Medication Management In Geriatric CKD

Transcription

1 Medication Management In Geriatric CKD 10 SEPTEMBER 2016 Jessica Goh Senior Pharmacist 1

2 Pharmacokinetic-Pharmacodynamic (PK-PD) Changes In Elderly 2

3 PHARMACOKINETICS (PK) ABSORPTION: process of drug entering blood stream DISTRIBUTION : dispersion/dissemination of drug to fluids and tissue in body METABOLISM : irreversible conversion of parent compounds to metabolites EXCRETION : elimination of metabolites from body 3

4 Absorption PO Meds PK CHANGES IN ELDERLY -Vitamin B12, Calcium and iron have absorption in elderly due to gastric ph or GI motility -Patients with heart failure may have blood flow to the GIT, leading to absorption Topical -Skin atrophies with aging reduced blood flow, impaired transdermal absorption IM/SC meds -Elderly have muscle mass poorer perfusion 4 Delafuente et al. Consult Pharm 2008

5 Distribution PK CHANGES IN ELDERLY - total body water Affects watersoluble drugs (eg digoxin, theophylline, morphine) due to Vd Higher serum drug concentrations - muscle mass Distribution to lean tissue is smaller Lower doses required -Higher body fat Affects lipid soluble drugs (eg phenytoin,valproate, diazepam) as they have larger Vd Longer duration of action as they are bound to the body longer -Lower dose or frequency interval required Delafuente et al. Consult Pharm

6 PK CHANGES IN ELDERLY Distribution - albumin concentrations (malnourished/frail/prolonged illness) More unbound drugs Higher serum concentrations of free drug -Uremic toxins protein binding affinity for drugs (eg penicillins, phenytoin,theophylline) = free (unbound)drug concentrations Delafuente et al. Consult Pharm

7 Metabolism PK CHANGES IN ELDERLY -Drugs undergoes metabolism in the liver via Phase 1 and Phase 2 reactions -Aging causes liver to be smaller poorer liver blood perfusion -Phase 1 (oxidation/reduction/hydrolysis) liver metabolism is in older patients -CYP system is responsible for Phase 1 reactions of many medications. >50% of drugs undergo CYP3A4 metabolism -Phase 2 reactions : not affected with aging Delafuente et al. Consult Pharm

8 PK CHANGES IN ELDERLY Elimination -as CrCl drug clearance by tubular secretion and glomerular filtration -Renal function may be overestimated due to low muscle mass Delafuente et al. Consult Pharm

9 PD CHANGES IN ELDERLY -Blunted baroreflex responses - inotropic and chronotropic responses to β 1 adrenergic stimulation -Increased sensitivity to agents that act on the central nervous system (CNS) Delafuente et al. Consult Pharm

10 ADJUSTING MEDICATIONS IN GERIATRIC CKD -General rule of thumb: Start low, Go s l o w -Avoid long acting agents in elderly -Some dosage adjustments may be based on CrCl (derived from Cockcroft-Gault equation) or egfr -Beers Criteria *Adjustments quoted in the following slides are for non-dialysis CKD patients 10

11 Antibiotics In Geriatric CKD 11

12 PO ACYCLOVIR Drugs Renal Fxn Dose Max Dose Acyclovir CrCl Recommended Dose q8h CrCl <10 Recommended Dose q12h 800mg/dose 2.4g/day 800mg/dose 1.6g/day Caution Potential risk for crystalluria Nephrotoxicity risk with concurrent nephrotoxic agents (ACE/ARB, NSAIDs, Colchicine) or dehydration Potential Risk for neurotoxicity UptoDate

13 ACYCLOVIR TOXICITY IN CKD The College Mirror, Vol 42, March

14 ACYCLOVIR NEUROTOXICITY IN CKD The College Mirror, Vol 42, March

15 ANTIBIOTIC ASSOCIATED DELIRIUM 15

16 ANTIBIOTIC ASSOCIATED DELIRIUM 16

17 ANTIBIOTIC ASSOCIATED DELIRIUM 17

18 DRUG ASSOCIATED WITH COGNITIVE IMPAIRMENT IN ELDERLY Moore AR et al.drugs Aging

19 Drugs PO ANTIBIOTICS Renal Function Dose Max Dose Amoxicillin CrCl mg BD 0.5-1g/day CrCl <10 500mg OD Augmentin CrCl mg BD Penicillin V CrCl <10 Use with caution in renal dysfunction 625mg OD Usual: 500mg q6h 4g/day UptoDate, Micromedex

20 PO ANTIBIOTICS Drugs Bactrim Dosed based on TMP component Single Strength:(TMP 80 mg/smx 400 mg)=480mg Double Strength:(TMP 160 mg/smx 800 mg)=960mg *Maintain adequate hydration to prevent crystalluria Nitrofurantoin Avoid in elderly due to risk for pulmonary toxicity Renal Fxn Dose CrCl CrCl <15 50% of dose Avoid Contraindicated in CrCl <60ml/min (ineffective) UptoDate, Micromedex

21 SULFONAMIDE CRYSTALLURIA UptoDate

22 PO ANTIBIOTICS Drugs Cefuroxime Renal Function Dose Max Dose CrCl mg q24h 500mg/day CrCl <10 500mg q48h 250mg/day Nitrofurantoin Avoid in elderly due to risk for pulmonary toxicity Contraindicated in CrCl <60ml/min UptoDate, Micromedex

23 ANTIBIOTICS NO RENAL ADJUSTMENT REQUIRED Drugs Max Dose (per day) Azithromycin 500mg Cloxacillin 6g Clindamycin 1.8g Doxycycline 200mg Ceftriaxone 4g Metronidazole 4g** Moxifloxacin 400mg **varying practice UptoDate, Micromedex

24 PO ANTIBIOTICS Drugs Renal Fxn Dose Ciprofloxacin CrCl <30 Levofloxacin 500mg OM CrCl mg/day: 500 mg STAT, then 250 mg q24h 750mg/day: 750mg q48h CrCl mg/day: 500 mg STAT, then 250 mg q48h 750mg/day: 500 mg STAT, then 500mg q48h UptoDate, Micromedex

25 DRUG-DRUG INTERACTIONS 25

26 Oral Hypoglycemic Agents (OHGAs) 26

27 METFORMIN -First line agent for Type 2 Diabetes -Low hypoglycemic risks egfr Dose adjustments 45 to <60 ml/min Monitor renal function 3-6monthly 30 to <45 ml/min <30 ml/min Avoid Use with caution, may consider dosage reduction American Diabetes Association, UptoDate, Micromedex

28 SULPHONYLUREAS UptoDate, Micromedex 2016 Drug Duration Excretion Renal Adjustment First Generation Chlorpropamide 24-72h Urine (unchanged drug and as hydroxylated metabolites) T/12 : ~36 hrs; prolonged in elderly.esrd : hrs Tolbutamide 14-16h Urine (75% -85% as metabolites. Metabolism not affected by age Second Generation Glipizide 14-16h Urine (<10% as unchanged drug; 80% as metabolites) Glicazide 24 h Urine (60% to 70%; <1% as unchanged drug Glibenclamide h Urine (50%)metabolites Glimepiride 24+ h Urine (60%, 80% -90% as M1 and M2 metabolites) CrCl >50 ml/min: by50%. CrCl <50 ml/min: Avoid use. No dosage adjustment available Less hypoglycemia in renal impairment than other SUs. Start low dose. Mild to Mod: Adjust slowly Severe impairment: Avoid egfr <60 ml/min: Avoid Severe impairment: Avoid 28

29 HSA ALERT -GLIBENCLAMIDE 29

30 -Low hypoglycemic risks DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS Drug Renal Function Elimination Dose Adjustment Sitagliptin CrCl ml/min CrCl <30 ml/min Excretion: Urine 87% (~79% as unchanged drug, 16% as metabolites) 50mg OD 25mg OD Saxagliptin CrCl 50 ml/min Urine (75%) 2.5 mg OD Linagliptin Regardless of renal function 80% cleared in feces 5mg OD None required UptoDate, Micromedex

31 Drug MEGLITINIDES Faster onset and shorter duration of effect than sulfonylureas Low risk of hypoglycemia Good for patient who are sulfonamides or sulphur allergy Duration Repaglinide 4-6h Nateglinide 4h Renal function CrCl CrCl <20 N/A Dosage adjustment Initial: 0.5 mg with meals; titrate carefully. Not studied No adjustment required Elimination Feces (~90%) Urine (83%) UptoDate, Micromedex

32 OTHER OHGAs Drug Renal function Adjustment Alpha-Glucosidase Inhibitors Eg Acarbose CrCl <25 ml/min or Scr >2mg/dL or 177umol/L Sodium-Glucose Cotransporter 2 Inhibitors Canagliflozin Dapagliflozin Avoid egfr 45 to <60 ml/min Max 100mg egfr <45 ml/min Avoid egfr 30 to <60 ml/min Avoid Empagliflozin egfr <45 ml/min Avoid Thiazolidinediones None required. Need to adjust for hepatic Avoid in patients with advanced CKD, especially those with preexisting heart failure, given the risk of edema and heart failure UptoDate, Micromedex

33 SUMMARY SLIDE ON OHGAs CKD Stage egfr Metformin SU Meglitnide DPP4 SGLT2 Acarbose Thiazolidinediones 3A * 3B * * X X * * * X X * 5 <15 X * * * X X * *requires renal adjustment/only certain agents in drug class recommended-conditions apply 33

34 PAINKILLERS IN GERIATRIC CKD 34

35 PAINKILLERS 2012 AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults 35

36 PAINKILLERS 2012 AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults 36

37 PAINKILLERS 2012 AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults 37

38 PAINKILLERS-START LOW UptoDate

39 DRUG ASSOCIATED WITH COGNITIVE IMPAIRMENT IN ELDERLY Moore AR et al.drugs Aging

40 Antihypertensives In Geriatric CKD 40

41 ACEI/ARB + DIURETICS + NSAIDS & NEPHROTOXICITY Acute kidney injury risk increases by 31%, with the highest risk occurring in the first month of use Triple whammy! Lapi et al. BMJ. 2013;346:e

42 WHAT BP TARGETS DO WE USE FOR ELDERLY? Guidelines Population Goal BP, mm Hg Remarks JNC General 60 y <150/90 Diabetes <140/90 CKD <140/90 ESH/ESC 2013 General elderly <80 y <150/90 *For fragile General 80 y <150/90 elderly, SBP goals should be Diabetes <140/85 adapted to CKD no proteinuria <140/90 individual CKD + proteinuria <130/90 tolerability CHEP 2013 General 80 y <150/90 Diabetes <130/80 CKD <140/90 NICE 2011 General 80 y <150/90 42 Abbreviations: CHEP, Canadian Hypertension Education Program; JNC, Joint National Committee; ESC, European Society of Cardiology; ESH, European Society of Hypertension; NICE, National Institute for Health Clinical Excellence.

43 ANTIHYPERTENSIVES ARE ASSOCIATED WITH FALL RISKS!! 43

44 ADVERSE DRUG EVENTS Hanlon JT et al. J Am Geriatr Soc

45 POLYPHARMACY- BANE OR BOON? 45

46 TAKE HOME MESSAGES Start low, Go s l o w Avoid polypharmacy Consider potential drug interactions Review patients & medications regularly Keep regimens simple Br J Clinc Pharmaco 1998; 46:

47 THANK YOU! 47

48 CASE STUDY 1 68y M, was found drowsy and referred to ED for hypoglycemia.he was recently prescribed a week course of Clarithromycin 500mg BD for URTI. PMH:T2DM, Hypertension, Parkinson disease, Dyslipidaemia and CKD Stage 3 What do you think could have caused his hypoglycemia? Medication list Aspirin 100 mg OM Metformin 250g BD Glibenclamide 10 mg BD Madopar 62.5mg qds during waking hours Lactulose 10ml BD Simvastatin 40 mg ON

49 HSA ALERT -GLIBENCLAMIDE 49

50 DRUG-DRUG INTERACTIONS 50

51 CASE STUDY 2 70y M, taxi driver, was referred to Nephrology clinic for AKI. Serum creatinine was 131umol/L. PMH: Gout, Hypertension What do you think could have caused his AKI? At the clinic, he brought his own meds from GP. Co-Diovan(Valsartan 80mg/HCTZ 12.5mg) 1/1 OM Allopurinol 100mg OM withheld by GP due to ARF Colchicine 500mcg TDS prn for gout flare Diclofenac 50mg TDS prn

52 ACEI/ARB + DIURETICS + NSAIDS & NEPHROTOXICITY Acute kidney injury risk increases by 31%, with the highest risk occurring in the first month of use Triple whammy! Lapi et al. BMJ. 2013;346:e

53 THANK YOU! 53