{"id":939,"date":"2020-02-18T10:43:17","date_gmt":"2020-02-18T05:13:17","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=939"},"modified":"2020-02-18T10:43:17","modified_gmt":"2020-02-18T05:13:17","slug":"chronopharmacology","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/chronopharmacology\/","title":{"rendered":"Chronopharmacology"},"content":{"rendered":"\n
Chronopharmacology<\/strong><\/p>\n\n\n\n Chronos in greek means time. Chronopharmacology is the investigative science concerned with the effects of drugs upon the timing of biological events and rhythms.<\/strong> It also links effects of drugs on biological timing to get the dynamic activity.<\/p>\n\n\n\n Biorhythms<\/strong><\/p>\n\n\n\n The Biological Clock<\/strong><\/p>\n\n\n\n Circadian Rhythm<\/strong><\/p>\n\n\n\n Zeitgeber<\/strong><\/p>\n\n\n\n Molecular Basis of Circadian Rhythm<\/strong><\/p>\n\n\n\n Circadian rhythm modulators<\/strong><\/p>\n\n\n\n Physiologic variations in relation to Circadian changes<\/strong><\/p>\n\n\n\n Disease pattern due to circadian changes<\/strong><\/p>\n\n\n\n Divisions of Chronopharmacology<\/strong><\/p>\n\n\n\n ChronoPK<\/strong><\/p>\n\n\n\n Chronopharmacokinetics is subdivision of chronopharmacology which deals with the study of the temporal changes in the pharmacokinetics of the drugs with respective time.<\/p>\n\n\n\n Time-dependent changes in pharmacokinetics may proceed from 24 hr rhythms in each process, e.g. absorption, distribution, metabolism and elimination.<\/p>\n\n\n\n Thus, 24 hr rhythms in gastric acid secretion and pH, motility, gastric emptying time, gastrointestinal blood flow, drug protein binding, liver enzyme activity and\/or hepatic blood flow, glomerular filtration, renal blood flow, urinary pH and tubular resorption may play a role in such pharmacokinetic variations.<\/p>\n\n\n\n Absorption:<\/strong><\/p>\n\n\n\n Circadian patterns of absorption are most pronounced in lipophilic drugs, with greater absorption occurring during the day than at night eg. Propanolol.<\/p>\n\n\n\n As a result of these diurnal variations in physiologic parameters and transporters\/efflux pumps, the absorption on many drugs, including diazepam, acetaminophen, theophylline, digoxin, propranolol, nitrates, nifedipine, and amitriptyline is sensitive to the time of day of administration. The absorption of most drugs is greater in the morning, paralleling morning increases in gut perfusion and gastric pH.<\/p>\n\n\n\n Distribution:<\/strong><\/p>\n\n\n\n It depends mainly on drug\u2019s lipophilicity and plasma protein binding affinity<\/strong>.<\/p>\n\n\n\n The degree of protein binding<\/strong> of several drugs, including the antiepileptic agents valproic acid and carbamazepine, and the chemotherapeutic cisplatin, varies in a diurnal manner<\/strong> which correlates appropriately with changes in plasma albumin level. a variety of drug transporters which are critical for drug distribution in tissues are regulated by circadian mechanisms.<\/p>\n\n\n\n Metabolism:<\/strong><\/p>\n\n\n\n Diurnal variation in the levels and activity of various phase I metabolic enzymes specially CYP450 in the liver of rodents has been long appreciated.<\/p>\n\n\n\n Phase II metabolism<\/strong> is also regulated by circadian mechanisms. Initial studies in mice demonstrated diurnal variation in hepatic glutathione-S-transferase (GST) activity, with greatest activity being present during the dark (active) phase<\/strong>.<\/p>\n\n\n\n Excretion:<\/strong><\/p>\n\n\n\n diurnal variation in renal parameters including glomerular filtration rate, renal plasma flow, and urine output have been described, it is not surprising that diurnal variation in the urinary excretion of several drugs has been observed.<\/p>\n\n\n\n Circadian regulation of urinary pH could also contribute to variations in drug excretion, as many drugs become protonated at high pH which enhances excretion.<\/p>\n\n\n\n Affecting the route of administration<\/strong><\/p>\n\n\n\n alternative routes of drug administration, including oral, cutaneous\/transdermal, and intravenous, have differences in drug absorption rates influenced by circadian rhythms.<\/p>\n\n\n\n It has been demonstrated previously that local anesthetic agents have varying penetration rates through the skin in a circadian time-dependent manner. Therefore, drug formulation, route of administration and circadian rhythms influences should all be taken into account when treating a disease.<\/p>\n\n\n\n ChronoPD<\/strong><\/p>\n\n\n\n Rhythmic alterations in the expression of target receptors, transporters and enzymes, intracellular signaling systems, and gene transcription all have been reported, and have the potential to impact the efficacy of therapeutics.<\/p>\n\n\n\n PR prolongation was significantly greater when verapamil is given in morning than evening.<\/p>\n\n\n\n Chronesthesy<\/strong><\/p>\n\n\n\n Biological rhythms at the cellular and subcellular level can give rise to significant dosing-time differences in the pharmacodynamics of medications that are unrelated to their pharmacokinetics. This phenomenon is termed chronesthesy.<\/p>\n\n\n\n Chronotherapeutics<\/strong><\/p>\n\n\n\n Discipline of medical treatment which allows for the consideration of a patient\u2019s biological rhythm, changes in the severity of a disease state during the day, and the synchronizing of dosing and delivery of a particular drug to allow for the optimal efficacy in the patient.<\/p>\n\n\n\n Many studies have shown that cardiovascular related events, such as myocardial infarction and stroke, often occur in the early morning due to circadian changes regulating blood pressure, heart rate, vasodilating hormones, etc.<\/p>\n\n\n\n Dihydropyridine calcium channel blockers, have been shown that time of day dosing, particularly evening, is the most advantageous for efficacy of the treatment and normalizing changes in blood pressure rhythms to reduce early morning cardiac events.<\/p>\n\n\n\n Chronotoxicity<\/strong><\/p>\n\n\n\n predictable- in-time variation in patient vulnerability to the side effects of medications due to biological rhythm determinants.<\/p>\n\n\n\n Chronotoxicities are known especially with antitumor agents. For example, the body weight loss with irinotecan<\/strong> hydrochloride (CPT-11) of nocturnally active mice is more serious in the late active phase and the early rest phase and milder in the late rest phase and the early active phase.<\/p>\n\n\n\n Chrono Drug Delivery Systems (Chrono-DDS)<\/strong><\/p>\n\n\n\n The technologies in chronopharmaceutics includes:<\/p>\n\n\n\n Applied Chronopharmacology<\/strong><\/p>\n\n\n\n Morning daily or alternate day dosing strategy for methylprednisolone<\/strong> that was introduced during the 1960sconstitutes the first chronotherapy<\/strong> to be incorporated into clinical practice.<\/p>\n\n\n\n Asthma<\/strong><\/p>\n\n\n\n One of the most extensively studied examples of time-dependent dosing on drug effect and toxicity is glucocorticoid receptor (GR) agonists.<\/p>\n\n\n\n The natural ligands for GR are glucocorticoids, predominantly cortisol, and are synthesized from cholesterol precursors in the adrenal cortex under tight regulation from hypothalamo-pituitary axis.<\/p>\n\n\n\n Circulating levels of glucocorticoids fluctuate in a circadian manner, with the highest levels observed in the morning and the lowest levels in the late evening in diurnal animals.<\/p>\n\n\n\n the timing of prednisone was absolutely critical for the relief of the nocturnal worsening of the symptoms and the 1500 h administration of prednisone was effective while dosing at either 0800 h or 2000 h was ineffective.<\/p>\n\n\n\n Asthma- The risk of asthmatic attack is almost 70 times higher in patients at 04:00-05:00.<\/p>\n\n\n\n Theophylline chronotherapy \u2013 Evening, once daily dosing of specially formulated theophylline tablets for nocturnal asthma. Therapeutic drug concentrations during the night and avoiding toxic levels during the day.<\/p>\n\n\n\n Oral prednisone (3 pm) is much more effective in improving nocturnal asthma rather than 8 am and 8 pm dose barely better than placebo.<\/p>\n\n\n\n Allergic rhinitis<\/strong><\/p>\n\n\n\n The major symptomes are usually worst in the morning and evening.<\/p>\n\n\n\n Chronotherapy: non-sedating antihistamine once daily before bedtime to control overnight exacerbations morning oral corticosteroid therapy for severe allergic rhinitis.<\/p>\n\n\n\n Arthritis<\/strong><\/p>\n\n\n\n symptoms of rheumatoid arthritis are always worse in the morning.<\/p>\n\n\n\n Taking long-acting NSAIDs like flubiprofen, ketoprofen and indomethacin at bedtime optimizes their therapeutic effect and minimizes or averts their side effects.<\/p>\n\n\n\n osteoarthritis, the most common form of the disease, tend to have less pain in the morning and more at night. The optimal time for a NSAIDs such as ibuprofen would be around noon or mid-afternoon.<\/p>\n\n\n\n Circadian changes in the pH levels of the stomach.<\/strong><\/p>\n\n\n\n Acidity (H+) reaches its peak in the evening in both the healthy and patients affected by gastric ulcers. In peptic ulcer patients, there will be a maximum acid secretion, ulcer pain, and exacerbation during night.<\/p>\n\n\n\n Administration of H antagonists drugs at bedtime is more effective in reducing acid secretion and promoting ulcer healing. Evening administration of ranitidine is justified from the point of view of chronopharmacology.<\/strong><\/p>\n\n\n\n Congenital adrenal hyperplasia<\/strong> \u2013<\/p>\n\n\n\n Bedtime corticosteroid dosing controls excessive hormone secretion Bedtime ADH analogue dosing helps to alleviate nocturnal bedwetting<\/strong> in children and nocturia in adults.<\/p>\n\n\n\n Morning application of testosterone drug-delivery patch<\/strong> systems to achieve physiologic androgen-replacement therapy.<\/p>\n\n\n\n Myocardial infarction<\/strong><\/p>\n\n\n\n A 40% increase in risk of myocardial infarction occurs between 6 am and noon<\/strong>. A 29% of increase in sudden cardiac death in early morning hours and 49% increase in stroke risk between 6 am and noon have been noted.<\/p>\n\n\n\n faster reduction in BP with morning dose of enalapril,<\/strong> maximum vasodilatation occurs with morning dose of nitrates, 3hydroxy3methylglutarylcoenzyme A (HMGCoA) reductase inhibitor being more effective when administered in the evening with exception of atorvastatin.<\/p>\n\n\n\n Before-bedtime administration of verapamil<\/strong> HCL as a unique controlled onset extended-release 24 hr dosage form to optimize the treatment of patients with ischemic heart disease and\/or essential hypertention.<\/p>\n\n\n\n Evening administration of HMG-CoA-reductase antagonists for the management of hyperlipidemia.<\/strong><\/p>\n\n\n\n Anticancer<\/strong><\/p>\n\n\n\n Many anticancer therapeutics have been shown to exhibit differing effects and toxicity based on administration time<\/p>\n\n\n\n Colorectal cancer- Oxaliplatin is given in during daytime & flurouracil at night.<\/p>\n\n\n\n Chronopharmacology in Ayurveda<\/strong><\/p>\n\n\n\n Altered chronobiology (study of alterations of each organisms temporal structure under various situations) manifested as vitiated dosas because of change of seasons or altered habits does decrease the performance, that\u2019s why Ayurveda suggests avoidance of sahasa (stress) and observance of regular habits in the form of dinacarya. Ayurveda recommends the consumption of preparations at specific times during the day<\/p>\n\n\n\n Chronopharmacology Chronos in greek means time. Chronopharmacology is the investigative science concerned with the effects of drugs upon the timing of biological events and rhythms. It also links effects of drugs on biological timing to get the dynamic activity. Biorhythms A daily cycle or periodicity affects biochemical, physiological, or behavioral process of living being is[…]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/939"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=939"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/939\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=939"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=939"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=939"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}Abhakta<\/td> Drugs in morning absorption is maximum and more efficient<\/td><\/tr> Pragbhakta<\/td> Just before food. For diseases of apana vayu \u2013 for strengthening and preventing the disease of lower half of body and treating obesity.<\/td><\/tr> Madhyabhakta<\/td> In between foods. For diseases of samana vayu, disease of koshtas and for paittic diseases.<\/td><\/tr> Sanya Pscadbhakta<\/td> In evenings after food. For diseases of udana vayu.<\/td><\/tr> Muhurmuhuh<\/td> Drugs given repeatedly for treating swasa (dyspnoea), kasa (cough), hikka (hiccoughs), chardi (vomitting), visa (poisoning) and pipasa (Thirst).<\/td><\/tr> Samudga<\/td> Before and after light food in hikka, akepsa(convulsions) and in diseases of head and neck.<\/td><\/tr> Sabhakta<\/td> Drugs as appetizers with food, in children with weak constitution.<\/td><\/tr><\/tbody><\/table><\/figure>\n","protected":false},"excerpt":{"rendered":"