Pharmacy Practice Therapeutics

Questions: 1. Discuss digoxin and its place in therapy. Include in your answer (but not limited to) aspects that relate to how it works, what it is used for, therapeutic drug monitoring and patient specific information. Make use of published studies as well as reference books. 2. Choose one of the newer (novel) anticoagulant drugs (NOACS) and discuss its place in therapy. Make particular note of recent studies for evidence of safety and efficacy. 3. Discuss long acting beta agonists (LABAs) and their use. Include (but not limited to) aspects that relate to pharmaceutical care of patients that may be using these drugs as well as more specific information relating to the class of drug. Answers: 1. Digoxin, a pharmacologically active compound extracted from the foxglove plant Digitalis lanata is a common purified cardiac glycoside possessing a myriad of therapeutic benefits with certain limitations and side effects with respect to the case history and individual patient situation. It is mainly suited for treating patients with heart failure (HF) associated with chronic atrial fibrillation (AF), supraventricular tachyarrhythmias and increased rate of ventricular contraction. Elimination of digoxin mainly occurs via the renal route and therefore is suitable to administer the drug to patients with hepatic diseases. However, despite of the advantage of digoxin to rapidly enter into the target sites and harbor positive therapeutic outcomes, reports of narrow therapeutic index culminating in some toxicity issues affecting the central nervous system, gastrointestinal tract in addition to opthalmic complications, anorexia, nausea, vomiting and other cardio-related malfunctioning and neuropsychological difficulties have challenged the safety and efficacy of the drug (Stucky Goldberger, 2015). The mechanism of action of digoxin emanates from the drugs ability to inhibit the action of the membrane bound Na+/K+ ATPase enzyme in the myocardium, thereby fostering positive inotropic effect resulting in increased myocardial contractility. This pump enzymes inhibition also augments the Na+-Ca++ exchange and subsequently facilitates the rise in Ca++ concentration. This increase in intracellular Ca++ concentration in turn causes increased release of Ca++ ions from the sarcoplasmic reticulum adding to the increased contractility of the cardiomyocytes. Additionally, the antisympatheitc effect of digoxin is evident from its diminished sympathetic nervous system activity and contrasting rise in the parasympathetic activity. Moreover, the drug possesses a negative chronotropic effect due to reduced conduction velocity in the atrioventricular node and slower firing rate disch arge in the sinoatrial node (Chhabra Chhabra, 2012). Advancement and emergence of novel therapeutics to treat the ambulatory patients with HF and reduced ejection fraction have gradually taken over the use and application of digoxin. However contemporary reports suggest further research and insight into matters concerning the use of digoxin for patients with worsening chronic HF in order to ameliorate the signs and symptoms thereby reduce HF-case specific hospitalizations (Ambrosy et al., 2014). 2. The novel oral anticoagulants (NOACs) have received much attention in recent times following their potential applications and effectiveness in treating and preventing strokes in patients with non valvular AF compared to the parenteral antithrombotics and other blood thinners such as Warfarin. Among these newly evolved NOACs, apixaban, dabigatran and rivaroxaban are the prominent ones. Another NOAC namely edoxaban is however under trial and awaiting further approval by the competent authorities. In this context, the role of the apixaban NOAC may be discussed. Apixaban is an extremely selective, potent, orally administered drug capable of directly inhibiting the factor Xa of the blood clotting process, thereby rendering the anticoagulant capacity to prevent strokes in patients with AF, provide remedy for venous thrmboembolic events and thromboprophylaxis in patients who have underwent hip or knee replacement surgery (Frost et al., 2013). The pharmacodynamics including the plasma con centration of apixaban can be accurately measured by chromogenic anti Xa assays without the need for therapeutic monitoring except for clinical recurrence of stroke or bleeding in some cases. The mode of action of Apixaban is achieved by both reversibly and directly inhibiting the free and clot-bound factor Xa. The factor Xa is the ultimate enzyme of the coagulation cascade that catalyzes the conversion of prothrombin to thrombin thereby contributing to the formation of fibrin clot finally. Through thrombin induction, apixaban indirectly inhibits platelet aggregation as well. Studies relevant to apixaban drug by means of post hoc analysis of the randomized control data adjusted for gender, age and nationality, suggest the safe usage and efficacy of the drug in treating atrial fibrillation in patients encountering stroke or systemic embolism, compared to other anticoagulants like Warfarin. In such patients less bleeding and reduced rates of mortality was observed and hence claiming t he superiority of apixaban over warfarin (Focks et al., 2016). Further research regarding prospective uses and efficacy of apixaban reveals that it is suitable for decreasing the major or clinically pertinent non major bleeding for cases of mild type of renal impairment only in comparison to the conventional anticoagulants (Ribic Clase, 2015). 3. Long acting beta agonists (LABAs) are the group of drugs that are generally utilized in alleviating the symptoms in patients with moderate to severe asthma. Normally LABAs are prescribed in combination with the inhaled corticosteroids (ICS) to better tackle the asthma related health issues compared to the short acting products like salbutamol or fenoterol, thereby preventing the exacerbations in the long run (Mascarenhas et al., 2015). LABAS are essentially the ?2 agonists that are potent bronchodilators capable of relaxing the smooth muscles of the airways to allow adequate air to flow in and out of the lungs. LABAa are known to exert their effects by means of binding to the ?2 adrenoceptors on the airways smooth muscle that in turn lead to triggering of several signalling cascades lead to activation of a number of molecular events which together result in dilatation of the passage of the airways thereby making the process of breathing easier. LABAs itself form a separate group o f drugs meant to offer respite from the debilitating conditions of asthma and chronic obstructive pulmonary diseases (COPDs). Salmeterol fluticasone, formoterol and budesonide are some of the common generic names of the LABAs. The route of administration of the LABAs involves inhalation of the single ingredient component or the combinatorial corticosteroid medication through the mouth into the lungs by virtue of an inhaler or a nebulizer device. The duration of action for the LABAs prevail for approximately 12 hours and even 24 hours for certain ultra LABAs attributable to high potency and specificity for the beta-2 adrenoceptors and accounting for low oral bioavailability post inhalation, high systemic clearance and finally resulting in rapid onset of action. The ultra LABAs have been consented for long term management of COPD in Europe and USA following a 9once a daily drug regime. Overall the safety profiles of LABAs are acceptable. However, increased risk of pneumonia has been r eported in studies where the dual mode of actions of the ICS/LABA is adopted for treatment modality for patients with COPD. Ongoing research and innovation regarding the combined use of ultra-LABA and long acting muscarinic receptor antagonist (LAMA) offer hope for better health implications in COPD patients in near future (Cazzola et al., 2013). References: Ambrosy, A. P., Butler, J., Ahmed, A., Vaduganathan, M., van Veldhuisen, D. J., Colucci, W. S., Gheorghiade, M. (2014). The use of digoxin in patients with worsening chronic heart failure: reconsidering an old drug to reduce hospital admissions. Journal of the American College of Cardiology, 63(18), 1823-1832. Cazzola, M., Page, C. P., Rogliani, P., Matera, M. G. (2013). 2-agonist therapy in lung disease. American journal of respiratory and critical care medicine, 187(7), 690-696. Chhabra, N., Chhabra, S. (2012). A Case Oriented Approach Towards Biochemistry. JP Medical Ltd. Focks, J. J., Brouwer, M. A., Wojdyla, D. M., Thomas, L., Lopes, R. D., Washam, J. B., ... Alexander, J. H. (2016). Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the Aristotle trial. bmj, 353, i2868. Frost, C., Nepal, S., Wang, J., Schuster, A., Byon, W., Boyd, R. A., ... LaCreta, F. (2013). Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects. British journal of clinical pharmacology, 76(5), 776-786. Mascarenhas, A., Sayal, R., Khan, S., Moore, J. (2015). The Ontario Drug Policy Research Network Drug Class Review on Combination Inhaled Corticosteroids and Long Acting Beta Agonists (ICS/LABA) for the Treatment of Asthma. Ribic, C. M., Clase, C. M. (2015). Review: In renal impairment, apixaban reduces, or does not increase, bleeding compared with other anticoagulants. Cardiol, 115, 323-7. Stucky, M. A., Goldberger, Z. D. (2015). Digoxin: its role in contemporary medicine. Postgraduate medical journal, postgradmedj-2014.