Aznan Lelo

Dep. Farmakologi & Terapeutik,

Fakultas Kedokteran Universitas Sumatera Utara

1 Juni 2013, FK UNBRAH, Padang

Objectives
Geriatrics Antibiotics Priscribing cascade Polypharmacy Drug interaction
Antibiotic - drugs Antibiotic antibiotic

Geriatrics as an increasing segment of the population

1 in 8 is > 64yo in 1994 1 in 5 projected to be > 64yo in 2030
Geriatric criteria based on WHO : Middle age : 45-59 Years Elderly : 60-74 Years Old : 75-90 Years Very old : > 90 Years

Problem in prescribing medicines for geriatrics

getting older co-morbid - Cardiovascular (CHD, CHF) - Degenerative (OA) - Metabolic (DM), dll polypharmacy - ACE-inhibitor - NSAID - OAD, etc drug interaction side effects . . .

Medications in the Elderly

General
2/3 of elderly take Rx or OTC meds Avg of 5 Rx and 2 OTC/pt (more in NH) 30% of all RX written for pts > 65 yrs old Biochemistry of medications in the elderly Longer duration of activity More frequent adverse drug effects Increase likelihood of drug toxicity Lower doses needed to obtain therapeutic levels

ADEs: Aging or Age-related?

% Patients with ADEs
10 8 6 4 2 0 18-24 25-34 35-44 45-54 55-64 65-74 >75

AGE
Hutchinson et al J Chronic Dis 1986;39:533-42

ADRs and Age

Incidence of ADR increases with age
ADR are 7 times more common in the elderly Account for 16% of hospital admission and 50% of medication related deaths

Elderly receive more medicines

Incidence of ADR increases the more prescribed medicines taken (exponentially?)

Grymonpre et al (1988) study > 50 yrs

ADR rates 5% for 1 or 2 medicines Increased to 20% when >5 medicines

Most frequent drug class causing ADR in elderly

Drug Class N %

Cardiovascular active agents Analgesics (opioid mainly) Antibiotics Hypoglycemic agents Psychotropic agents Anticoagulants Others

28 15 12 8 6 4 10

34 18 15 10 7 5 12

JAMA 2006; 296:185866, JAGS 2004;52:134954, NEJM 2003;348:155664

Common Conditions Could Really Be Adverse Drug Effects

Constipation Calcium Channel Blockers; Iron Incontinence -blockers Memory loss Antihistamines Syncope
Falls

Tricyclics, -blockers
Benzodiazepines

Weight loss Fluoxetine

Factors contributing to adverse drug reactions in elderly patients

Many elderly people receive 12 medications per day

Prescribing in Geriatrics

Risks Benefits

Elderly have unique pharmacokinetics

Water comp, Plasma Protein Respond sensitivity Unbound drug Unchanged drug

Biotransformation

Clearance

T-1/2
Drug accum.

Toxicity

Kinetic profile of drug in young and elderly subjects

800 700 600 500 400 300 200 100 0 0 2 4 6 8 10 12 14 16 18 20 22 24

young elderly

time (hour)

Long t-1/2 associated to drug accumulation give once daily of short half-life

blindness anorexia
heart disease liver impairment cancer arthralgia

dementia hearing loss

dyspnoe renal impairment constipation weakness

Pharmacological problems in the elderly

I have got them, but how to consume the drugs

Where are my medicines ?

Have I taken them before?

3x11x3 Therapeutic effect Adverse effect Avoid the dangerous drug . . . . . . . . . . . . . . . . choose the safest one

Drug Use in Community Dwelling Elderly*

*1996: N=27,285,988 Percentage (%)

Moxey, Health Care Financing Review 2003

Antibiotics
One of the most commonly used group of drugs May account for up to 50% of a hospitals drug expenditure Studies worldwide has shown a high incidence of inappropriate use

etc, etc,etc etc crying anxiety

fever

cough

cipro
insomnia

antimicrobial penem agents

dyspnea diarrhea

ANTIBIOTIKA bukan ANTIPIRETIKA

ANTI-TUSIVA
ANTI-DIARE ANTI-ANXIETY

ANTIBIOTIKA hanya diberikan bila terbukti atau disangka kuat ada proses INFEKSI (kuman, jamur, virus, protozoa)
ANTIBIOTIKA TUNGGAL lebih baik daripada ANTIBIOTIKA KOMBINASI Waspada terhadap interaksi ANTIBIOTIKA dengan OBAT LAIN

Infections in Elderly
Risk factors of elderly Common infections of elderly
RTI: Pneumonia, Influenza, TB Skin and Soft tissue infections
Shingles Leg Ulcers

GIT: C. Difficile UTI: ESBLs

Infections in the elderly: characteristics

Increased susceptibility to infections High morbidity and mortality Atypical clinical presentation Presumtion diagnostic rather than etiologic diagnostic Side effects of antibiotic treatment High cost of treatment
TT Yoshikawa. Clin Inf Dis. 2000; 30:931-933

Antibiotics adverse effects

Antibiotics
Macrolides Aminoglycoside Metronidazole Fluoroquinolones Doxycycline

Adverse effects
nausea, vomitus, allergy, hepatitis, ototoxicity Interaction with cytochrome P450 3A4 (inhibition) nephrotoxicity; irreversible hearing loss neuromuscular blocking; respiratory depression; Metallic taste, dark urine CNS more common in elderly, QTc prolongation diarrhea, photosensitivity; rash; hepatitis; and, particularly in elderly patients esophageal ulcerations or strictures allergy

Beta-lactams

Prescribing Cascade
obat 1

Drug 1

Adverse drug effect misinterpreted as new medical condition efek samping obat diinterprestasikan sebagai suatu kondisi klinis baru

obat 2

Drug 2
Rochon PA, Gurwitz JH. BMJ. 315:1096-9,1997.

Adverse drug effect efek samping obat

Initial condition

Therapy

New symptom

Subsequent therapy

HYPERTENSION

ACE-I COUGH

Antibiotic Diarrhea Laxantia

Constipation

Atropin

fever

cough AntiRp biotic

diarrhea

allergy

diarrhea nausea Iatrogenic diseases

etc

Rp CTM

loperamide antivomitus Rp Rp Iatrogenic COST

Rp etc

Prescribing Cascade

A Vicious Cycle...
Elderly Patient

Risk of Adverse Effects

Multiple Medical Problems

Multiple Multiple Medications Medications

New Drug Added

Failure to Recognize

Polypharmacy
Polypharmacy means "many drugs. The use of more medication than is clinically indicated or warranted.
4 or more drugs 7 or more drugs

Polypharmacy in the Elderly

Many elderly patients visit several doctors, each of whom may prescribe different medications use over-the-counter medication regularly including jamu containing steroid get medications from more than one pharmacy, or from friends

Polypharmacy in the Elderly

Polypharmacy leads to:
More adverse drug reactions Drug-drug interactions Duplication of drug therapy Decreased adherence to drug regimens Suggested contribute to at least 1015% hospital admissions

Polypharmacy in the Elderly

Polypharmacy leads to patient outcomes
Poor quality of life High rate of symptomatology (Unnecessary) drug expense

Potential Drug Interactions

Antibiotic - Drug Interactions

Antimicrobial
Aminoglycosides
NSAID Diuretics (ethacrynic acid, furosemide), quinine

Interacting Drug

Concern
Nephrotoxicity Ototoxicity

Doxycycline

Antacids, Ferrous sulfate, Cimetidine

Anticonvulsants (barbiturates, phenytoin, carbamazepine) Digoxin OCP

Decreased doxycycline absorption

enhanced hepatic metabolism Digoxin toxicity Pregnancy Increased anticoagulation

Trimethoprim and sulfamethoxazole

Warfarin

Phenytoin
Methotrexate Glipizide

Phenytoiin toxicity
Bone marrow suppression Hypoglycemia

Antibiotic - Drug Interactions

Antimicrobial
Fluoroquinolones

Interacting Drug
Antacids, Ferrous sulphate, Zinc, Sucralfate

Concern
Decreased quinolon absorption

Type IA,C, II antiarrhythmics

Warfarin Ciprofloxacin Beta-lactams (acidic drugs) Theophylline PPI (omeprazole, etc) Probenecid, disulfiram Allopurinol Macrolides Warfarin

Arrhytmia
Bleeding Theophyline toxicity, Beta-lactam absorption may be impaired Beta-lactam levels increased decreases ampicillin effects Bleeding

Clarithromycin

Omeprazole

increase concentration of both drugs

Antibiotic - Antibiotic interactions

Antimicrobial Interacting Drug
Amphotericin B Ceftazidime

Concern
Nephrotoxicity

Vancomycin Aminoglycosides
Erythromycin

Azythromycin Vancomycin
Beta-lactamas

Ototoxicity

Synergic antibiotics

Antibiotic Combination Therapy

infection is caused by multiple microorganisms, e.g.:
anaerobe (Bacteroides fragilis) and gram negative bacilli (E. coli) metronidazole and third generation cephalosporins or fluoroquinolon Gram negative bacilli and gram positive coccus aminoglycoside and beta-lactams

Nosocomial infections Serious infections in which a combination is synergistic

Antibiotic combination
Trimethoprimc and sulfixazole cotrimoxazole Amoxicillin and clavulanic acid coamoxiclav Ampicillin and sulbactam OAT combination

 Elderly have unique pharmacokinetics Elderly receive more medicines

Incidence of ADR increases with age

Antibiotic is one of the most commonly used agents combined with other drugs
Antibiotics may induce a prescribing cascade

Polypharmacy antibiotics in geriatrics may be dangerous