Pharmacy and Pharmaceutical Sciences Commons^™

Identifikasi Senyawa Antioksidan Dalam Spons Callyspongia Sp Dari Kepulauan Seribu, Endang Hanani

Majalah Ilmu Kefarmasian

Antioxidant activity and identification of antioxidative compounds of Callyspongia sponge from Seribu Island (Kepulauan Seribu) were investigated. The sponge was extracted with acetone and the extract was concentrated using rotary vacuum evaporator. DPPH and tiocyanate methods were used to examine the antioxidant activity of the extract. The extract exhibited strong antioxidant activity in DPPH method with IC50 of 41.21 µg/ml. Chemical analysis indicated that the antioxidative compound in the sponge was alkaloid group.

Application Of Polyelectrolyte Layer-By-Layer Nano-Assembly For Surface Modification, Encapsulation And Controlled Release, Nikhil Anil Pargaonkar

Doctoral Dissertations

In this study, we applied the traditional Electrostatic layer-by-layer (ELBL) assembly procedure to fabricate nanothin films over flat surfaces, and modify particle surfaces to influence the drug particle size, and drug release. The ELBL assembly has previously been applied to fabricate multilayer nano-scale thin films, but its ability to instantaneously influencing particle size is unique. Other unique observations such as influence on drug release as a result of polymer complexation, and thermal changes occurring during layer fabrication are recorded.

The ELBL self-assembly process was applied to produce dexamethasone particles layered with various polyelectrolyte layer combinations. These combinations were further applied …

Rna Therapeutic, Pendekatan Baru Dalam Terapi Gen, Amarila Malik

Majalah Ilmu Kefarmasian

Some diseases, such as cancer, hereditary and genetic diseases, as well as viral infectious diseases, have been treated unsatisfied by the conventional therapy so far, and even more, by the gene therapy. Together with the pharmaceutical industries, researchers put their best effort to hunt some molecules that can be more favorable for such kind of therapy. After a pivotal study reported in May, 2001, it is certain that Ribonucleic acid (RNA) could effectively silence gene expression in mammalian cell line, so it was then proposed in 2004 the term RNA therapeutics. Antisense RNA therapy which came into the stage earlier …

Non-Human Primates In Medical Research And Drug Development: A Critical Review, Jarrod Bailey

Laboratory Experiments Collection

There is much current debate surrounding the use of non-human primates (NHPs) in medical research and drug development. This review, stimulated by calls for evidence from UK-based inquiries into NHP research, takes a critical view in order to provide some important balance against papers supporting NHP research and calling for it to be expanded. We show that there is a paucity of evidence to demonstrate the positive contribution or successful translation of NHP research to human medicine, that there is a great deal of often overlooked data showing NHP research to be irrelevant, unnecessary, even hazardous to human health and …

Mouse Cytomegalovirus M33 Is Necessary And Sufficient In Virus-Induced Vascular Smooth Muscle Cell Migration, Ryan Melnychuk, Patsy Smith, Craig N. Kreklywich, Franziska Ruchti, Jennifer Totonchy, Laurel Hall, Lambert Loh, Jay A. Nelson, Susan L. Orloff, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Mouse cytomegalovirus (MCMV) encodes two potential seven-transmembrane-spanning proteins with homologies to cellular chemokine receptors, M33 and M78. While these virus-encoded chemokine receptors are necessary for the in vivo pathogenesis of MCMV, the function of these proteins is unknown. Since vascular smooth muscle cell (SMC) migration is of critical importance for the development of atherosclerosis and other vascular diseases, the ability of M33 to promote SMC motility was assessed. Similar to human CMV, MCMV induced the migration of mouse aortic SMCs but not mouse fibroblasts. To demonstrate whether M33 was required for MCMV-induced SMC migration, we employed interfering-RNA technology to specifically …

Entrepreneurial Orientation As A Basis For Classification Within A Service Industry: The Case Of Retail Pharmacy Industry, Thanigavelan Jambulingam, Ravi Kathuria, William R. Doucette

Business Faculty Articles and Research

To date, service classification research has primarily taken a macro view, creating service typologies or taxonomies by using dimensions such as customer contact or degree of labor intensity. Such classification schemes, though helpful in deciphering critical management issues and positioning strategies between service industries, tend to treat an entire industry, such as airlines, as a single homogenous entity. However, organizations in the same industry often use intangible resources, such as entrepreneurial orientation processes, to compete with one another. Resource-advantage theory suggests that organizations utilize intangible resources to build long-term strategies and a sustainable competitive advantage leading to superior performance. We …

Purchasing Pharmaceuticals (Health, Nutrition And Population (Hnp) Discussion Paper), Ulrika Enemark, Anita Alban, Enrique Seoane-Vazquez

Pharmacy Faculty Books and Book Chapters

This paper discusses the purchasing of pharmaceuticals as a key component of costeffective and equitable healthcare delivery. Pharmaceuticals account for a high, sometimes the dominant share of health expenditures in developing countries, but the desired health outcomes can only be achieved if the adequate medicines reach the right people and are used in the correct way. This requires purchasing arrangements that take into account the information asymmetry between patients and providers, ensure selection of effective, safe and affordable medicines and set economic incentives in a way that encourages rational drug use. The organizational and institutional frameworks define the roles of …

Pembuatan Niosom Berbasis Maltodekstrin De 5-10 Dari Pati Singkong (Manihot Utilissima), Mahdi Jufri, Effionora Anwar, Joshita Djajadisastra

Majalah Ilmu Kefarmasian

Niosomes are non ionic surfactant vesicles that have potential application in the delivery of hydrophobic or amphilic drugs. We developed proniosomes, a dry formulation using a maltodextrin as a carrier coated with non ionic surfactant, which can be used to produce niosomes within a minutes by addition of hot water followed by agitation. A novel method is reported here for rapid preparation of proniosomes with wide range of surfactant loading. Maltodextrin DE 5-10 was hidrolyzed from tapioca starch using Thermamyl L 120 da Novo at 85ºC. The result from SEM analyses shown that proniosomes appear very similar to the maltodextrin, …

Penyuluhan Penggunaan Oralit Untuk Menanggulangi Diare Di Masyarakat, Harianto Harianto

Majalah Ilmu Kefarmasian

Diarrhea is one of the common deseases and a attack any level of ages. Diarrhea can be tuated effectively by using oralit to replace the lost of body water. To increase the use of oralit against diarrhea, this trestment should be socialized to public with undergo a general lecture to enhanced the public knowledges cncerning diarrhea and causing factors, to make a group discussion of senior citizen and public figures to build positive attitude in using oralit, and to demonstrate the processing of oralit/LGG and how to use it to people.

Pemberian Vaksin Melalui Tanaman Transgenik, Maksum Radji

Majalah Ilmu Kefarmasian

Vaccines have played an important role in preventive medicine since Edward Jenner discovered that cowpox induced protection against human smallpox. Until recently, a vaccination has meant a needle in the arm. However, with the increasing need for inexpensive, easily administered vaccines, along with the improvements in genetic engineering, the concept of edible vaccines is fast becoming reality. This is especially important in developing countries, where it is estimated that three to five million children die each year from common diseases, which could have easily been prevented with the proper vaccination. Compared to traditional lab-synthesized vaccines, plants are capable of producing …

Pengaruh Kandungan Pati Singkong Terpregelatinasi Terhadap Karakteristik Fisik Tablet Lepas Terkontrol Teofilin, Juheini Juheini, Iskandarsyah Iskandarsyah, Animar J.A, Jenny Jenny

Majalah Ilmu Kefarmasian

In order to make use of pregelatinized Manihot starch in controlled release tablet, the research was done by heating the starch suspension up to its gelatinized temperatur, then dried. The particle size of pregelatinized Manihot starch used were (100-150 mesh) : (150-250 mesh) : smaller than 200 mesh = 3,5 : 1 : 1. The effect of pregelatinized Manihot starch on physical characteristic of Theophyllin controlled relase tablet was known by using 4 formulas containing variety of pregelatinized starch as follows: 30%, 40%, 50%, and 60%. Evaluation on the tablet results including tablet mass and size uniformity, hardness and friability. …

Pemanfaatan Maltodekstrin Pati Terigu Sebagai Eksipien Dalam Formula Sediaan Tablet Dan Niosom, Effionora Anwar, Joshita Djajadisastra, Arry Yanuar, Anton Bahtiar

Majalah Ilmu Kefarmasian

The Use of Maltodextrin from Wheat Starch as an Exipient in Formula Tablet and Niosom dosage form. Wheat starch normally can be used as a tablet filler only, because the flow rate and binding capacity are not good enough. The wheat starch should be treated as follows : protein and amine free Bogasari wheat flour starch were hydrolyzed by α-amylase enzyme (Liquezym EX®) at variable temperature and time incubation to produce maltodextrin with different Dextrose Equivalent (DE) value. The maltodextrin could be used as tablet binder on wet granulation, tablet filler and binder on direct compress, a proniosom carrier to …

Optimasi Biotransformasi Total Sterol Limbah Tahu Menggunakan Mycobacterium Phlei Dsm 43286 Menjadi 1,4-Androstadien-3,17-Dion, Dengan Pengaruh Variasi Konsentrasi Inhibitor A, A’- Dipiridil, Maryati Kurniadi, Usman Sumo Friend Tambunan, Harmita Harmita

Majalah Ilmu Kefarmasian

Isolation of total sterol from waste product of soy bean cake has been conducted, followed by biotransformation to 1,4-androstadien-3,17-dione (ADD). The waste product consist of; β-sitosterol, stigmasterol, kaemfesterol, which are isolated by column chromatography technique using silica gel as stationary phase and chloroform as mobile phase. Biotransformation was conducted by using Mycobacterium phlei DSM 43286 in the present of α, α’- dipiridil as an inhibitor with concentration of 0,5; 1; 1,5; 2,0 mM. The main product of biotransformation were ADD and pregnenolon. The optimum yield of ADD 0,48% is achieved by adding 1,5 mM α, α’- dipiridil are two hours …

Nitric Oxide Inhibition Of Adenylyl Cyclase Type 6 Activity Is Dependent Upon Lipid Rafts And Caveolin Signaling Complexes, Rennolds S. Ostrom, Richard A. Bundey, Paul A. Insel

Pharmacy Faculty Articles and Research

Several cell types, including cardiac myocytes and vascular endothelial cells, produce nitric oxide (NO) via both constitutive and inducible isoforms of NO synthase. NO attenuates cardiac contractility and contributes to contractile dysfunction in heart failure, although the precise molecular mechanisms for these effects are poorly defined. Adenylyl cyclase (AC) isoforms type 5 and 6, which are preferentially expressed in cardiac myocytes, may be inhibited via a direct nitrosylation by NO. Because endothelial NO synthase (eNOS and NOS3), β-adrenergic ( AR) receptors, and AC6 all can localize in lipid raft/caveolin-rich microdomains, we sought to understand the role of lipid rafts in …

The Evolving Role Of Lipid Rafts And Caveolae In G Protein-Coupled Receptor Signaling: Implications For Molecular Pharmacology, Rennolds S. Ostrom, Paul A. Insel

Pharmacy Faculty Articles and Research

The many components of G-protein-coupled receptor (GPCR) signal transduction provide cells with numerous combinations with which to customize their responses to hormones, neurotransmitters, and pharmacologic agonists. GPCRs function as guanine nucleotide exchange factors for heterotrimeric (α, β, γ) G proteins, thereby promoting exchange of GTP for GDP and, in turn, the activation of ‘downstream’ signaling components. Recent data indicate that individual cells express mRNA for perhaps over 100 different GPCRs (out of a total of nearly a thousand GPCR genes), several different combinations of G-protein subunits, multiple regulators of G-protein signaling proteins (which function as GTPase activating proteins), and various …

Ethical Issues In The Use Of Animals In Biomedical And Psychopharmocological Research, John P. Gluck, Jordan Bell

Experimentation Collection

Rationale: The ethical debate concerning the use of animals in biomedical and pharmacological research continues to be replete with misunderstandings about whether animals have moral standing. Objectives: This article briefly reviews the central ethical positions and their relationship to the basic parameters of research regulation from an international perspective. The issues associated with the validation of animal models will then be discussed. Finally, suggestions for empirical ethics research will be presented. Methods: Recent literature reviews were accessed and analyzed. Results: This review summarizes the pertinent ethical and research literature. Conclusions: In summary, regardless of the ethical perspective one favors, there …

Hypertonic Stress Co-Stimulates T Cell Il-2 Expression Through A Feedback Mechanism Involving Atp Release And P2 Receptor Activation Of P38 Map Kinase, William H. Loomis, Sachiko Namiki, Rennolds S. Ostrom, Paul A. Insel, Wolfgang G. Junger

Pharmacy Faculty Articles and Research

Hypertonic stress (HS) can alter the function of mammalian cells. We have reported that HS enhances differentiated responses of T cells by increasing their ability to produce interleukin (IL)-2, a finding of clinical interest because hypertonic infusions may modulate immune function in patients. HS shrinks cells and mechanically deforms membranes, which results in ATP release from many cell types. Here we investigate if ATP release is an underlying mechanism through which HS augments T cell function. We found that mechanical stress and HS induced rapid ATP release from Jurkat T cells. HS and exogenous ATP mobilized intracellular Ca2+, activated p38 …

Angiotensin Ii Enhances Adenylyl Cyclase Signaling Via Ca2+/Calmodulin. Gq-Gs Cross-Talk Regulates Collagen Production In Cardiac Fibroblasts, Rennolds S. Ostrom, Jennifer E. Naugle, Miki Hase, Caroline Gregorian, James S. Swaney, Paul A. Insel, Laurence L. Brunton, J. Gary Meszaros

Pharmacy Faculty Articles and Research

Cardiac fibroblasts regulate formation of extracellular matrix in the heart, playing key roles in cardiac remodeling and hypertrophy. In this study, we sought to characterize cross-talk between Gq and Gs signaling pathways and its impact on modulating collagen synthesis by cardiac fibroblasts. Angiotensin II (ANG II) activates cell proliferation and collagen synthesis but also potentiates cyclic AMP (cAMP) production stimulated by β-adrenergic receptors (β-AR). The potentiation of β-AR-stimulated cAMP production by ANG II is reduced by phospholipase C inhibition and enhanced by overexpression of Gq. Ionomycin and thapsigargin increased intracellular Ca2+ levels and potentiated isoproterenol- and forskolin-stimulated cAMP production, whereas …

Human Cytomegalovirus Chemokine Receptor Us28-Induced Smooth Muscle Cell Migration Is Mediated By Focal Adhesion Kinase And Src, Daniel N. Streblow, Jennifer Totonchy, Patsy Smith, Ryan Melnychuk, Laurel Hall, Dora Pancheva, Martine Smit, Paola Casarosa, David D. Schlaepfer, Jay A. Nelson

Pharmacy Faculty Articles and Research

The human cytomegalovirus-encoded chemokine receptor US28 induces arterial smooth muscle cell (SMC) migration; however, the underlying mechanisms involved in this process are unclear. We have previously shown that US28-mediated SMC migration occurs by a ligand-dependent process that is sensitive to proteintyrosine kinase inhibitors. We demonstrate here that US28 signals through the non-receptor protein-tyrosine kinases Src and focal adhesion kinase (FAK) and that this activity is necessary for US28-mediated SMC migration. In the presence of RANTES (regulated on activation normal T cell expressed and secreted), US28 stimulates the production of a FAK Src kinase complex. Interestingly, Src co-immunoprecipitates with US28 in …

Polymerase Chain Reaction: An Emerging Tool For Research In Pharmacology, Rishi Sharma, Manjeet Singh, Ajay Sharma

Pharmacy Faculty Articles and Research

Polymerase chain reaction (PCR) is a technique that can amplify a specific DNA segment in vitro using two site specific primers that hybridise to opposite DNA strands. The method produces large amounts of specific DNA from a complex DNA template in a single enzymatic reaction within a matter of hours. Reaction mixture contains a double helix DNA, two target specific primers, dNTPs, a DNA polymerase and a Mg2+ containing buffer. PCR is carried out in three distinct steps i.e. denaturation step, annealing step and extension step, which are repeated many times. The efficiency of PCR is measured in terms of …

Dextran-Methylprednisolone Succinate As A Prodrug Of Methylprednisolone: Plasma And Tissue Disposition, Xiaoping Zhang, Reza Mehvar

Pharmacy Faculty Articles and Research

Plasma and tissue disposition of a macromolecular prodrug of methylprednisolone (MP), dextran (70 kDa)–methylprednisolone succinate (DMP), was studied in rats. Single 5‐mg/kg doses of DMP or unconjugated MP were administered into the tail veins of different groups of rats (n  = 4/group/time point). Blood (cardiac puncture) and tissues (liver, spleen, kidney, heart, lung, thymus, and brain) were collected at various times after DMP (0–96 h) or MP (0–2 h) injections. Concentrations of DMP and MP in samples were analyzed by size‐exclusion chromatography (SEC) and reversed‐phase high‐performance liquid chromatography (HPLC), respectively. Conjugation of MP with 70‐kDa dextran resulted in 22‐, …

Receptor Number And Caveolar Co-Localization Determine Receptor Coupling Efficiency To Adenylyl Cyclase, Rennolds S. Ostrom, Caroline Gregorian, Ryan M. Drenan, Yang Xiang, John W. Regan, Paul A. Insel

Pharmacy Faculty Articles and Research

Recent evidence suggests that many signaling molecules localize in microdomains of the plasma membrane, particularly caveolae. In this study, overexpression of adenylyl cyclase was used as a functional probe of G protein-coupled receptor (GPCR) compartmentation. We found that three endogenous receptors in neonatal rat cardiomyocytes couple with different levels of efficiency to the activation of adenylyl cyclase type 6 (AC6), which localizes to caveolin-rich membrane fractions. Overexpression of AC6 enhanced the maximal cAMP response to β1-adrenergic receptor (β1AR)-selective activation 3.7-fold, to β2AR-selective activation only 1.6-fold and to prostaglandin E2 (PGE2) not at all. Therefore, the rank order of efficacy in …

Cellular Release Of And Response To Atp As Key Determinants Of The Set-Point Of Signal Transduction Pathways, Rennolds S. Ostrom, Caroline Gregorian, Paul A. Insel

Pharmacy Faculty Articles and Research

The determinants of “basal” activity of signaling pathways regulating cellular responses are poorly defined. One possibility is that cells release factors to establish the set-point of such pathways. Here we show that treatment of Madin-Darby canine kidney cells with the nucleotidase apyrase decreases basal arachidonic acid release and cAMP production 30–40% and that inhibitors of P2Y receptor action also affect basal and forskolin-stimulated cAMP accumulation. Changing medium prominently increases extracellular levels of ATP in Madin-Darby canine kidney, COS-7, and HEK-293 cells. Mechanical stimulation of ATP release likely occurs in virtually every experimental protocol with cultured cells, implicating such release and …

Effect Of Actinomycin D And Cycloheximide On Ischemic Preconditioning-Induced Delayed Cardioprotective Effect In Rats, Devinder Singh, Ajay Sharma, Manjeet Singh

Pharmacy Faculty Articles and Research

The present study was designed to investigate the effect of actinomycin D, a transcription inhibitor, and cycloheximide, a translation inhibitor, on the delayed cardioprotective effect of ischemic preconditioning. Left thoracotomy was performed in anaesthetized rats at 4th/5th intercostal space and polypropylene suture (5-0) was employed to occlude left common coronary artery. Ischemic preconditioning was produced by four episodes of 5 min of coronary artery occlusion followed by 5 min of reperfusion and thoracic cavity was sutured. Left thoracotomy was performed again after 24 hr of ischemic preconditioning and left coronary artery was occluded for 30 min followed by reperfusion for …

Role Of KAtp Channels In Reduced Antinociceptive Effect Of Morphine In Streptozotocin-Induced Diabetic Mice, Vivek Sood, Ajay Sharma, Manjeet Singh

Pharmacy Faculty Articles and Research

The nociceptive effect was measured using withdrawal latency in tail flick test in mice rendered diabetic by administering streptozotocin (200 mg/kg, i.p.). The antinociceptive effect of morphine (4 and 8 mg/kg, s.c.) and cromakalim, a KATP channel opener, (0.3, 1 and 2 micrograms, i.c.v.) was significantly reduced in diabetic mice. Moreover, co-administration of cromakalim(0.3 microgram) did not alter the reduced antinociceptive effect of morphine(4 mg/kg) in diabetic mice. Spleenectomy in diabetic mice restored the decrease in antinociceptive effect of morphine and cromakalim. Multiple dose treatment with insulin to maintain euglycaemia for 3 days in diabetic mice prevented the decrease in …

Protein Adducts Of Iso[4]Levuglandin E2, A Product Of The Isoprostane Pathway, In Oxidized Low Density Lipoprotein, Robert G. Salomon, Wei Sha, Cynthia Brame, Kamaljit Kaur, Ganesamoorthy Subbanagounder, June O'Neil, Henry F. Hoff, L. Jackson Roberts Ii

Pharmacy Faculty Articles and Research

Levuglandin (LG) E₂, a cytotoxic seco prostanoic acid co-generated with prostaglandins by nonenzymatic rearrangements of the cyclooxygenase-derived endoperoxide, prostaglandin H₂, avidly binds to proteins. That LGE₂-protein adducts can also be generated nonenzymatically is demonstrated by their production during free radical-induced oxidation of low density lipoprotein (LDL). Like oxidized LDL, LGE₂-LDL, but not native LDL, undergoes receptor-mediated uptake and impaired processing by macrophage cells. Since radical-induced lipid oxidation produces isomers of prostaglandins, isoprostanes (isoPs), via endoperoxide intermediates, we postulated previously that a similar family of LG isomers, isoLGs, is cogenerated with isoPs. Now …

Inhibition Of Cpla2-Mediated Arachidonic Acid Release By Cyclic Amp Defines A Negative Feedback Loop For P2y-Receptor Activation In Mdck-D1 Cells, Mingzhao Xing, Steven Post, Rennolds S. Ostrom, Michael Samardzija, Paul A. Insel

Pharmacy Faculty Articles and Research

In Madin-Darby canine kidney D1cells extracellular nucleotides activate P2Y receptors that couple to several signal transduction pathways, including stimulation of multiple phospholipases and adenylyl cyclase. For one class of P2Y receptors, P2Y2 receptors, this stimulation of adenylyl cyclase and increase in cAMP occurs via the conversion of phospholipase A2 (PLA2)-generated arachidonic acid (AA) to prostaglandins (e.g. PGE2). These prostaglandins then stimulate adenylyl cyclase activity, presumably via activation of prostanoid receptors. In the current study we show that agents that increase cellular cAMP levels (including PGE2, forskolin, and the β-adrenergic agonist isoproterenol) can inhibit P2Y receptor-promoted AA release. The protein kinase …

An Overview Of The Methylxanthines And Their Regulation In The Horse, J Daniel Harkins, W. Allen Rees, G. D. Mundy, Scott D. Stanley, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Caffiene, theophylline and theobromine are naturally occurring members of the methylxanthine family;pentoxfylline, dyphylline and enprofylline are structurally related synthetic pharmaceuticals. Caffiene has predominantly central nervous system effects, theophylline, dyphylline and enprofylline have predominantly bronchodilator effects, while theobromine is associated with diuretic responses. Pentoxfylline is thought to increase red cell deformability and facillitate blood flow through capillary beds. The methylxanthines are not highly potent agents; they are typically administered in gram doses and they tend to have relatively long half-lives. They remain detectable in plasma and urine for relatively long periods. Similarly, traces of the naturally occurring members of this family …

What Is The Risk Of Teratogenicity With The Use Of Selective Serotonin Reuptake Inhibitors During Pregnancy?, Michael Z. Wincor, Mary Gutierrez, Ann Nguyen

Pharmacy Faculty Articles and Research

"The lifetime prevalence of major depressive disorder in women is 10 to 25%, with an average age of onset in the mid-20s.1 Over the nine years that the selective serotonin reuptake inhibitors (SSRis) have been available, for many prescribers, they have become first-line agents in the treatment of depression. In addition, sorne of them are also being used in the treatment of obsessive- compulsive disorder and panic disorder. In light of these facts, itis not unlikely that women of childbearing age would be treated with one of the SSRis. In considering the risks of exposing a fetus to an SSRI, …

Ls There Any Risk Of A Withdrawal Syndrome Associated With Abrupt Discontinuation Of Selective Serotonin Reuptake Inhibitors?, Rene A. Endow, Mary Gutierrez, Michael Z. Wincor

Pharmacy Faculty Articles and Research

"With the availability of the newer selective serotonin reuptake inhibitors (SSRis), concern over a 'cholinergie rebound' seemed unnecessary since these agents demonstrate little or no anticholinergic activity. However, a review of the literature indicates that there may be other withdrawal symptoms associated with discontinuation of the SSRis. The time course and, perhaps to a lesser extent, the frequency of these symptoms appear to be correlated with the elimination half-lives of the agents."