2Assessing Older Adults Assessment DomainScreening MethodsFurther Assessment (if screen is positive)See:MedicalMedical illnessesHx, screening physical examinationAdditional targeted physical examination, laboratory and imaging testsMedicationsMedications reviewPharmacy referralAppropriate Prescribing, Medication AssessmentNutritionInquire about weight loss (>10 lbs in past 6 mo), weigh patientDietary hx, malnutrition evaluationDentitionOral examinationDentistry referral
3Assessing Older Adults Assessment DomainScreening MethodsFurther Assessment (if screen is positive)See:MedicalHearingHandheld audioscope, Brief Hearing Loss Screener, whisper testEar examination, audiology referralHearing Impairment, Brief ScreenerVisionInquire about vision changes, Snellen chart testingEye examination, ophthalmology referralVisual ImpairmentPainInquire about painPain inventoryPain InventoryUrinary incontinenceInquire if patient has lost urine >5 times in past yearUI evaluationUrinary Incontinence
4Assessing Older Adults Assessment DomainScreening MethodsFurther Assessment (if screen is positive)See:MentalCognitive status,3-item recall, Mini-Cog MMSEMental status examination, dementia evaluationMini-CogEmotional statusGDS or other depression screen, inquire “Do you ever feel sad or blue?”In-depth interviewGDSSpiritual statusSpiritual hxIn-depth interview, chaplain or spiritual advisor referral
5Assessing Older Adults Assessment DomainScreening MethodsFurther Assessment (if screen is positive)See:PhysicalFunctional statusADLs, IADLsPT/OT referralBalance and gaitObserve patient getting up and walking, orthostatic BP and HRPOMA scalePOMAFallsInquire about falls in past yearFalls evaluation
6Assessing Older Adults Assessment DomainScreening MethodsFurther Assessment (if screen is positive)See:EnvironmentSocial, financial status Social hxIn-depth interview, social work referralEnvironmental hazardsInquire about living situation, home safety checklistHome evaluation
7Causes of Alteration of Drug Response in the Elderly Pharmacokinetic- Absorption- Distribution- Metabolism- ExcretionPharmacodynamicDrug interactions
9Altered Drug Action with Aging Pharmacokinetics: What the body does to the drug- Absorption of the drug- Distribution of the drug to various organs and tissues in the body- Metabolism of the drug- Renal excretion
10Altered Drug Action with Aging galactose, calcium, thiamine, iron AbsorptionThe gastrointestinal tract undergoes both physiologic and anatomic changes with agingabout 30% decrease in mucosal absorption surface in the small bowel and GI motility40% reduction in small intestine blood flowgalactose, calcium, thiamine, iron
11Altered Drug Action with Aging Absorption: Most frequently does not result in clinically relevant changes in drug absorption after oral administration: Factors that can alter drug absorption- swallowing difficulties- poor nutritional status- interaction with other prescription andnon prescription medications
12Altered Drug Action with Aging DistributionThe body composition is altered by agingdecrease in total body massdecrease in total body waterdecrease in lean body massdecrease in liver massincrease in total body fat
13Altered Drug Action with Aging DistributionVolume of distribution (Vd) of lipophilic drug is increased in the elderlyt 1/2 = xVdplasma clearanceProlong half life (t ½ )
14Altered Drug Action with Aging Alteration in protein binding of drugs. DistributionAlteration in protein binding of drugs.(decrease of albumin).acidic drugs and high protein binding drugs eg. phenytoin, phenylbutazone, warfarin may increase free drug concentration.
15Metabolism : The effect of age on hepatic clearance of drugs Altered Drug Action with AgingMetabolism : The effect of age on hepatic clearance of drugsHepatic clearance of drugs is determined by1.Intrinsic ability of the liver to metabolize drugsphase I reaction by the microsomal mixed function oxidase system. Aging decrease phase I reactionphase II conjugation not affected by aging2.Liver blood flow is reduced in the elderly
16Case 1 หญิง 73 ปี หกล้ม หน้าซีกซ้ายเขียว ในโรงพยาบาล 4 วันก่อน admitted เพราะไข้สูง ซึมลงประวัติ HT 12 ปี มี minor stroke left hemiparesis, good recoveryDx PneumoniaRx Antibiotic, hydration, oxygenation
18Case 1In the next morning the patient was well, refused any problem last night.Next night at 2 AM. She confused and agitated again. Diazepam 10 mg given orally and she slept for over 24 hr.
19Case 1When she woke up, brought to bathroom in wheel chair and fell in the bathroom. Bruise over her left face.Please discuss about her agitation and proper management
20Drug Young Old Diazepam 24 75 Chlordiazepoxide 10 30 Oxazepam 10 10 MEAN ELIMINATION HALF - LIFE (HOURS)Drug Young OldDiazepamChlordiazepoxideOxazepamLorazepamAlprazolamImipramineAmitriptylineDesipramineNortriptyline
21Altered Drug Action with Aging DistributionThe body composition is altered by agingdecrease in total body massdecrease in total body waterdecrease in lean body massdecrease in liver massincrease in total body fat
24Benzodiazepines Depressogenic Ataxia --- leading to falls and fracturesConfusionDisinhibition -- aggression & sexually inappropriate behaviourWithdrawal symptomsAVOID long acting Benzo’s such as diazepam and flurazepam (except may be in alcohol withdrawal)
25Benzodiazepines Short and intermediate acting preferred Used as adjunctive therapy mostly (potentiating agent)Sometimes indicated as a hypnotic – after organic and other psychiatric disorders have been ruled out
26Sedative-Hypnotic and Anxiolytic Drugs in the Elderly ActivityT1/2hrDoseNameFlurazepamHypnotic50-10015 mg hsDalmadormDiazepamAnxiolytic20-1002 mg/d or bidValiumTriazolam2-30.125 mgHalcionMidazolam7.5 mgDormicum
27and Anxiolytic Drugs in the Elderly Sedative-Hypnoticand Anxiolytic Drugs in the ElderlyDrugActivityT1/2hrDoseNameLorazepamAnxiolytic10-200.5-2 mg/dAtivanAlprazolam12-150.25 mg/d-1.0 mg/dXanaxTemazepamHypnotic5-1515 mg hsEuhypnosOxazepam5-2010 mg X 3/dSerax
28Case 2 หญิง 75 ปี BW 45 Kg. CC : N/V 2 วัน PI : case angina pectoris Rx : Propanolol and ASA gr V9 วันก่อน มี chest pain พบมี Atrialfibrillation (rate 126/m)Lab Cr = 0.9 mg%
29อาการของผู้ป่วยเกิดจากอะไร ? Case 2Rx : Digoxin (0.25 mg V x 3 ทุก 2 ชม. )HR /min ดีขึ้นD/C home ยา Digoxin (0.25) 1 tab ODกลับบ้านได้ 2 วัน เริ่มซึมลง คลื่นไส้ อาเจียนPE : P 42/min irregular, BP 90/60 mmHgอื่น ๆ ปกติอาการของผู้ป่วยเกิดจากอะไร ?
31Estimating Renal Function Creatinine clearance(Clcr) is used to assess renal function, and can be estimated by the Cockroft and Gault equationClcr = (140-Age)(Wt) *S(72)(Scr)where Clcr is the creatinine clearance in mL/minAge is in yearsWt is the lean or ideal body weight in kgScr is the serum creatinine concentration in mg/dLS = 1.0 for males and 0.85 for femalesภญ. ศุภศิล สระเอี่ยม
32Estimating Renal Function It is important to recognize that due to age-dependent declines in renal function, elderly patients with “normal” serum creatinines may have Clcr requiring dosage adjustmentA. 60 kg, 30-year-old man with serum creatinine 1 mg/dLClcr = (140-30)(60) *1 = mL/min(72)(1)B. 60 kg, 70-year-old man with serum creatinine 1 mg/dLClcr = (140-70)(60) *1 = mL/minภญ. ศุภศิล สระเอี่ยม
34Cardio-vascular drugs DigoxinHigh incidence of ADRs :(digoxin toxicity: nausea, vomitting, anorexia,cardiac arrhythmia, dead)Plasma digoxin levelsHalf-life of digoxin increase with agingภญ. ศุภศิล สระเอี่ยม
35Digoxin Special consideration Subacute toxicity of anorexia with weight loss more common initial sign than other GI of cardiovascular effectsBaseline an follow up ECG essentialDose on lean body weight and creatinine clearance with attention to electrolyte and thyroid statusภญ. ศุภศิล สระเอี่ยม
36Digoxin Adjust dose with Renal impairment and aged patients. Older adults may develop exaggerated serum/tissue concentration due toDecreased lean body massDecreased total body waterAge – related reduction in renal functionDrug InteractionsMost common : K wasting diuretic: amiodaroneภญ. ศุภศิล สระเอี่ยม
38Case 3 FU ครั้งสุดท้าย 8 วัน ก่อนมาโรงพยาบาล INR 2.46 Complaint ไข้ ไอ เจ็บคอDx. PharyngitisRx. Clarithromycin added(Hx of penicillin allergy)
39Case 3เช้าวันนี้ตื่นนอนปกติ หลังอาหารเช้า ไอมาก แล้วปวดศีรษะ หมดสติ ญาติพามาโรงพยาบาลPE : coma,pupil dilated left side 4 mm.sluggish react to lightright 3 mm.decorticate posture
40Problem Coma : acute cerebral hemorrhage Underlying DM, HT Atrial fibrillation with anticoagulant
41Anticoagulants Heparin Warfarin Special consideration : Increase risk of bleeding with ageWarfarinStrongly protein - bound and metabolized by the liverDose required for proper anticoagulation is lower in elderlyภญ. ศุภศิล สระเอี่ยม
42Increase the effect of Warfarin ยาที่อาจเกิด Drug Interaction กับยา WarfarinSignificance level 1 (Major severity)*Increase the effect of WarfarinReduce the effect of WarfarinAmiodaroneAndrogens (Danazol, Methyltestosterone, Oxymetholone, Stanozolol)Azole Antifungal Agents (Fluconazole, Itraconazole, Ketoconazole, Miconazole )CimetidineFibric acid (Fenofibrate, Gemfibrozil)Macrolide Antibiotics (Azitromycin, Clarithromycin, Erythromycin)MetronidazoleBarbiturates (Phenobarbital)ภญ. ศุภศิล สระเอี่ยม
43Increase the effect of Warfarin ยาที่อาจเกิด Drug Interaction กับยา WarfarinSignificance level 1 (Major severity)*Increase the effect of WarfarinReduce the effect of WarfarinPhenylbutazoneQuinine derivatives (Quinine, Quinidine)Salicylates (Aspirin)Sulfonamide (Sulfasalazine, Sulfamethoxazole, Trimethroprim- Sulfamethoxazole)Tetracycline derivatives (Tetracycline, Doxycycline, Oxytetracycline)Thyroid hormones (Levothyroxine)Vitamin Eภญ. ศุภศิล สระเอี่ยม
44Drug InteractionsSignificance RatingA number 1 through 5 will be assigned to each interaction monograph, based on the Editorial Group’s assessment of the interaction’s Severity and Documentation (defined below)is a severe and well documented interaction.is an interaction of no more than unlikely or possible documentation.Major : The effects are potentially life-threatening or capable of causing permanent damageภญ. ศุภศิล สระเอี่ยม
46Key Elements of Patient Education Regarding Warfarin Identification of generic and brand namesPurpose of therapyExpected duration of therapyDosing and administrationVisual recognition of drug and tablet strengthWhat to do if a dose is missedImportance of prothrombin time/INR monitoringRecognition of signs and symptoms of bleedingWhat to do if bleeding occursภญ. ศุภศิล สระเอี่ยม
47Ten Most Common Drug-Drug Interactions in the Elderly Adverse eventWarfarin sodium (Coumadin)NSAIDsCelecoxib (Celebrex), ibuprofen (Advil,Motrin), naproxen (Aleve, Anaprox,Naprosyn), rofecoxib (Vioxx), sulindac(Clinoril), tolmetin (Tolectin) and othersPotentially serious gastrointestinal bleeding due to gastric irritation and erosion of the protective lining of the stomach;ability of platelets to form clotsWarfarin sodiumSulfonamidesSulfamethizole (Thiosulfil Forte),sulfamethoxazole (Gantanol), sulfisoxazole(Gantrisin) and othersMechanism unknown; probably due to competitive protein binding, and possibly also due to prolongation of warfarin's activity related to decreased production of vitamin K by intestinal floraMacrolidesAzithromycin (Zithromax), clarithromycin(Biaxin), erythromycin, troleandomycin (Tao)and otherseffects of warfarin, bleeding potential, possibly due to decreased production of vitamin K by intestinal flora and inhibited metabolism and clearance of warfarinQuinolonesAlatrofloxacin (Trovan), ciprofloxacin(Cipro), gatifloxacin (Tequin), lomefloxacin(Maxaquin), levofloxacin (Levaquin),moxifloxacin (Avelox), norfloxacin (Noroxin),ofloxacin (Floxin), sparfloxacin (Zagam),trovafloxacin (Trovan) and othersPhenytoinPhenytoin (Dilantin)effects of warfarin and/or phenytoin, possibly due to liver metabolism
48Ten Most Common Drug-Drug Interactions in the Elderly Adverse eventACE inhibitorsBenazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), ramipril (Altace), trandolapril (Mavik) and othersPotassium supplementsPotassium acetate, potassium acid phosphate, potassium bicarbonate, potassium chloride, potassium citrate, potassium gluconate and othersserum potassium;ACE inhibition decreases aldosterone production and decreases potassium excretionACE InhibitorsSpironolactone (Aldactone)unknown, possibly additive effectCardiac glycosidesDigoxinAntiarrhythmic agentsAmiodarone (Cordarone, Pacerone)Digoxin toxicity;mechanism unknown, possibly decreased clearance of digoxinCalcium channel blocking agentsVerapamil (Calan, Isoptin, Verelan)Digoxin toxicitydue to slowed impulse conduction and muscle contractility, leading to bradycardia and possible heart blockBronchodilatorsAminophylline (Phyllocontin, Truphylline), oxtriphylline (Choledyl), theophyllineQuinolonesAlatrofloxacin, ciprofloxacin, gatifloxacin, lomefloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin and othersTheophylline toxicitydue to inhibition of hepatic metabolism of theophylline by the quinolones
49Case 4 ชาย 72 ปี high fever and chill 3 hrs PTA Underlying DM, HT for 10 yearsRecent history of ischemic stroke with right hemiparesis 6 month ago.
50Case 4 On the last visit 1 mo ago, the family reported frequent crying with desire todeath because of dependency.Nortriptaline 10 mg was added to drugregiment. The patient seemed less crying
51Case 4History of frequent urination for 1 wk. and drowsy with low grade feverPE : full urinary bladder up to umbilicus
612002 Criteria for potentially inappropriate medication use in older adults : Considering diagnoses or conditionsDisease or ConditionDrugConcernSeverity Rating (High or Low)HypertensionPhenylpropanolamine hydrochloride (removed from the market in 2001), pseudoephedrine; diet pills , and amphetaminesMay produce elevation of blood pressure secondary to sympathomimetic activity.HighBeers Criteriaภญ. ศุภศิล สระเอี่ยม
622002 Criteria for potentially inappropriate medication use in older adults : Considering diagnoses or conditionsDisease or ConditionDrugConcernSeverity Rating (High or Low)Bladder outflow obstructionAnticholinergics and antihistamines, gastrointestinal antispasmodics, muscle relaxants, oxybutynin (Ditropan), flavoxate, decongestants, and tolterodine (Detrol)May decrease urinary flow, leading to urinary retentionHighBeers Criteriaภญ. ศุภศิล สระเอี่ยม
632002 Criteria for potentially inappropriate medication use in older adults : Considering diagnoses or conditionsDisease or ConditionDrugConcernSeverity Rating (High or Low)Syncope or fallsShort-to intermediate-acting benzodiazepine and tricyclic antidepressants (imipramine hydrochloride, doxepin hydrochloride, and amitriptyline hydrochloride)May produce ataxia, impaired psychomotor function, syncope, and additional falls.HighBeers Criteriaภญ. ศุภศิล สระเอี่ยม
642002 Criteria for potentially inappropriate medication use in older adults : Considering diagnoses or conditionsDisease or ConditionDrugConcernSeverity Rating (High or Low)Chronic constipationCalcium channel blockers, anticholinergics, and tricyclic antidepressant (imipramine hydrochloride, doxepin hydrochloride, and amitriptyline hydrocholoride)May exacerbate constipationLowBeers Criteriaภญ. ศุภศิล สระเอี่ยม
65HOW TO PRESCRIBE APPROPRIATELY Obtain a complete drug history.previous treatments and responsesallergiesOTC drugsnutritional supplementsalternative medicationsalcohol, tobacco, caffeine, and recreational drugs.Avoid prescribing before a diagnosis is made.Review medications regularly and before prescribing a new medication.D/C medications no longer needed.Monitor the use of prn and OTC drugs.
66HOW TO PRESCRIBE APPROPRIATELY Know the actions, adverse effects, and toxicity profiles of the medications you prescribe. Consider how these might interact or complement existing drug therapy.Start chronic drug therapy at a low dose and titrate dose on the basis of tolerability and response.Use drug levels when available.Attempt to reach a therapeutic dose before switching or adding another drug.
67HOW TO PRESCRIBE APPROPRIATELY Educate patient and/or caregiver about each medication.regimentherapeutic goalcostpotential adverse effectsdrug interactionswritten instructions.Avoid using one drug to treat the adverse events caused by anotherAttempt to use one drug to treat two or more conditions.
68HOW TO PRESCRIBE APPROPRIATELY Use combination products cautiously.Establish need for more than one drug.Titrate individual drugs to therapeutic dosesswitch to combinations if appropriate.Communicate with other prescribers.Don't assume patients will—they assume you do!Avoid using drugs from the same class or with similar actionseg. alprazolam and zolpidem
69CRITERIA FOR DRUGS OF CHOICE FOR OLDER ADULTS Established efficacyCompatible safety and adverse-event profileLow risk of drug or nutrient interactionsHalf-life <24 h with no active metabolitesElimination does not change with age or known dose adjustments for renal or hepatic functionConvenient dosing — single or twice dailyStrength and dosage forms match recommended doses for older adultsAffordable to the patient
70WAYS TO REDUCE MEDICATION ERRORS Be knowledgeable about the medication's dose, adverse events, interactions, and monitoring.Write legiblyto avoid misreading of the drug name (Celexa versus Celebrex).Write out the directions, strength, route, quantity, and number of refills.Always precede a decimal expression of <1 with a zero (0);never use a zero after a decimal.
71WAYS TO REDUCE MEDICATION ERRORS Avoid abbreviations, esp easily confused ones (qd and qid).Do not use ambiguous directions, eg, as directed (ud) or as needed.Include the medication's purposein the directions (eg, for high blood pressure).Write dosages for thyroid replacement therapy in μg not mg.Always re-read what you've written.
72Age-Associated Changes in Pharmacokinetics and Pharmacodynamics
73COMPLICATING FACTORS Physical Interactions Mg++, Ca++, Fe++, Al++, or zinc can lower oral absorption of levothyroxine and some quinolone antibiotics.Tube feedings decrease absorption of oral phenytoin and levothyroxine.
74COMPLICATING FACTORS Decreased Drug Effect Warfarin and vitamin K-containing foods (eg, green leafy vegetables, broccoli, brussels sprouts, greens, cabbage)Decreased Oral Intake or Appetitealter the taste of food (dysgeusia)decrease saliva production (xerostomia)making mastication and swallowing difficult.dysgeusia include captopril and clarithromycin.cause xerostomia include antihistamines, antidepressants, antipsychotics, clonidine, and diuretics.
75COMPLICATING FACTORS Drug-Drug Interactions impaired absorption eg, sucralfate and ciprofloxacindisplacement from protein-binding siteseg, warfarin and sulfonamidesinhibition or induction of metabolic enzymestwo or more drugs have a similar pharmacologic effecteg, potassium-sparing diuretics, potassium supplements, and ACE inhibitors
76COMPLICATING FACTORS Drug-Drug Interactions: Digoxin increase digoxin concentration or effect, or both:amiodaronediltiazemerythromycinesmolol flecainidehydroxychloroquineIbuprofenindomethacindecrease digoxin concentration or effect, or both:aminosalicylic acidantacids antineoplasticscholestyraminecolestipolnifedipinequinidinequininespironolactonetetracyclinetolbutamideverapamilkaolinpectinmetoclopramidepsylliumsulfasalazineSt. John's wort
77Enzyme Inhibitors and Inducers Selected CYP Isozyme Substrates, Inducers, and Inhibitors
78Enzyme Inhibitors and Inducers Selected CYP Isozyme Substrates, Inducers, and Inhibitors
79Enzyme Inhibitors and Inducers Selected CYP Isozyme Substrates, Inducers, and InhibitorsCYP2D6
80Medication Review for the 10-Minute Consultation: The NO TEARS Tool Need/indicationOpen questionsTestsEvidenceAdverse effectsRisk reductionSimplification/switches
81Age-related factors can change drug metabolism 4 major age-related pharmacokinetic alterationsdecreased eliminationdecreased hepatic metabolismaltered distribution in various body compartmentsaltered absorption
82Age-related factors can change drug metabolism Drug absorptionaffected by alterations in gastric pH and gastrointestinal motilitymay delay or increase the absorption of drugs.Distributionaffected by the alterations in protein bindingdecreased protein-rich lean body mass or low serum albumin levelsdrugs compete for the same protein-binding sites
85PolypharmacyThe administration of numerous medicines, often for multiple indications, at the same time.
86PolypharmacyThe administration of numerous medicines, often for multiple indications, at the same time.Derogatory senseThe probability of adverse drug events increases with the number of drugs prescribed
87Polypharmacy Six adverse consequences of polypharmacy Nonadherence (probability increases with complexity of the drug regimen)Adverse drug reactionsDrug-drug interactionsrisk of hospitalizationsMedication errors(e.g., taking too much of one drug + not enough of another)costs, from treatment of adverse events