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Hormones of the Adrenal Gland
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
The different adrenoreceptors mediate a large number of physiological effects. The predominant action of catecholamines on the heart is mediated by β1 receptors, resulting in an increase in the heart rate (chronotropic effect) and the force of contraction (inotropic effect) giving rise to increased cardiac output and myocardial oxygen consumption. Electrical conduction is enhanced, and this can result in cardiac arrhythmias (dromotropic effect).
Antihypertensive Drug Classes
Published in Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei, Manual of Hypertension of the European Society of Hypertension, 2019
Engi Abdel-Hady Algharably, Reinhold Kreutz
The CCBs are generally well-tolerated drugs. Their adverse effects derive from their pharmacologic properties (2). Gastrointestinal adverse effects include gastroesophageal reflux, slowed gastrointestinal transit and constipation (particularly with verapamil). Gingival hypertrophy can occur with all CCBs. Flushing, headache, tachycardia and peripheral oedema are more common with DHP. Peripheral oedema is not due to fluid retention but occurs because of the imbalance between upstream arteriolar vasodilatation and downstream venoconstriction, which causes transudation of fluid from the vascular compartments into the dependent tissues. It is dose-dependent and not responsive to diuretic therapy, and can be treatment-limiting. Oedema can slowly resolve without intervention but is alleviated adding an RAS blocker. Verapamil and diltiazem are negative inotropic and dromotropic agents, which is the basis for their use as heart rate—lowering drugs as alternatives to beta-blockers (2).
Pharmacokinetic-Pharmacodynamic Modeling of Reversible Drug Effects
Published in Hartmut Derendorf, Günther Hochhaus, Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
The situation can further be complicated by the appearance of active metabolite(s) during first-pass metabolism following oral administration of the parent compound. If equilibrium of the metabolite(s) to their site of action is rapid compared to the absorption of the drug into the system, the effect might actually precede the cp for the parent compound and lead to clockwise hysteresis. Another consequence of first-pass metabolism can be the preferential degradation of stereoisomers of the racemic parent compound and/or the preferential formation of active stereoisomeric metabolites that have different potency. This has been demonstrated45 for the negative dromotropic effect of verapamil on the atrioventricular node, where the more potent l-isomer undergoes a higher degree of first-pass metabolism than the less potent d-isomer following oral administration of the racemic mixture.46 This phenomenon leads to an apparent shift in the E-cp profile for the oral racemic mixture to the right with respect to the E-cp for the IV racemic mixture, i.e., after oral administration, the racemic mixture has apparently lost potency compared to the IV racemic dose. If the cp for the l-isomer is measured, and the E-cp profiles are plotted, however, this apparent discrepancy disappears.
Complete atrioventricular block with diastolic mitral regurgitation due to severe lithium intoxication. A case report
Published in Acta Cardiologica, 2022
Theodoros Kalpakos, Gaëlle Vermeersch, Bart Hendriks, Paul Vermeersch
As far as the aetiology of complete AV block is concerned, there was no other obvious cause of AV dissociation except for lithium intoxication. We performed extensive toxicology tests which showed severely elevated lithium blood levels (5.9 mmol/L, limit 1.5 mmol/L), whereas the rest of the toxicology screening was negative. The patient was not taking any beta blockers or other medicine with negative chronotropic or dromotropic effects. There were no arguments for acute myocardial ischaemia: anamnesis and hetero-anamnesis were both negative, the patient had a low cardiovascular risk profile, the ECG’s showed no signs of ischaemia and the cardiac ultrasound revealed a normal regional LV wall motion with a hyperkinetic LV due to hypovolemia. Mild troponinemia was present, however, without kinetics. We attributed mild troponinemia to hypovolemic shock, acute kidney failure and AV conduction abnormalities [5].
New anti-seizure medication for elderly epilepsy patients - a critical narrative review
Published in Expert Opinion on Pharmacotherapy, 2021
A Rohracher, G. Kalss, G. Kuchukhidze, C. Neuray, M. Leitinger, J. Höfler, R. Kreidenhuber, F. Rossini, K. Volna, M. Mauritz, N. Poppert, S. Lattanzi, F. Brigo, E. Trinka
Although LCM is on the market for around 10 years, there is only a limited number of studies focusing on elderly patients [73–75]. These studies, as well as data on elderly patients participating in the monotherapy trial [71], suggest a good efficacy and an adverse event profile comparable to that observed in younger patients. LCM is generally well tolerated; central nervous system-related AEs are dose-dependent and the risk of their occurrence can be mitigated by lowering the starting and target doses. Even low target doses of 200 mg daily proved to be effective in the elderly population [75]. The availability of an intravenous formulation is a great advantage in patients who are temporarily unable to swallow and in the emergency setting. Increasing evidence on the use of LCM in SE [76,77] suggests high efficacy and safety with low risk of cardiorespiratory depression in critically ill patients. Hence, LCM is a valuable option for emergency situations, especially in elderly patients. Furthermore, the favorable pharmacokinetic profile of LCM and the low drug-drug- interaction potential represent great advantages in elderly patients. Regular monitoring with focus on cardiac conduction abnormalities (PR prolongation, AV block) should be performed in patients with cardiovascular disease, especially if dromotropic co-medication is taken. An ECG before treatment initiation is recommended for ruling out preexisting abnormalities of heart rhythm and conduction.
Inorganic clay nanocomposite system for improved cholinesterase inhibition and brain pharmacokinetics of donepezil
Published in Drug Development and Industrial Pharmacy, 2020
Anurag Kumar Singh, Sunil Kumar Mishra, Gaurav Mishra, Anand Maurya, Rajendra Awasthi, Mukesh Kumar Yadav, Neelam Atri, Pawan Kumar Pandey, Santosh Kumar Singh
Donepezil (DZ) is the first member of the second generation AChEIs. DZ was developed for the treatment of Alzheimer’s disease (AD) after the postulation that AD was associated with a central cholinergic deficit [22]. It is USFDA approved anti-Alzheimer’s drug used in mild to moderate conditions. The cytochrome enzymes involved in metabolism of DZ are CYP3A4, CYP1A2, and CYP2D6. DZ enhances acetylcholine level (cholinergic neurotransmission) by the inhibition of acetylcholinesterase action. Increased acetylcholine level can have a number of effects on cholinoceptive neurons, with the precise action, including non-cholinergic actions depending upon the function of the neuron and the location of acetylcholine receptors [22,23]. The changed and unchanged forms of DZ are excreted through urine (79%) and feces (21%). DZ can cause cardiovascular effects like fibrillation in the patients treated for AD. However, this limitation can be overcome by co-administration of negatively chronotropic or dromotropic drugs to the AD patients [24].