Cardiac safety activity

Nonclinical safety pharmacology studies submitted to regulatory agencies are outlined in ICH Guidance S7A (2001), and the basic package includes evaluation of a drug candidate s effects on the central nervous system, respiration, and the cardiovascular system. Cardiovascular system evaluation includes assessment of cardiac function and cardiac electrophysiological activity. 

As a first step, the group distributed a survey to active members of SPS to collect frequency/type data on the commonly used ion channels in their laboratories to obtain qualitative information on their relevance to drug-induced cardiac safety concerns, with a specific focus on proarrhythmia. The survey was critical in identilying seven ionic currents that are routinely studied because of perceived safety concerns I, /ks, to, h, ca, Na[ st], Hud /Na[iate] these currents were described in Table 9.1. Consequently, protocols are being developed for each of these ionic currents, with the intent of gathering key data to be used for in siUco action potential reconstructions. 

Cardiovascular Ventricular tachycardia/ fibrillation in an otherwise healthy 48-year-old woman who was taking no medications other than phentermine was attributed to sympathetic activation [103" ]. The cardiac safety concern of phentermine suggested by these authors has been debated [104"]. 

ED and vascular disease commonly coexist. They share the same risk factors and endothelial dysfunction is the common denominator. ED may develop in an otherwise asymptomatic male and be an important predictor of subsequent acute or chronic cardiac events. ED may therefore offer an opportunity for risk assessment and therapeutic intervention to reduce the chance of a subsequent cardiac presentation. Cardiac patients with ED need a careful assessment to judge the safety of sexual activity and suitability for ED treatment. Properly assessed and counselled patients can safely enjoy sexual activity. ED therapy with phosphodiesterase type five inhibitors is safe and effective providing the patient and partner are advised on their use and the importance of avoiding drug interactions, especially with nitrates. 

ED is common in patients with cardiovascular disease and should be routinely enquired about. The cardiac risk of sexual activity in patients with cardiovascular disease is minimal in properly assessed patients. The restoration of a sexual relationship is a possibility for the majority of patients with cardiovascular disease and ED using oral PDE5 inhibitors, which have an excellent safety profile (avoiding nitrate use). ED is a marker for cardiovascular disease as well as its consequence therefore, its identification (in the asymptomatic male) provides the opportunity to address other cardiovascular risk factors and detect silent but significant vascular pathology. 

Cells by themselves or by secreting pharmacologically active substances may have effects on the CNS, cardiac, respiratory, renal, or GI systems. Safety pharmacology should therefore be considered on a case-by-case basis depending on the specific characteristics of the cell-based product [52], In general, specific assessments are made as part of the toxicology assessments rather than as stand-alone studies consistent with the assessments made with protein-based biopharmaceuticals [50]. The fundamental physiological differences (e.g., total blood volume,pulmonary capillary surface area, and volume) should... 

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