Drugs that poison the elderly Brent Tipping Sub-specialist Geriatrician and Specialist Physician Division of Geriatric Medicine, Department of Medicine University of the Witwatersrand
To treat or not to treat? RISKS BENEFITS One of the four principles central to medical ethics: Non-maleficence above all (or first) do no harm (global)
82 year old lady with newly diagnosed hypertension. Three weeks previously she had been commenced on hydrochlorothiazide 12.5mg, enalapril 10mg and then amlodipine 5mg was added 2 weeks later. Blood pressure initially 199/104mmHg and 2 weeks later 175/98mmHg.
Which of the following could contribute to this presentation? 1. Hyponatremia 2. Overzealous lowering of her blood pressure 3. Orthostasis because standing blood pressure was no measured 4. Poor adherence 5. All of the above
Falls are an adverse drug event Rationalising medications lowers fall risk by 70% Estimated all-cause and hip-fracture-associated mortality rates Hypertensive elderly persons who began receiving treatment have increased risk of having a hip fracture during the first 45 days following treatment initiation (incidence rate ratio, 1.43; 95% CI, 1.19-1.72). Particularly at risk are older persons who have fallen (OR 2.31(1.01-5.29) Calcified tissue int. 1997;61:1630-1636. Butt et al. Arch Intern Med. 2012;172(22):1739-1744 Tinetti et al. JAMA Intern Med. 2014;174(4):588-595.
The Trial: International, multi-centre, randomised double-blind placebo controlled Inclusion Criteria: Age 80 or more Systolic BP; 160 199 mmhg + diastolic BP < 110mmHg Informed consent Exclusion Criteria: Standing SBP < 140mmHg Stroke in last 6 months Dementia Need daily nursing care Step III + perindopril 4 mg n = 3845 Step II + perindopril 2 mg Step I indapamide SR 1.5 mg Placebo Target BP 150/80 mmhg Placebo + Placebo + Placebo M-2 M-1 M0 M3 M6 M9 M12 M18 M24 M60 Bulpitt C, et al. Drugs and Aging 2001;18(3):151-164
Reduction in Mortality All cause Mortality Patients at risk placebo active ------ Placebo Active 21% reduction Number of reported serious adverse events: 448 in the placebo group vs 358 in active (p=0.001) Fewer fractures in the actively treated group (38 vs. 52) active treatment was associated with a reduction in incident fractures (HR 0.58, 95% CI 0.33 1.00, P=0.0498) Becket NS, et al. NEJM 2008;358:1887-1898
Risk of Thiazide-Induced Metabolic Adverse Events in Older Adults Veterans aged 65 and older newly prescribed a thiazide (N = 1,060) compared with propensity matched users of other antihypertensive medications (N = 1,060) Over 9 months of follow-up 14.3% of new thiazide users developed an AE, compared with 6.0% of nonusers (number needed to harm (NNH) 12, 95% confidence interval (CI) = 9 17, P <.001) 1.8% of new users developed a severe AE, compared with 0.6% of nonusers (NNH = 82, P =.008) 3.8% of new users had an emergency department visit or hospitalization with an AE compared with 2.0% of nonusers (NNH = 56, P =.02). Makam et al. J Am Geriatr Soc 2014; 62:1039 1045
You are consulted by the surgical team to review a 76 year old lady known with depression, chronic peripheral vascular disease and a painful septic stump with VRE cultured on tissue from the stump. She has developed atrial fibrillation with rapid ventricular rate, sweating, dyskinesia/tremor, and a severe hyperactive delirium. Review of her medications shows the following: linezolid 600mg 12 hourly citalopram 20mg daily tramadol 100mg 8 hourly paracetamol 1g 8 hourly atorvastatin 20mg at night clexane 40mg s/c 12 hourly aspirin 150mg daily
Which drug is contributing to this drug reaction? 1. Linezolid 2. Fluoxetine 3. Tramadol WHAT DRUG REACTION DOES THIS PATIENT HAVE?
Serotonin syndrome Boyer et al. N Engl J Med 2005;352:1112-20
78 year old lady presents for evaluation of 17kg of weight loss (now 45kg). She reports poor appetite and lethargy. She is known with long standing hypertension.
Which drug is most likely causing her side effects? 1. Verapamil 2. Bisoprolol 3. Ivabradine 4. Digoxin 5. Amiodarone
Which drug is most appropriate for her now if her resting ventricular response rate is 124/minute. 1. Verapamil 2. Bisoprolol 3. Ivabradine 4. Digoxin 5. Amiodarone
84 year old lady in the ICU. Known with late onset Alzheimer s type dementia. Significant BPSD s and TF. Presented with a hypoactive delirium, marked generalized rigidity, temp. swing of 35.5 to 38 degrees), with blood pressure and heart rate lability. BP swings from 210/102 to 90/54 within a two hour period. Therapy included: galantamine 8mg BD, carbamazepine 400mg BD, amitriptyline 25mg night, and risperidone 0.5mg BD. In view of some recent agitation the dose of risperidone had been increased 3 days prior. CK 150 (normal <170).
The most likely diagnosis is: 1. Urinary retention and delirium worsened by the amitriptyline 2. Aspiration pneumonia due to excessive sedation 3. Neuroleptic malignant syndrome 4. Accidental overdose of the carbamazepine 5. Galantamine withdrawal syndrome
Neuroleptic malignant syndrome DIAGNOSIS REQUIRES 4 FEATURES: Altered sensorium, eg, confusion, clouding of consciousness, disorientation, mutism, stupor or coma. Muscular rigidity Hyperpyrexia of unknown origin (greater than 39ºC ) Autonomic dysfunction including at least 2 of the following: rapid pulse (more than 90/min) rapid respiration (more than 25/min) blood pressure fluctuations (at least a change of 33 mm Hg in systolic pressure or 15 mm Hg in diastolic pressure) excessive sweating incontinence
Pathophysiology of Neuroleptic Malignant Syndrome
Information for Healthcare Professionals - Antipsychotics In April 2005, FDA notified healthcare professionals that patients with dementia related psychosis treated with atypical antipsychotic drugs are at an increased risk of death. FDA ALERT [16/06/2008]: FDA is notifying healthcare professionals that both conventional and atypical antipsychotics are associated with an increased risk of mortality in elderly patients treated for dementia-related psychosis. Antipsychotics are not indicated for the treatment of dementia-related psychosis.
BLACK BOX WARNING Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death. Analysis of seventeen placebo controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in the drug-treated patients of 1.7 times the risk in placebo treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug treated patients was about 4.5% compared to a rate of about 2.6% in the placebo group. Although the cause of death were varied, most of the deaths appeared to be either cardiovascular or infectious in nature.
Adjusted Incidence-Rate Ratios for Sudden Cardiac Death among Current Users of Six Frequently Prescribed Antipsychotic Drugs, According to Dose N Engl J Med 2009;360:225-35.
Risk of pneumonia and effect of duration of antipsychotic treatment No clear dose-response relationship J Am Geriatr Soc 56:661 666, 2008.
Neuroleptics in the elderly BENEFITS RISKS
82 year old lady known with moderately severe COPD presents with an third infective exacebation in 6 months. She is known with mild vascular dementia and resides in a mid-care institutional setting. Which of the following antibiotic choices is the least likely to result in cognitive deterioration? 1. Moxifloxacin 2. Levofloxacin 3. Cefepime 4. Ertapenem 5. Piperacillin-tazobactam
75 year older gentleman day 2 post-total hip replacement has a temporary pacemaker in situ because of heart block. Develops severe agitation, punching the nurse and kicking the registrar across the high care cubicle. You are phoned at 3am. Which option would be optimal: 1. Physically immobilise him with 4 point restraints, no chemical sedation. 2. Sedate him with lorazepam (ativan) 2mg IVI or IMI and 2mg IMI/IVI haloperidol (or ziprazidone 10mg IMI). 3. Sedate him with clotiapine (etomine) 80mg IVI and clonazepam 1mg IVI. 4. Sedate him with haloperidol 10mg IVI (or ziprazidone 20mg IMI) and Diazepam 10mg IVI. 5. Call the psychiatrist.
Thank you As medical practitioners we need to poison the diseases, not the patients. The line gets finer as one collects more diseases.