NUS6521-WK2-ASS: Patient HM has a history of atrial fibrillation and a transient ischemic attack.

Answer

• Case Scenario: Patient with a History of Atrial Fibrillation and a Transient Ischemic Attack

              Genetics is an important factor that can influence HM’s pharmacokinetic and pharmacodynamics changes. HM’s genetic makeup can result in drug responses that are quantitatively and qualitatively different from those of the population at large. Genetic variants can modify drug metabolism. Genetic factors can either slow or accelerate the metabolism of the prescribed drugs. The most common effect can be increase in drug toxicity or reduction in efficacy (Burchum & Rosenthal, 2019). For drugs that have high therapeutic index, changed rate of drug metabolism is associated with little effects on the clinical outcomes. On the contrary drugs with narrow of low therapeutic index, small increases in drug levels can result in drug toxicity and relatively small decreases in drug levels may result in therapeutic failure (Burchum & Rosenthal, 2019).

              Genetic variation can play an important role in development of adverse drug reactions. The risk of adverse drug-drug interactions associated with genetic variation is high since the patient is taking multiple (six) medications (Malki & Pearson, 2020). Gene variants in drug metabolizing enzymes including CYP2C9, CYP2D6, and CYP2C19 is associated with 19% of adverse drug reactions due drug-drug-gene interactions and 15% of drug-gene interactions. Since large numbers of genes are involved in drug transport and metabolism, the role played by genetic variation in development of potential clinically critical adverse drug reactions cannot be underestimated (Malki & Pearson, 2020).

              Changes in pharmacokinetic and pharmacodynamic processes might alter the patient’s recommended drug therapy. Genetic factors may increase or reduce therapeutic effects and/or adverse effects. Idiosyncratic responses associated with the patient’s genetic makeup may also occur (Burchum & Rosenthal, 2019). In consideration of the recommended drug therapy, CYP2C9 variants can increase the risk of drug toxicity. In patients with an abnormal CYP2C9, warfarin can accumulate to levels that can cause bleeding. Similarly, VKORC1 variants may increase sensitivity to warfarin. VKORC1 variant is inhibited by warfarin, thus, anticoagulation can be achieved with reduced warfarin dosage (Burchum & Rosenthal, 2019). On the other hand, atenolol is a beta blocker and if the patient has ADRB1 variants, it can increase the drug’s therapeutic effect. Beta₁ receptors that are produced by ADRB1 variant genes tend to respond intensely to beta-agonists, resulting in enhanced effects of blockade by beta antagonists such as atenolol (Burchum & Rosenthal, 2019). 

              Genetic testing for the administered drugs may be considered for this patient to enhance therapeutic effects as well as reduce harm. Testing may help improve the patient’s drug therapy plan with respect to pharmacodynamic and pharmacokinetic changes. In fact, genetic testing is recommended for warfarin but it is not required. Genetic testing allows healthcare professionals to pick relevant drugs and determine the effective dosage in accordance with the patient’s genotype; thus, reducing the risk of adverse reactions, decrease cost, increase likelihood of strong therapeutic response, reduce inconvenience, and reduce the risks associated with prescription of a drug to which HM is unlikely to respond (Burchum & Rosenthal, 2019). If the patient has VKORC1 variant then warfarin dosage should be reduced to reduce the risk of bleeding (Burchum & Rosenthal, 2019).

              Other strategies for improving therapeutic effects may include increased or reduced drug dosage as necessary. In addition, medication reconciliation should be conducted so as to identify and take intervention measures on adverse drug-drug interactions (Malki & Pearson, 2020). The Joint Commission necessitates conduction of medications for all patients. The purpose of medication reconciliation will be to reduce duplications, omissions, and dosing errors as adverse interactions and events. Medication reconciliation should also take into consideration nutritional supplements, vitamins, and over-the-counter drugs with respect to currently prescribed medications (Burchum & Rosenthal, 2019).

  In addition, it is important to review patient’s medical history to identify drug allergies and sensitivities to reduce the risk of adverse effects. For example, ibuprofen (Motrin) is contraindicated in patients with non-steroidal anti-inflammatory drugs hypersensitivity or salicylate hypersensitivity and who have experienced urticaria, asthma, or allergic reactions. Since the patient has been prescribed aspirin and ibuprofen, it increases cross-sensitivity and adverse events such as fatal skin reactions including Stevens-Johnson syndrome, exfoliative dermatitis, and toxic epidermal necrolysis. In addition, concomitant use of ibuprofen with aspirin is not recommended due to elevated risk of gastrointestinal bleeding and bleeding in other sites. Use of aspirin together with ibuprofen tends to enhance ibuprofen therapeutic effects; therefore, they should not be used together. An alternative option is to reduce ibuprofen dosage (Prescribers’ Digital Reference, 2020). Patient should also be monitored for medication adverse events. For examples, the patient should be monitored for ibuprofen adverse events including gastrointestinal perforation, gastro-intestinal bleeding, hearing loss, heart failure, stroke, coma, seizures, fluid retention, constipation, and hypotension (Prescribers’ Digital Reference, 2020).