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Drugs Contraindicated in Dementia Joseph H. Flaherty, M.D. Division of Geriatric Medicine Saint Louis University Health Sciences Center St. Louis VA Medical.

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Presentation on theme: "Drugs Contraindicated in Dementia Joseph H. Flaherty, M.D. Division of Geriatric Medicine Saint Louis University Health Sciences Center St. Louis VA Medical."— Presentation transcript:

1 Drugs Contraindicated in Dementia Joseph H. Flaherty, M.D. Division of Geriatric Medicine Saint Louis University Health Sciences Center St. Louis VA Medical Center GRECC Downloaded from www.pharmacy123.blogfa.com

2 Drugs Contraindicated in Dementia: Propensity to Cause Mental Status Change

3 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

4 ANY* DRUG can cause Mental Status Change Refs: Almost any Lipowski ZJ, NEJM 1989; Virtually any Carter GL, Drug Safety 1996 Attitude

5 CNS Vulnerability in Medically Ill Persons Alzheimers DementiaCholinergic System* Vascular DementiaCirculation ParkinsonsDopaminergic & Cholinergic *Noradrenergic & Serotonergic systems may play role here too. Skills

6 PHARMACOKINETICS (moving the drug through) Medically Ill Persons Postgastrectomy, Malabsorption CHF, Dehydration, Malnutrition Renal or Hepatic Insufficiency Skills

7 Age……Disease Process ---->>>>> Functional Capacity Function Dys-Function EAMA student 80 y/o NH resident with dementia Functional Capacity Age……Disease Process ---->>>>> Skills

8 ANTICHOLINERGICS #1 DELIRIUM Knowledge

9 The POWER of ANTICHOLINERGICS u 1% scopolamine eye drops u scopolamine transdermal patch Ref: Danielson et al. 1981, MacEwan et al. 1985 Knowledge

10 DRUGS THAT CAUSE DELIRIUM ACUTE CHANGE IN MS Knowledge

11 DRUGS THAT CAN CAUSE A CHANGE IN MENTAL STATUS A C I M C H N S UA TN EG E

12 u 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

13 CORTICOSTEROIDS u Steroid psychosis u Dose related Up to 18% if >80 mg/day u Variety of MS changes: depressive/manic, paranoid/hallucinatory, confusion u Withdrawal may precipitate Refs:Ling PH, 1981, Glaser GH, 1953,VonArnim T 1976 (book), Dixon RB, 1980 ACUTE CHANGE IN MS

14 URINARY INCONTINENCE u Action: (-) muscarinic action of acetylcholine on smooth muscle, i.e. ANTICHOLINERGIC Oxybutinin (DITROPAN*), Flavoxate (URISPAS) Retention=>Delirium Incontinence ACUTE CHANGE IN MS

15 THEOPHYLLINE u Theophylline madness Hyperactive periods with periods of withdrawal and mutism May herald onset of seizures u Usually related to toxic levels Refs: Wasser WG 1981, Culberson CG 1979,Paloucek FP 1988 ACUTE CHANGE IN MS

16 EMPTYING DRUGS u Metoclopramide (REGLAN) u Antagonism of peripheral and central dopamine receptors (x-es BBB!) u Restlessness, drowsiness, depression, confusion Refs: Anderson H 1994, Bottner RK 1985, Fishbain DA 1987, Ritchie IH 1997 ACUTE CHANGE IN MS

17 CV DRUGS u Clonidine u Digoxin u Antiarrhythmics (PDQ) u Beta-blockers u Calcium Channel Blockers Refs: Hoffman & Ladogana 1981; Jacobson et al. 1987; Eisendrath & Sweeney 1987; Kuhr 1979; McGahan et al 1984. ACUTE CHANGE IN MS

18 H2 BLOCKERS u Widely Prescribed => Increases Chances u Anticholinergic? Physostigmine can reverse cimetidine induced delirium u Older persons with Renal Insuf. Refs: Jenike & Levy 1983, Schentag et al. 1979 ACUTE CHANGE IN MS

19 ANTIMICROBIALS u Mostly case reports Ciprofloxacin, Sulfamethoxazole, Cephalosporins, Procaine PCN, Clarithromycin, Gent, Tobra, Strepto Isoniazid Acyclovir Chloroquine, Quinacrine ACUTE CHANGE IN MS

20 NARCOTICS u Acute users > Chronic users e.g. hospitalized pt u Meperidine (DEMEROL) - metabolite normeperidine has anticholinergic effects u Tramadol (ULTRAM) - centrally acting pain med ACUTE CHANGE IN MS

21 GEROPSYCHIATRY DRUGS u Act centrally >> risk u Mechanisms are not pure u TCAs vs SSRIs Anticholinergic vs hyponatremia, serotonin syndrome, interactions u BDZs ACUTE CHANGE IN MS

22 ENT u Antivertigo medications Meclizine (ANTIVERT), dimenhydrinate (DRAMAMINE) AntihistaminIC action: STRONG Anticholinergic action: WEAK, but present ACUTE CHANGE IN MS

23 ENT u Cold/Sinus medications: ANY Antihistamine DANGER –chlorpheniramine, astemizole Decongestant DANGER –sympathomimetics: pseudoephedrine Expectorant & Antitussive- probably okay –guaifenesin & dextromethorphan COMBINATIONS DANGER ACUTE CHANGE IN MS

24 INSOMNIA DRUGS u OTC may be worse than RX Antihistamine (Diphenhydramine) u Anything-PM u Withdrawal Insomnia (and daytime anxiety) ACUTE CHANGE IN MS

25 NSAIDS u ANY u Most Risky: Protein Bound u Indomethacin: Dont use in older persons ACUTE CHANGE IN MS

26 MUSCLE RELAXANTS u 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

27 SEIZURE DRUGS u Related to serum levels u Protein bound? u Usually drowsiness, occasional agitation, depression, psychosis ACUTE CHANGE IN MS

28 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

29 DRUGS THAT CAN CAUSE A CHANGE IN MENTAL STATUS A NTIPARKINSON C V DRUGS I NSOMNIA M USCLE RELAX. C ORTICOSTER. H 2 BLOCKERS N SAIDS S EIZURE U RIN INCONT A NTIBIOTICS T HEOPHLLYINE N ARCOTICS E MPTYING DRUGS G ERO-PSYCH E NT

30 Why Older Persons So Susceptible to Psychiatric Side Effects Pharmacodynamics CNS Vulnerability Pharmacokinetics How the body Absorbs Distributes Metabolizes Excretes

31 Starting a New Drug 1. How is it going to ACT on my patient ? 2. How is it going to MOVE THROUGH my patient ?

32 ANXIETY u Caffeine Inc. Sensitivity; May be in OTCs u Sympathomimetics i.e. most Cold/Sinus meds e.g. SUDAFED, ENTEX, NEO-SYNEPHRINE u Withdrawal from: Alcohol, Narcotics, Sedative-Hypnotics

33 ANXIETY u Thyroxine u Antiparkinsonian (L-Dopa, Bromocriptine) 10-15% will develop anxiety u Theophylline Ref: Cummings 1991

34 DEPRESSION Reserpine Methyldopa Propranolol...the rest of the story. (Paul Harvey)

35 DEPRESSION u Reserpine Catecholamine depleting antihypertensive 20% of pt.s Generally resolves with discontinuation Ref: Goodwin & Bunney 1971

36 DEPRESSION u 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.

37 DEPRESSION u Propranolol B-adrenoreceptor antihypertensive Lipophilic => crosses BBB u Atenolol Less lipophilic => probably <1% 1.1% Ref: Paykel et al. 1982. Reviewed 65 clinical trials, n=2,320 patients.

38 DEPRESSION u Clonidine Centrally acting a-agonist antihypertensive 1.5% Ref: Paykel et al. 1982. Reviewed 65 clinical trials, n=2,320 patients.

39 DEPRESSION u Digoxin Even at therapeutic levels Watch it: undernourished, dehydrated, or renally impaired older persons u H2 Blockers Not just Cimetidine u Corticosteroids Refs: Pascualy & Veith 1989, Billings & Stein 1986, Billings et al. 1981

40 HALLUCINATIONS C (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.)

41 Risk Factors for Psychiatric Side Effects of Drugs u Age u More MEDs, more ADEs u OTC users u Brain Dysfunction u Medical Illnesses

42 Recommendations u Identify those at RISK u Remember: ANY drug can do it u Dont add til you TAKE AWAY u Dont be afraid to TAKE AWAY

43 GUIDELINES for Medication Reduction u JUST DO IT u Caution: Taper Clonidine, B-blockers, Reserpine, Narcotics, BDZs, Corticosteroids, Barbituates u Careful but DO IT (esp if pt in hosp!) Cardiac drugs (digitalis, antiarrhythmics) u Close follow-up! Home care, social worker

44 Drugs OTC >>> Rx 300,000* 65,000 *Includes different package sizes, dose strengths, and forms. Ref: 1995 PDR for Nonprescription Drugs

45 $13 Billion/Year in America Increases 8-10%/year OTCs (Over the Counter Drugs) Ref:1995 PDR for Nonprescription Drugs Note: Total Health Care Expenditures = $750 Billion in 1991

46 Self-Medication with OTCs Frequency% of Consumers Frequently76% Occasionally17% Rarely4% Never1% No Response2% Ref: Gannon 1990.

47 How People Treat Common Health Complaints with OTCs 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

48 ADEs ADVERSE DRUG EVENTS 2-3 x More Likely to Happen in Older Persons Ref:Vestal & Cusak 1990

49 Hospital Admissions for ADEs All Hosp. Age >65 Psych Adms Adms % Ref.s: Beard 1992, Col 1990, Nelson & OMalley 1988.

50 DELIRIUM: INSOMNIA DRUGS u OTC may be worse than RX Antihistamine (Diphenhydramine) u Anything-PM u Withdrawal Insomnia (and daytime anxiety)

51 Pharmacodynamics: CNS Vulnerability u Neuronal cell number u Neurotransmitter production and breakdown u Pre- and post-synaptic receptors u CNS concentration of drugs Skills

52 ANTICHOLINERGICS 60% of NH Residents 23% of Community Dwelling Elders TAKE AT LEAST ONE Ref: Blazer et al. 1983 Knowledge

53 INCONTINENCE-BOWEL u i.e. IRRITABLE BOWEL SYNDROME u Action: ANTICHOLINERGIC u Hyoscyamine (DONNATAL, LEVSIN, LEVSINEX), Dicyclomine (BENTYL) DONNATAL = Atropine + Hyoscyamine + Scopolamine + Phenobarbital ACUTE CHANGE IN MS


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