. Lower urinary tract symptoms, benign prostatic hyperplasia d. Stress or mixed urinary incontinence

a. IV and V NSAIDs Triamterene (alone or in combination) May increase risk of kidney injury Avoid NSAIDs: moderate Triamterene: low NSAIDs: strong Triamterene: weak b. Estrogen oral and transdermal (excludes intravaginal estrogen) Aggravation of incontinence Avoid in women High Strong c. Inhaled anticholinergic agents Strongly anticholinergic drugs, except antimuscarinics for urinary incontinence (see Table 9 for complete list) May decrease urinary flow and cause urinary retention Avoid in men Moderate Inhaled agents: strong All others: weak d. Alpha blockers Doxazosin Prazosin Terazosin Aggravation of incontinence Avoid in women Moderate Strong

Gastrointestinal a. Metoclopramide b. Mineral oil, oral c. Trimethobenzamide

a. Can cause extrapyramidal effects including tardive dyskinesia; risk may be even greater in frail older adults Avoid, unless for gastroparesis Moderate evidence Strong reco b. Potential for aspiration and adverse effects; safer alternatives available Avoid Moderate evidence Strong reco c. One of the least effective antiemetic drugs; can cause extrapyramidal adverse effects Avoid Moderate evidence Strong reco

Complementary Alternative Medicine (CAM) and OTC Medication Use (book)

book Between 30% and 70% of children with a chronic illness like asthma, ADHD, autism, cancer or disability use cams. cams can include mind body therapy like imagery or hypnosis, energy field therapies like acupuncture and acupressure, massage, antioxidants like vitamin C and E, herbs like St. John's wort kava, ginger, valarian, prayer, immune modulators like echinacea or other folk/home remedies. it is important to encourage communication about CAM use including interdisciplinary discussion between cam providers and pediatric healthcare providers. it is critical to appreciate that there are limited data establishing efficacy of various cam therapies in children. for example colic is a condition of unclear etiology in which an infant cries inconsolably for over a few hours in a 24 hour period, Usually during the same time of day. symptoms of excessive crying usually improve by the third month of life and often resolve by nine months of age. no medication has been approved by the FDA for this condition. some parents are advised by family and friends to use alternative treatments such as gripe water to treat colic. gripe water is an oral solution containing a combination of ingredients such as chamomile and sodium bicarbonate not regulated by the FDA. in addition some gripe water products may contain alcohol which is not recommended for infants due to their limited metabolism ability like alcohol dehydrogenase. some cam products like Saint johns wort can interact with prescription drugs and produce undesired outcomes. It is important to assess over-the-counter products in pediatric patients. for example, treatment of the common cold in children is similar to adults including symptom control with adequate fluid intake, rest, use of saline nasal spray and Tylenol 10 to 15 mg per kilogram per dose every 6 to 8 hours or ibuprofen 4 to 10 milligrams per kilogram per dose every eight hours for relief of discomfort and fever. other products such as topical vapor rub or oral honey have demonstrated some potential for alleviation of symptoms such as cough, based on survey studies of parents for children of two years and older. unlike adults symptomatic relief through the use of pharmacologic agents, such as over-the-counter combination cold remedies is not recommended for pediatric patients younger than four years. Currently the FDA does not recommend the use of over-the-counter cough and cold medications like that diphenhydramine and dextromethorphan in children younger than two years, however the consumer healthcare products association with the support of the FDA has voluntarily changed product labeling of over-the-counter cough and cold medications to say do not use in children under four years of age. this is due to increased risk for adverse effects like excessive sedation, respiratory depression, and no documented benefit in relieving symptoms. it has also been noted that these medications may be less effective in children younger than six years compared with older children and adults. also noteworthy is the potential for medication error with the use of over-the-counter products and older children such as cold medication containing diphenhydramine and Tylenol. a parent/caregiver may inadvertently overdose a child on one active ingredient such as Tylenol by administering Tylenol suspension for fever and a Tylenol containing combination product for cold symptoms. the use of aspirin in patients younger than 18 years with viral infections is not recommended due to the risk of Reye syndrome. **while making an appropriate recommendation for an over-the-counter product for a pediatric patient the parent caregiver should always be referred to their pediatrician for further advice and evaluation when severity of illness is a concern. clinician should respect parents caregivers believes in the use of cam and over-the-counter products and encourage open discussion with the intention of providing information regarding the risks and benefits to achieve desired health outcomes as well as optimize medication safety.

Specific Considerations in Drug Therapy (book)

book In addition to differences in pharmacokinetics and pharmacodynamics parameters, other factors including dosage formulations, medication administration techniques, and parent/caregiver education should be considered when selecting drug therapy

Absorption Peds (book)

book oral absorption maybe different in premature infants and neonates due to differences in gastric acid secretion and pancreatic and biliary function. neonates and infants have increased gastric pH like pH 6-8 due to lower gastric acid output by bodyweight, reaching adult values by approximately two years of age. low gastric acid secretion can result in an increased serum concentration of weak bases and acid-labile medication such as penicillin and decreased serum concentrations of weak acid medication such as phenobarbital due to increased ionization. additionally, gastric emptying time and intestinal transit time are delayed in premature infants increasing drug contact time with the gastrointestinal mucosa and drugs absorption. diseases such as gastroesophageal reflux, respiratory distress syndrome and congenital heart disease may further delay gastric emptying time. pancreatic exocrine and biliary function is reduced in newborns with about 50% less secretion of amylase and lipase than adults, reaching adult values as early as the end of the first year and as late as five years of age. deficiency and pancreatic secretions and bile salts in newborns can decrease by availability of prodrug esters such as erythromycin which require solubilization or intraluminal hydrolysis. due to limited data on oral bioavailability of medications and infants and children for newer agents, some drug dosing recommendations may be extrapolated from adult safety and efficacy studies in case reports. topical or percutaneous absorption in neonates and infants is increased due to a thinner stratum corneum, increased cutaneous perfusion and greater body surface to weight ratio. hence application of topical medication such as corticosteroid should be limited to the smallest amount possible. limiting exposure can help minimize serum concentrations of active drug as well as inactive yet potentially harmful additives such as propylene glycol. Intramuscular absorption and premature and full-term infants can be erratic due to variable perfusion, poor muscle contraction and decreased muscle mass compared with older patients. intramuscular administration may be appropriate for some medications, however, use of this route of administration can be painful and is usually reserved when other routes are not accessible for example initial IV doses of ampicillin and gentamicin for neonatal sepsis. Intrapulmonary absorption and disposition is largely due to anatomical size of the Lungs and drug delivery. the smaller airway of neonates and lower inspiratory volume can result in greater drug concentration in the upper and central airways. particle size, breathing pattern, and route like oral vs nasal, can impact the amount of drug absorbed and should be considered when utilizing pulmonary drug delivery devices such as nebulizers or inhalers. Rectal exemption can also be erratic due to uncontrollable pulsatile contraction and risk of expulsion in younger patients like infants and young children. thus it is not commonly recommended if other routes are available. this route is useful in cases of severe nausea and vomiting or seizure activity for medications that undergo extensive first pass metabolism. bioavailability increases as the blood supply bypasses the liver from the lower rectum directly to the inferior vena cava. availability of rectal dosage forms varies and use of oral medication or other dosage forms rectally is based on limited studied and case reports

geriatric- a list of six "how" questions to ask when assessing medication adherence:

how do you take your medicines? how do you organize your medicines to help you remember to take them? how do you schedule your meals and medicine times? how do you pay for your medicine? how do you think the medicine are working for your conditions? how many times in the last week or month have you missed your medicine?