Paper 4 Answers
James Day, Amy Thomson, Tamsin McAllister, Nawal Bahal in Get Through, 2014
Hyoscine, also known as scopolamine, is an alkaloid drug that has muscarinic antagonist effects. It is extracted from the nightshade family of plants. Scopolamine is named after the plant genus Scopolia. Hyoscine is from the scientific name for henbane, Hyoscyamus niger. Phenylephrine is a synthetic sympathomimetic. Digoxin is derived from the foxglove plant, Digitalis, and is a purified cardiac glycoside. Heparin is found naturally in the liver (hence the name) and in mast cell granules. It is a glycosaminoglycan and is used therapeutically as an anticoagulant. Its physiological role is less clear as anticoagulation is achieved mostly through heparin sulphate derived from endothelial cells. Ephedrine is a naturally occurring sympathomimetic. It is an alkaloid derived from the plants of the genus Ephedra. The plant grows on shores or on sandy soils, and the common name is Joint-pine or Brigham tea.
Isolated Atrial Preparations
John H. McNeill in Measurement of Cardiac Function, 2020
The main area of interest in pharmacological studies which use atrial preparations is in drugs which either alter contractility and/or rate, and rhythm. Neurotransmitters and hormones may alter contractility (inotropism) and often alter rate (chronotropism) and/or rhythm of atria. Thus, agonist and antagonist drugs may increase, or decrease, force and rate. For example, stimulation of atrial beta-adrenoceptors (β1) results in elevation of the second messenger cyclic-AMP, and subsequent phosphorylation of proteins. This, in turn, results in an increase in calcium current and enhanced calcium binding to the sarcoplasmic reticulum, producing an increase in contractility. On the other hand, inhibition of the Na/K-ATPase by cardiac glycosides (such as digitalis) results in an elevation of intracellular calcium and positive inotropism. Agents which promote (caffeine), or inhibit (ryanodine), the release of calcium from the sarcoplasmic reticulum will augment or attenuate, respectively, atrial contractions.6
Toxins in Neuro-Ophthalmology
Vivek Lal in A Clinical Approach to Neuro-Ophthalmic Disorders, 2023
Visual side effects of digitalis are less common than cardiac or other noncardiac symptoms. The spectrum of toxicity varies and includes decreased visual acuity, central scotomas or visual field reduction, photopsia most pronounced in daylight, photophobia, blurry or snowy vision, visual hallucinations, diplopia and dyschromatopsia including xanthopsia (yellow vision), cyanopsia (blue vision) and chloropsia (green vision). Dyschromatopsia can remain asymptomatic and detected only by formal testing. The mechanism of ocular toxicity postulated to be Na+ K+ ATPase inhibition [37–39]. Most appropriate test to support a diagnosis of digoxin ocular toxicity is photopic and scotopic electroretinogram (ERG) seeking for b-wave-delayed implicit time and decreased b-wave amplitude.
Henry Herbert Donaldson’s (1857–1938) contribution to an organized approach to the experimental study of the mammalian central nervous system
Published in Journal of the History of the Neurosciences, 2018
Before his thesis work with Hall, which reflected their psychological interests, Donaldson pursued physiological issues related to the heart, showing Martin’s influence. He, along with fellow students M. Warfield and L. T. Stevens, experimented with the effects of digitaline [sic]3Also spelled digitalin, it is a powerful cardiac stimulant containing the active components of digitalis., digitalis, and quinine on heart and other circulatory organs. One of these efforts was published in the Journal of Physiology in 1883 (Donaldson and Stevens, 1883). With another fellow student, William Henry Howell (1860–1945, eventually Professor of Physiology at Johns Hopkins University and Dean of the Medical School), he experimented with coagulation of blood, blood volume of the left ventricle, venous pressure, arterial pressure, and pulse rate.
Selectivity analyses of γ-benzylidene digoxin derivatives to different Na,K-ATPase α isoforms: a molecular docking approach
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Marco T. C. Pessôa, Silmara L. G. Alves, Alex G. Taranto, José A. F. P. Villar, Gustavo Blanco, Leandro A. Barbosa
In the 1990s, some researchers observed that ouabain exerted effects on NKA that were independent from inhibition of the enzyme and rather resulted from the activation of a cascade of intracellular events that caused cardiomyocyte hypertrophy11–14. This revealed a new function for the NKA and showed that it can function as a receptor and signal transducer that mediates the effects of ouabain in cells. This role of NKA has been the topic of intense research, with the goal of exploiting NKA signalling for its use in disease and cancer. Several laboratories have designed and generated, particularly via hemi-synthesis, novel CTS derivatives15–17. Our group is interested in developing new CTS derivatives which can exert effects that are more specific. We have generated a series of compounds by modifying the lactone ring of the CTS digoxin. One of these synthetic digoxin analogues, 21-benzylidene digoxin (21-BD), presented cytotoxic and antiproliferative effects when used on HeLa cancer cells, via inducing apoptosis in those cells, but inhibiting NKA activity just at high micromolar levels18,19. Subsequently, starting with the structure of digoxin, we synthesised a series of γ-benzylidene derivatives and showed that they have cytotoxic effects on HeLa and RKO cancer cell lines that are independent from the modulation of NKA activity20.
Preventable ADRs leading to hospitalization — results of a long-term prospective safety study with 6,427 ADR cases focusing on elderly patients
Published in Expert Opinion on Drug Safety, 2018
S Schmiedl, M Rottenkolber, J Szymanski, B Drewelow, W Siegmund, M Hippius, K Farker, I R Guenther, J Hasford, P A Thuermann
Regarding all ADR patients, preventable ADRs were most frequently caused by digitoxin, low-dose ASA, and phenprocoumon. Whereas in younger patients, phenprocoumon was the drug most frequently involved in preventable ADRs, most preventable ADRs in elderly patients were associated with digitoxin. Despite a narrow therapeutic range, digitalis glycosides are still recommended to some extent for patients with atrial fibrillation and/or heart failure, chronic conditions with increased prevalence in older people [37,38]. Regarding other studies evaluating the risk of digitalis (digoxin)-related hospitalizations, a wide range of risk estimates was reported. Taking into account pharmacokinetic differences between digoxin and digitoxin, there is a debate whether digoxin (shorter half-life, predominantly renal excretion) or digitoxin (longer half-life, predominantly hepatic excretion) has a better risk-benefit profile, in particular in elderly patients with age-related renal dysfunction [39–41]. During the study period, digitoxin was the most frequently prescribed digitalis glycoside in Germany [42], explaining to some extent the predominance of digitoxin- (and not digoxin-) related ADRs. By comparing the incidence rates of digitoxin- and digoxin-related ADRs, similar estimates were found in prior analyses [33,43].
Related Knowledge Centers
- Atrial Fibrillation
- Atrial Flutter
- Blood Pressure
- Cardiology
- Heart Rate
- Muscle Contraction
- Stroke Volume
- Cardiovascular Disease
- Heart Failure
- Myocardial Contractility