GP educational update in geriatrics May 2015 Agnes Toth.

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