DRUG NUTRIENT

INTERACTIONS
IN OLDER ADULTS

Prof. dr. M. Aris Widodo, MS, Sp.FK, Ph.D

Populasi manula
heterogen, tidak
homogen

Manula rentan
terhadap interaksi
obat-makanan (DNI)
karena praktek
polifarmasi, jumlah
macam obat >> dan
dosis besar

Mekanisme DNI pada

Manula
Makanan berperan dalam:

Tujuan pengobatan pada manula

Epidemiology of Drug-Drug or
Drug-Disease Interactions

Incidence of potential drug-drug interactions ranges from 217% of all Rx's and up to 6-42% of elderly patients.

Incidence of potentially clinically significant drug interactions

is low in the elderly (usually must involve narrow therapeutic
range drug and inhibitor/inducer of drug metabolism or renal
excretion)

There is evidence suggesting that adverse health outcomes

associated with drug-drug interactions is infrequent.

Drug-disease interactions occur in 6.2-40% of elderly patients

Drug disease interactions may result in higher risk of adverse

outcomes (e.g., decline in functional status and increased
health services use) due to alterations in homeostatic
mechanisms and diminished functional reserve.

Manula banyak mendapatkan obat (usa)

Bagaimana di Indonesia ?
Tidak semua manula mampu membeli obat
Beralih ke alternatif herbal
Obat yang banyak digunakan oleh manula
OBAT CARDIOVASCULER
33.3%
OBAT CNS
27.8 %
MUSKULOSKELETAL
9.7%
RESPIRSI
5.6 %
ENDOKRIN
4.2%
GI-TRACT
2.8%

Prevalensi efek samping obat pada manula

DI MASYARAKAT
2.5-50,6%
DI LONG TERM CARE
9.5-67.4%
DI RUMAH SAKIT
1.5-44%

Obat yang sering menyebabkan efek samping di RS:

CORTICOSTEROID, DIGOXIN, NSAIDs , ANTI HIPERTENSI
BENZODIAZEPINE.

Efek samping meningkat pada manula oleh karena:

Jumlah macam obat yang diberikan (polifarmasi)
Banyaknya penyakit yang diderita saat masuk rs
Perubahan farmakodinami dan farmakokinetik

Perubahan fisiologis komposisi lemak dan otot

Perubahan penyerapan obat, metabolisme dan ekskrsi
Obat serta perubahan farmakodinami menyebabkan
Interaksi obat dan makanan meningkat pada manula

Drug Interactions Are Avoidable

Previous
adverse Contraindicated
Drug
reactions
drugs
interactions

Totals

Avoidable

57

67

131

Probably
avoidable

----

----

37

37

Uncertain

----

29

32

60

133

200

Total

Gosney et al. Lancet 1984;2:564

Tipe interaksi obat

Drug-Drug Pharmacokinetic

KOMPOSISI TUBUH
1) Total air tubuh turun
2) Lean body mass turun
3) Lemak tubuh meningkat
4) Albumin turun
5) Glikoprotein meningkat
KULIT
1) Collagen elastin turun
2) Melanosit turun
3) Folikel rambut turun
SENSORIS
1) Hearing loss
2) Degenrasi macula
3)Penglihatan turun
JANTUNG PEMBULUH DARAH
1) Masa jantung berkurag
2) Hipertropi
3) Sensitivitas rec. Beta kurang
4) Cop turun
5) Resistensi periper meningkat

PERUBAHAN FISIOLOGIS MANULA

1) Penurunan fungsi organ
2) Penurunan mekanisme homeostatis
3) Penurunan kapasitas cadangan
tidak mampu menghadapi stres fisik &
psikis
GI-TRACT
1) Tekanan spincter turun
2) ph lambung meningkat
3) Pengosongan lambung lama
4) Aliran darah usus turun
5) Mukosa uus kurang
HEPAR
1) Masa liver menurun
2) Aliran darah hepar menurun
3) Metabolisme obat menurun
GINJAL
1) Massa ginjal turun
2) Aliran darah urun
3) Fungsi tubulus gnjal turun
4) Filtrasi glomerulus naik
5) Fraksi filtrsi meningkat

PERUBAHAN PADA GI-TRACT

ORAL ULCERATION, POOR ORAL HYGIENE, POOR NUTRITION
BEBRAPA OBAT SEPERTIPENITOIN, COTIO STEROID IMMUNO SUPRESANT
ANTIBIOTIK. MENYEBABKAN HAL DIATAS
MULUT KERING XEROSTOMIA
SERING PADA MANULA DAN DAPAT DIPERBERAT OLEH OBAT ANTI KOLIN
NERGIK. (ANTI HISTAMIN, DECONGESTAN, IPRATROPIM, ANTIPSYCHOTIK
ANTI DPRESANT, ANTISPASMODIK
ACHLORHYDRIA, PENGOSOGAN LAMBUNG TERHAMBAT, LUAS MUKOSA LAMBUNG <
FUNGSI HEPAR MENRUN 40% PADA MANULA 80 TAHUN OLEH KARENA
MASA BERAT TURUN, ALIRA DARAH KEHEPAR MENURUN MENYEBABKAN
PENURUNAN METABOLISME. MENINGKATKAN KADAR OBAT PLASMA

EKSKRESI GINJAL PENURUNAN FUNGSI GINJAL BERDAMPAK JELAS PADA

PENGOBATAN
MASA GINJAL MENURUN, ALIRAN DARAH GINJAL MENURUN,
PENURUNAN GLOMERULI YANG FUNGSIONAL
TUBULAR FUNCTION BERKURANG
KREATINI N CLEARANCE MENURUN SETELAH USIA 40 TAHUN PENINGKATAN
SERUM KREATININ DIARTIKAN KADAR OBAT JUGA MENINGKAT KARENA
PENURUNAN EKSKRESI OBAT OLEH GINJAL.

PROSES PENUAAN MENYEBABKAN

PERUBAHAN FARMAKOKINETIK PADA
ABSORBSI OBAT
DISTRIBUSI OBAT
METABOLISME OBAT
EKSKRESI OBAT
DOSIS, INTERVAL DISESUAIKAN
EFEK PENUAAN PADA METABOLISME
MENGURANGI EFEK SAMPING

ABSORBSI OBAT
KECEPATAN DAN JUMLAH
ABSORBSI PER ORAL <<
ABSORBSI SUBCUTANT TIDAK
BERUBAH
ABSORBSI OBAT (FIRST PASSED
METABOLISME) >>
ABSORBSI DENGAN ACTIVE
TRANSPORT << Ca DAN VIT D

DISTRIBUSI OBAT
ALBUMIN TURUN OBAT YANG
MENGIKAT ABUMIN 90% AKAN
MENINGKATKAN OBAT BEBAS.
PENINGKATAN ALPHA 1 ACID GLICO
PROTEIN MENURUNKAN KONS.
OBAT YANG SIFATNYA BASA
PENURUNAN DISTRIBUSI WATER
SOLUBLE DRUGS CONC. OBAT
MENINGKAT.
PENIGKATAN DISTRIBUSI LIPID
SOLUBLE DRUGS MENURUNKAN
CONCENTRASI OBAT
PERUBAHAN VOLUME DISTRIBUSI
MENYEBABKAN PERUBAHAN
LOADING DOSE

METABOLISME
OBAT DENGAN RASIOEKSTRAKSI YANG TINGGI DIPENGARUHI KONDISI
MANULA ( ALIRAN DARAH BERKURANG) SEHINGGA KADAR OBAT DALAM
PLASMA MENINGKAT (BIOAVAILABILTY MENINGKAT MISALNYA OBAT
PROPANOLOL, VERAPRAMIL)
METABOLISME OBAT KELOMPOK BENZODIAZEPIN, (DIAZEPAM,
CHLORDIAZEPOXIDE DIPERPANJANG TERJADI AKUMULASI EFFEK
MANULA SENSITIF TERHAAP PENGOBATAN BENZODIAZEIN MENINGKATKAN
EFEK SEDATIF DAN ANXIOLITIC. ,

EKSKRESI OBAT
CLEARNCE CREATININ MENURUN SERU CRETININ NORMAL OLEH KARENA
PRODUKSI CREATININ PADA MANULA JUGA MENURUN.
DOSIS OBAT HARUS DISESUAIKAN PADA MANULA OLEH KARENA DAPAT
MENYEBABKAN EFEK TOKSIK DAN EFEK SAMPING DAN JUGA ENINGKATKAN
KEMUNGKINAN INTERAKSI OBAT.

Perubahan Farmakodinami pada

Lansia

Perubahan Farmakodinami pada

Lansia

Perubahan Status Gizi pada

Lansia
Pada

Perubahan Status Gizi pada

Lansia
S SADNESS
MEDICATION
SOCIAL
A
ALBUMIN
PROBLEMS
MENURUN
/ETNIC
ORAL PROBLEMS
(INABILITY
PROVIDING MEALS)
EATING
S
SHOPHING
PROBLEMS
PROBLEM
SWALOWING
C
CHOLESTEROL
/ DYSPHAGIA
MENURUN
NOEATING
E
MONEYPROBLEMS
/ FOOD
ENTERIC
L
LOSS OF
/ MALABSORBTION
WEIGHT
ALKOHOLIS / ANOREXIA
LOW SALT/ LOW FAT
HYPERTHYROID
WANDERING / DEMENTIA
LATE LIFE PARANOIA
EMOTIONAL / DEPRESION

Mekanisme DNI pada manula

Mekanisme DNI pada

manula

Mekanisme DNI pada

manula

Drug-Food/Nutrient Interactions
Drug

Effect

Phenytoin

Folate

Isoniazid

Vit B6

Phenytoin

Absorption with NG feedings

Levodopa

High protein meals effect bloodbrain transport

Altered taste sensation

Captopril

Clinically Significant
Drug St. John Wort Interactions
Object Drug
Outcome
Antidepressants serotonergic syndrome
Cyclosporine levels, transplant rejection
Digoxin digoxin levels
Estrogen breakthrough bleeding
Indinavir indinavir levels
Methadone withdrawal sxs
Tacrolimus levels
Theophylline Theophylline levels
Warfarin INR
CPT 2004;75:1-12

Other Clinically Significant HerbDrug Interactions

Object Drug

Interacting Drug

Outcome

Anticonvulsants
Wormwood
seizure threshold
Anticonvulsants
Gingko biloba
seizure threshold
Digoxin
Hawthorne
digoxin activity
Saquinavir
Garlic
saquinavir levels
Warfarin
Feverfew
risk of bleeding
Warfarin
Garlic
risk of bleeding
Warfarin
Ginger
risk of bleeding
Warfarin
Ginkgo
risk of bleeding
Warfarin
Ginseng
anticoagulant
Lancet 2000;355:134-8.

Drug-Drug Interactions Affecting

Absorption and Distribution

Precipitant Drug(s) Object Drug(s)

Outcome
Antacids, Iron Tetracycline, Ciprofloxacin abs.
Chloral hydrate Warfarin
Pl con

Generally absorption and distribution drug-druginteractions are not clinically important.

Drugs & Aging 1998;12:485-94

Hepatic Metabolism
Phase I (CYP 450)
Oxidation
Hydroxylation
Dealkylation
Sulfoxidation
Reduction
Hydrolysis

Phase II
Conjugation
GLUCURONIDATIO
N
SULFATION
GLYCINE
ACETYLATION

Cytochrome P450 Phase I Isoenzymes,

% Total and Substrate Examples
Isoenzymes %
Substrate
CYP1A2 17 Olanzapine, Theophylline
CYP2C9/19 26 Phenytoin, Warfarin
CYP2D6 2-4Codeine, Desipramine, Tramadol
CYP2E1 9-10 Chlorzoxazone, Ethanol
CYP3A4 35-45 Diazepam, Triazolam, Quinidine,
Methadone, Carbamazepine

www.drug-interactions.com

Inhibitors of Hepatic Cytochrome

P450
1A2
2C9/19
2D6
3A4
Fluvoxamine Amiodarone Fluoxetine Erythromycin
Cimetidine
Fluconazole Paroxetine Azole antifungal
Ciprofloxacin FluvastatinQuinidine Nefazodone
Fluoxetine Ritonavir Clarithromycin
Isoniazid Bupropion Ritonavir
Sertraline Cimetidine Cimetidine
Omeprazole
Cimetidine

www.drug-interactions.com

Strategies to Prevent/Manage
Drug Interactions

1. Encourage patients to report all prescription, overthe- counter and complementary and alternative
drugs at every health care encounter.
2. Support the implementation of electronic prescribing
and/or the use by patients of one pharmacy with
updated drug interaction software.
3. Work with pharmacists and be familiar with drug
interaction information sources
4. Consider whether drug therapy is necessary
5. When adding a new drug to regimen, screen for
potential drug-drug interactions.

Strategies to Prevent/Manage
Drug Interactions

6. When adding a new drug to regimen in a patient,

screen for potential drug-disease interaction.

7. If drug interaction can not be avoided, adjust
doses and or/dosage intervals for affected
medication and monitor the patient closely.
8. Carefully monitor other drug therapy when
withdrawing a drug that can inhibit or induce
hepatic metabolism.
9. Regularly review the need for chronic
medications-reduce polypharmacy

Drugs That Interact with

Theophylline

Inhibitors
Cimetidine
Propafenone
Mexiletine
Propranolol
Erythromycin
Ciprofloxacin
Fluvoxamine

Inducers
Barbiturates
Phenytoin
Smoking
Rifampin
Carbamazepine

Drugs Aging. 2003;20:71-84

JAPHA 2004;44:142-51

Drug-Drug Interactions With Warfarin

Interacting Drug Mechanism
Aspirin
PD

Barbiturate
PK

Cimetidine
PK

Dipyridamole
PD
Fibrates
PD

Fluvoxamine
PK

Macrolides
PK
Phenytoin
PK

Quinolones
PK

Rifampin
PK

Sulfinpyrazone PK/PD

Thyroid hormones PD
Ticlopidine
PD

Anticoagulant Effect

N Engl J Med. 2003; 14;349:675-83; JAPHA 2004;44:142-51

Clinically Significant
Drug-Drug Interactions with AEDs
Object Drug
Interacting Drug Outcome
Carbamazepine Danazol
CBZ level
Carbamazepine Diltiazem
CBZ level
Carbamazepine Macrolides
CBZ level
Carbamazepine Propoxyphene
CBZ level
Carbamazepine Verapamil
CBZ level
Phenytoin
Amiodarone
DPH level
Phenytoin
Cimetidine
DPH level
Phenytoin
Fluoxetine
DPH level
Phenytoin
INH
DPH level
Phenytoin
Omeprazole
DPH level
Neuropharmacology 2002;5:280-9

Inducers of Hepatic Cytochrome

P450
1A2
2C9/19
2D6
3A4
Smoking Rifampin
None
Carbamazepine
Omeprazole Phenobarbital
Phenytoin
Phenytoin Phenytoin
Phenobarbital
Rifampin
St. Johns wort
www.drug-interactions.com

Selected Phenytoin
Induction Interactions
Object Drug
Methadone
Quinidine
Theophylline
Warfarin

Interacting Drug
Phenytoin
Phenytoin
Phenytoin
Phenytoin

Neuropharmacology 2002;5:280-9.

CYP Isoenzyme Induced

3A4
3A4
1A2
2C9

Selected Drugs Secreted

by Renal Tubules
Basic (cationic) Agents
Amiodarone
Cimetidine
Digoxin
Procainamide
Quinidine
Ranitidine
Trimethoprim
Verapamil

Acidic (Anionic) Agents

Cephalosporins
Indomethacin
Methotrexate
Penicillins
Probenecid
Salicylates
Thiazides

Drug-Drug Interactions With

Digoxin
Interacting Drug
Amiodarone
Clarithromycin
Propafenone
Quinidine
Verapamil

Effect on Levels

Drug Saf. 2000;23:509-32; JAPHA 2004;44:142-51

Drugs that Interact with Lithium

Diuretics
ACE-I
NSAIDs

Drug-Drug PD Interactions
Object Drug
Interacting Drug (s)
ACE-I
K+ & K+ sparing diuretics
Beta blockers Verapamil
Digoxin
Diuretics
MAOI
SSRI, Dextromethorphan,
Pseudoephedrine, Anorexiants
Meperidine
MAOI
Hydroxyine
Thioridazine

Drug- TCA PD Interactions

Concurrent use with any other drugs with

antimuscarinic properties
Concurrent MAOI
Type I antiarrhythmics
Clonidine
Guanadrel
Guanethidine

Drug-NSAID PD Interactions
Object Drug Interacting Drug Outcome
Antihypertensives NSAIDs
BP
Corticosteroids NSAIDs
risk of PUD
Diuretics
NSAIDs
diuretic effect
Triamterene Indomethacin K+
Warfarin
NSAIDs
anticoagulant
effect

CNS Polypharmacy and Falls in

Elderly Persons

Weiner D, et al. Gerontol 1998;44:217-21

Clinically Important Drug-Disease Interactions Determined by Expert Panel

Consensus

Drug
Disease
Anticholinergics
BPH, constipation, dementia
Antiarrhythmics (Type 1A) CHF (systolic dysfunction)
Amphetamines
HTN, insomnia
Aspirin
PUD
Atypical antipsychotics
DM
Barbiturates
Depression
Benzodiazepines
COPD,dementia, falls
Beta-blockers
COPD, DM, syncope
CCB 1st generation
CHF (systolic dysfunction)
Chlorpromazine
Postural hypotension, seizures
Clozapine
Seizures
Corticosteroids
DM, PUD
Decongestants
Insomnia
Digoxin
Heart block
Lindblad C, Hanlon J et al. (abstract) J Am Geriatr Soc 2004;52:S135

Clinically Important Drug-Disease

Interactions Determined by Expert Panel
Consensus

Drug
Disease
Metoclopramide
Parkinsons disease
Nitrofurantoin
Chronic renal failure
Non-aspirin NSAIDs
CRF, CHF, HTN
Non-aspirin, non-COX II NSAIDs
PUD
Opioid analgesics
BPH, constipation, dementia
Sedative/hypnotics
Falls
Skeletal muscle relaxants BPH
SSRIs
Falls
Theophylline
Insomnia
Thioridazine
Postural hypotension, seizures
Thorazine
Seizures
Tricyclic antidepressants
Arrhythmias, BPH, constipation
dementia, falls, heart block
postural hypotension
Typical antipsychotics
Falls

SELAMAT BELAJAR