Effects Of Drugs On Organ Transplants

Chapter 6_ Drug Interactions Learning Objectives 1. Describe the consequences of drug–drug interactions, the basic mechanisms of drug– drug interactions, and the critical steps in minimizing adverse drug–drug interactions. ● Consequences of drug-drug interactions can include intensifying the effects of one drug, reducing the effects of another, or producing new and unpredictable responses. The basic mechanisms of drug-drug interactions include intensification of effects, reduction of effects, direct chemical or physical interactions, pharmacokinetic interactions (competition for protein binding, altered distribution, altered metabolism), pharmacodynamic interactions (producing new responses), and combined toxicity. To minimize adverse drug-drug interactions, it is important to consider drug-food interactions, the impact of food on drug absorption, metabolism, and toxicity, as well as the timing of drug administration with respect to meals. Drug-supplement interactions should also be taken into account. Additionally, monitoring for inhibitory interactions and taking steps to adjust dosages when necessary can help minimize the risk of adverse drug-drug interactions. 2. Explain the effect of food on drug absorption, on drug metabolism (e.g., grapefruit juice), and on drug toxicity and action, as well as the timing of drug administration with respect to meals. ● Food can have various effects on drug interactions. For drug absorption, some foods can impact the rate and extent of drug absorption, either by enhancing or reducing it. For drug metabolism, grapefruit juice can inhibit enzymes responsible for drug metabolism, leading to increased drug levels and potential toxicity. Food can also affect drug toxicity and action by interacting with drug targets or altering drug effects. Timing of drug administration with meals can be important, as some drugs may need to be taken with food to enhance absorption or reduce gastrointestinal side effects, while others should be taken on an empty stomach to avoid interactions with food components. Chapter 6 Readings Drug-drug interactions can lead to three possible outcomes: intensification of effects, reduction of effects, or the production of a new response. Intensification of effects can be beneficial or detrimental, while reduction of effects can be either beneficial or detrimental as well. It is important to minimize adverse drug-drug interactions to ensure optimal therapeutic outcomes. Bullet points Drug Interactions ● ● ● Combining drugs with narrow therapeutic ranges can cause increased toxicity When drugs with overlapping toxicity are combined, it can lead to more injury Food can affect the absorption and metabolism of drugs ● ● ● Drug-drug interactions can alter the efficacy and safety of some drugs High-fiber foods can reduce the absorption of certain drugs Grapefruit juice can increase the levels of certain drugs, leading to potential toxicity Effects of drugs on organ transplants ● ● Sirolimus and tacrolimus - Prevent rejection of organ transplants Toxicity - Increased therapeutic effects; if levels rise too high, renal and hepatic toxicity will occur Drugs and their associated toxicities ● ● ● ● ● SSRIs (fluoxetine, fluvoxamine, sertraline) - Depression; Toxicity: serotonin syndrome Pimozide - Tourette's syndrome; Toxicity: QT prolongation resulting in a life-threatening ventricular dysrhythmia Praziquantel - Schistosomiasis; Toxicity: unknown Dextromethorphan - Cough; Toxicity: unknown Sildenafil - Erectile dysfunction; Toxicity: unknown Impact of food on drug metabolism ● ● ● ● Grapefruit juice can inhibit the metabolism of certain drugs, thereby raising their blood levels Grapefruit juice has little or no effect on drugs administered intravenously Inhibition of CYP3A4 is dose dependent. The more grapefruit juice consumed, the greater the inhibition Grapefruit juice can increase blood levels of felodipine, lovastatin, cyclosporine, midazolam, and many other drugs Factors influencing the effects of grapefruit juice ● ● Compounds contributing to the inhibitory effects of grapefruit juice are bergapten, 6',7'dihydroxybergamottin, naringin, and naringenin Effects of grapefruit juice vary among individuals due to variation in levels of CYP3A4 Timing of drug administration with respect to meals ● Administration of drugs at the appropriate time with respect to meals can impact their effectiveness and metabolism Impact of grapefruit juice on drug absorption ● ● ● ● Grapefruit juice can increase the risk of serious toxicity for some drugs It can decrease the absorption of certain drugs It can intensify therapeutic effects for other drugs Patients should avoid grapefruit juice if their drugs can be affected by it Impact of food on drug absorption ● ● ● Some drugs should be taken on an empty stomach to enhance absorption Other drugs should be taken with meals to increase absorption Patients should follow the instructions given for their specific drugs Impact of food on drug toxicity ● ● ● Drug-food interactions can increase toxicity For example, monoamine oxidase inhibitors combined with tyramine-rich foods can lead to dangerous increases in blood pressure Patients should be aware of the potential interactions and avoid certain foods