Choosing Antiseizure Medication

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Choosing antiseizure YOUNG EPILEPSY medication SECTION Based on Asadi-Pooya, AA, Beniczky, S, Rubboli, G, Sperling, MR, Rampp, S, Perucca, E. A pragmatic algorithm to select appropriate antiseizure medications in patients with epilepsy. Epilepsia. 2020; 61: 1668– 1677; available online as EpiPick tool How to 1 Select a seizure 2Up- or downgrade 3 Select the type and see how the medications medication use it medications are based on modiﬁers ranked ﬁrst ranked (see the back side) Type First level Second level Third level LEV, ZNS, ACT, Absence ETS, VPA LTG CLB, CLN TPM, ZNS Myoclonic CLN, VPA, LEV CLB PB, NTR OXC, CLB, ZNS, LCM, TMP, PB, Prim. GTC VPA LTG, LEV PER, PHT, CBZ, BRV CLN, LTG, ZNS, Prim. GTC+ CLB, TPM, PB, VPA LEV myoclonic PER, PHT, LCS, BRV Prim. GTC + TPM, ZNS, VPA LTG, LEV absence CLB Prim. GTC + TPM, ZNS, myoclonic + VPA LTG, LEV CLB, CLN absence Myoclonic + TPM, ZNS, VPA, ETS LTG, LEV absence CLB, CLN LEV, CBZ, LTG TPM, VPA, PER, CLB, PB, Focal OXC, ESL, LCM PHT, BRV, ZNS GBP, PGB VPA, PER, PHT, Unknown + LEV, CBZ, LTG BRV, ZNS, PB, GBP, PGB age ≥ 21 OXC, ESL, LCM TPM, CLB Unknown + CLB, CBZ, PER, VPA, LTG, LEV PB, TPM, ZNS age < 21 ESL, OXC, LCM Abbreviations: ACT, acetazolamide; BRV, brivaracetam; CBZ, carbamazepine; CLB, clobazam; CLN, clonazepam; ESL, eslicarbazepine acetate; ETS, ethosuximide; GBP, gabapentin; LCM, lacosamide; LEV, levetiracetam; LTG, lamotrigine; NTR, nitrazepam; OXC, oxcarbazepine; PB, phenobarbital; PER, perampanel; PGB, pregabalin; PHT, phenytoin; TPM, topiramate; VPA, valproic acid; ZNS, zonisamide; Prim. GTC; primary generalized tonic-clonic Follow YES-ILAE on social media: Join YES-ILAE Check EpiPick online @yesILAE @yesILAE @yes_ILAE Premenopausal women Oral contraceptive intake Focal seizures: discard PER, TPM VPA GTCS: 2nd level downgrade by one level Other types: ESL, CBZ, OXC, PB, PHT 3rd choice downgrade by two levels LTG LTG, LEV GTCS: 1st choice Estrogen reduces LTG levels; LTG moderately reduces levonorgestrel levels Age > 65 years GBP, LCM, upgrade by Bleeding disorders LEV, LTG one level VPA Generalized Neutropenia downgrade by one level Focal or unknown downgrade by downgrade by two levels CBZ, PHT one level Co-medications Diabetes mellitus (except contraceptives) downgrade by CBZ, PER, CBZ, PB, downgrade by one level PHT, VPA PHT one level Focal or Hx of irritability BRV, GBP, LCM, unknown: LEV, LTG, upgrade by downgrade by LEV, PER, PER, ZNS one level PB, TPM one level Generalized: ETS, LCM, LEV, upgrade by LTG, PER, ZNS one level Migraine upgrade by TPM, VPA one level Obesity GBP, PGB downgrade by one level Renal stones VPA Generalized ACT, TPM, downgrade by downgrade by one level ZNS one level Focal or unknown downgrade by two levels Brain tumor requiring chemo-/radiotherapy Allergy to any drug ESL, CBZ, LTG, ESL, CBZ, PB, OXC, PHT downgrade by downgrade by two levels OXC, PB, PHT, ZNS one level Hepatic GBP, LCM, LEV VPA failure upgrade by one level downgrade by two levels CLB, ETS, LTG, Renal All other drugs CBZ, PHT downgrade by one level failure upgrade by one level LTG CLB, CNZ, LEV, NTZ, PB Depression upgrade by one level downgrade by one level © The International League Against Epilepsy .

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Eslicarbazepine Acetate Longer Procedure No
European Medicines Agency London, 19 February 2009 Doc. Ref.: EMEA/135697/2009 CHMP ASSESSMENT REPORT FOR authorised Exalief International Nonproprietary Name: eslicarbazepine acetate longer Procedure No. EMEA/H/C/000987 no Assessment Report as adopted by the CHMP with all information of a commercially confidential nature deleted. product Medicinal 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK Tel. (44-20) 74 18 84 00 Fax (44-20) 74 18 84 16 E-mail: [email protected] http://www.emea.europa.eu TABLE OF CONTENTS 1. BACKGROUND INFORMATION ON THE PROCEDURE........................................... 3 1.1. Submission of the dossier ...................................................................................................... 3 1.2. Steps taken for the assessment of the product..................................................................... 3 2. SCIENTIFIC DISCUSSION................................................................................................. 4 2.1. Introduction............................................................................................................................ 4 2.2. Quality aspects ....................................................................................................................... 5 2.3. Non-clinical aspects................................................................................................................ 8 2.4. Clinical aspects....................................................................................................................
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Chapter 25 Mechanisms of Action of Antiepileptic Drugs
Chapter 25 Mechanisms of action of antiepileptic drugs GRAEME J. SILLS Department of Molecular and Clinical Pharmacology, University of Liverpool _________________________________________________________________________ Introduction The serendipitous discovery of the anticonvulsant properties of phenobarbital in 1912 marked the foundation of the modern pharmacotherapy of epilepsy. The subsequent 70 years saw the introduction of phenytoin, ethosuximide, carbamazepine, sodium valproate and a range of benzodiazepines. Collectively, these compounds have come to be regarded as the ‘established’ antiepileptic drugs (AEDs). A concerted period of development of drugs for epilepsy throughout the 1980s and 1990s has resulted (to date) in 16 new agents being licensed as add-on treatment for difficult-to-control adult and/or paediatric epilepsy, with some becoming available as monotherapy for newly diagnosed patients. Together, these have become known as the ‘modern’ AEDs. Throughout this period of unprecedented drug development, there have also been considerable advances in our understanding of how antiepileptic agents exert their effects at the cellular level. AEDs are neither preventive nor curative and are employed solely as a means of controlling symptoms (i.e. suppression of seizures). Recurrent seizure activity is the manifestation of an intermittent and excessive hyperexcitability of the nervous system and, while the pharmacological minutiae of currently marketed AEDs remain to be completely unravelled, these agents essentially redress the balance between neuronal excitation and inhibition. Three major classes of mechanism are recognised: modulation of voltage-gated ion channels; enhancement of gamma-aminobutyric acid (GABA)-mediated inhibitory neurotransmission; and attenuation of glutamate-mediated excitatory neurotransmission. The principal pharmacological targets of currently available AEDs are highlighted in Table 1 and discussed further below.
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Comparison of Short-And Long-Acting Benzodiazepine-Receptor Agonists
J Pharmacol Sci 107, 277 – 284 (2008)3 Journal of Pharmacological Sciences ©2008 The Japanese Pharmacological Society Full Paper Comparison of Short- and Long-Acting Benzodiazepine-Receptor Agonists With Different Receptor Selectivity on Motor Coordination and Muscle Relaxation Following Thiopental-Induced Anesthesia in Mice Mamoru Tanaka1, Katsuya Suemaru1,2,*, Shinichi Watanabe1, Ranji Cui2, Bingjin Li2, and Hiroaki Araki1,2 1Division of Pharmacy, Ehime University Hospital, Shitsukawa, Toon, Ehime 791-0295, Japan 2Department of Clinical Pharmacology and Pharmacy, Neuroscience, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan Received November 7, 2007; Accepted May 15, 2008 Abstract. In this study, we compared the effects of Type I benzodiazepine receptor–selective agonists (zolpidem, quazepam) and Type I/II non-selective agonists (zopiclone, triazolam, nitrazepam) with either an ultra-short action (zolpidem, zopiclone, triazolam) or long action (quazepam, nitrazepam) on motor coordination (rota-rod test) and muscle relaxation (traction test) following the recovery from thiopental-induced anesthesia (20 mg/kg) in ddY mice. Zolpidem (3 mg/kg), zopiclone (6 mg/kg), and triazolam (0.3 mg/kg) similarly caused an approximately 2-fold prolongation of the thiopental-induced anesthesia. Nitrazepam (1 mg/kg) and quazepam (3 mg/kg) showed a 6- or 10-fold prolongation of the anesthesia, respectively. Zolpidem and zopiclone had no effect on the rota-rod and traction test. Moreover, zolpidem did not affect motor coordination and caused no muscle relaxation following the recovery from the thiopental-induced anesthesia. However, zopiclone significantly impaired the motor coordination at the beginning of the recovery. Triazolam significantly impaired the motor coordination and muscle relaxant activity by itself, and these impairments were markedly exacerbated after the recovery from anesthesia.
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Acetazolamide
Cambridge University Press 978-0-521-68716-4 - The Epilepsy Prescriber’s Guide to Antiepileptic Drugs Philip N. Patsalos and Blaise F. D. Bourgeois Excerpt More information the epilepsy prescriber’s guide to antiepileptic drugs ACETAZOLAMIDE A Therapeutics Chemical name and structure: Acetazolamide, N-(5-(aminosulfonyl)-1,3,4-thiadiazol-2-yl)-aceta- mide, is a white to faintly yellowish white odorless crystalline powder with a molecular weight of 222.25. Although a sulfonamide compound, it is unlike sulfonamide anti- biotic compounds. It does not contain an arylamine group at the N4-position, which contributes to allergic reactions associated with sulfonamide antibiotics. The structure of acetazolamide bears some similarity to that of zonisamide. Its empirical formula is C4H6N4O3S2. NN O CH3 CNH SO2NH2 S THERAPEUTICS Brand names: r Acetadiazol; Acetak; Albox; Apo-Acetazolamide; Azol r Carbinib; Cetamid r Diamox; Diamox Sequals; Diamox Sustets; Diluran; Diural; Diuramid r Evamox r Fonurit r Glaupax r Huma-Zolamide r Ledamox; Lediamox r Medene r Optamide r Renamid r Stazol; Synomax r Uramox r Zolmide Generics available: r Yes Licensed indications for epilepsy: r Adjunctive treatment of generalized tonic–clonic and partial seizures (UK-SPC) r Adjunctive treatment of atypical absences, atonic, and tonic seizures (UK-SPC) r Intermittent therapy of catamenial seizures (UK-SPC) Licensed indications for non-epilepsy conditions: r Adjunctive treatment of glaucoma (UK-SPC; FDA-PI) r Prevention or amelioration of symptoms associated with acute mountain sickness (FDA-PI) 1 © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-68716-4 - The Epilepsy Prescriber’s Guide to Antiepileptic Drugs Philip N.
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Red with Nitrazepam and Placebo in Acute Emergency Driving Situations and in Monotonous Simulated Driving
109 A 1986 The Carry-over Effects of Triazolam Compa- red with Nitrazepam and Placebo in Acute Emergency Driving Situations and in Mono- tonous Simulated Driving Hans Laurell and Jan Törnroos Reprint from Acta Pharmacologica et toxicologica 1986 v Väg06/7 Efi/( Statens väg- och trafikinstitut (VTI) * 581 01 Linköping [St]tlltet Swedish Road and Traffic Research Institute * S-581 01 Linköping Sweden Acta pharmacol. et toxicol. 1986, 58, 182186. From the National Swedish Road and Traffic Research Institute, (V.T.I.), S-58 101 Linköping, Sweden The Carry-over Effects of Triazolam Compared with Nitrazepam and Placebo in Acute Emergency Driving Situations and in Monotonous Simulated Driving Hans Laurell and Jan Törnros (Received October 9, 1985; Accepted January 9, 1986) Abstract: Eighteen healthy volunteers of both sexes, aged 2034, were tested in the morning while undertaking real car driving avoidance manoeuvres and during monotonous simulated driving after 1 and 3 nights of medication with triazolam 0.25 mg, nitrazepam 5 mg or placebo. The study was a double-blind, randomized, cross-over study, where a minimum of 7 days wash-out separated the 3 treatment periods. Nitrazepam was found to impair performance in the simulated task after 1 but not after 3 nights of medication. Performance in the triazolam condition was not signicantly different from the other conditions on this task on either day. However, after one night of medication triazolam tended to score worse than placebo but better than nitrazepam. In real car driving a tendency was noted for nitrazepam to score worst, whereas the difference between placebo and triazolam was hardly noticeable.
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Calculating Equivalent Doses of Oral Benzodiazepines
Calculating equivalent doses of oral benzodiazepines Background Benzodiazepines are the most commonly used anxiolytics and hypnotics (1). There are major differences in potency between different benzodiazepines and this difference in potency is important when switching from one benzodiazepine to another (2). Benzodiazepines also differ markedly in the speed in which they are metabolised and eliminated. With repeated daily dosing accumulation occurs and high concentrations can build up in the body (mainly in fatty tissues) (2). The degree of sedation that they induce also varies, making it difficult to determine exact equivalents (3). Answer Advice on benzodiazepine conversion NB: Before using Table 1, read the notes below and the Limitations statement at the end of this document. Switching benzodiazepines may be advantageous for a variety of reasons, e.g. to a drug with a different half-life pre-discontinuation (4) or in the event of non-availability of a specific benzodiazepine. With relatively short-acting benzodiazepines such as alprazolam and lorazepam, it is not possible to achieve a smooth decline in blood and tissue concentrations during benzodiazepine withdrawal. These drugs are eliminated fairly rapidly with the result that concentrations fluctuate with peaks and troughs between each dose. It is necessary to take the tablets several times a day and many people experience a "mini-withdrawal", sometimes a craving, between each dose. For people withdrawing from these potent, short-acting drugs it has been advised that they switch to an equivalent dose of a benzodiazepine with a long half life such as diazepam (5). Diazepam is available as 2mg tablets which can be halved to give 1mg doses.
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Topiramate Is More Effective Than Acetazolamide at Lowering
University of Birmingham Topiramate is more effective than acetazolamide at lowering intracranial pressure Scotton, William J; Botfield, Hannah F; Westgate, Connar Sj; Mitchell, James L; Yiangou, Andreas; Uldall, Maria S; Jensen, Rigmor H; Sinclair, Alex J DOI: 10.1177/0333102418776455 License: Creative Commons: Attribution (CC BY) Document Version Publisher's PDF, also known as Version of record Citation for published version (Harvard): Scotton, WJ, Botfield, HF, Westgate, CS, Mitchell, JL, Yiangou, A, Uldall, MS, Jensen, RH & Sinclair, AJ 2018, 'Topiramate is more effective than acetazolamide at lowering intracranial pressure', Cephalalgia. https://doi.org/10.1177/0333102418776455 Link to publication on Research at Birmingham portal Publisher Rights Statement: William J Scotton, Hannah F Botfield, Connar SJ Westgate, James L Mitchell, Andreas Yiangou, Maria S Uldall, Rigmor H Jensen, and Alex J Sinclair, Topiramate is more effective than acetazolamide at lowering intracranial pressure, Cephalalgia, First Published June 13, 2018; https://doi.org/10.1177/0333102418776455. Checked 02/07/2018. General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. •Users may freely distribute the URL that is used to identify this publication. •Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. •User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?) •Users may not further distribute the material nor use it for the purposes of commercial gain.
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Approach to Managing Patients with Sulfa Allergy Use of Antibiotic and Nonantibiotic Sulfonamides
CME Approach to managing patients with sulfa allergy Use of antibiotic and nonantibiotic sulfonamides David Ponka, MD, CCFP(EM) ABSTRACT OBJECTIVE To present an approach to use of sulfonamide-based (sulfa) medications for patients with sulfa allergy and to explore whether sulfa medications are contraindicated for patients who require them but are allergic to them. SOURCES OF INFORMATION A search of current pharmacology textbooks and of MEDLINE from 1966 to the present using the MeSH key words “sulfonamide” and “drug sensitivity” revealed review articles, case reports, one observational study (level II evidence), and reports of consensus opinion (level III evidence). MAIN MESSAGE Cross-reactivity between sulfa antibiotics and nonantibiotics is rare, but on occasion it can affect the pharmacologic and clinical management of patients with sulfa allergy. CONCLUSION How a physician approaches using sulfa medications for patients with sulfa allergy depends on the certainty and severity of the initial allergy, on whether alternatives are available, and on whether the contemplated agent belongs to the same category of sulfa medications (ie, antibiotic or nonantibiotic) as the initial offending agent. RÉSUMÉ OBJECTIF Proposer une façon d’utiliser les médicaments à base de sulfamides (sulfas) chez les patients allergiques aux sulfas et vérifier si ces médicaments sont contre-indiqués pour ces patients. SOURCES DE L’INFORMATION Une consultation des récents ouvrages de pharmacologie et de MEDLINE entre 1966 et aujourd’hui à l’aide des mots clés MeSH «sulfonamide» et «drug sensitivity» a permis de repérer plusieurs articles de revue et études de cas, une étude d’observation et des rapports d’opinion consensuelles (preuves de niveau III).
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Intermittent Treatment of Febrile Convulsions with Nitrazepam Michel Vanasse, Pierre Masson, Guy Geoffroy, Albert Larbrisseau and Pierre C
LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES Intermittent Treatment of Febrile Convulsions with Nitrazepam Michel Vanasse, Pierre Masson, Guy Geoffroy, Albert Larbrisseau and Pierre C. David ABSTRACT: Intermittent oral or rectal administration of diazepam for the prophylactic treatment of febriie convulsions has given results comparable to the continuous use of phenobarbital while limiting side effects and risks of toxicity. Since we believe that nitrazepam is a better anticonvulsant than diazepam, we performed a study to evaluate the effectiveness of this medication in the prophylactic treatment of febrile convulsions. Nitrazepam was given only when the children had fever and almost exclusively in children with a high risk of recurrence (less than 12 months of age at first convulsion; atypical convulsion; one or several previous convulsions). Thirty one children with a high risk of recurrence received nitrazepam. The rate of recurrence in this group was 19.3% after a follow-up of 16 months, compared to 45.8% in 24 children who also had a high risk of recurrence but in whom the parents refused the medication or gave it inadequately (p<0.05). Fifty one children with a low risk of recurrence also were evaluated and followed for at least 12 months (mean 15.4 months). Six were treated with nitrazepam, mostly because of parental anxiety, and none had a recurrence; of the 45 untreated children in this group, 6 (13.6%) had another convulsion. These results show the efficiency of nitrazepam in the prophylactic treatment of febrile convulsions. RESUME: L'utilisation intermittente du diazepam par voie orale ou rectale pour le traitement prophylactique des convulsions febriles a donne d'aussi bons resultats que l'utilisation continue du phenobarbital.
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Diamox/Aldactone to Increase the Urinary Excretion of Sodium: an Investigational Study in Congestive Heart Failure
Official Title: Diamox/Aldactone to Increase the URinary Excretion of Sodium: an Investigational Study in Congestive Heart Failure NCT01973335 Date: August 27, 2015 DIURESIS-CHF – Study protocol version August 27, 2015 1 1. Background Aging of the population and prolongation of the lives of cardiac patients by modern therapeutic innovations have led to an increased incidence of congestive heart failure (CHF).1 During the last two decades, important progress has been made in the treatment of ambulatory CHF patients with reduced ejection fraction. Renin-angiotensin system blockers, β-blockers, mineralocorticoid receptor antagonists (MRA), ivabradine and cardiac resynchronization therapy have all demonstrated to reduce morbidity and/or mortality in ambulatory CHF patients.2-17 Despite these important advances, many patients are still hospitalized frequently with signs and symptoms of systemic congestion, which is associated with worse outcome.18 Treatment in these cases mainly focuses on symptomatic relief through administration of diuretics, although clear evidence on the optimal agent, dosing schedule, and administration route is lacking. Coexisting renal dysfunction often complicates decongestive treatment and worsening renal function (WRF), often defined as a 0.3 mg/dL rise in serum creatinine (Cr), is a common finding in this context.19 However, the prognostic impact of WRF, defined as Cr change is unsure as it might be associated with worse, neutral or even better outcome.20-22 In contrast, persistent congestion, as a reflection of the inability of the kidneys to preserve sodium homeostasis, has been more consistently associated with higher mortality and more frequent readmissions in CHF.23 This suggests that achieving a negative sodium balance might be an attractive treatment target in heart failure.
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Which Diuretics Are Safe and Effective for Patients with a Sulfa Allergy?
From the CLINIcAL InQUiRiES Family Physicians Inquiries Network Ron Healy, MD University of Washington, Which diuretics are safe Seattle; Alaska Family Medicine Residency, Anchorage and effective for patients Terry Ann Jankowski, MLS University of Washington, Seattle with a sulfa allergy? Evidence-based answer Diuretics that do not contain a sulfonamide subsequent allergic reactions to commonly group (eg, amiloride hydrochloride, used sulfonamide-containing diuretics eplerenone, ethacrynic acid, spironolactone, (eg, carbonic anhydrase inhibitors, loop and triamterene) are safe for patients with an diuretics, and thiazides) (strength of allergy to sulfa. The evidence is contradictory recommendation: C, based on case series ® as to whether a history Dowdenof allergy to Healthand poor Media quality case-control and cohort sulfonamide antibiotics increases the risk of studies). Copyright Clinical commentaryFor personal use only Are all sulfa drugs created equal? agents and off-patent, with no company Historical bromides commonly fall by the to take up their cause, no one has been FAST TRACK wayside as better evidence becomes willing to challenge outdated package Reasonable available. Who would have thought 15 insert warnings. years ago that we would be promoting As clinicians who regularly work evidence supports beta-blockers for patients with congestive without a net, we are accustomed to what many of us heart failure? prescribing medications in less than ideal are doing: Using Likewise, with closer inspection, we circumstances. Thankfully, reasonable cheap thiazides have learned that not all sulfa drugs are evidence is available to support what many created equal. The stereospecificity due of us are already doing—using cheap for patients to the absence of aromatic amines in thiazides for patients despite a history of with a history common diuretics means they are safe sulfa allergy.
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Pharmacology
STATE ESTABLISHMENT «DNIPROPETROVSK MEDICAL ACADEMY OF HEALTH MINISTRY OF UKRAINE» V.I. MAMCHUR, V.I. OPRYSHKO, А.А. NEFEDOV, A.E. LIEVYKH, E.V.KHOMIAK PHARMACOLOGY WORKBOOK FOR PRACTICAL CLASSES FOR FOREIGN STUDENTS STOMATOLOGY DEPARTMENT DNEPROPETROVSK - 2016 2 UDC: 378.180.6:61:615(075.5) Pharmacology. Workbook for practical classes for foreign stomatology students / V.Y. Mamchur, V.I. Opryshko, A.A. Nefedov. - Dnepropetrovsk, 2016. – 186 p. Reviewed by: N.I. Voloshchuk - MD, Professor of Pharmacology "Vinnitsa N.I. Pirogov National Medical University.‖ L.V. Savchenkova – Doctor of Medicine, Professor, Head of the Department of Clinical Pharmacology, State Establishment ―Lugansk state medical university‖ E.A. Podpletnyaya – Doctor of Pharmacy, Professor, Head of the Department of General and Clinical Pharmacy, State Establishment ―Dnipropetrovsk medical academy of Health Ministry of Ukraine‖ Approved and recommended for publication by the CMC of State Establishment ―Dnipropetrovsk medical academy of Health Ministry of Ukraine‖ (protocol №3 from 25.12.2012). The educational tutorial contains materials for practical classes and final module control on Pharmacology. The tutorial was prepared to improve self-learning of Pharmacology and optimization of practical classes. It contains questions for self-study for practical classes and final module control, prescription tasks, pharmacological terms that students must know in a particular topic, medical forms of main drugs, multiple choice questions (tests) for self- control, basic and additional references. This tutorial is also a student workbook that provides the entire scope of student’s work during Pharmacology course according to the credit-modular system. The tutorial was drawn up in accordance with the working program on Pharmacology approved by CMC of SE ―Dnipropetrovsk medical academy of Health Ministry of Ukraine‖ on the basis of the standard program on Pharmacology for stomatology students of III - IV levels of accreditation in the specialties Stomatology – 7.110105, Kiev 2011.
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