Obat-Obat Yang Bersifat Toksik

Karena Interaksi Obat

Interaksi Obat
• Interaksi Obat Secara farmakokinetik lebih
mudah untuk ditebak dibandingkan interaksi
obat secara farmakodinamika
• Interaksi Farmakodinamik terjadi pada saat
obat kedua berkompetensi menduduki reseptor
Interaksi Obat
• Ada beberapa contoh interaksi obat yang
mengancam jiwa salah satu contohnya adalah
aritmia yang fatal yang diakibatkan dari
interaksi antara terfenadine dan ketoconazole
Epidemiologi
• Salah satu efek dari interaksi obat adalah
munculnya ADR (adverse drug reactions) yang
dikenal juga dengan reaksi obat yang merugikan
• ADR di US sekitar 4.2-6 % dari seluruh patien
yang masuk RS
• Interaksi obat yang terjadi juga tergantung dari
jenis pasiennya dan obat yang diterima dari
pasien itu sendiri sebagai contoh pasien HIV /
AIDS akan beresiko untuk terjadi interaksi obat
DI Minor
• Minor drug interactions usually have limited
clinical consequences and require no change in
therapy. An example of a minor interaction is
that which occurs between hydralazine and
furosemide. The pharmacologic effects of
furosemide may be enhanced by concomitant
administration of hydralazine, but generally not
to a clinically significant degree (9). While minor
drug interactions can generally be disregarded
when assessing a medication regimen
DI Moderate
• moderate interactions often require an
alteration in dosage or increased monitoring.
Combining rifampin and isoniazid, for instance,
leads to an increase in the incidence of
hepatotoxicity. Despite this interaction, the two
drugs are still used in combination along with
frequent monitoring of liver enzymes.
DI Severe
• Severe interactions, on the other hand, should
generally be avoided whenever possible, as they
result in potentially serious toxicity. For
example, ketoconazole causes marked increases
in cisapride exposure, which may lead to the
development of QT prolongation and life-
threatening ventricular arrhythmia. It is
recommended that these drugs not be used in
combination.
• Pharmacodynamic interactions do not involve
changes in the concentration of drug in plasma
or at the targeted site of action.
• Pharmacokinetic interactions, on the other
hand, occur when one drug alters the
absorption, distribution, metabolism, or
elimination of another drug, thereby changing
its concentration in plasma and, consequently, at
the targeted site of action. Clinically significant
drug interactions are most often due to
alterations in pharmacokinetics, secondary to
modulation of drug metabolism.
• In some cases a significant interaction may
result from a combination of both
pharmacokinetic and pharmacodynamic
mechanisms. For instance, the interaction
between cerivastatin and gemfibrozil,
which has resulted in cases of severe
rhabdomyolysis, is likely due to the
inhibition of cerivastatin metabolism by
gemfibrozil (i.e., pharmacokinetic
interaction), in addition to the propensity
of both drugs to cause skeletal muscle
toxicity (i.e., pharmacodynamic
interaction)
• Food interactions are typically pharmacokinetic
in origin. Most commonly, food can affect the
absorption of drugs. The simplest example of
this is when food delays gastric emptying,
slowing down the passage of drug into the small
intestine, the primary site for drug absorption.
However, there are some notable
pharmacodynamic drug interactions involving
food. One of the most important examples of a
food-drug interaction involves the anticoagulant
warfarin and its interaction with green leafy
vegetables, which contain vitamin K.
Alcohol
The role of alcohol in pharmacokinetic
interactions changes depending on whether use is
chronic or acute. Acutely, ethanol competitively
inhibits CYP450 enzymes, whereas chronic use
leads to CYP450 induction as the body tries to
increase its ability to eliminate ethanol.
Smoking/Environtment

• Cigarette smoking induces CYP450 enzymes

Pertanyaan

• 1. Seorang pasien 60 tahun diberikan prasugel

dan warfarin dengan dosis lazim. Namun setelah
beberapa jam pemakaian pasien tersebut
mengalami pendarahan?
Jelaskan apa yang terjadi?
Cari !!!
Drug Interactions with St John’s Wort (Hypericum perforatum)
Drug Interactions with Grapefruit (Citrus paradisi)
Drug Interactions with Echinacea (Echinacea spp.)
Drug Interactions with Ginkgo (Gingko biloba)
Drug Interactions with Ginseng
Drug Interactions with Garlic (Allium sativum)
Drug Interactions with Saw Palmetto (Serenoa repens)
Drug Interactions with Kava (Piper methysticum)
Drug Interactions with Ginger (Zingiber officinale)
Drug Interactions with Valerian (Valeriana officinalis)
Drug Interactions with Goldenseal (Hydrastis canadensis)
Drug Interactions with Green Tea (Camellia sinensis)
Drug Interactions with Curcumin (Curcuma longa)
Drug Interactions with Black Cohosh (Actaea racemosa)
Drug Interactions with Milk Thistle (Silybum marianum)
Daftar Pustaka
• 1. Koda-kimble
• 2 Drug Interactions
• 3. Medscape
• 4. Drugs Interaction-Overview Elsevier
THANK YOU