obat pada anak & manula
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Drug Therapy in InfantsDrug Therapy in Infants
PHARMACODYNAMICSPHARMACODYNAMICS
Factors Affecting Drug Effects on the Infant:Factors Affecting Drug Effects on the Infant:
I. Drug AbsorptionI. Drug Absorption
II. Drug DistributionII. Drug Distribution
III. Drug MetabolismIII. Drug MetabolismIV. Drug ExcretionIV. Drug Excretion
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Drug Therapy in InfantsDrug Therapy in Infants
I. Drug AbsorptionI. Drug Absorption Absorption in infants and children follows the Absorption in infants and children follows the
same rules as in adults.same rules as in adults.
Factors affecting absorption are determined byFactors affecting absorption are determined bythe physiologic status of the infant or child andthe physiologic status of the infant or child and
are influenced by:are influenced by:
.! "lood flow at the site of administration..! "lood flow at the site of administration.
#.! $astrointestinal function.#.! $astrointestinal function.
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Drug Therapy in InfantsDrug Therapy in Infants
Drug Absorption inDrug Absorption in
DrugDrug
Acetaminophen Acetaminophen
Ampicillin AmpicillinDia%epamDia%epam
DigoxinDigoxin
&enicillin $&enicillin $&henobarbital&henobarbital
&henytoin&henytoin
'ulfonamides'ulfonamides
the neonate compared to adults.the neonate compared to adults.
(ral Absorption(ral Absorption
DecreasedDecreased
IncreasedIncreased)ormal)ormal
)ormal)ormal
IncreasedIncreasedDecreasedDecreased
DecreasedDecreased
)ormal)ormal
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Drug Therapy in InfantsDrug Therapy in Infants
.! "lood flow at the site of administration..! "lood flow at the site of administration.* &hysiological conditions that might affect blood flow are: cardio+ascular* &hysiological conditions that might affect blood flow are: cardio+ascular
shoc,- +asoconstriction sympathomimetic agents!- and heartshoc,- +asoconstriction sympathomimetic agents!- and heart
failure.failure.
* Diminished muscle mass in i/ch may reduce blood flow causing* Diminished muscle mass in i/ch may reduce blood flow causing
irregular and unpredicatble absorption. Drug will concentrate in theirregular and unpredicatble absorption. Drug will concentrate in themuscle and if perfusion suddenly increases- drug may reach toxicmuscle and if perfusion suddenly increases- drug may reach toxic
concentrations.concentrations.
e.g. cardiac glycosides- aminoglycoside antibiotics- and anticon+ulsants.e.g. cardiac glycosides- aminoglycoside antibiotics- and anticon+ulsants.
#.! $astrointestinal function.#.! $astrointestinal function.
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#.! $astrointestinal function.#.! $astrointestinal function.
'ignificant changes occur in the neonate shortly after'ignificant changes occur in the neonate shortly after
birth.birth.
$astric acid secretion commences soon after birth$astric acid secretion commences soon after birth
and increases gradually o+er se+eral hours. Inand increases gradually o+er se+eral hours. In
preterm infants it appears slowly.preterm infants it appears slowly. Drugs affected byDrugs affected by
gastric p0 should not be administered orally.gastric p0 should not be administered orally.$astric emptying is prolonged in the first day of life.$astric emptying is prolonged in the first day of life.
1hus- drugs absorbed through $I may be more1hus- drugs absorbed through $I may be more
completely absorbed than anticipated.completely absorbed than anticipated.
&eristalsis in the neonate is slow.&eristalsis in the neonate is slow. If drugs areIf drugs are
absorbed in the small intestine- their effect may beabsorbed in the small intestine- their effect may be
delayed.delayed. Diarrhea causes decrease absorption inDiarrhea causes decrease absorption in
small intestine.small intestine.
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Drug Therapy in InfantsDrug Therapy in Infants
II. Drug DistributionII. Drug Distribution As body composition changes with de+elopment so As body composition changes with de+elopment so
does the distribution +olume of drugs.does the distribution +olume of drugs.
In the neonate- 23*245 of body weight is water +sIn the neonate- 23*245 of body weight is water +s645 in preterm +s 43*735 in the adult.645 in preterm +s 43*735 in the adult.
Most neonates will experience diuresis in the firstMost neonates will experience diuresis in the first
#8*86hrs of life.#8*86hrs of life.
In neonate 835 of body weight is extracellularIn neonate 835 of body weight is extracellularwater +s #35 in the adult.water +s #35 in the adult.
In the neonate total body fat is 45 +s 5 inIn the neonate total body fat is 45 +s 5 in
preterm.preterm.
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Drug Therapy in InfantsDrug Therapy in Infants
II. Drug DistributionII. Drug Distribution"inding to &lasma protein"inding to &lasma protein
&rotein binding of drugs is reduced in the&rotein binding of drugs is reduced in the
neonate.neonate. 1herefore- concentration of free drug1herefore- concentration of free drugin plasma is increased 9 increased effectin plasma is increased 9 increased effect oror
increase toxicity.increase toxicity.
Drugs e.g. sulfonamide antibiotics! thatDrugs e.g. sulfonamide antibiotics! that
displace bilirubin from albumin may causedisplace bilirubin from albumin may cause
,ernicterus.,ernicterus. ;on+ersely- bilirubin may also;on+ersely- bilirubin may also
displace protein*bound drugs e.g. phenytoin!.displace protein*bound drugs e.g. phenytoin!.
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III. Drug MetabolismIII. Drug Metabolism
Metabolism of most drugs occurs in the li+er.Metabolism of most drugs occurs in the li+er.
1he metaboli%ing acti+ity of cytochrome &843*1he metaboli%ing acti+ity of cytochrome &843*dependent mixed*function oxidases is reduced independent mixed*function oxidases is reduced inneonates 43*235 of adult +alues!.neonates 43*235 of adult +alues!.
$lucoronide formation doesn<t occur until the =th$lucoronide formation doesn<t occur until the =th
*8rd years of life.*8rd years of life. 1hus- in the neonate- drugs1hus- in the neonate- drugsha+e slow clearance rates and prolonged half*ha+e slow clearance rates and prolonged half*li+es.li+es.
If the mother was ta,ing phenobarbital- neonatalIf the mother was ta,ing phenobarbital- neonatal
li+er en%ymes could ha+e been induced.li+er en%ymes could ha+e been induced. 1he1heability of the neonate to metaboli%e certain drugsability of the neonate to metaboli%e certain drugswould be greater than expected and the effectwould be greater than expected and the effectcould be less.could be less.
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IV. Drug ExcretionIV. Drug Excretion
$lomerular filtration is much lower =3*835 of$lomerular filtration is much lower =3*835 ofadult! in neonates for the first few days of life.adult! in neonates for the first few days of life.
>ithin a wee, glomerular filtration and plasma>ithin a wee, glomerular filtration and plasmaflow increase by 435 and reach adult +aluesflow increase by 435 and reach adult +alueswithin 7*# months.within 7*# months. Drugs that depend on renalDrugs that depend on renalflow are eliminated +ery slowly in the first fewflow are eliminated +ery slowly in the first few
wee,s of life penicilins- aminoglycosidewee,s of life penicilins- aminoglycosideantibiotics- digoxin!antibiotics- digoxin!
Ampicillin Ampicillin
? 2 days old9 43*33 mg/@g/d - #d at # hr? 2 days old9 43*33 mg/@g/d - #d at # hrinter+als.inter+als.
2 days old 9 33*#33 mg/@g/d- =d at 6 hr 2 days old 9 33*#33 mg/@g/d- =d at 6 hrinter+als.inter+als.
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D N t l A N t t A# lt t
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Drug Neonatal Age Neonates t 1/
!hours"
A#ults t 1/
!hours"
Acetaminophn #.#4 3.B#.#Dia%epam #4B33 83B43
Digoxin 73B23 =3B73
&henobarbital 3B4 days #33 78B83
4B4 days 33
B=3 months 43
&henytoin 3B# days 63 #B6
=B8 days 68B43 days 7
'alicylate 8.4B 3B4
1heophylline )eonate =B#7 3B4
;hild =B8
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Dosage Forms and ;ompliance:Dosage Forms and ;ompliance:
1o ease administration and compliance-1o ease administration and compliance-
drug manufacturers prepare drugsdrug manufacturers prepare drugsas:as:
a!a! Elixirs.Elixirs. Alcoholic solutions in which the Alcoholic solutions in which the
drug molecules are dissol+ed and e+enlydrug molecules are dissol+ed and e+enlydistributed.distributed.
b!b! 'uspensions.'uspensions. ;ontain undissol+ed;ontain undissol+ed
particles of drug which must beparticles of drug which must bedistributed throughout the +ehicle bydistributed throughout the +ehicle bysha,ing to pre+ent une+en drugsha,ing to pre+ent une+en drugdispensing.dispensing.
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$eight
!%g" !l&" Age Surfa'eArea!("
Per'ent ofA#ultDose
) *+* Ne,&orn -+ 1
* 1)+ ) (onths -+) 1.
1- 1 year -+0 .
- 0+0 years -+. .
)- ** years 1 *-
- .. 1 years 1+) 2.
0- 11- 1 years 1+0 -
*- 1) A#ult 1+2 1-
2- 10 A#ult 1+2* 1-)
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Age !Young3s rule"4
$eight !so(e,hat (ore pre'ise is Clar%3s rule"4
; ff; li b diffi lt t hi i
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;ompliance may be difficult to achie+e in;ompliance may be difficult to achie+e in
pediatric medicine and may pro+e apediatric medicine and may pro+e a
challenge when ta,ing into account:challenge when ta,ing into account:
measuring errorsmeasuring errors
spillsspills
spittingspitting A calibrated medicine spoon should be A calibrated medicine spoon should be
recommended.recommended.
&arents should be told to repeat dosage or not after&arents should be told to repeat dosage or not after
spitting or whether to wa,e up the child e+ery 7spitting or whether to wa,e up the child e+ery 7
hr dose day or night. &ossible drug*drughr dose day or night. &ossible drug*drug
interactions with (D; medications should beinteractions with (D; medications should be
discussed.discussed.
Drug Effect on Comments
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Drug Effect on
Infant
Comments
Ampicillin Minimal No significant adverse effects; possible
occurrence of diarrhea or allergicsensitization.
Aspirin Minimal Occasional doses probabl safe; high
doses ma produce significant
concentration in breast mil!" but infantdose is nevertheless lo#.
Caffeine Minimal Caffeine inta!e in moderation is safe;
concentration in breast mil! is about$% of that in maternal blood.
Chloral
hdrate
&ignificant Ma cause dro#siness if infant is fed at
pea! concentration in mil!.
Chloramphe
nicol
&ignificant Concentrations too lo# to cause gra
bab sndrome; possibilit of bonemarro# suppression does e'ist;
recommend not ta!ing chloramphenicol#hile breast(feeding.
)hiazide Minimal No adverse effects reported.
C*+ Minimal Appears insignificant.Codeine Minimal No adverse effects re orted.
Dia5epa( Signifi'ant May 'ause se#ation in &reast6fe# infants7 'lini'al
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Dia5epa( Signifi'ant May 'ause se#ation in &reast6fe# infants7 'lini'al(onitoring re'o((en#e#+
Di'u(arol Mini(al No a#8erse si#e effe'ts reporte#+
Digo9in Mini(al Insignifi'ant :uantities enter &reast (il%+
;thanol Mo#erate <arge a(ounts 'onsu(e# &y (other 'an pro#u'eal'ohol effe'ts in infant+
Heroin Signifi'ant ;nters &reast (il% an# 'an prolong neonatal nar'oti'#epen#en'e+
Io#ine !ra#" Signifi'ant ;nters (il% in :uantities suffi'ient to 'ause thyroi#suppression in infant+
Isonia5i#!INH"
Mini(al Mil% 'on'entrations e:ual (aternal plas(a'on'entrations+ Possi&ility of pyri#o9ine #efi'ien'y#e8eloping in the infant+
=ana(y'in Mini(al No a#8erse effe'ts reporte#+
<ithiu( Signifi'ant >reast6fee#ing ,ith 'aution7 le8els 'an &e (easure# in(il%+
Metha#one Signifi'ant !See heroin+" ?n#er 'lose physi'ian super8ision@ &reast6fee#ing 'an &e 'ontinue#+ Signs of opioi#,ith#ra,al in the infant (ay o''ur if (other stopsta%ing (etha#one or stops &reast fee#ing a&ruptly+
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Oral'ontra'epti8es
Mini(al May suppress la'tation in high #oses+
Peni'illin Mini(al ery lo, 'on'entrations in &reast (il%+
Pheno&ar&ital Mo#erate Hypnoti' #oses 'an 'ause se#ation in the infant+ Close(onitoring of infant+
Phenytoin Mo#erate A(ounts entering &reast (il% are not suffi'ient to 'ausea#8erse effe'ts in infant+
Pre#nisone Mo#erate <o, (aternal #oses !0 (g/#" pro&a&ly safe+ Doses t,o or(ore ti(es physiologi' a(ounts !B 10 (g/#" shoul#pro&a&ly &e a8oi#e#+
Propranolol Mini(al ery s(all a(ounts enter &reast (il%+
Propylthioura'il Signifi'ant May suppress thyroi# fun'tion in infant+
Spironola'tone Mini(al ery s(all a(ounts enter &reast (il%+
Tetra'y'line Mo#erate Possi&ility of per(anent staining of #e8eloping teeth inthe infant+ Shoul# &e a8oi#e# #uring la'tation+
Theophylline Mo#erate Can enter &reast (il% in (o#erate :uantities &ut not li%elyto pro#u'e signifi'ant effe'ts+
Thyro9ine Mini(al No a#8erse effe'ts in therapeuti' #oses+
Tol&uta(i#e Mini(al <o, 'on'entrations in &reast (il%+
$arfarin Mini(al ery s(all :uantities foun# in &reast (il%+
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Drug Therapy in InfantsDrug Therapy in Infants
DrugsDrugs
;ontraindicated;ontraindicated
Amphetamine Amphetamine
"romocryptine"romocryptine
;ocaine;ocaine
;yclophosphamide;yclophosphamide
;yclosporine;yclosporineDoxorubicinDoxorubicin
during Cactation:during Cactation:
ErgotamineErgotamine
0eroin0eroin
CithiumCithium
MariuanaMariuana
MethotrexateMethotrexate
)icotine)icotine&henindione&henindione
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("A1 &ADA MA)CA("A1 &ADA MA)CA
)oor >iayahadi)oor >iayahadi
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Medications Most ;ommonly sedMedications Most ;ommonly sed
in the ;ommunityin the ;ommunity
Analgesics Analgesics
DiureticsDiuretics;ardio+ascular ;ardio+ascular
'edati+e*hypnotics'edati+e*hypnotics
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Medications Most ;ommonly sedMedications Most ;ommonly sed
in the )ursing 0omein the )ursing 0ome
Antipsychotics Antipsychotics
'edati+e*hypnotics'edati+e*hypnotics
DiureticsDiuretics
Antihypertensi+es Antihypertensi+es
Analgesics Analgesics
;ardio+ascular ;ardio+ascular
Antibiotics Antibiotics
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ManulaManula esi,o tinggi mengalamiesi,o tinggi mengalami
efe, merugi,an dari obatefe, merugi,an dari obat
Fa,tor penderitaFa,tor penderita B Age*associated changes in Age*associated changes in pharmaco,ineticspharmaco,inetics
B Age*associated changes in Age*associated changes in pharmacodynamicspharmacodynamics
B ;omorbidity;omorbidity: drug*disease interactions: drug*disease interactions B &olypharmacy&olypharmacy: drug*drug interactions: drug*drug interactions
B @emampuan homeostasis ber,urang@emampuan homeostasis ber,urang
B Fungsi organ ber,urangFungsi organ ber,urang
Fa,tor sistem layanan medi,Fa,tor sistem layanan medi, B Fragmentation of care &oly*doctoring!Fragmentation of care &oly*doctoring!
B InadeGuate training in principles of geriatric practiceInadeGuate training in principles of geriatric practice
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1herapeutic esponse
1oxic esponse
Therapeutic Window
Age
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Increasing Age
“The Precipice”
&hysiologic
eser+es
A+ailable
&hysiologic
eser+es
Already In se
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Masalah UtamaMasalah Utama
Pilihan obat atau dosis yang tidak tepatPilihan obat atau dosis yang tidak tepat
Concomitant diseaseConcomitant disease affect metabolismaffect metabolism
of or response to drugof or response to drug
PolypharmacyPolypharmacy drug - drug interactionsdrug - drug interactions
Patient behavioural factorsPatient behavioural factors
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Perubahan PHARMACO!"#$!C%Perubahan PHARMACO!"#$!C%
AbsorptionAbsorption
active transferactive transfer
&ody composition&ody composition
lean body masslean body mass
body fatbody fat
plasma albuminplasma albumin
'iver metabolism'iver metabolismo(idation ) microsomal en*ymeso(idation ) microsomal en*ymes
Renal clearanceRenal clearance
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PerubahanPerubahan
PHARMACO+,"AM!C%PHARMACO+,"AM!C%
&rain sensitivity&rain sensitivity &en*odia*epines and&en*odia*epines and
narcotic analgesics more effectivenarcotic analgesics more effective
Coagulation mechanism controlCoagulation mechanism control
Anticoagulants more potentAnticoagulants more potent
Adrenergic receptor sensitivityAdrenergic receptor sensitivity
&-blockers less effective&-blockers less effective
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Penurunan fungsi homeostasisPenurunan fungsi homeostasis
&aroreceptor sensitivity&aroreceptor sensitivity
postural hypotensionpostural hypotension
$hermoregulation$hermoregulation
hypothermiahypothermia
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COMMO" P!$A''% . /COMMO" P!$A''% . /
0agal mengobati kondisi yang seharusnya0agal mengobati kondisi yang seharusnyabisa diobati 1treatable conditions2bisa diobati 1treatable conditions2
$hrombolytic therapy$hrombolytic therapythe older the patient3 the greater the benefitthe older the patient3 the greater the benefit
the older the patient3 the less likely to bethe older the patient3 the less likely to be
thrombolysedthrombolysed
HypertensionHypertension45 - 657 decrease in risk of C8A if !%H treated45 - 657 decrease in risk of C8A if !%H treated
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&'OO+ PR#%%UR# A"+ A0#&'OO+ PR#%%UR# A"+ A0#
-
-
-
*-
.-
1--
1-
1-
1*-
)- - 0- *- 2- .-
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COMMO" P!$A''% 9 /COMMO" P!$A''% 9 /
Prescribing for symptom and not forPrescribing for symptom and not for
diagnosisdiagnosis
: A pill for every ill ;
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PR#%CR!P$!O"% &, A0#PR#%CR!P$!O"% &, A0#1!tems per person per year21!tems per person per year2
* 0- 0 0. * ** 2- 2 2. . .* --
0
1-
10
-
0
)-
)0
-
* 0- 0 0. * ** 2- 2 2. . .* -
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##C$!8# PR#%CR!&!"0 .##C$!8# PR#%CR!&!"0 .
Utamakan non-pharmalogical treatmentUtamakan non-pharmalogical treatment
modify dietmodify diet
stop smoking3 reduce alcoholstop smoking3 reduce alcohol
physical e(ercisephysical e(ercise
<alking aids3 household adaptations<alking aids3 household adaptations
social supportssocial supports
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##C$!8# PR#%CR!&!"0 9##C$!8# PR#%CR!&!"0 9
$reat conditions in order of$reat conditions in order of prioritypriority
PertimbangkanPertimbangkan kegagalan fungsi organkegagalan fungsi organ
%tart lo<%tart lo< mulai dosis kecilmulai dosis kecil 3 naikkan3 naikkan
dengan hati-hatidengan hati-hati
0unakan0unakan formulariumformularium yang terbatasyang terbatas
MonitorMonitor compliance and responsecompliance and response
Revie<Revie< pemakaian obat secara regulerpemakaian obat secara reguler
!kut sertakan P#"+#R!$A!kut sertakan P#"+#R!$A
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>ho 1a,es the Most MedicationsH>ho 1a,es the Most MedicationsH
>omen>omen
Indi+iduals withIndi+iduals with
multiple healthmultiple health
conditionsconditions
Frail elderlyFrail elderly
)ursing home)ursing home
residentsresidents
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Medications Most ;ommonly sedMedications Most ;ommonly sed
in the ;ommunityin the ;ommunity
Analgesics Analgesics
DiureticsDiuretics;ardio+ascular ;ardio+ascular
'edati+e*hypnotics'edati+e*hypnotics
hi hi
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mur mempengaruhimur mempengaruhi
metabolisme obatHmetabolisme obatH
&ada manula:&ada manula:
B 'lower organ function'lower organ function
B 'lower blood circulation'lower blood circulation
B Increased body fatIncreased body fat
obat bertahan lama di dalam tubuhobat bertahan lama di dalam tubuh
resi,o ter,ena efe, samping obatresi,o ter,ena efe, samping obat
mening,atmening,at
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Age*elated ;hanges: Age*elated ;hanges:
1otal body water menurun1otal body water menurun ,onsentrasi dalam,onsentrasi dalam
darah obat yang larut*air mening,atdarah obat yang larut*air mening,at
&erubahan berat badan&erubahan berat badan
mempengaruhi dosismempengaruhi dosisyang diperlu,an dan lama obat dalam tubuh:yang diperlu,an dan lama obat dalam tubuh:
B More body fatMore body fat prolonged half*lifeprolonged half*life
B Cess lean body massCess lean body mass increased drug concentrationincreased drug concentration
&erubahan sistem pencernaan&erubahan sistem pencernaan mempengaruhi ,ecepatan absorbsi obatmempengaruhi ,ecepatan absorbsi obat
onset obat lebih lamaonset obat lebih lama
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Age*elated ;hanges: Age*elated ;hanges:
'lower circulation'lower circulation delay drugs gettingdelay drugs getting
to li+er and ,idneysto li+er and ,idneys
'low down of li+er and ,idneys'low down of li+er and ,idneys
affectsaffects
time it ta,es for medication to brea, downtime it ta,es for medication to brea, down
and lea+e bodyand lea+e body
Cess absorption from transdermal patchesCess absorption from transdermal patches
Drug receptorJ sites may be different inDrug receptorJ sites may be different in
older adultsolder adults
;
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;hanges in &harmaco,inetics;hanges in &harmaco,inetics
&erubahan fisiologis dan fungsi organ pada&erubahan fisiologis dan fungsi organ pada
manulamanula perubahan Farma,o,ineti,perubahan Farma,o,ineti,
&harmaco,inetics is the time course of a drug&harmaco,inetics is the time course of a drug
and its metabolites through the bodyand its metabolites through the body B Absorption Absorption
B DistributionDistribution
B ;learance: elimination renal!- metabolism li+er!;learance: elimination renal!- metabolism li+er!
#338: ;usac,- Amer. K of $eriatric &harmacotherapy#338: ;usac,- Amer. K of $eriatric &harmacotherapy
Volume of Distribution Vd!Volume of Distribution Vd!
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Volume of Distribution Vd!Volume of Distribution Vd!
&roporsi lema, mening,at dan +olume otot&roporsi lema, mening,at dan +olume otot
ber,urangber,urang merubah Vdmerubah VdVd obat larut lema, Vd obat larut lema, fat soluble drugfat soluble drug!!
mening,atmening,at wa,tu paro mening,at:wa,tu paro mening,at:
#ia5epa(@#ia5epa(@ thiopental@ tra5a#onethiopental@ tra5a#oneVd obat larut air Vd obat larut air water soluble drugwater soluble drug!!
menurunmenurun ,adar obat dalam plasma,adar obat dalam plasma
mening,at:mening,at: ethanol@ lithiu(@ethanol@ lithiu(@a(inogly'osi#es@ al'ohol@ #igo9ina(inogly'osi#es@ al'ohol@ #igo9in
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&rotein "inding&rotein "inding
albumin ber,urangalbumin ber,urang chronic disease:chronic disease:
e.g.-malnutrition- li+er or ,idney conditions.e.g.-malnutrition- li+er or ,idney conditions.
obat dengan i,atan protein tinggiobat dengan i,atan protein tinggi ,adar,adar
obat bebas mening,at.obat bebas mening,at.
ceftriaxone-dia%epam- phenytoin-ceftriaxone-dia%epam- phenytoin-
warfarin.warfarin.
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;li(inasi O&at (enurun;li(inasi O&at (enurun
Fungsi ginal menurunFungsi ginal menurun eliminasi oleh ginaleliminasi oleh ginalber,urang.ber,urang.
E+en in the absence of ,idney disease renal clearanceE+en in the absence of ,idney disease renal clearance
may be reduced =4*435.may be reduced =4*435. therapeutic effect dan resi,o to,sisitas mening,attherapeutic effect dan resi,o to,sisitas mening,at
perlu pengurangan dosis atau perubahan inter+alperlu pengurangan dosis atau perubahan inter+alpemberian obat.pemberian obat.
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Metabolisme hepar ber,urangMetabolisme hepar ber,urang
•Phase I, terutama reaksi oksidatif menurun
•Phase II, terutama reaksi konjugasi relatif tidak berubah.
diazepam is metabolized via Phase I reactions in the liver,
at least initially.
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Drugs with ;ytochrome &843 EffectsDrugs with ;ytochrome &843 Effectspartial!partial!
!nhibitors !nducers
Allopurinol Metronida*ole &arbiturates
Amiodorone =uinolones Carbama*epineA*ole antifungals Phenytoin
Cimetidine Rifampin
!"H $obacco
%%R!s
$acrine
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0epatic Metabolism0epatic Metabolism
Decreased li+er si%e and hepatic blood flow.Decreased li+er si%e and hepatic blood flow.
egional blood flow to the li+er at age 74 is reduceegional blood flow to the li+er at age 74 is reduceby 83*845 compared to a #4 year old.by 83*845 compared to a #4 year old.
Metabolic clearance of drugs by the li+er may beMetabolic clearance of drugs by the li+er may bereduced.reduced.
Disease effects: li+er congestion from heart failureDisease effects: li+er congestion from heart failuredecreases warfarin metabolism and an increaseddecreases warfarin metabolism and an increasedpharmacologic response.pharmacologic response.
En+ironmental effects: smo,ing stimulatesEn+ironmental effects: smo,ing stimulatesmonoxygenase en%ymes and increases clearancemonoxygenase en%ymes and increases clearanceof theophylline.of theophylline.
;h i &h d i;h i &h d i
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;hanges in &harmacodynamics;hanges in &harmacodynamics
(lder patients may ha+e more sedation and(lder patients may ha+e more sedation and
impaired function after a single dose ofimpaired function after a single dose of
ben%odia%epines than younger persons.ben%odia%epines than younger persons.
After single dose of nitra%epam older patients After single dose of nitra%epam older patientsmade more mista,es on psychomotor testingmade more mista,es on psychomotor testing
compared to placebo while younger patientscompared to placebo while younger patients
had no impairment .had no impairment .
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'uboptimal Luality'uboptimal Luality
1ypology of Luality &roblems:1ypology of Luality &roblems:
B (+eruse &olypharmacy!(+eruse &olypharmacy!
B nderusenderuse
B Misuse Inappropriate &rescribing!Misuse Inappropriate &rescribing!
B ErrorsErrors
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'uboptimal &rescribing'uboptimal &rescribing
&olypharmacy&olypharmacy
nderuse of Effecti+e Medicationsnderuse of Effecti+e Medications
Drug*Drug InteractionsDrug*Drug Interactions
Drug*Disease InteractionsDrug*Disease Interactions
InadeGuate MonitoringInadeGuate Monitoring
Inappropriate DosingInappropriate Dosing
Inappropriate DurationInappropriate Duration
Drugs to A+oidDrugs to A+oid
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Drug*Drug InteractionsDrug*Drug Interactions
Penye&a& tersering ;SO pa#a (anulaPenye&a& tersering ;SO pa#a (anulau(lahnya sangat &anya%u(lahnya sangat &anya% Al(ostAl(ost'ountless'ountless peresepan ele%troni%peresepan ele%troni%
So(e 'o((on e9a(plesSo(e 'o((on e9a(ples B 'tatins and erythromycin and other antibiotics'tatins and erythromycin and other antibiotics
B 1;As and clonidine or type Anti*arrythmics1;As and clonidine or type Anti*arrythmics
B >arfarin and multiple drugs>arfarin and multiple drugs
B A;E inhibitors increase hypoglycemic effect of A;E inhibitors increase hypoglycemic effect ofsulfonylureassulfonylureas
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Drug*disease InteractionsDrug*disease Interactions
&atient with &D ha+e increased ris, of drug&atient with &D ha+e increased ris, of druginduced confusioninduced confusion
)'AIA and ;(*#<s! s can exacerbate ;0F)'AIA and ;(*#<s! s can exacerbate ;0F
rinary retention in "&0 patients onrinary retention in "&0 patients ondecongestants or anticholinergicsdecongestants or anticholinergics
;onstipation worsened by calcium-;onstipation worsened by calcium-ahticholinergics- calcium channel bloc,ersahticholinergics- calcium channel bloc,ers
)euroleptics and Guinolones lower sei%ure)euroleptics and Guinolones lower sei%urethresholdsthresholds
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&olypharmacy&olypharmacy
Polyphar(a'y pe(&erian &anya%Polyphar(a'y pe(&erian &anya%
o&at (ele&ihi in#i%asi penggunaano&at (ele&ihi in#i%asi penggunaan
0E (anula (en#apat o&at tanpa0E (anula (en#apat o&at tanpa
in#i%asi yang Felas+in#i%asi yang Felas+
00E (anula (en#apat o&at00E (anula (en#apat o&at tanpatanpa
in#i%asiin#i%asi@ )+2E (en#apat@ )+2E (en#apat o&at yango&at yang
ti#a% efe%tif ti#a% efe%tif @ 1*+.E (en#apat@ 1*+.E (en#apat o&ato&at#upli%asi#upli%asi#33: 0anlon- KA$'#33: 0anlon- KA$'
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nderusenderuse
A(ong patients el#erly patients ,ithA(ong patients el#erly patients ,ith'ar#io8as'ular #isease an# #ia&etes@ only'ar#io8as'ular #isease an# #ia&etes@ only1+1E of patients ,ere pres'ri&e# statins+ In1+1E of patients ,ere pres'ri&e# statins+ Inpatients ** to 2 years ol#@ the a#Fuste#patients ** to 2 years ol#@ the a#Fuste#
pro&a&ilities of statin pres'ription ,ere )2+2E@pro&a&ilities of statin pres'ription ,ere )2+2E@*+2E@ an# )+E in the 'ategories of lo,@*+2E@ an# )+E in the 'ategories of lo,@inter(e#iate@ an# high &aseline ris%@inter(e#iate@ an# high &aseline ris%@respe'ti8ely+respe'ti8ely+
The li%elihoo# of statin pres'ription ,as *+EThe li%elihoo# of statin pres'ription ,as *+Elo,er !a#Fuste# o##s ratio@ -+7 0Elo,er !a#Fuste# o##s ratio@ -+7 0E'onfi#en'e inter8al@ -+)6-+0" for ea'h year of'onfi#en'e inter8al@ -+)6-+0" for ea'h year ofin'rease in age an# ea'h 1E in'rease inin'rease in age an# ea'h 1E in'rease in
pre#i'te# )6year (ortality ris%+pre#i'te# )6year (ortality ris%+#338: @o- KAMA#338: @o- KAMA
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Inappropriate &rescribingInappropriate &rescribing
#3*#25 manula mendapat resep yang#3*#25 manula mendapat resep yang
tida, diperlu,an inappropriate!.tida, diperlu,an inappropriate!.
Inappropriate prescribing mening,at,anInappropriate prescribing mening,at,an
resi,o atuh- fra,tur femur- cogniti+eresi,o atuh- fra,tur femur- cogniti+e
impairment- diminished independence-impairment- diminished independence-
dan mortalitasdan mortalitas
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inappropriate drug prescribing toinappropriate drug prescribing to
the elderlyHthe elderlyH
The Beers List The Beers List .
a list of medications identified by an expert
panel as being inappropriate for older persons
because of ineffectiveness or because they
pose a high risk for adverse drug events.
>eers MH Arch Intern Med 12
1h " Ci
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1he "eers Cist1he "eers Cist
1he "eers Cist- berisi == obat dalam =1he "eers Cist- berisi == obat dalam =,ategori:,ategori:
3. Drugs ith some indications, but that are often
misused.
!. Drugs that are rarely appropriate.
". Drugs that should always be avoided .
Ghan et al+ JAMA --1
D A d D t A idD A d D t A id
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Drugs And Dosages to A+oidDrugs And Dosages to A+oid
Meperi#ineMeperi#ine
Diphenhy#ra(ineDiphenhy#ra(ine
The (ost anti'holinergi' tri'y'li's4The (ost anti'holinergi' tri'y'li's4
a(itryptiline@ #o9epin@ i(ipra(inea(itryptiline@ #o9epin@ i(ipra(ine<ong a'ting &en5o#ia5epines su'h as<ong a'ting &en5o#ia5epines su'h as
#ia5epa(#ia5epa(
<ong a'ting NSAIDs su'h as piro9i'a(<ong a'ting NSAIDs su'h as piro9i'a(High #ose thia5i#es !B0(g"High #ose thia5i#es !B0(g"
Iron4 )0 (g on'e #aily is enoughIron4 )0 (g on'e #aily is enough
drugs that should always be drugs that should always be
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drugs that should always be drugs that should always be
a+oided in the elderly:a+oided in the elderly:
"arbiturates"arbiturates
;hlorpropamide;hlorpropamide
Flura%epamFlura%epam
MeperidineMeperidine
MeprobamateMeprobamate
&enta%ocine&enta%ocine
"elladonna al,aloids"elladonna al,aloids
DicyclomineDicyclomine
0yoscyamine0yoscyamine
&ropantheline&ropantheline
1rimethoben%amide1rimethoben%amide
Ghan et al+ JAMA --1
1angga &eresepan1angga &eresepan
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a gga e esepagg p
&rescribing ;ascade!&rescribing ;ascade!
#he prescribing cascade terjadi
bila satu obat diresepkan,
$enyebabkan timbulnya
efek samping obat % adverse
drug event &'D(),
$endorong peresepan obat
kedua untuk mengatasi (*+
sebelumnya
rug 1
rug 2
A E
Ro'hon PA et al@ BMJ 12
1he &rescribing ;ascade1he &rescribing ;ascade
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1he &rescribing ;ascade1he &rescribing ;ascade
$etoclopramide
(xtrapyramidal (ffects
evodopa -x
#here are numerous examples of the prescribing cascade in the
medical literature.
or example, it has been observed that patients prescribed
metoclopramide & a gastric motility agent) are more likely to be initiated
on treatments generally reserved for the management of idiopathic
Parkinson/s Disease &e.g. Drugs containing evodopa).
In this case, metoclopramide use
can lead to extrapyramidal
symptoms, hich may be
misdiagnosed as Parkinson/s
Disease.
A8orn et al@ JAMA 10
1h & ibi ; d1he &rescribing ;ascade
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0*'ID -x
'ntihypertensive -x
1lood Pressure
1he &rescribing ;ascade1he &rescribing ;ascade
'nother example relates to the fact that older persons ho have
been prescribed 0*'IDs appear to be at increased risk for beinginitiated on antihypertensive therapy.
In this case, 0*'ID useincreases blood pressure
leading to the need for blood
pressure loering therapy.
In both examples, the initiation of ne drug treatments in older persons
could have been avoided if there as recognition of the risks of certain
drug treatments &e.g. metoclopramide and 0*'IDs) in elderly patients.
ur,it5 H et al@ JAMA 1
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1he &rescribing ;ascadeJ1he &rescribing ;ascadeJ
Penye&a& uta(a polyphar(a'y pa#aPenye&a& uta(a polyphar(a'y pa#a(anula(anula
So(e 'o((on e9a(plesSo(e 'o((on e9a(ples B )'AID *01)*antihypertensi+e therapy)'AID *01)*antihypertensi+e therapy B Metoclopromide *&ar,insonism *'inemetMetoclopromide *&ar,insonism *'inemet
B Dihydropyridine * edema *furosemideDihydropyridine * edema *furosemide
B )'AIA *0# bloc,er *delirium *haldol)'AIA *0# bloc,er *delirium *haldol
B 0;1N *gout*)'AIA *#nd antihypertensi+e0;1N *gout*)'AIA *#nd antihypertensi+e
B 'udafed *urinary retention *alpha bloc,er 'udafed *urinary retention *alpha bloc,er
B Antipsychotic *a,ithesia *more meds Antipsychotic *a,ithesia *more meds
)'AID Anti inflamasi non steroid!)'AID Anti inflamasi non steroid!
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)'AID Anti*inflamasi non*steroid!)'AID Anti*inflamasi non*steroid!
Efe,tifitas &arasetamol 9 )'AIDs padaEfe,tifitas &arasetamol 9 )'AIDs padaosteoartritis ringanosteoartritis ringan
)'AIDs side effects)'AIDs side effects
B $I hemorrhage$I hemorrhage B Decline in $FDecline in $F
Decreased effecti+eness of diuretics- anti*Decreased effecti+eness of diuretics- anti*hypertensi+e agentshypertensi+e agents
Indication should ustify the increased toxicityIndication should ustify the increased toxicityof )'AIDsof )'AIDs
D d ; iti I i t
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Drugs and ;ogniti+e ImpairmentDrugs and ;ogniti+e Impairment
Anti'holinergi' #rugs are 'o((onAnti'holinergi' #rugs are 'o((onoffen#ers !TCAs@ &ena#ryl an# otheroffen#ers !TCAs@ &ena#ryl an# other
antihista(ines@ (any others"antihista(ines@ (any others"Other offen#ers 'i(eti#ine@ steroi#s@Other offen#ers 'i(eti#ine@ steroi#s@NSAIAsNSAIAsMe#i'al <etter --- Drug Safety 1 Drugs an# Aging 1Me#i'al <etter --- Drug Safety 1 Drugs an# Aging 1
Drugs and FallsDrugs and Falls
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Drugs and FallsDrugs and Falls
"iggest ris, drugs are long acting ben%odia%epines"iggest ris, drugs are long acting ben%odia%epinesand other sedati+e*hypnoticsand other sedati+e*hypnotics
"oth ''Is and 1;As associated with increased"oth ''Is and 1;As associated with increasedris, of fallingris, of falling
"eta bloc,ers )(1 associated with increased ris,"eta bloc,ers )(1 associated with increased ris,of falling in published literatureof falling in published literature
Mild increase in fall ris, from diuretics- type AMild increase in fall ris, from diuretics- type Aanti*arrythmics- and digoxinanti*arrythmics- and digoxin
Ceip%ig- KA$'Ceip%ig- KA$'
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Drug*Food InteractionsDrug*Food Interactions
Interactions between drugs and foodInteractions between drugs and food B warfarin and Vitamin @ containing foodswarfarin and Vitamin @ containing foods
remember green tea- as well!remember green tea- as well!
B &henytoin O +itamin D metabolism&henytoin O +itamin D metabolism B Methotrexate and folate metabolismMethotrexate and folate metabolism
Drug impact on appetiteDrug impact on appetite
B Digoxin may cause anorexiaDigoxin may cause anorexia B A;E inhibitors may alter taste A;E inhibitors may alter taste
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Anticipate 'ide Effect Anticipate 'ide Effect
Nar'oti'sNar'oti's B >egin la'tulose or sor&itol an# a sti(ulant la9ati8e>egin la'tulose or sor&itol an# a sti(ulant la9ati8e
B Cola'e is NOT suffi'ient in (ost instan'esCola'e is NOT suffi'ient in (ost instan'es
Steroi#sSteroi#s
B Thin% a&out osteoporosis pre8entionThin% a&out osteoporosis pre8ention B Re(e(&er steroi# in#u'e# #ia&etesRe(e(&er steroi# in#u'e# #ia&etes
<e8othyro9ine<e8othyro9ine B Cal'iu( interferes ,ith a&sorption of le8othyro9ineCal'iu( interferes ,ith a&sorption of le8othyro9ine
Drug DiscrepanciesDrug Discrepancies
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Drug DiscrepanciesDrug Discrepancies
Difference between medical record andDifference between medical record and
medication bottles in 275 of casesmedication bottles in 275 of cases
B 45 of time medication not recorded45 of time medication not recorded
B #5 medication recorded that patient not#5 medication recorded that patient notta,ingta,ing
B #35 dosage discrepancy#35 dosage discrepancy
is, Factors: Age- number of medicationsis, Factors: Age- number of medications B "edell et al Arch Intern Med 73- #333"edell et al Arch Intern Med 73- #333
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0igh is, 'ituations0igh is, 'ituations
Patient seeing (ultiple pro8i#ersPatient seeing (ultiple pro8i#ers
Patient on (ultiple #rugsPatient on (ultiple #rugs
Patient li8es alone an#/or hasPatient li8es alone an#/or has
'ogniti8e i(pair(ent'ogniti8e i(pair(ent
Dis'harge fro( hospital or anyDis'harge fro( hospital or any
'hange in 8enue'hange in 8enue
0ospitali%ation: A 0igh is, 1ime0ospitali%ation: A 0igh is, 1ime
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0ospitali%ation: A 0igh is, 1ime0ospitali%ation: A 0igh is, 1ime
At hospitali5ation4At hospitali5ation4
-E of a#(ission (e#i'ations stoppe#-E of a#(ission (e#i'ations stoppe#
0E of #is'harge (e#i'ations ,ere starte#0E of #is'harge (e#i'ations ,ere starte#Serious pres'ri&ing pro&le(s in ESerious pres'ri&ing pro&le(s in E
Other pres'ri&ing pro&le(s in **EOther pres'ri&ing pro&le(s in **E
B >eers AS 1.@ <ipton Me#i'al Care 1>eers AS 1.@ <ipton Me#i'al Care 1
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)onadherence)onadherence
<a'% of un#erstan#ing of ho, to ta%e<a'% of un#erstan#ing of ho, to ta%e B High ris% ti(es4 Hospital #is'harge@ ne, (e#sHigh ris% ti(es4 Hospital #is'harge@ ne, (e#s
a##e#@ 'o(ple9 regi(ensa##e#@ 'o(ple9 regi(ens
?na&le to ta%e?na&le to ta%eCons'ious nona#heren'eCons'ious nona#heren'e B Si#e effe'tsSi#e effe'ts
B <a'% of un#erstan#ing of &enefits of #rug<a'% of un#erstan#ing of &enefits of #rug B inan'ialinan'ial
Complementary TherapiesComplementary Therapies
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Complementary TherapiesComplementary Therapies
Very commonly used in the elderlyVery commonly used in the elderly'ome common herbs and alternati+e therapies:'ome common herbs and alternati+e therapies:
B Anti*agingJ Anti*agingJ D0EA- growth hormoneD0EA- growth hormone
B DementiaDementia $ing,o biloba$ing,o biloba
B "&0"&0 'aw palmetto- &;*'&E''aw palmetto- &;*'&E'
B (A(A ;hondroiton sulfate-;hondroiton sulfate-
glucosamineglucosamine
B DepressionDepression 't. Kohn<s wort- 'AMe't. Kohn<s wort- 'AMe
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Adulterants in &roducts Adulterants in &roducts
California Depart(ent of HealthCalifornia Depart(ent of HealthSer8i'es@ oo# an# Drug >ran'hSer8i'es@ oo# an# Drug >ran'h B s'reene# 0- Asian her&al pro#u'tss'reene# 0- Asian her&al pro#u'ts
B'olle'te# fro( her&al stores in California'olle'te# fro( her&al stores in California
B assaye# pro#u'ts using gas 'hro(atography@assaye# pro#u'ts using gas 'hro(atography@(ass spe'tro(etry@ an# ato(i'6a&sorption(ass spe'tro(etry@ an# ato(i'6a&sorptionte'hni:ueste'hni:ues
B =o@ N;M 1.7 ))7 .2=o@ N;M 1.7 ))7 .2
)E 'ontaine# unla&ele# (e#i'ations@)E 'ontaine# unla&ele# (e#i'ations@1E (er'ury@ 1E arseni'@ 1-E lea#1E (er'ury@ 1E arseni'@ 1-E lea#
0erbals and 'upplements:0erbals and 'upplements:
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egulationegulation
Demonstration of safety is )(1 reGuired prior toDemonstration of safety is )(1 reGuired prior tomar,etingmar,eting
Manufacturing standards are not reGuiredManufacturing standards are not reGuired
;an ha+e;an ha+e healthhealth claims- but not claims aboutclaims- but not claims abouttreating- pre+enting- or curingtreating- pre+enting- or curing
For glucosamine/chondroitin- on third ofFor glucosamine/chondroitin- on third of
combinations did not contain listed ingredientcombinations did not contain listed ingredient
www.consumerlabs.com has some drugwww.consumerlabs.com has some drug
informationinformation
0erbals and 'upplements:&otential0erbals and 'upplements:&otential
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pppp
interactions with x Drugsinteractions with x Drugs
SAMe (ay in'rease ho(o'ysteineSAMe (ay in'rease ho(o'ysteine
le8elsle8els
St+ ohnJs ,ort an# Oral 'ontra'epti8esSt+ ohnJs ,ort an# Oral 'ontra'epti8es
in%go (ay in'rease anti'oagulantin%go (ay in'rease anti'oagulant
effe'ts of ASA@ ,arfarin@ NSAIAs@effe'ts of ASA@ ,arfarin@ NSAIAs@
ti'lopi#ine@ an# (ay intera't ,ith MAOIsti'lopi#ine@ an# (ay intera't ,ith MAOIs
>otto( line4 Try to %no, ,hat your>otto( line4 Try to %no, ,hat your
patient is ta%ing@ an# as% in apatient is ta%ing@ an# as% in a
nonFu#g(ental ,aynonFu#g(ental ,ay
& i i M (b t& i i M (b t
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&rinsip Manaemen (bat&rinsip Manaemen (bat
iwayat pema,aian obat yang leng,ap-iwayat pema,aian obat yang leng,ap-termasu, obat herba/tradisional/obat bebastermasu, obat herba/tradisional/obat bebas
0indari pemberian obat bila0indari pemberian obat bila,euntungan/benefit ,ecil - atau ada alternatif,euntungan/benefit ,ecil - atau ada alternatif
pengobatan non*farma,ologispengobatan non*farma,ologis&ertimbang,an harga&ertimbang,an harga
'tart low- go slow- but get thereP'tart low- go slow- but get thereP
"uat cara pemberian yang sederhana"uat cara pemberian yang sederhana1ulis cara pema,aian seelas mung,in1ulis cara pema,aian seelas mung,in
Minta penderita membawa seluruh obat yangMinta penderita membawa seluruh obat yangsedang diminum setiap ,ali peri,sasedang diminum setiap ,ali peri,sa
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&rinciples continued!&rinciples continued!
&ertimbang,an pema,aian ,ota, obat harian&ertimbang,an pema,aian ,ota, obat harianatau medisetJatau medisetJ
0enti,an pema,aian obat yang tida, elas0enti,an pema,aian obat yang tida, elas
,euntungannya atau resi,o efe, sampingnya,euntungannya atau resi,o efe, sampingnya
lebih merugi,anlebih merugi,an
0ati*hati pema,aian obat baru newer drugs!0ati*hati pema,aian obat baru newer drugs!
0indari penggunaan obat 4 macam0indari penggunaan obat 4 macam
;onsider if the benefit of the 2th or 6th drug is;onsider if the benefit of the 2th or 6th drug issufficient to ustify the cost- increase insufficient to ustify the cost- increase in
complexity of regimen- and ris, of side effectscomplexity of regimen- and ris, of side effects
)ewer drugs)ewer drugs
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gg
$hat is uni:ue a&out this 'o(poun#K$hat is uni:ue a&out this 'o(poun#K
$hat 'lini'al #ata is a8aila&leK$hat 'lini'al #ata is a8aila&leK
Ho, #oes it 'o(pare ,ith tra#itionalHo, #oes it 'o(pare ,ith tra#itional
therapyKtherapyK
Ho, e9pensi8e is itKHo, e9pensi8e is itK
$ith thir# party payers 'o8er this$ith thir# party payers 'o8er this
pro#u'tKpro#u'tK
Does the potential a#8antage of this ne,Does the potential a#8antage of this ne,
#rug Fustify the ris% of using a ne, #rugK#rug Fustify the ris% of using a ne, #rugK
1h M f 1 d1h M f 1 d
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1he Message for 1oday1he Message for 1oday
'tart low'tart low
$o slow but get to therapeutic le+els!$o slow but get to therapeutic le+els!
'ometimes say no how about other non*drug'ometimes say no how about other non*drugtreatmentsH!treatmentsH!