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Kytril

By H. Gamal. Bethany Lutheran College.

Genetic profile Enzyme—A protein that catalyzes a biochemical reaction or change without changing its own PKU symptoms are caused by alterations or muta- structure or function cheap kytril 1 mg with mastercard. Mutations in the PAH gene prevent the liver from producing ade- Gene—A building block of inheritance proven kytril 2 mg, which quate levels of the PAH enzyme needed to break down contains the instructions for the production of a phenylalanine purchase kytril 1 mg fast delivery. The PAH gene and its PKU mutations are particular protein proven 2 mg kytril, and is made up of a molecular found on chromosome 12 in the human genome purchase 2mg kytril free shipping. Each gene is detail generic kytril 2mg free shipping, PKU mutations can involve many different types found on a precise location on a chromosome. The term autosomal means that the gene for inheritance and expression of a genetic mutation. A recessive genetic trait, such as PKU, is one true or chronological age and multiplies that ratio that is expressed—or shows up—only when two copies by 100. A person with one normal and one PKU gene is Metabolism—The total combination of all of the called a carrier. A carrier does not display any symptoms chemical processes that occur within cells and tis- of the disease because their liver produces normal quan- sues of a living body. However, PKU carriers can Mutation—A permanent change in the genetic pass the PKU genetic mutation onto their children. Two material that may alter a trait or characteristic of carrier parents have a 25% chance of producing a baby an individual, or manifest as disease, and can be with PKU symptoms, and a 50% chance having a baby transmitted to offspring. Although PKU conforms to these basic genetic patterns of inheritance, the actual Myelin—A fatty sheath surrounding nerves in the expression, or phenotype, of the disease is not strictly an peripheral nervous system, which help them con- “either/or” situation. Although some PKU Nervous system—The complete network of mutations cause rather mild forms of the disease, others nerves, sense organs, and brain in the body. The more severe the PKU mutation, the Phenylalanine—An essential amino acid that must greater the effect on cognitive development and perform- be obtained from food since the human body can- ance (mental ability). Also, it must be remembered that human cells con- Protein—Important building blocks of the body, tain two copies of each type of gene. Different combina- composed of amino acids, involved in the forma- tions of any two PKU mutations tend to produce a wide tion of body structures and controlling the basic spectrum of physiological and psychological symptoms. For example, patients who receive two “severe” PKU Recessive—Genetic trait expressed only when mutations from their parents can potentially develop present on both members of a pair of chromo- more serious symptoms than people who possess a com- somes, one inherited from each parent. To further complicate the genetic picture of PKU, 920 GALE ENCYCLOPEDIA OF GENETIC DISORDERS other types of genes have been identified which seem to be responsible for the abnormal processing of phenylala- nine in brain tissue. These abnormalities add to the sever- ity of PKU symptoms experienced by patients who inherit these genes. In more detail, the association of multiple types of genes with a single condition, such as PKU, is referred to as molecular heterogeneity. Demographics One in 50 individuals in the United States have inherited a gene for PKU. Studies indicate that the incidence of this disease in Caucasian and Native American populations is higher than in African- American, Hispanic, and Asian populations. Signs and symptoms Untreated PKU patients develop a broad range of symptoms related to severely impaired cognitive func- tion, sometimes referred to as mental retardation. Other symptoms can include extreme patterns of behavior, delayed speech development, seizures, a characteristic body odor, and light body pigmentation. The light pig- mentation is due to a lack of melanin, which normally colors the hair, skin, and eyes. Melanin is made from the amino acid tyrosine, which is lacking in untreated cases of PKU.

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Ribo- amino acids are required as the signal for the somes can add approximately 10–20 amino entry of proteins into the nucleus order kytril 1mg line. In the atdifferentsites cheap kytril 2mg amex,aproteinissynthesizedmuch case of the cytoplasmic receptor for glucocor- faster than its mRNA kytril 1mg free shipping. C 2mg kytril with mastercard, F) hormone binds cheap 1mg kytril free shipping, thereby freeing hsp90 from plays a central role in the synthesis of proteins the receptor cheap 2mg kytril with amex. The “activated” receptor then and lipids; it also serves as an intracellular Ca2+ reaches the cell nucleus, where it binds to store (! The ER consists of a net-like specific DNA sequences and controls specific system of interconnected branched channels genes. The The nuclear envelope consists of two mem- enclosedspaces(cisterns)makeuparound10% branes (=two phospholipid bilayers) that of the cell volume, and the membrane com- merge at the nuclear pores. The two mem- prises up to 70% of the membrane mass of a branes consist of different materials. Ribosomes can attach to the cytosolic sur- 10 ternalmembraneiscontinuouswiththemem- face of parts of the ER, forming a rough endo-! Theseribosomessyn- Hence, the Golgi apparatus represents a thesize export proteins as well as transmem- central modification, sorting and distribution brane proteins (! G) for the plasma mem- centerforproteinsandlipidsreceivedfromthe brane, endoplasmic reticulum, Golgi appara- endoplasmic reticulum. Thestartofproteinsynthe- Regulation of gene expression takes place sis (at the amino end) by such ribosomes (still on the level of transcription (! Cells intensely active in meta- proteins is interrupted several times (depend- bolic and transport activities are rich in mito- ing on the number of membrane-spanning chondria—e. Mitochondriaareen- sure, and the corresponding (hydrophobic) closed in a double membrane consisting of a peptide sequence is pushed into the phos- smooth outer membrane and an inner mem- pholipid membrane. The latter is deeply infolded, forming a reticulum (SER) contains no ribosomes and is series of projections (cristae); it also has im- the production site of lipids (e. The mitochondrial vesicles which are transported to the Golgi ap- DNA (mtDNA) of bacterial origin and the paratus. Mitochondria also has sequentially linked functional compart- contain ribosomes which synthesize all pro- ments for further processing of products from teins encoded by mtDNA. F) that arise from Golgi network (entry side facing the ER), the ER (via the Golgi apparatus) and are in- stackedflattenedcisternae(Golgistacks)anda volved in the intracellular digestion of macro- trans-Golginetwork(sortinganddistribution). These are taken up into the cell Functions of the Golgi complex: either by endocytosis (e. Early and late endosomes below); are intermediate stages in this vesicular trans-! Late endosomes and lysosomes contain into secretory vesicles (secretory granules), the acidic hydrolases (proteases, nucleases, li- contents of which are exocytosed into the ex- pases, glycosidases, phosphatases, etc. Protein synthesis, sorting, recycling, and breakdown Nucleus Cytosol Transcription mRNA Free ribosomes Cytosolic ER-bound proteins ribosomes Protein and lipid synthesis Mitochondrion Endoplasmatic reticulum (ER) cis-Golgi network Auto- Protein and lipid modification Golgi stacks phagosome Micro- tubule f g Sorting trans-Golgi Breakdown network of macro- Protein breakdown molecules M6P receptor Recycling Lysosome Secretory Late vesicle endosome Signal Early endosome Cytosol Phagocytosis Protein inclusion in cell membrane Extra- Recycling cellular of receptors space Clathrin Exocytose Endocytosis Controlled Bacterium protein Constitutive secretion secretion 1313 Control Despopoulos, Color Atlas of Physiology © 2003 Thieme All rights reserved. Cholesterol (present in both layers) re- an acidic (pH5) interior environment within duces both the fluidity of the membrane and the lysosomes and assorted transport proteins its permeability to polar substances. These enzymes and transport pro- membrane) of the membrane mass, depend- teins are delivered in primary lysosomes from ing onthe membrane type. G2) (transmembrane proteins), bindstoM6PreceptorsintheGolgimembrane thereby serving as ion channels, carrier pro- which, as in the case of receptor-mediated en- teins, hormone receptors, etc. The M6P receptor by the glycocalyx, which consists of sugar no longer recognizes the dephosphorylated moieties of glycoproteins and glycolipids in proteins, which prevents them from returning the cell membrane (! The glycocalyx mediates cell– Peroxisomes are microbodies containing cell interactions (surface recognition, cell enzymes (imported via a signal sequence) that docking, etc. For example, components of the permit the oxidation of certain organic glycocalyx of neutrophils dock onto en- molecules (R-H ),2 such as amino acids and dothelial membrane proteins, called selectins fatty acids: R-H2 + O2! G) well as microtubules and intermediate fila- is to separate the cell interior from the extra- ments (e.

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Hep B = hepatitis B vaccine; DtaP = diphtheria and tetanus toxoids and acellular pertussis vaccine order 2 mg kytril otc. Usually determined 1 min after birth and again at 5 min buy kytril 2 mg visa, the score is the sum of points gained on assessment of color buy kytril 1 mg with visa, heart rate trusted 1 mg kytril, reflex irritability discount 2mg kytril fast delivery, muscle tone trusted kytril 2mg, and respirations. BODY SURFACE AREA Adult Figure A–1 is a nomogram for determining the body surface area of an adult. Children Figure A–2 is a nomogram for determining the body surface area of children. CANCER SCREENING RECOMMENDATIONS Table A–3 lists the recommendations from the American Cancer Society for cancer screen- ing programs in average risk, asymptomatic people. These are the recommendations of the ACS and may not be supported by other organizations. EPIDEMIOLOGY BASICS Number of persons who have a disease at one point in time Prevalence = Number of persons at risk at that point (continued on page 645) 639 Copyright 2002 The McGraw-Hill Companies, Inc. Source: United States Department of Agriculture and United States Department of Health and Human Resources, 1990. The point of intersection on the body surface line gives the body surface area (in m2). The point of intersection on the body surface line gives the body surface area (in m2). Appendix 645 (continued from page 639) Number of new cases of a disease over a period of time Incidence = Number of persons at risk during that period Sensitivity = Proportion of subjects with the disease who have a positive test = (a/a + c) Specificity = Proportion of subjects without the disease who have a negative test = (d/b + d) Predictive value = Positive: likelihood of a positive test indicates disease = (a/a + b) = Negative: likelihood of a negative test indicates lack of disease = (d/c + d) Disease + (Present) (Absent) (+) a b Test ( ) GLASCOW COMA SCALE The Glasgow Coma Scale (EMV Scale) gives a fairly reliable, objective way to monitor changes in levels of consciousness. Household 1 teaspoon (tsp) = 5 mL 1 tablespoon (tbsp) = 15 mL 1 ounce (oz) = 30 mL 8 ounces (oz) = 1 cup = 240 mL 1 quart (qt) = 946 mL Apothecary 1 grain (gr) = 60 mg 30 gram (g) = 1 oz 1 g = 15 gr SI PREFIXES AND SYMBOLS Factor Prefix Symbol 109 giga G 106 mega M 103 kilo k 102 hecto h 101 deka da 10–1 deci d 10–2 centi c 10–3 milli m 10–6 micro µ 10–9 nano n 10–12 pico p 10–15 femto f PERFORMANCE STATUS SCALES Table A–5 lists the most common performance scales used clinically. RADIATION TERMINOLOGY Measure Old Term SI Unit Activity curie becquerel (Bq) Absorbed dose rad gray (Gy) TEMPERATURE CONVERSION Table A–6 gives information for converting temperature from the Fahrenheit (F) scale to the centigrade, or Celsius (C), scale and vice versa. Professor Emeritus Professor Department of Pharmacology Department of Pharmacology University of Kiel University of Kiel Germany Germany Klaus Mohr, M. Professor Professor Department of Pharmacology Division of Basic Medical Sciences and Toxicology Faculty of Medicine Institute of Pharmacy Memorial University of University of Bonn Newfoundland Germany St. IV Library of Congress Cataloging-in-Publication Data Taschenatlas der Pharmakologie. Research and clinical experience are This book is an authorized revised and ex- continually expanding our knowledge, in par- panded translation of the 3rd German edition ticular our knowledge of proper treatment and published and copyrighted 1996 by Georg drug therapy. Title of the any dosage or application, readers may rest as- German edition: sured that the authors, editors and publishers Taschenatlas der Pharmakologie have made every effort to ensure that such ref- Some of the product names, patents and regis- erences are in accordance with the state of tered designs referred to in this book are in knowledge at the time of production of the fact registered trademarks or proprietary book. Therefore, express any guarantee or responsibility on the the appearance of a name without designation part of the publishers in respect of any dosage as proprietary is not to be construed as a instructions and forms of application stated in representation by the publisher that it is in the the book. Such examination is tostat reproduction, copying, mimeographing particularly important with drugs that are or duplication of any kind, translating, prepa- either rarely used or have been newly released ration of microfilms, and electronic data pro- on the market. The au- ©2000 Georg Thieme Verlag, Rüdigerstrasse14, thors and publishers request every user to re- D-70469 Stuttgart, Germany port to the publishers any discrepancies or in- Thieme New York, 333 Seventh Avenue, New accuracies noticed. York, NY 10001, USA Typesetting by Gulde Druck, Tübingen Printed in Germany by Staudigl, Donauwörth ISBN 3-13-781702-1 (GTV) ISBN 0-86577-843-4 (TNY) 1 2 3 4 5 6 Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. V Preface The present second edition of the Color Atlas of Pharmacology goes to print six years after the first edition. Numerous revisions were needed, highlighting the dramatic continuing progress in the drug sciences. In particular, it appeared necessary to in- clude novel therapeutic principles, such as the inhibitors of platelet aggregation from the group of integrin GPIIB/IIIA antagonists, the inhibitors of viral protease, or the non-nucleoside inhibitors of reverse transcriptase. In each instance, the primary emphasis was placed on essential sites of action and basic pharmacological princi- ples. Details and individual drug properties were deliberately omitted in the interest of making drug action more transparent and affording an overview of the pharmaco- logical basis of drug therapy. The authors wish to reiterate that the Color Atlas of Pharmacology cannot replace a textbook of pharmacology, nor does it aim to do so.

Because of its significant host cytotoxicity generic kytril 2 mg amex, idoxuri- Adverse Effects discount 1mg kytril otc, Contraindications proven 1 mg kytril, dine cannot be used to treat systemic viral infections purchase kytril 2 mg. The most frequent adverse reactions to trifluridine ad- Absorption order 1mg kytril, Metabolism kytril 2mg with mastercard, and Excretion ministration are transient burning or stinging and palpebral edema. Other adverse reactions include su- Idoxuridine is marketed strictly for topical ophthalmic perficial punctate keratopathy, epithelial keratopathy, use, and systemic exposure is insignificant. However, af- hypersensitivity, stromal edema, irritation, keratitis ter oral dosing, the drug is rapidly metabolized and ex- sicca, hyperemia, and increased intraocular pressure. Trifluridine is mutagenic in vitro and carcinogenic and teratogenic when administered subcutaneously to Clinical Uses animals. Topical trifluridine was not teratogenic in ani- The only FDA-approved use of idoxuridine is in the mal studies. Because it is applied topically in humans, treatment of herpes simplex infections of the eyelid, con- the likelihood of systemic effects is low. However, infection can occur in immunized nucleoside analogue containing arabinose in place of ri- persons, because influenza viruses mutate rapidly and bose. The tibioticus and has activity against HSV-1, HSV-2, VZV, following drugs are used in the treatment of influenza CMV, HBV, poxviruses, hepadnaviruses, rhabdoviruses, strains A and B and in some cases other viral infections. Cellular enzymes convert this drug to Amantadine and Rimantadine a triphosphate that inhibits DNA polymerase activity. Amantadine (Symmetrel) is a synthetic tricyclic amine, Vidarabine triphosphate competes with deoxyadeno- and rimantadine (Flumadine) is its -methyl derivative. Although subtypes of influenza A (H1N1, H2N2 and H3N2) and vidarabine is incorporated into host DNA to some ex- have negligible activity against influenza B. Vidarabine also inhibits ri- viral M2 protein, an integral membrane protein that acts bonucleoside reductase and other enzymes. In certain Absorption, Metabolism, and Excretion strains, the pH changes that result from M2 inhibition alter the conformation of hemagglutinin, hence inhibit Vidarabine is administered only as a topical ophthalmic viral assembly. It has relatively limited solubility and is not Viral resistance develops rapidly in approximately significantly absorbed after application to the eye. Resistant viruses are associated with the failure of pal metabolite, arabinosyl hypoxanthine, which retains drug prophylaxis in close contacts of infected individu- some degree of antiviral activity. Mutation in the transmembrane domain of the M2 pro- Clinical Uses tein is the most frequent cause of resistance to amanta- The principal use of vidarabine is in the treatment of dine and rimantadine. It is also used to treat super- ficial keratitis in patients unresponsive or hypersensi- Absorption, Metabolism, and Excretion tive to topical idoxuridine. Amantadine is rapidly and completely absorbed from the gastrointestinal tract, and peak blood levels are Adverse Effects, Contraindications, achieved in 2 to 5 hours. The serum half-life of amanta- and Drug Interactions dine averages 17 hours in young adults and 29 hours in The most commonly observed side effects associated the elderly. Most of the drug (90%) is eliminated un- with vidarabine are lacrimation, burning, irritation, changed by glomerular filtration and tubular secretion. Vidarabine has oncogenic and Rimantadine is well absorbed following oral admin- mutagenic potential; however, the risk of systemic ef- istration, with peak blood levels achieved in 5 to 7 fects is low because of its limited absorption. Its elimination half-life averages 25 hours in not be used in conjunction with ophthalmic cortico- young adults and 32 hours in the elderly. Less than 25% steroids, since these drugs increase the spread of HSV of the dose is excreted in the urine as unchanged drug; infection and may produce side effects such as in- the remainder is eliminated as hydroxylated or conju- creased intraocular pressure, glaucoma, and cataracts. Clinical Uses ANTIINFLUENZA AGENTS Amantadine and rimantadine are used for the treat- Influenza is responsible for several thousand deaths ment of diseases caused by influenza A strains.

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