Drugs Contraindicatedin

DementiaJoseph H. Flaherty, M.D.Division of Geriatric MedicineSaint Louis University Health Sciences CenterSt. Louis VA Medical Center GRECC

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Drugs Contraindicatedin

Dementia:Propensity to Cause

Mental Status Change

1. Attitude: High index of suspicion

2. Skills: a. Awareness of “at risk” patients

b. Identify subtle mental status changes

3. Knowledge: specific categories/drugs

Drugs Contraindicated in Dementia:Propensity to cause mental status change

ANY* DRUGcan cause

Mental Status ChangeRefs: “Almost any” Lipowski ZJ, NEJM 1989; “Virtually any” Carter GL, Drug Safety 1996

Attitude

CNS Vulnerability in Medically Ill PersonsAlzheimer’s Dementia Cholinergic System*

Vascular Dementia Circulation

Parkinson’s Dopaminergic &Cholinergic

*Noradrenergic & Serotonergic systems may play role here too.

Skills

PHARMACOKINETICS (moving the drug through)

Medically Ill PersonsPostgastrectomy, Malabsorption

CHF, Dehydration, Malnutrition Renal or Hepatic Insufficiency

Skills

Age……Disease Process ---->>>>>

Fun

ctio

nal C

apac

ity

Function

Dys-Function

“EAMA student”

80 y/o NH resident with dementia

Fun

ctio

nal C

apac

ity

Age……Disease Process ---->>>>>

Skills

ANTICHOLINERGICS

#1DELIRIUM

Knowledge

The POWER of ANTICHOLINERGICS

1% scopolamine eye drops scopolamine transdermal patch

Ref: Danielson et al. 1981, MacEwan et al. 1985

Knowledge

DRUGS THAT

CAUSE DELIRIUM

DRUGS THAT

CAUSE DELIRIUM

ACUTECHANGE

IN MS

Knowledge

DRUGS THAT CAN CAUSE A CHANGE IN MENTAL STATUS

A C I MC H N SU AT NE G

E

Levodopa, Bromocriptine, Amantadine• Up to 20% of pt.s• Most at risk: pt.s with cortical atrophy

Refs: Cummings 1991; DeSmet et al. 1982

ACUTE CHANGE IN MS

Antiparkinsonian Drugs

CORTICOSTEROIDS “Steroid psychosis” Dose related

• Up to 18% if >80 mg/day

Variety of MS changes: depressive/manic, paranoid/hallucinatory, confusion

Withdrawal may precipitateRefs:Ling PH, 1981, Glaser GH, 1953,VonArnim T 1976 (book), Dixon RB, 1980

ACUTE CHANGE IN MS

URINARY INCONTINENCE Action: (-) muscarinic action of

acetylcholine on smooth muscle, i.e. ANTICHOLINERGIC• Oxybutinin (DITROPAN*),

Flavoxate (URISPAS) Retention=>DeliriumIncontinence

ACUTE CHANGE IN MS

THEOPHYLLINE “Theophylline madness”

• Hyperactive periods with periods of withdrawal and mutism

• May herald onset of seizures Usually related to toxic levels

Refs: Wasser WG 1981, Culberson CG 1979,Paloucek FP 1988

ACUTE CHANGE IN MS

EMPTYING DRUGS Metoclopramide (REGLAN) Antagonism of peripheral and central

dopamine receptors (x-es BBB!) Restlessness, drowsiness, depression,

confusion

Refs: Anderson H 1994, Bottner RK 1985, Fishbain DA 1987, Ritchie IH 1997

ACUTE CHANGE IN MS

CV DRUGS Clonidine Digoxin Antiarrhythmics (PDQ) Beta-blockers Calcium Channel Blockers

Refs: Hoffman & Ladogana 1981; Jacobson et al. 1987; Eisendrath & Sweeney 1987; Kuhr 1979; McGahan et al 1984.

ACUTE CHANGE IN MS

H2 BLOCKERS Widely Prescribed => Increases Chances Anticholinergic?

• Physostigmine can reverse cimetidine induced delirium

Older persons with Renal Insuf.

Refs: Jenike & Levy 1983, Schentag et al. 1979

ACUTE CHANGE IN MS

ANTIMICROBIALS Mostly case reports

• Ciprofloxacin, Sulfamethoxazole, Cephalosporins, Procaine PCN, Clarithromycin, Gent, Tobra, Strepto

• Isoniazid• Acyclovir• Chloroquine, Quinacrine

ACUTE CHANGE IN MS

NARCOTICS Acute users > Chronic users

• e.g. hospitalized pt Meperidine (DEMEROL) - metabolite

normeperidine has anticholinergic effects Tramadol (ULTRAM) - centrally acting

pain med

ACUTE CHANGE IN MS

GEROPSYCHIATRY DRUGSGEROPSYCHIATRY DRUGS

Act centrally >> risk Mechanisms are not “pure” TCAs vs SSRI’s

• Anticholinergic vs hyponatremia, serotonin syndrome, interactions

BDZ’s

ACUTE CHANGE IN MS

ENT Antivertigo medications

• Meclizine (ANTIVERT), dimenhydrinate (DRAMAMINE)

• AntihistaminIC action: STRONG• Anticholinergic action: WEAK, but present

ACUTE CHANGE IN MS

ENT Cold/Sinus medications: ANY

• Antihistamine “DANGER” – chlorpheniramine, astemizole

• Decongestant “DANGER” – sympathomimetics: pseudoephedrine

• Expectorant & Antitussive- probably okay– guaifenesin & dextromethorphan

• COMBINATIONS “DANGER”

ACUTE CHANGE IN MS

INSOMNIA DRUGS OTC may be worse than RX

Antihistamine (Diphenhydramine)

“Anything”-PM Withdrawal Insomnia

(and daytime anxiety)

ACUTE CHANGE IN MS

NSAIDS ANY Most Risky: Protein Bound Indomethacin: Don’t use in older

persons

ACUTE CHANGE IN MS

MUSCLE RELAXANTS Action: Centrally Acting

Does not directly relax tense skeletal muscles. Through sedation =>

relaxes muscles

Methacarbamol (ROBAXIN)Carisoprodol (SOMA)Chlorzoxazone (PARAFON FORTE)

ACUTE CHANGE IN MS

SEIZURE DRUGS

Related to serum levels Protein bound? Usually drowsiness, occasional agitation,

depression, psychosis

ACUTE CHANGE IN MS

1. Attitude: High index of suspicion-> Almost ANY drug can cause MS changes

2. Skills: Curve of Life & awareness of subtle mental status changes

3. Knowledge:

Drugs Contraindicated in Dementia:THoM

ACUTE CHANGE IN MS

DRUGS THAT CAN CAUSE A CHANGE IN MENTAL STATUS

ANTIPARKINSON CV DRUGS INSOMNIA MUSCLE RELAX.

CORTICOSTER. H2 BLOCKERS NSAIDS SEIZURE

URIN INCONT ANTIBIOTICS

THEOPHLLYINE NARCOTICS

EMPTYING DRUGS GERO-PSYCH

ENT

Why Older Persons So Susceptible to Psychiatric Side Effects

Pharmacodynamics CNS Vulnerability

Pharmacokinetics How the body Absorbs Distributes Metabolizes Excretes

Starting a New Drug1. How is it going to ACT on my patient

?

2. How is itgoing toMOVE THROUGHmy patient

?

ANXIETYANXIETY Caffeine

• Inc. Sensitivity; May be in OTC’s Sympathomimetics

• i.e. most Cold/Sinus meds• e.g. SUDAFED, ENTEX, NEO-SYNEPHRINE

Withdrawal from:• Alcohol, Narcotics, Sedative-Hypnotics

ANXIETYANXIETY Thyroxine Antiparkinsonian (L-Dopa,

Bromocriptine)• 10-15% will develop anxiety

Theophylline

Ref: Cummings 1991

DEPRESSIONDEPRESSION

Reser

pine

Methyldopa

Propranolol

“...the rest of the story.”(Paul Harvey)

DEPRESSIONDEPRESSION Reserpine

• Catecholamine depleting antihypertensive

• 20% of pt.s

• Generally resolves with discontinuation

Ref: Goodwin & Bunney 1971

DEPRESSIONDEPRESSION Methyldopa

• Antihypertensive, effective and inexpensive• metabolite a-methyl norepinephrine

=> potent a2-adrenergic agonist

3.6%(Only 1.1% warranted d/c of drug)

Ref: Paykel et al. 1982. Reviewed 65 clinical trials, n=2,320 patients.

DEPRESSIONDEPRESSION Propranolol

• B-adrenoreceptor antihypertensive• Lipophilic => crosses BBB

Atenolol• Less lipophilic => probably <1%

1.1%

Ref: Paykel et al. 1982. Reviewed 65 clinical trials, n=2,320 patients.

DEPRESSIONDEPRESSION Clonidine

• Centrally acting a-agonist antihypertensive

1.5%

Ref: Paykel et al. 1982. Reviewed 65 clinical trials, n=2,320 patients.

DEPRESSIONDEPRESSION Digoxin

• Even at therapeutic levels• Watch it: undernourished, dehydrated, or

renally impaired older persons H2 Blockers

• Not just Cimetidine Corticosteroids

Refs: Pascualy & Veith 1989, Billings & Stein 1986, Billings et al. 1981

HALLUCINATIONSHALLUCINATIONSC (Dig, PDQ) I (Dir. & Indir.) M (Frail Elderly)

H (Usu. other MS) N (Indomethacin) S (Frail Elderly)

A (Definitely: Dopa & Antichol)

N (Possible)

G (Of course)

E (Dir. & Indir.)

Risk Factors for Psychiatric Side Effects of Drugs

Risk Factors for Psychiatric Side Effects of Drugs

Age More MEDs, more ADE’s OTC users Brain Dysfunction Medical Illnesses

RecommendationsRecommendations Identify those at RISK Remember: ANY drug can do it Don’t add ‘til you TAKE AWAY Don’t be afraid to TAKE AWAY

GUIDELINES for Medication Reduction

GUIDELINES for Medication Reduction

JUST DO IT Caution: Taper

• Clonidine, B-blockers, Reserpine, Narcotics, BDZ’s, Corticosteroids, Barbituates

Careful but DO IT (esp if pt in hosp!)• Cardiac drugs (digitalis, antiarrhythmics)

Close follow-up!• Home care, social worker

DrugsDrugs

OTC >>> Rx

300,000* 65,000

*Includes different package sizes, dose strengths, and forms.Ref: 1995 PDR for Nonprescription Drugs

$13 Billion/Year in America

Increases 8-10%/year

OTC’s(Over the Counter Drugs)

Ref:1995 PDR for Nonprescription DrugsNote: Total Health Care Expenditures = $750 Billion in 1991

Self-Medication with OTC’sSelf-Medication with OTC’s

Frequency % of Consumers

Frequently 76%Occasionally 17%Rarely 4%Never 1%No Response 2%

Ref: Gannon 1990.

How People Treat Common Health Complaints with OTC’s

How People Treat Common Health Complaints with OTC’s

Treatment 1982 1992

Treated with OTC 35% 38%Not treated 37% 30%Treated-Home remedy 14% 16%Treated-Previous Rx 11% 13%Sought Prof. help 9% 17%

Ref: Heller Research Group. 1992. n=1500; average person suffered 6 probs/2 wk

“ADE’s”

ADVERSE DRUG EVENTS

“ADE’s”

ADVERSE DRUG EVENTS

2-3 x More Likely to Happen in Older Persons

Ref:Vestal & Cusak 1990

Hospital Admissions for “ADE’s”

Hospital Admissions for “ADE’s”

0

2

4

6

8

10

12

14

16

18

1st Qtr 2nd Qtr 3rd QtrAll Hosp. Age >65 Psych Adm’s Adm’s

%

Ref.s: Beard 1992,Col 1990, Nelson& O’Malley 1988.

DELIRIUM: INSOMNIA DRUGS

DELIRIUM: INSOMNIA DRUGS

OTC may be worse than RX

Antihistamine (Diphenhydramine)

“Anything”-PM Withdrawal Insomnia

(and daytime anxiety)

Pharmacodynamics: CNS Vulnerability

Neuronal cell number Neurotransmitter production and

breakdown Pre- and post-synaptic receptors CNS concentration of drugs

Skills

ANTICHOLINERGICS

60% of NH Residents

23% of Community Dwelling Elders

TAKE AT LEAST ONE

Ref: Blazer et al. 1983

Knowledge

INCONTINENCE-BOWEL i.e. IRRITABLE BOWEL SYNDROME Action: ANTICHOLINERGIC Hyoscyamine (DONNATAL, LEVSIN,

LEVSINEX), Dicyclomine (BENTYL)

DONNATAL = Atropine + Hyoscyamine + Scopolamine +

Phenobarbital

ACUTE CHANGE IN MS