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Gestational hypertension and pre-eclampsia
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
If the patient develops severe hypertension during this time, the blood pressure may be controlled with oral nifedipine. In a double-blind study, Barton (117) evaluated the effect of nifedipine in postpartum patients with severe pre-eclampsia before delivery. They found oral nifedipine to be effective in the control of blood pressure as well as improving urine output during the 24 hours after delivery. In a subsequent report, Barton (118) studied the pharmacokinetic and pharmacodynamic parameters of oral nifedipine use in the immediate postpartum period. Based on the clinical pharmacology in this setting, they suggested that dosing should be every 3–4 hours. Most patients will be normotensive at the time of discharge from the hospital. A few patients may continue to have significant hypertension, and this can be controlled with additional oral blood pressure medications. Prophylactic anticonvulsive drugs such as phenobarbital are not needed. The patient is then seen at weekly intervals until her blood pressure is in the normal range without the use of medication. If this change does not occur by 6 weeks, a workup to assess hypertension should be performed.
Nanomedicine(s) under the Microscope *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Rarely do authors reflect on the potential safety of each component and/or the metabolites that might arise following in vivo degradation/metabolism of the nanomedicine they are proposing. The dose, frequency of dosing, and clinical setting are particularly relevant factors here. Increasing complexity of hybrid technologies (see The Future: Nanomedicines of Tomorrow?) and, additionally, introduction of novel polymers and linkers can potentially create a plethora of metabolites never before seen in humans. Although information is readily available regarding the exposure limits allowed for many inorganic components of nanosized particles (e.g., gold, silver, iron, cadmium, etc.) [155], the potential long-term hazards of novel polymers used to make and/or coat nanosized particles is frequently not known.
Drug Design, Synthesis, and Development
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
Complications in drug dosing arise due to differences in age, sex, and race etc. between different patients. For example, people who are obese present a particular challenge because it is hard to predict how much of the drug will be stored in fat tissue. The precise time of drug dosing is another aspect that is difficult to predict because metabolic reactions proceed at different rates throughout the day; medicines to be taken before bed, when metabolism is slower during sleep, will probably have a slower activity than medicines that need to be taken multiple times throughout the day. One crucial variable for determining how frequently drug dosing is needed is the drugs half-life (t1/2), which is the time taken for the blood concentration of the drug to fall by half. This depends on excretion and drug metabolism processes, which does not occur linearly with time. Half-lives may vary from a timescale of just a few minutes, such as some of the opiate analgesics, to a number of days, as with diazepam (Valium), where it can take over a week to recover from the effects.
Therapeutic drug monitoring: applying the ‘Goldilocks Principle’ to clinical pharmacology
Published in Expert Review of Clinical Pharmacology, 2023
Peter E Penson, Alice P McCloskey
Nevertheless, many important drugs have narrow therapeutic windows, meaning that accurate dosing is essential to ensure that treatment is effective, and to avoid toxicity. Furthermore, some classes of patients (particularly children, older adults, and those with co-morbidities) are often more susceptible to variability in the response to medicines. Therefore, particular care is needed in these situations to ensure treatment doses are appropriate to the patient and the situation. This can be achieved through therapeutic drug monitoring (TDM) ‘a multi-disciplinary clinical specialty aimed at improving patient care by individually adjusting the dose of drugs for which clinical experience or clinical trials have shown it improved outcome in the general or special populations’ [2]. Whilst the concept of TDM is not new, the field is rapidly evolving owing to developments in technology and clinical practice, and thus it is fitting that this special issue of Expert Review of Clinical Pharmacology is focused on the topic.
Saliva for Model Informed Precision Dosing
Published in Expert Review of Clinical Pharmacology, 2023
Another special group is the group of (premature) neonates. Neonates are sometimes treated with antibiotics such as gentamicin that have a narrow therapeutic index and risk for oto- and nephrotoxicity when exposure is too high. Dosing is complicated by high pharmacokinetic variability complicated by variation in body composition, kidney function, and organ maturation. Therapeutic drug monitoring is necessary to ensure adequate dosing regimens. In neonates. This requires repeated blood sampling from central venous lines or via heel lance, which is invasive, painful and may contribute to clinical anemia or infection. As a result, MIPD by plasma sampling is reduced to a minimum, however leading to suboptimal individual doses, thereby causing a decrease in therapeutic efficacy and an increased risk of toxicity. Recently the application of gentamicin monitoring via saliva has been reported [10].
Reply to: Weight and height adjusted dose regimen or fixed ED95 dose of intrathecal hyperbaric bupivacaine for cesarean delivery in parturients with different BMIs: which would be optimal?
Published in Current Medical Research and Opinion, 2022
Sapna Ravindranath, Unyime S. Ituk
Our dosing is based on several factors. A weight and height-adjusted (lower) dose may achieve an adequate initial sensory level in morbidly obese patients and decrease maternal hypotension, but it does not guarantee successful intraoperative anesthesia because of the longer duration of cesarean delivery in these patients. In the study by Harten and colleagues5, the patients in the adjusted dose group had a mean (SD) body weight of 76.2 (± 9) kg. compared with our study population2 with a mean body weight of 116 (± 23) kg. There is a greater prevalence of obesity in our patient population, and it is doubtful that we would have similar outcomes to their study if we used a height and weight adjusted dosing. Furthermore, the study by Carvalho and colleagues, reported a higher incidence of inadequate block duration in patients that received a lower dose of hyperbaric bupivacaine even though these patients had a successful induction defined as loss of pinprick sensation at T6 dermatome4. Adjusting the dose of hyperbaric bupivacaine for weight and height may carry the risk of failure of spinal anesthesia in an unacceptable number of our morbidly obese patients. Nevertheless, we also believe that a “one-size-fits-all” approach may not be ideal for every patient. For example, in patients with dwarfism it is reasonable to administer adjusted dose. Fortunately, none of the patients in our study had high spinal anesthetic experience despite the use of a fixed ED 95 dose of hyperbaric bupivacaine.