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
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