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

3. Drugs Contraindicated in Dementia: Propensity to cause mental status change
Attitude: High index of suspicion
Skills:
a. Awareness of “at risk” patients
b. Identify subtle mental status changes
Knowledge: specific categories/drugs

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

5. CNS Vulnerability in Medically Ill Persons
Skills
CNS Vulnerability in Medically Ill Persons
Alzheimer’s Dementia Cholinergic System*
Vascular Dementia Circulation
Parkinson’s Dopaminergic &
Cholinergic
*Noradrenergic & Serotonergic systems may play role here too.

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

7. Curve of Life Functional Capacity Functional Capacity Skills
“EAMA student”
Functional Capacity
Functional Capacity
80 y/o NH resident
with dementia
Function
Dys-Function
Age……Disease Process ---->>>>>
Age……Disease Process ---->>>>>

8. ANTICHOLINERGICS #1 DELIRIUM
Knowledge
ANTICHOLINERGICS #1
DELIRIUM

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

10. DRUGS THAT CAUSE DELIRIUM
Knowledge
ACUTE
CHANGE IN MS
DRUGS THAT CAUSE DELIRIUM

11. DRUGS THAT CAN CAUSE A CHANGE IN MENTAL STATUS
A C I M
C H N S
U A
T N
E G E

12. Antiparkinsonian Drugs
ACUTE CHANGE IN MS
Antiparkinsonian Drugs
Levodopa, Bromocriptine, Amantadine
Up to 20% of pt.s
Most at risk: pt.s with cortical atrophy
Refs: Cummings 1991; DeSmet et al. 1982

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

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

15. 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

16. EMPTYING DRUGS ACUTE CHANGE IN MS 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

17. CV DRUGS ACUTE CHANGE IN MS 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.

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

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

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

21. ACUTE CHANGE IN MS GEROPSYCHIATRY DRUGS Act centrally >> risk
Mechanisms are not “pure”
TCAs vs SSRI’s
Anticholinergic vs hyponatremia, serotonin syndrome, interactions
BDZ’s

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

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

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

25. NSAIDS ACUTE CHANGE IN MS ANY Most Risky: Protein Bound
Indomethacin: Don’t use in older persons

26. MUSCLE RELAXANTS ACUTE CHANGE IN MS
Action: Centrally Acting Does not directly relax tense skeletal muscles. Through sedation => relaxes muscles
Methacarbamol (ROBAXIN)
Carisoprodol (SOMA)
Chlorzoxazone (PARAFON FORTE)

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

28. Drugs Contraindicated in Dementia: THoM
Attitude: High index of suspicion-> Almost ANY drug can cause MS changes
Skills: Curve of Life & awareness of subtle mental status changes
Knowledge:
ACUTE CHANGE IN MS

29. 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

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 2. How is it going to going to MOVE ACT
THROUGH
my patient ?
1. How is it
going to
ACT
on my
patient ?

32. ANXIETY Caffeine Sympathomimetics Withdrawal from:
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

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

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

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

36. DEPRESSION 3.6% 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 Reviewed 65 clinical trials, n=2,320 patients.

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

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

39. DEPRESSION Digoxin H2 Blockers Corticosteroids
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

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

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

43. 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

44. OTC >>> Rx 300,000* 65,000 Drugs
300,000* ,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
OTC’s (Over the Counter Drugs)
$13 Billion/Year in America
Increases 8-10%/year
Ref:1995 PDR for Nonprescription Drugs
Note: Total Health Care Expenditures = $750 Billion in 1991

46. Self-Medication with OTC’s
Frequency % of Consumers
Frequently 76%
Occasionally 17%
Rarely 4%
Never 1%
No Response 2%
Ref: Gannon 1990.

47. How People Treat Common Health Complaints with OTC’s
Treatment
Treated with OTC % %
Not treated % %
Treated-Home remedy % %
Treated-Previous Rx % %
Sought Prof. help % %
Ref: Heller Research Group n=1500; average person suffered 6 probs/2 wk

48. “ADE’s” ADVERSE DRUG EVENTS
2-3 x More Likely to Happen in Older Persons
Ref:Vestal & Cusak 1990

49. Hospital Admissions for “ADE’s”%
Ref.s: Beard 1992,
Col 1990, Nelson
& O’Malley 1988.
All Hosp. Age > Psych Adm’s
Adm’s

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

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

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

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