Aznan Lelo

Dep. Farmakologi & Terapeutik,

Fakultas Kedokteran
UNIBA
7 September 2011, UNIBA, Batam
Background

Polypharmacy is common among supplement

users

Many assume herbs and supplements are safe

Many pharmacological actions but dangerous

side effects and interactions exist

Be sure to ask your patients (non-judgmental)

Knoledge is our best eapon and protection

A Good Medication History:
AVOID Mistakes

Allergies!

Vitamins and herbs!

Old drugs and "#$! (as ell as

current)

Interactions!

Dependence! %o you need a contract!

Mendel& 'amily (x of benefits or

problems ith any drugs!
Problems Associated with se o!
Herbal Medicines

)ack of *$ + standardisation

,dulteration ith other plants-

pharmaceutical drugs or hea.y metals

/nappropriate use 0 misleading claims

#ype , + B ,%1s

Potential !or drug interactions

)ack of knoledge re& interactions- ,%1s

steroids: prednisolone, hydrocortisone,

triamcinolone, methyltestosterone

benzodiazepines: diazepam, estazolam,

chlordiazepoxide

heavy metals: mercury, lead, arsenic, antimony,

cadmium

analgesics and NSIADs: acetaminophen,

aspirin, indomethacin, mefanamic acid

other drugs and chemicals:

hydrochlorothiazide, digitalis, cafeine, scopolamine,
atropine, strychnine, carbamazepine, phenytoin,
valproic acid, dipyrone, diacetyldiphenolisatin
Common Adulterants and
Contamnants
Fora!n! and "ar#estn!
Issues, problems, et$%&

isidenti!cation

"otencies vary from batch to batch#.

season to season#.

$hemical composition varies

bet%een cultivars, geography,
environmental conditions

$hanging nomenclature
2
&otanical and medical
Herbals and "u##lements:
Potential interactions with $% Drugs

3,Me may increase homocysteine le.els

3t4 5ohn6s ort and "ral contracepti.es

7inkgo may increase anticoagulant effects

of ,3,- arfarin- 83,/,s- ticlopidine- and
may interact ith M,"/s

Bottom line& #ry to kno hat your patient

is taking- and ask in a nonjudgmental ay
De!initions and &erms

3ide 9ffects& unintended- usually detrimental-

conse:uences

,d.erse& untoard- unintended- possibly causing harm

,9& ,d.erse 9.ent- 9ffect or 9xperience

,%9 (,9 associated ith a %rug)& an ,9 hich

happens in a patient taking a drug

,%1 (,d.erse %rug 1eaction)& an ,%9 in hich a

causal association is suspected beteen the drug and
the e.ent
;nfortunately- these terms are fre:uently used
interchangeably
I'(ID)'() o! AD$s

,%1s are alays under reported

,%1s are the <

th
-=
th
largest cause for mortality in
the ;3,
>

,%1s account for approximately >?@ of hospital

admissions
2 8oray >>4A@- 'rance >B4?@ ;K >=4?@
C

,%1s increase the length of hospital stay and

medical costs

>A-C?@ of hospital budget may be spent dealing

ith drug complications
B
1. Lazarou et al.JAMA 1998, 279(15) 1000-5
2. Safety of Medicie!. "#$%&'M%(SM%2002.2
). "*ite et al. +*ar,acoecoo,ic!,1999,15(5) --5--58
Drug $elated Ad*erse $eactions

identify the suspected drug

identify factors that contributed to the

occurrence of the ad.erse reaction such as

multiple drug therapy-

drug-drug interactions

drug+herbal interactions

%rug 2 food interactions

9xcipients- colouring agents

Garlic

9fficacy& ! benefit for use in hyperlipidemia4

Possible other cardio.ascular benefits4

3afety& good

%rug interactions& arfarinD possibly aspirin

and other antiplatelet adhesion drugs
(pharmacodynamic interaction)D not ith (/E
drugs (other B,< substrates!) but depends
on product (pharmacokinetic interaction)
(maybe ra garlic induces B,< but not
extracts,,-
'arl$

'eat and acid inactivate allicin, enteric

coated products sho% best results

ay increase efects of anticoagulants,

may inhibit thyroid preparations

"recautions and interactions( )nhibited

platelet aggregation *interaction %ith
anticoagulants+, may reduce blood
sugar so use %ith caution %ith various
hypoglycemic agents
)chinacea

9fficacy& e.idence for treatment not

pre.ention

3afety& goodD rare allergy

%rug interactions&

don6t gi.e to patients taking immunosuppressi.e drugs

,ntagonises immunosuppressants

/ncreased bleeding time

Pharmacokinetic&

may inhibit >,CD may inhibit intestinal B,< but induce

hepatic so clinical significance unclearD effect on C$F is
considered minor
Ginkgo biloba
2
9fficacy& good for dementia and poor
peripheral circulatory problems
2
3afety& goodD rare bleeding episodes
2
%rug interactions& no effect on B,<-C$F or
C%= but may induce C$>FD may inhibit
platelet adhesionD .o!!i/le (not
necessarily probableG) interaction ith
Hblood thinnersI and arfarin so a.oid or
close monitoring needed4
7inkgo and coagulation and
pharmacodynamic interactions ith
antiplatelet adhesion inhibitors
$oagulation in healthy adults (in absence of other
drugs)
Kohler et al4 Blood $oagul 'ibrinolysis4 C??<D>A&B?B-F4
(company study)4 8o effect on coagulation parameters
in healthy adults after Jd of 97bJ=> >C?mg0d4 nKA?4
Ginkgo biloba

L %iclofenac or L #olbutamide (uman 3tudies

$onclusions

8o difference as obser.ed in the metabolic

ratio beteen the to arms of the study
(tolbutamide alone and tolbutamide L 7inkgo)

8o difference as seen beteen the clearances

of the to arms of the study (diclofenac alone
and diclofenac L 7inkgo)

7inkgo extract does not appear to interact ith

$MPC$F substrates in humans
Ginkgo biloba

Precautions and interactions&

2
7inkolide is a selecti.e antagonist of platelet
aggregation4 $ase reports of subdural hematoma
and spontaneous bleeding ith ,3, use4 1eports
of 7/ disturbances and $83 symptom
2
7inkgo and caffeine may increase risk of subdural
hematomas
2
7inkgo helped 331/ induced sexual dysfunction
F>@ in omen- J=@ in men ($ohen and Bartlik
>FFN)

;se ith extreme caution ith stimulants

"oy
2
9fficacy& increased soy ingestion may
decrease hot flashes and other
postmenopausal symptomsD
cardio.ascular benefits as ell4
2
3afety& good but use in breast cancer may
be risky
2
%rug interactions& not ith ith tamoxifen
but effect on $MPB,< is unlikely
Ginseng

9fficacy& some e.idence for applications in

geriatric patients (impro.ed H:uality of lifeI)
and in diabetes

3afety& goodD

%rug interactions& no apparent induction of

$MP B,< but induction of C$F (arfarin) ith
,m ginseng (Panax :uin:uifolius) but
maybe not Panax ginseng4 May precipitate
hypoglycemia ith insulin or oral
hypoglycermics4
Ginseng

Precautions and interactions& May increase BP4

".eruse can cause headaches- insomnia-
palpitations4 9strogen affects may cause .aginal
bleeding- fibrocystic breasts
/nteracts ith )asix- decreases diuretic action

"ne study demonstrates enhanced alcohol

clearance in healthy men ()ee et al- >FNJ)

May induce mania hen used concurrently ith

antidepressants (7onOaleO-3eiji et al- >FFA)

May potentiate M," inhibitors (3hader et al- >FNN)

May inhibit metabolism of barbituates

May potentiate stimulants (caffeine most studied)

May cause (aloperidol catalepsy

"aint .ohn/s 0ort

$ontraindications& 3e.ere depression ith

akinetic mutism- suicidal tendencies- se.ere
agitation- hypersensiti.ity and pregnancy
(estrogen effects)

Precautions& photosensiti.ity

/nteractions& May precipitate hypertensi.e crisis

ith M," inhibitors (Mueller + 3haefer->FF=)

May induce Hserotonin syndromeI ith 331/6s

and ith #riptans

/nterferes ith cyclosporine- may cause

transplant rejection

May cause hypertension ith tyramine

containing foods

3afe ith benOodiaOapines

"t1 .ohn/s 0ort
2
9fficacy& good e.idence for mild to
moderate depression
2
3afety& don6t combine ith other
medications unless under close
monitoringD possible photosensiti.ity
2
%rug interactions& a problemG /s a broad
spectrum P<A? inducer and a p-
glycoprotein inducer4
Drug CYP Effect Management
HIV protease inhibitors

(nelfinavir,ritonavor,saquinavir
In!uce "#$

%top an! measure
viral loa!
HIV non&nucleosi!e '(I
(efaviren),nevirapine
In!uce "#$

%top an! measure
viral loa!
*arfarin In!uce +C,

%top an! a!-ust *arfarin
!ose
c.closporin In!uce P&
gl.coprotein

%top an! a!-ust
c.closporine !ose
oral contraceptives In!uce "#$

%top an! use alternate
birth control
anticonvulsants In!uce "#$

%top an! a!-ust
anticonvulsant !ose
!igo/in In!uce P&
gl.coprotein

%top an! a!-ust !igo/in
!ose
theoph.lline In!uce 0#+

%top an! a!-ust
theoph.lline !ose
(riptans
(sumatriptan
Increase
serotonin

%top
%%'I
(fluo/etine,sertraline, etc
Increase
serotonin

%top

Summar( o) S*+ Intera$tons
*adapted from 'enderson et al. &r , $lin "harmacol -..-/01(2134215+
"t1 .ohn/s 0ort

Pith 331/s- triptans - symptoms

characteristic of serotonin syndrome

#heophylline ($MP>,C)- cyclosporin

($MPB,<) and arfarin ($MPC$F) -
reports of a reduction in the serum concs

Pith $"$ - reports of breakthrough

bleeding - reduced efficacy!

,d.ice published by the /MB and $3M

"aw Palmetto

;ses& 'or male genitourinary problems (BP()-

prostate cancer- antisepsis

)ikely safe in usual doses for up to one year

)ikely effecti.e for BP( symptoms

Possibly effecti.e for adjuncti.e therapy for

prostate cancer

Precautions and interactions& %ue to anti-

testosterone action do not use in pregnancy or
children- can cause stomach upset- no
psychotropic interactions
&estosterone "ynthesis
$holesterol Pregnenolone
%(9,
,ndrostenedione
#estosterone
)*ening Primrose

;ses& )oer cholesterol- treat atopic

dermatitis- arthritis- PM3- mastalgia

(igh in gamma-linolenic acid (7),) and linolenic

acid- prostaglandin precursors- essential fatty acids

3afe in usual doses- increases deli.ery

complications

Precautions and interactions& May aggra.ate

temporal lobe epilepsy- interacts ith some anti-
seiOure medications- case reports of seiOures in
schiOophrenics on phenothiaOines
Valerian

0aleriaa officiali! root extract used to

promote sleep

/ncreases le.els of 7,B, in $83

Possibly safe in short term (>< days)-

possibly unsafe for long term use
(ithdraal)

Possibly effecti.e for subjecti.e sleep

:uality

May potentiate $83 depressants

especially benOodiaOapines
2e*er!ew

;ses& Migraine headaches (.asoconstricti.e)-

used for menstrual problems and fe.er

Possibly safe in usual doses

Possibly effecti.e in pre.enting and decreasing

se.erity of migraines

Precautions and interactions& )ea.es can cause

mouth ulcerations- may cause menstrual or
lactation problems- occasional 7/ side effects-
may increase effects of anticoagulants- re.orted
*y.erte!i1e cri!i! 2it* tri.ta!
)#hedra Problems
3ynergistic effect ith caffeine- decongestants-
and stimulants
Pro-arrhythmic effects ith cardiac glycosides
and halothane
M," inhibitors potentiate stimulation effects
$an increase agitation associated ith 331/6s
".erdose syndrome can be fatal
May be detected in urine screening as a banded
substance
3a*a 3a*a

;ses& 8er.ous tension (anxiety)- stress and

agitation- insomnia
2
)ikely effecti.e& (ead to (ead comparison to
benOodiaOapines shoed e:ual efficacy for anxiety
(Poelk- >FFB)

Ka.a pyrones ha.e central muscle-relaxing-

anticon.ulsi.e- hypnotic0sedati.e effects by
interaction ith ion channels and 7,B, sites

li.er failures e.en ith short term use

3a*a 3a*a Interactions

3ynergy ith ,lcohol4 9t"( potentiates

Ka.a toxicity

1eports of coma ith Ka.a and Qanax

Potentiates all $83 depressants

,ntagoniOes dopamine- do not use in

Parkinson6s patients

/nteraction ith cimetidine causes

confusion and disorientation
/nteraksi obat-temulaak

,nti-platelet & dapat menyebabkan resiko

perdarahan

Parfarin & peningkatan efek antikoagulan

sehingga terjadi perdarahan

$amptohecin & penghambatan kerja

camptothecin dalam menginduksi apoptosis sel
kanker payudara

/buprofen & peningkatan resiko perdarahan

Meclorethamin & Penghambatan kerja

meclorethamin dalam
menginduksi apoptosis sel
kanker payudara

Bromelain & peningkatan efek anti-

agregasi

7inkgo biloba& peningkatan efek ginkgo

biloba menyebabkan
resiko perdarahan

Baang putih & #erjadi penurunan gula

darah
"eem to ha*e low
#harmacokinetic drug interaction
#otential

7inger

Ealerian

Milk thistle

3a palmetto

Black cohosh

$o*>?

glucosamine
0hat can we do,

dialog ith 8%s and other prescribers

recommend the best products

ask patients about herbals they may be taking

herbals should not usually be recommended for

acute or serious illnesses

a.oid herbal use ith drugs ith narrow

thera#eutic window- esp4 arfarin- cyclosporin-
digoxin- (/E protease inhibitors- theophylline-
carbamaOepine

stay informed
"te#s !or Detecting and Ad*ising on
Herbal4Drug Interactions
2
/s the patient taking any herbal supplements!
2
%oes the herbal ha.e efficacy for the intended
use!
2
/s the product reliable! (i4e4-hat are they
19,))M taking!)
2
/s the 1x drug one ith a narro therapeutic
margin!
)*aluation o! Herbal4Drug Interactions

3peculati.e or #heoretical
2
e4g4 3t4 5ohn6s Port and tyramine containing foods
due to M,"/ effects or e.ening primrose oil and risk
for bleeds ith arfarin

/n .itro effects
2
e4g4 ginkgo and microsomal studies shoing inhibition
of $MPC$F

/n .i.o - animal studies

2
e4g4 ka.a and alcohol

/n .i.o - human case reports

2
e4g4 ginkgo and arfarin bleeds

/n .i.o - healthy human .olunteer studies

2
e4g4 indini.ir and 3t4 5ohn6s Port

/n .i.o - clinical studies in patients

'erbal edicines
................. Not all that is
natural is
harmless
,erb -ru! Intera$tons
-on! .ua( taken for menopausal symptom control. Do not
mix Dong 6uai %ith %arfarin *anticoagulants+, 7t ,ohn8s 9ort
and some antibiotics such as sulfonamides, :uinolones.
/$"na$ea( mostly taken as an immune boost to prevent cold
and ;u. Do not mix <chinacea %ith some heart medications,
antifungal medications, ')= medications and anti4anxiety
medications.
/p"edra( > po%erful decongestant. $ontains ephedrine, %hich
can open up bronchial passages. )t8s controversial because it8s
a po%erful stimulant that can raise blood pressure, cause
insomnia and high blood pressure. Do not mix %ith heart
medications or if you are being treated for high blood pressure,
glaucoma or thyroid problems.
Fe#er)e0( taken to reduce the severity of migraines. Do not
take %ith other migraine medications, as, it may raise heart
rate and blood pressure. Feverfe% has the potential to react
%ith %arfarin anti4coagulants, increasing the thinning of blood.
,erb -ru! Intera$tons
'nk!o( increases blood ;o% and circulation throughout the body, can
also help improve memory. ay interact %ith anti4coagulant medications
such as >spirin, $oumadin, heparin and %arfarin, causing the blood to
thin too much, and provoking a serious bleeding disorder. > recent report
in the ?e% <ngland ,ournal of edicine describes a case of a man %ho8d
been taking >spirin to prevent a heart attack and had spontaneous
bleeding into the eye from the iris %ithin a %eek of taking a daily dose of
ginkgo.
'arl$( is thought to help lo%er cholesterol and prevent the formation of
blood clots that could lead to heart attacks. @arlic capsules may increase
blood thinning if you are already on anti4coagulants. Do not take %ith
diabetes medication because it may cause a decrease in blood sugars.
'nsen!( used to help reduce stress, boost energy and improve stamina,
and may also help lo%er cholesterol. $an cause nervousness and
excitation, and overuse can lead to headaches, insomnia and heart
palpitations. $an increase blood pressure. 7hould not be used if you are
taking prescriptions for high blood pressure or $oumadin.
,a0t"orn( claimed to be efective in helping reduce angina attacks by
lo%ering blood pressure and cholesterol levels. 7hould not be taken
digoxin, a heart medication. The mix may lo%er heart rate too much.
,erb -ru! Intera$tons
Ka#a( is used to treat anxiety. )t8s also used to relieve
insomnia and nervousness. Do not take Aava if you have a
history of liver problems. >lso do not mix %ith
antidepressants, sedatives, and do not mix Aava %ith
alcohol.
L$or$e( used to treat coughs, colds and peptic ulcers.
'igh doses can lead to increased blood pressure, %ater
retention and potassium loss. Do not use %ith diuretics or
digoxin because it could lead to further loss of potassium,
essential for heart function.
St& *o"n1s 0ort( a natural anti4depressant for mild to
moderate depression. Do not take %ith other anti4
depressants, ')= medications, oral contraceptives, some
heartBblood thinning medications and Tamoxifen *a cancer
drug+.
2aleran( a mild sedative %ith hypnotic efects, used to
promote sleep, 7hould not be taken %ith alcohol or =alium.