Herbal Medicines Interactions

Marianne
 Some Facts About Herbal Medicines
Interactions
The use of herbal medicines and nutritional supplements is
increasing dramatically in many parts of the world, as part of the
popularity of complementary and alternative medicine (CAM)

People are taking herbal and nutritional products at the same time
as conventional medicines is significant

No reliable information currently available about interaction

between herbal medicines and conventional drugs

Clinical significance of some reported cases cannot be accurately

evaluated due to the variation in the nature of the herbs itself and
products made from it.
 Who Uses Herbal Medicines?
Cancer patients
Using of flaxseed, green tea, vitamin C and E

Patients on weight-loss programmes

Using ephedra, caffeine, bitter orange

Hospital inpatiens
Differences in Herbal Use in
Specific Population Grow
The elderly age 65
Children 16% of children
Gender woman > men
Educational level and knowledge of herbal
products usage is similar across most
education level
Rural populations rural populations 92% >
urban populations 70%
 Attitudes to the Use of Herbal
Medicines
People report their primary source of
information as friends or relatives in 80%
cases, and only 45% of those giving their
children herbal products report discussing it
with either their doctor or pharmacist
In one study, 44.7% never reported herbal
usage to their physician, and 11% did so only
rarely.
 Interactions Between Herbal
Medicines and Conventional Drugs
Interaction is occur when the effects of one
drug are changed by the presence of another
substance, including herbal medicines, food,
drink and environmental chemical agents.
 Mechanism of Drug Interactions
Pharmacokinetic interactions while conventional drugs
and herbal medicines interact each other in absorption,
distribution, metabolism and excretion phase.
Enzyme induction
Enzyme inhibition
Drug transporter protein

Pharmacodynamic interactions sometimes the drugs

directly compete for particular receptors but often the
reaction is more indirect and interference with
physiological mechanisms. These interactions are much less
easy to classify neatly than those of pharmacokinetic type.
Additive or synergistic interactions
Antagonistic or opposing interactions
 Enzyme Induction
Some herbal medicines can have a marked effect on
the extent of first-pass metabolism of conventional
drugs by inducing the cytochrome P450 isoenzymes in
the gut wall or in the liver
It may take days or even 2 to 3 weeks to develop fully,
and may persist for a similar length of time when the
enzyme inducer is stopped.
Enzyme induction interactions can be delayed in onset
and slow to resolve
Effect: reducing effect of particular drug
Solution: rising the dosage of the drug affected
(monitoring, remember to reduce dose when herbal
medicines is stopped)
 Enzyme Inhibition
More common than enzyme induction
Occur within 2-3 days, resulting in the rapid
development of toxicity
Effect: reducing metabolism of an affected
drug, so that it may begin to accumulate
within the body, the effect usually being
essentially the same as when the dosage is
increased.
Solution: lowering the dose of particular drug
Inducers Inhibitors Substrates
Cannabis Boswellia Caffeine
Danshen Chamomile Clomipramine
Liquorice Dandelion Clozapine
St Johns Wort Feverfew Duloxetine
Ginkgo Frovatripan
Olanzapine
Rasagiline
Ropinirole
Tacrine
Theophyline
Tizanidine
Zolmitriptan
Inducers Inhibitors Substrates
Echinacea Bearberry Antiarrhytmics
(amiodarone, lidocaine
oral, etc)
Ginkgo Garlic Anticholinesterase,
centrally acting
(donepezil, galantamine)
Liquorice Ginseng Antihistamines
(astemizole, terfenadine)
Rooibos Cats claw Antimigraine drugs
(Eletriptan, ergot
derivatives)
St Johns wort Cranberry Antipsychotic (Pimozide,
Quetiapine)
 Drug Transporter Protein
The most well-known drug transporter protein
is P-glycoprotein (Pgp): an efflux pump found
in the membranes of certain cells, which can
push metabolites and drugs out of the cells
and have an impact on the extent of:
Drug absorption (via the intestine)
Distribution (to the brain, testis or placenta)
Elimination (in the urine and bile)
 Example
Pgp in the cells of the gut lining can eject some
already-absorbed drug molecules back into the
intestine resulting in a reduction in the total
amount of drug absorbed (Pgp as barrier to
absorption)
Pgp in the endothelial cells of the blood-brain
barrier can also eject certain drugs from the
brain, limiting CNS penetration and effects.
Pgp in the tubule proximal can eject certain drugs
from blood vessel into tubule proximal
 Example
Capsicum and digoxin AUC digoxin
Additive or Synergistic Interactions
If two drugs that have the same
pharmacological effect are given together the
effects can be additive.
Example: alcohol depresses the CNS and, if
taken in moderate amounts with normal
therapeutic doses of herbal medicines
(e.g. valerian)
Antagonistic or Opposing Interactions
Drugs with activities that are opposed to one
another
Example: alfalfa and warfarin
 Ginkgo + Propranolol
Clinical evidence: no interactions
found

Mechanism: ginkgo may induce the

activity of cytochrome P450
isoenzyme CYP1A2, which is one of
the major enzymes involved in the
metabolism of propanolol. Ginkgo
would therefore reduce the levels
of propranolol by inducing its
metabolism

Management: unlikely to be
clinically important
 Grapefruit + CCB
Clinical evidence: available

Mechanism: grapefruit appears to

inhibit the activity of the cytochrome
P450 isoenzymes CYP3A4 subfamily
in the intestinal wall so that the first-
pass metabolism of these CCB is
reduced, thereby increasing their
bioavailability and therefore their
effects.

Management: avoid whole grapefruit

and other products made from whole
grapefruit.
 St Johns Wort + SNRIs
Clinical evidence: available

Mechanism: a pharmacodynamic
interaction may occur between St
Johns wort and venlafaxine
because they can both inhibit the
reuptake of serotonin and can
cause serotonine syndrome (faint,
anxious, diaphoresis, shivering and
tachycardia)

Management: use with caution

 Conclusions
Human being does not respond uniformly to one
or more drugs or even herbal medicines.
There are some broad general principles that are
worth remembering:
Be on the alert with any drugs that have a narrow
therapeutic window or where it is necessary to keep
serum levels at or above a suitable level (e.g.
anticoagulants, antidiabetic drugs, antiepileptics,
antihypertensives, anti-infectives, antineoplastic
cytotoxics, digitalis glycosides, immunosuppressants,
etc)
 Conclusions
Think about the basic pharmacology of the drugs
under consideration so that obvious problems
(additive CNS depression, for example) are not
overlooked, and try to think what might happen if
drugs that affect the same receptors are used
together. And dont forget that many drugs affect
more than one type of receptor
Keep in mind that the elderly are at risk because
of reduced liver and rrenal function on which drug
clearance depends
 References
Stockley, I. 2009. Stockleys Herbal Medicines
Interactions. Editor: Williamson, E., Driver, S.,
Baxter, K. London: PhP Pharmaceutical Press
 Pengenalan herba
Contoh obat yang berinteraksi dengan herba,
mekanisme, solusi
Contoh obat yang berinteraksi dengan
suplemen makanan, mekanisme, solusi