gp educational update in geriatrics may 2015 agnes toth
TRANSCRIPT
GP educational update in geriatrics
May 2015
Agnes Toth
• Cases from the rapid response/OPDAS clinic
• Drug therapies in older people
• STOPP/START medication reviews
• Anticholinergics and cognitive impairment
Patient examples from rapid response /OPDAS clinic
2/1
• 82 yr old male• 4/52 of SOB, significantly
worse on exertion, leg oedema • No chest pain
• PMHx: • LVF, AF (2005)-seen privately
by local cardiologist, • AAA repair 2005; • intermittent claudication 2005; • moderate, stable COPD 2010;
• Medication
• Frusemide 40mg bd• Digoxin 125mcg od• Bisoprolol 1.25mg od• Ramipril 10mg od• Rivaroxaban 15 mg od• Seretide, Tiotropium inhalers• Simvastatin 20 mg od
2/2
• Increasing Frusemide to 120 mg od –no effect in 1/52
• Added Prednisolone 30 mg od-no effect in 1/52
• Referred to rapid response clinic
2/3
• On exam: SOB+++ on getting in and out of chair
• pale• Slow AF, LAD, HR 50• BP 100/48 supine, 100/38 erect• JVP 3 cm• Pitting oedema to knees
2/4
• decision to admit • HB 55, MCV 74• OGD- chronic
duodenitis Colonoscopy/CT CAP: diverticular disease
• ECHO-LVEF 73%, mild RVF, moderate AS
2/5
• Transfused • Fe sulphate• Stopped Rivaroxaban• Continued Bisoprolol 1.25 and Digoxin 62.5• Frusemide 40 mg bd, Ramipril 10mg od
3/1
• 95 yr old lady• Seen 1st time by (this)GP • Lower back pain• CCF-oedema to mid thigh, clinical pleural effusion• Bumetanide doubled to 2 mg/day
• Bradycardia-slow AF-refused PPM as “doesn’t want to prolong life” HR 45
• Parotid swelling-currently being treated with Co-Amoxyclav, USS arranged after call to geriatrician of the day
• MGUS• DNAR
3/2
• Stopped Perindopril 2/52 before due to renal failure (RF not worse on results from 2/12 prior)
• Started Doxazosin same time• Bisoprolol 2/12
3/3
• HR 36, AF• Oedema to mid thigh• Dull chest bases, CXR bilateral effusions
3/4
• Stop Bisoprolol• Iv diuresis, fluid restriction• Apixaban
• D/C after 8 days as inpatient on• Perindopril 4 mg od• Frusemide 40 mg od• Bisacodyl 5mg od
3/5
• PPM 4 weeks later as day case
4/1
• 91 yr old lady• PMHx • Type II DM• Severe LVF diagnosed on ECHO 1995-20 yrs
ago!• AF since 1992• Essential hypertension• Femoral stents for arterial vascular disease• CRF stage 3.• Recent osteomyelitis of toe
4/2
• Medication:• Digoxin 125mcg od• Bumetanide 1 mg od• Ramipril 5 mg od• Apixaban 2.5mg od
4/3
• Increasing SOB and oedema• Refusing to come to hospital
4/4
• Exam: • AF 90 bpm• BP 140/80• Oedema to sacrum and large bilateral pleural
effusions, swollen hands and face
Toilet/bath and bedroom upstairs
4/5
• Bloods• HB 105• U 18 (up from 13)• Cr 180 (up from 130)• eGFR 24 (down from 30)
4/6
• Plan• Bumetanide 1 mg bd or up to 2 mg bd• Metolazone 5 mg 2x weekly• Twice weekly bloods• Palliative care• HF nurse in community• Communication of this potentially being terminal • Door remains open
Message
• Heart failure is leading cause of admission amongst elderly
• Complex• Being “too good” at keeping patients out of
hospital• Conflict• Bleep 0818 via switch
Drug therapiesSTOPP/START
ANTICHOLINERGICS
Prescribing (for the Older Patient)
• Does this agent reflect the priorities of the patient?
• Are there better alternatives? (efficacy, effectiveness, tolerability)
• Are the dose, frequency, formulation appropriate?
• How does this prescription relate to the concurrent medication?
“I’ve been feeling so much better since I’ve run out of those pills you gave me”
STOPP/START
• STOPP-Screening Tool for Older Persons Prescriptions
• START- Screening Tool to Alert Doctors to Right Treatment
http://ageing.oxfordjournals.org March 2015 Supplementary data, Appendix 1-4
Use of STOPP / START
• Secondary Care • Potentially inappropriate prescribing (STOPP) 34%• Potential Omissions (START) 57%
Gallagher et al, Age and Aging, 2008
• Nursing Homes • Potentially inappropriate prescribing (STOPP) 55%
Ryan et al, Ir J Med Sci, 2009O’Sullivan et al, Eur Ger Med,
2010• Primary Care• Potentially inappropriate prescribing (STOPP) 21%• Potential Omissions (START) 22%
Ryan et al,Br J Clin Pharm, 2009
STOPP: Urogenital System
• Antimuscarinic drugs with dementia or chronic cognitive impairment or narrow angle glaucoma or chronic prostatism
• Selective alpha-1 blockers in those with symptomatic orthostatic hypotension or micturition syncope
STOPP: Central Nervous System and Psychotropic Drugs
• Anticholinergics/antimuscarinics to treat extra-pyramidal side effect of neuroleptic medications
• Anticholinergics/antimuscarinics in patients with dementia
• Neuroleptic antipsychotics in patients with behavioural and psychological symptoms of dementia unless symptoms are severe and other non-pharmacological options have failed
• Neuroleptics as hypnotics-unless sleep disorder is due to psychosis or dementia
Effects of anticholinergics/antimuscarinics
• Central
• Acute impairment of:• Working memory• Attention deficit• Psychomotor speed• hallucinations
• Global cognitive impairment
• Peripheral
• Dry mouth• Tachycardia• Urinary retention• Constipation• Worsening of
glaucoma
Anticholinergic/antimuscarinic drugs in the elderly
• Prevalence of anticholinergic use 8-37% in older adults
• Primary care urban setting USA-60%
• Nursing homes-30% takes more than 2 drug, 5% up to 5 drugs!
Shelly L. at al.: Cumulative use of Strong Anticholinergic Medications and Incident Dementia, JAMA Internal Medicine, March 2015 (2)
• Prospective cohort study, based in Seattle• 3,434 participants aged ≥65 with no known dementia• Most common anticholinergics – antidepressants, antihistamines,
bladder antimuscarinics (>90% anticholinergic exposure)• Followed up over 10 year period• Cognitive function assessed biannually by neurologists,
geriatricians and neuropsychological testing• Pharmacy dispensing data analysed to assess cumulative
anticholinergic exposure• Over mean follow-up of 7.3 years 797 participants (23%)
developed dementia.• Concluded that higher cumulative anticholinergic medication use
is associated with an increased risk for dementia.
Comparison
• Prevalence of dementia in ≥65: 7.1% (Alzheimer’s UK, 2013 population data)
VS
• Prevalence of dementia in those using anti-cholinergics: 23%
• Higher cumulative use of anticholinergics is associated with increased risk for dementia
Why are older adults more susceptible?
• Age-related changes in pharmacokinetics and pharmacodynamics
• Reduced acetylcholine mediated transmission in the brain
• Increased permeability of the blood-brain barrier
Possible biological mechanisms
• Possible pathologic changes similar to Alzheimer’s disease• Amyloid plaque densities were more than 2.5-fold higher in
Parkinson’s patients treated with anticholinergics• Neurofibrillary tangle densities were also higher
Perry at al. 2003
• Genetic component: Increased cognitive sensitivity in subjects with ApoE ɛ4 allele after acute anticholinergic administration
• Disruption of cholinergic neurons throughout the basal and rostral pathways
• Level of acetylcholine reduced
• Cognitive impairment and behavioural symptoms
Pharmacological antagonism
cholinesterase inhibitors
anticholinergics
Atropine –successful antidote for cholinesterase inhibitor overdose
Anticholinergic activity of drugs
• Anticholinergic activity as measured by pmol/ml of Atropine equivalent
• 15+ amitriptyline, atropine, clozapine,, doxepin, L-hyoscyamine, thioridazine, and tolterodine
• 5-15 Chlorpromazine, nortriptyline, olanzapine, oxybutynin, paroxetine
• <5 Citalopram, escitalopram, fluoxetine, lithium, mirtazapine, quetiapine, ranitidine, temazepam
• Chew at al, J. American Geriatric Society, 2008
Determining the anticholinergic effect of medications
• Serum Radio-receptor Anticholinergic Assay (SAA)
• In vitro measurement of drug affinity to muscarinic receptors
• Expert based list of medications with anticholinergic affinity
Tools to determine anticholinergic risk
• Anticholinergic Risk Scale ARS (0-3)
• Anticholinergic Drug Scale ADS (0-3)
• Anticholinergic Cognitive Burden Score ABS
Score 1 Score 2 Score 3
Atenolol Amantadine Amitriptyline
Captopril Belladonna alkaloids Atropine
Chlorthalidone Carbamazepine Benztropine
Cimetidine Cyproheptadine (antihist.) Brompheniramine
Ranitidine Meperidine (pethidine) Chlorpheniramine
Codeine Levomepromazine Chlorpromazine
Colchicine Oxcarbazepine Clomipramine
Diazepam Pimozide Clozapine
Digoxin Darifenacin
Dypiridamole Desipramine
Fentanyl Dicyclomine
Frusemide Doxepin
Fluvoxamine Flavoxate
Haloperidol Hydroxyzine
Hydralazine Hyoscyamine
Hydrocortisone Imipramine
Isosorbide Nortriptyline
Loperamide Olanzapine
Score 1 Score 2 Score 3
Metoprolol Oxybutinine
Morphine Paroxetine
Nifedipine Procyclidine
Prednisone Promazine
Quinidine Promethazine
Risperidone Quetiapine
Theophylline Scopolamine
Trazodone Thioridazine
Triamterene Tolterodine
Trifluoperazine
Trimipramine
NICE
• CG 171(2013-Urinary incontinence in women)• When offering antimuscarinic drugs to treat OAB always
take account of: • the woman's coexisting conditions (for example, poor bladder
emptying)• use of other existing medication affecting the total anticholinergic
load• risk of adverse effects. [new 2013]
• Do not offer oxybutynin (immediate release) to frail older women[8]. [new 2013]
• Review women who remain on long-term drug treatment for UI or OAB every 6 months for women over 75). [new 2013]
NICE
• CG 42 (2006, Dementia)Antidepressant drugs with anticholinergic effects should be avoided because they may adversely affect cognition…
TA 290 (2013, Mirabegron) is recommended as an option for treating the symptoms
of overactive bladder for people in whom antimuscarinic drugs are contraindicated or clinically ineffective, or have unacceptable side effects.
CG185 (Sept. 2014 (Bipolar disorder) take into account the negative impact that anticholinergic
medication, or drugs with anticholinergic activity can have on cognitive function and mobility…
Drug management of overactive bladder
• Conservative interventions for incontinence in people with dementia or cognitive impairment, living at home: a systematic review- Drennan at al., BMC Geriatr. 2012; 12:77
• Insufficient evidence, from any studies to recommend any strategies
• Does Oxybutynin add to the effectiveness of prompted voiding for
urinary incontinence among nursing home residents?-Ouslander at
al. J. Am Geriatric Soc. 1995 • Statistically significant but clinically not
meaningful
Practical implications
• Older adult with cognitive symptoms, dementia, MCI or delirium
• Taking one medication with ACB score of >2 or total ACB score 3+
• Consider alternative medication with ACB score <3 or reduce total score <3
• Discuss benefits and risks before starting therapy
• Use lowest effective dose
• Discontinue if ineffective
