Michał Karbownik Department of Pharmacology Medical University of Łódź
|
|
- Denis Randall
- 6 years ago
- Views:
Transcription
1 Antiviral drugs Michał Karbownik Department of Pharmacology Medical University of Łódź Virus structure Virus life cycle 1. Attachment and penetration 2. Uncoating (amantadine) 3. Replication (nucleoside analogues) 4. Translation (interferon) 5. Post-translational modification 6. Assembly (protease inhibitors) 7. Releasing (neuraminidase inhibitors) 1
2 Bacteria vs viruses Bacteria Viruses Size: Larger (1000nm) Smaller (20-400nm) Beneficial?: Some beneficial bacteria (e.g. certain bacteria required in the gut) Viruses are not beneficial. However, a particular virus may be able to destroy brain tumors. Viruses can be useful in genetic engineering. Can cause disease?: Yes Yes Ribosomes: Present Absent Outermost structure: Nucleic acid: Living attributes: Peptidoglycan cell wall or capsule/slime layer in some. Protein coat or viral envelope DNA and RNA. Exists as DNA or RNA. can be doublestranded or single-stranded, double-stranded and circular in shape. circular or linear. Living organism Enzymes: Yes Yes, in some Considered living and nonliving Bacterium Drugs affect typical bacteria cell targets Virus Drugs affect viral replication processes in host cell: Inhibit penetration Inhibit replication Inhibit releasing Why is the antiviral therapy difficult? 1. Difficult to find speciffic targets for antiviral drugs 2. Viruses easily develop resistance: In 2009 H1N1 influenza swine flu neuraminidase (N) were to acquire the tamiflu-resistance (His274Tyr) mutation which is currently widespread in seasonal H1N1 strains Altered or defficient thymidine kinase and DNA polimerases have been found in some viral strains of Herpesviridae 3. Clinical symptoms appear late in the course of the disease, at the time when most of the virus particles have replicated 2
3 Influenza Influenza Influenza Common cold Influenza virus Type A, B, C Rhinovirus Parainfluenzaviruses The most virulent Less common and less genetically diverse Less common, usually causes mild infections in children Influenza A virus 3
4 Influenza Prophylaxis preferred approach active immunization Treatment antiviral agents M2 protein membrane matrix Influenza virus protein (ion channel) important role in uncoating of the virus Hemagglutinin glycoprotein responsible for binding the virus to the cell Neuraminidase (sialidase) enzyme that cleave the sialic acid groups from host glycoproteins and enables the virus to be released Helical RNA Influenzavirus A subtypes H1N1, which caused Spanish flu in 1918, and the 2009 flu pandemic (swine flu) H2N2, which caused Asian Flu in 1957 H3N2, which caused Hong Kong Flu in 1968 H5N1, a current pandemic threat H7N7, which has unusual zoonotic potential H1N2, endemic in humans and pigs H9N2 H7N2 H7N3 H10N7 H1N1 4
5 Drugs classes 1. Neuraminidase inhibitors 2. Inhibitors of viral uncoating 3. Ribavirin 1. Neuraminidase inhibitors Prevent the release of new virons and their spread from the cell to cell. Active against influenza A and B. Should be administered prior to exposure or within the first houres Oseltamivir (Tamiflu) Zanamivir (Relenza) Neuraminidase inhibitors Oseltamivir Zanamivir Route of administration P.O. Inhaled intranasally Active substance Prodrug Active substance Biotransformation No No Excretion Adverse effects Gastrointestinal Psychiatric halucynations, mood changes Irritation of the respiratory tract Drug resistance: mutation in neuraminidase. These mutants are fortunatelly less infective and virulent. 5
6 Peramivir Experimental antiviral drug Authorised for critically ill 2009 A(H1N1) subtype patients: Tamiflu-resistant patients unable to take Relenza inhalations peramivir I.V. administration 2. Inhibitors of viral uncoating Block the viral membrane matrix proteine M2, and inhibit internalization of the virus. Active against influenza A (prvention: effective in 70-90% and treatment) Should be administered within first 48 houres of infection amantadine rimantadine Inhibitors of viral uncoating Amantadine Route of administration P.O. P.O. Rimantadine Distribution Crosses BBB Does not cross BBB Biotransformation No Yes Excretion Adverse effects CNS problems: insomnia, dizziness, ataxia, seizures Gastrointestinal Embriotoxic, teratogenic Gastrointestinal Embriotoxic, teratogenic Resistance can be developed among 50% of treated individuals, and resistant strains can be transmitted to close contacts! 6
7 3. Ribavirin Active against broad spectrum of RNA and DNA viruses: 1. Infants and young children infected with Respiratory Syncytial Virus (RSV) 2. Chronic hepatitis C infections (in combination with interferon-α-2b) 3. Reduces the mortality and viremia of Lassa fever Ribavirin nucleozide analog Mode of action: blocks RNA-dependent RNA polimerase preventing replication Administration: P.O., I.V., aerosol anemia, elevated bilirubin (aerosol can be a bit safer) Contraindicated in pregnancy Hepatic viral infections HAV HEV HBV HCV HDV Transmission Enteric Enteric Parenteral Parenteral Parenteral Classification Picornavirus Hepevirus Hepadnavirus Hepacivirus Deltavirus Genome +ssrna +ssrna +dsdna +ssrna -ssrna Antigens HBsAg,HBeAg Core antigen Delta antigen Incubation period days days days days days Chronicity No No Yes (uncommon) Yes (common) Yes - with hepatitis B Acute viral hepatitis require symptomatic treatment Hepatitis B Remission (anti-hbe) Infection 1-6 months Acute hepatitis (HBsAg HBeAg anti-hbc) 5-10% Chronic hepatitis (HBsAg HBeAg) Cirrhosis Hepatocelular carcinoma A simplified drawing of the HBV particle and surface antigen 7
8 Drugs classes 1. Interferon 2. Nucleotide and nucleoside analoges Hepatic viral infections Treatment: Chronic hepatitis B: Interferon-α + lamivudine Chronic hepatitis C: Interferon-α + ribavirin Avoid drinking alcohol!!! 1. Interferon Family of naturally occuring glicoproteins cytokines: Interfere with viral replication (in vivo active only against hepatitis viruses and Papillomaviruses) Activate immune cells (NK, macrophages) Up-regulate antigen presentation to Human interferon-α structure T-lymphocytes (increase recognition of infection or tumor cells) During the infection: Certain host symptoms, such as aching muscles and fever, are related to the production of IFNs 8
9 Indications: 1. Hepatitis B and C Interferon 2. Condylomata acuminata (Papillomavirus HPV) 3. Cancers Hairy-cell leukemia Kaposi sarcoma Administration: Intralesionally I.V. S.C. Biochemical modification: PEG-chain attached: prolonged action (once-a-week dosing) Interferon Flu-like symptoms (fever, chills, myalgias, arthralgias, GI disturbances) Bone marrow suppresions (can potentiate the myelosuppresion caused by other bonemarrowdepressing agents zidovudine) Autoimmune disorders 2. Nucleotide and nucleoside analoges 9
10 5 3 replication 3 5 -OH HO- Must be phosphorylated to triphosphate 3 nucleoside nucleotide 10
11 Lamivudine Nucleoside analog (must be phosphorylated by host cellular enzymes) Stops HBV DNA-polymerase HIV reverse transcriptase P-lamivudine Administration: P.O. Well tolerated (headache, dizziness) Lamivudine alternatives 1. Adefovir nucleotide analog Well tolerated 2. Entecavir nucleoside analog (against lamivudine-resistant strains of HBV) Adverse effect: Renal, liver toxicity (even several months after discontinuation of therapy) Human Herpes Viruses Herpes Simplex Viruses (HSV-1, HSV-2) Varicellovirus (varicella-zoster virus VZV) Epstein-Barr Virus (EPV) Cytomegalovirus (CMV) HHV-1, HHV-2 HHV-3 HHV-4 HHV-5 dsdna 11
12 Overview of herpesvirus infections 1. Gingivostomatitis (HSV-1) oral herpes, cold sores 2. Sexually transmitted diseases (HSV-2) genital herpes Overview of herpesvirus infections 3. Skin infections (VZV) Varicella (chicken-pox) Zoster (shingles) Overview of herpesvirus infections 4. Pharyngitis (EBV) Mononucleosis ANTIVIRAL TREATMENT IS INEFFECTIVE 5. Eye infections (CMV) CMV retinitis Immunocompromised patients 12
13 Treatment of herpesvirus infections Acute phase Latent phase antiviral medications can only reduce the frequency, duration, and severity of outbreaks Treatment of herpesvirus infections 1. Nucleotides and nucleosides analoges 2. Antisense oligonucleotide 3. Foscarnet 4. Hyperimmune globulins Treatment of herpesvirus infections 1. Acyclovir Penciclovir Famciclovir Vidarabine Ganciclovir Cidofovir 2. Fomivirsen HSV, VZV CMV 3. Foscarnet 13
14 1. Nucleotides and nucleosides analoges Acyclovir guanosine analog Active against: HSV-1 HSV-2 VZV, some EBVs CMV resistant lack of specific thymidine kinase Acyclovir Thymidine kinase herpesvirus-encoded enzyme triphosphate (nucleotide) Host cell enzymes monophosphate Clinical application: Acyclovir 1. HSV encephalitis (drug of choice) 2. Genital herpes infections 3. Prophylaxis among immunocompromised patients after organ transplantation before bone marrow transplant during anticancer chemotherapy Pharmacokinetics: Acyclovir Administration: PO, IV, topical Valacyclovir valyl ester greater oral bioavailability doubtful efficiacy Distribution: well, including CSF 14
15 Adverse efects: PO IV Acyclovir Well tolerated headache, GI disturbances transient renal dysfunction Topical local skin irritation Resistance: due to altered thymidine kinase DNA polimerase Guanosine analog Active against: HSV, VZV Administered topically Well tolerated Penciclovir Famciclovir Guanosine analog Active against: VZV (acute herpes zoster infections) Administered orally headaches, GI problems Prodrug metabolised to penciclovir Natural adenosine analog Vidarabine Antiviral activity described in 1964 Active against: HSV, VZV Clinical application limited to: herpetic keratitis and keratoconjunctivitis However, inhibits DNA synthesis Available as an ophtalmic ointment 15
16 Ganciclovir Aciclovir derivative Lack of thymidine kinase OTHER VIRAL ENZYMES Triphosphate active form DNA polymerisation Clinical application: CMV retinistis in immunocompromised patients CMV prophylaxis in transplant patients Pharmacokinetics: Administration: IV Ganciclovir Valgancyclovir valyl ester PO administrated Distribution: well, including CSF 1. Severe dose-dependent neutropenia (zidovudine, immunosupresives can increase the risk of neutropenia) 2. Carcinogenic, teratogenic, embryotoxic Cytosine analog (nucleotide) Clinical application: Cidofovir CMV-induced retinitis in AIDS patients Do not need enzymatic activation Administration: IV, intravitreal injection Nefrotoxicity contarindicated in renallycompromised patients or taking nephrotoxic drugs Neutropenia, metabolic acidosis, ocular hipotony 16
17 2. Antisense oligonucleotide Fomivirsen against CMV mrna Clinical application: CMV retinitis in patients Fomivirsen who cannot tolerate or have failed other therapies Administration: Intravitreally Iritis, vitritis, changes in vision Clinical application: 3. Foscarnet CMV retinitis in immunocompromised patients Acyclovir-resistant HSV infections Herpes zoster infections No cross-resistance with acyclovir and gancyclovir phosphonophormate Inhibits viral DNApolimaerase 17
18 3. Foscarnet Administration: IV Asverse effects: Nephrotoxicity Anemia, GI problems Hipokaliemia, hipomagnesemia, hipocalcemia (seizures, arrhythmias) K +, Mg 2+, Ca Hyperimmune globulines Passive immunization VZV Administered for: immunocompromised patients random exposure to VZV in the last week of pregnancy One single dose Hyperimmune globulines available: anti-vzv (Varitect) anti-hbv anti-hcv AIDS Acquired Immune Deficiency Syndrome HIV Human Immunodeficiency Virus AIDS HIV-1 More virulent, infective Globally occuring HIV-2 Less virulent, infective West Africa 18
19 HIV - retrovirus Viral RNA Reverse transcriptase (RT) Viral DNA 2-4 weeks of asymptomatic incubation period Infection of HIV Acute infection (fever, swollen lymph nodes,pharyngitis, rash) 1. Blood, tissue fluids 2. Intensive sexual contact 3. Perinatal infection Without treatment 10 years With treatment > 30 years 2 weeks 20 years Latency stage CD4+ cells 350/ul AIDS (opportunistic infections) 19
20 CD4+ cells/ul AIDS A Asymptomatic B Neither A nor C C AIDS symptoms >500 A1 B1 C A2 B2 C2 <200 A3 B3 C3 According to Center for Disease Control, Atlanta, Georgia, USA, 1993 AIDS: USA: C1, C2, C3 Europe: C1, C2, C3, A3, B3 20
21 AIDS treatment NRTIs NNRTIs PIs 3 AIDS treatment AIDS treatment 1987 years Decreasing the occurence of opportunistic infections Highly HAART Active AntiRetroviral Therapy 21
22 Diagnostic methods assesing the efficiency of therapy: CD4+ cells/ul Virus load HAART 1. NRTI NRTI NNRTI 2. NRTI NRTI PI 3. NRTI NRTI NNRTI or PI EI and/or II I. NRTIs inhibit RT host cell mitochondrial DNA-polimerase DNA-polimerase Bone marrow supression Peripheral neutropathy Potentially fatal liver toxicity: Except for: Lamivudine Abacavir 22
23 1. Zidovudine (AZT) The first drug active against HIV (1987) Clinical application: Children Adults Prevention: prenatal infection individuals exposed to HIV Contraindication: co-administration of drugs being glucuronylated: Pharmacokinetics: acetaminophen Administration: PO (paracetamol), Distribution: into CSF lorazepam, cimetidine Bone marrow suppression, anemia, leukopenia seizures 2. Didanosine (ddi) The second approved drug Clinical application: Children Adults Pharmacokinetics: Administration: PO (buffered tablets or solutions), without food Distribution: into CSF Pancreatitis Peripheral neutropathy Contain sodium, phenylalanine Contraindication: Phenylketonuria Sodium-restricted diet 23
24 Pharmacokinetics: Administration: PO, without food and Al, Mg-containing antacids Distribution: not into CSF 3. Zalcitabine (ddc) As those of didanosine Pharmacokinetics: Administration: PO, not affected by food Distribution: into CSF 4. Stavudine (d4t) Peripheral neuropathy Clinical application: HIV 5. Lamivudine (3TC) often used with HBV zidovudine (Combiwir ) Pharmacokinetics: Administration: PO Does not affect mitochondrial DNA-polimerase Well-tolerated 24
25 Clinical application: 6. Abacavir For patients who cannot tolerate or have failed current regimens Only some cross-resistance with other NRTIs Pharmacokinetics: Administration: PO Quite well tolerated GI problems, headache, rash 7.Tenofovir Nucleotide analog but needs to be converted to active form Clinical application: For patients who cannot tolerate or have failed current regimens Only some cross-resistance with other NRTIs (as abacavir) Pharmacokinetics: Administration: PO, should be taken with a meal to increase its bioavailability GI problems 8. Emtricitabine Clinical application: HIV Pharmacokinetics: Administration: PO lamivudine fluoro-derivative active against HBV, but not used Hyperpigmentation of soles and palms 25
26 II. NNRTIs Non-Nucleoside Reverse Transcriptase Inhibitors Nevirapine Delavirdine Efavirenz NNRTIs Non-nucleoside reverse transcriptase inhibitors 1. Inhibit RT inducing conformational change of the enzyme (not competiting with nucleosides and terminating DNA synthesis) 2. Do not require activation by cellular enzymes 3. Do not inhibit mitochondrial DNA-polimerase lack of bone marrow suppression 4. No cross-resistance with NRTIs 1. Nevirapine Clinical application: Children Adults Prevention prenatal infection (zidovudine alternative) Pharmacokinetics: Administration: PO well absorbed Distribution: into CSF Severe dermatologic effects (Stevens-Johnson syndrome, toxic epidermal necrolysis) hepatotoxicity CYP450 inducer Increases metabolism of PIs Should not be administrated with saquinavir (PI) 26
27 Pharmacokinetics: 2. Delavirdine Administration: PO well absorbed Distribution: into CSF extensively bound to plasma proteins Rash GI problems CYP450 inhibitor Decreased metabolism of PIs 3. Efavirenz Pharmacokinetics: Administration: PO well absorbed with a high fat meal once-a-day dosing Distribution: into CSF extensively bound to plasma proteins Transient CNS problems in 50% of patients: headache, dizziness, vivid dreams, loss of concentration Rash Modest inducer of CYP450 Increases metabolism of Pis III. PIs Protease Inhibitors Introduced in 1995 active in 60-95% of HAART taking patients decreased number of active deaths due to AIDS 27
28 RNA Reverse transcription DNA Transcription PIs PIs Selective affinity to viral protease mrna Translation Enzymatic claveage HIV aspartyl protease Viral essential proteins: enzymes, structural, etc. Pharmacokinetics: Administration: PIs Specially formulated capsules of saquinavir PO poor (high fat meals increase bioavailability) Distribution: Substrates of gp-p bound to plasma proteins (α 1 -acid glicoprotein) Biotransformation: CYP3A4 potent inhibitors of CYP450 sedation from midazolam bleeding from warfarin respiratory depression from fentanyl the concentration of α 1 -acid glicoprotein increases in response to trauma and surgery PIs GI problems paresthesias disturbances in glucose and lipid metabolism: hypertriglyceridemia hypercholesterolemia hyperglycemia fat redistribution: buffalo hump 28
29 Saquinavir Oral absorption: 12% Should be given with other antiretroviral drugs that inhibits CYP450: saquinavir + delavirdine (NNRTI) ritonavir (PI - the most potent CYP inhibitor) drugs inducing CYP450 should be avoided: rifampin nevirapine efavirenz Ritonavir Oral absorption: ~60% (unaffected by food) Ritonavir pharmacokinetic enhancer (concominant administration): increases other PIs bioavailability diminishes the impact of the meal Other PIs Indinavir quite well tolerated, SE: nephrolithiasis Nelfinavir - SE: diarrhea (can be controlled by loperamide) Amprenavir Lopinavir for patients who are not responding to others Pis Atazanavir composed with ritonavir (Kaletra ) 29
30 IV. Other novel agents salvage therapy can be combined with HAART extremally expensive (>25,000 USD/year) Entry Inhibitors (EIs) Enfuvirtide (2003) Maraviroc (2007) Integrase Inhibitors (EIs) Raltegravir (2007) 30
Antiviral Agents DEPARTEMEN FARMAKOLOGI & TERAPEUTIK FK USU. 06 August
Antiviral Agents Dr. Yunita Sari Pane, MS DEPARTEMEN FARMAKOLOGI & TERAPEUTIK FK USU 06 August 2009 1 VIRUSES Obligate intracellular parasites Consist of a core genome in a protein shell and some are surrounded
More informationAnti-viral drugs. Certain viruses multiply in the cytoplasm but others do in the nucleus Most multiplication take place before diagnosis is made
Anti-viral Drugs Viruses have no cell wall and made up of nucleic acid components Viruses containing envelope antigenic in nature Viruses are obligate intracellular parasite They do not have a metabolic
More informationTreatment of respiratory virus infection Influenza A & B Respiratory Syncytial Virus (RSV)
Treatment of respiratory virus infection Influenza A & B Respiratory Syncytial Virus (RSV) Amantadine and Rimantadine Use is limited to Influenza A infection. Very effective in preventing infection if
More informationAntiviral Chemotherapy
Viruses are intimate intracellular parasites and their destruction may cause destruction of infected cells. Many virus infections were considered to be self-limited. Most of the damage to cells in virus
More informationAnti-viral drugs. Certain viruses multiply in the cytoplasm but others do in the nucleus Most multiplication take place before diagnosis is made
Anti-viral Drugs Viruses have no cell wall and made up of nucleic acid components Viruses containing envelope antigenic in nature Viruses are obligate intracellular parasite They do not have a metabolic
More information- They come in all sizes. -- General Structure is similar.
- They come in all sizes. -- General Structure is similar. Centers for Disease Control (CDC) and Prevention. Influenza Prevention and Control. Influenza. Available at: http://www.cdc.gov/ncidod/diseases/flu/fluinfo.htm.
More informationSteps in viral replication (I)
Antiviral agents Steps in viral replication (I) Recognition of the target cell Attachment Penetration Uncoating Macromolecular synthesis Assembly of virus Buddding of enveloped viruses Release of virus
More informationAntiviral Drugs Lecture 5
Antiviral Drugs Lecture 5 Antimicrobial Chemotherapy (MLAB 366) 1 Dr. Mohamed A. El-Sakhawy 2 Introduction Viruses are microscopic organisms that can infect all living cells. They are parasitic and multiply
More informationStructure of viruses
Antiviral Drugs o Viruses are obligate intracellular parasites. o lack both a cell wall and a cell membrane. o They do not carry out metabolic processes. o Viruses use much of the host s metabolic machinery.
More informationUnderstanding Viruses CHAPTER 38. Antiviral Agents. Understanding Viruses (cont'd) Viral Infections (cont'd) Viral Infections.
Understanding Viruses CHAPTER 38 Antiviral Agents Viral replication A virus cannot replicate on its own It must attach to and enter a host cell It then uses the host cell s energy to synthesize protein,
More informationHSV DNA replication. Herpesvirus Latency. Latency and Chemotherapy. Human Herpesviruses - subtypes. Acyclovir (acycloguanosine) {Zovirax}
Human Herpesviruses - subtypes Herpes Simplex I (HSVI) - herpes labialis (cold sores) herpes keratitis (eye infections) HSVII - herpes genitalis (genital herpes) Varicella Zoster virus (VZV) Chicken pox
More informationViral genetics VIRAL GENETICS
Viral genetics Lecturer Dr Ashraf Khasawneh Department of Biomedical Sciences VIRAL GENETICS VIRUSES GROW RAPIDLY A SINGLE PARTICLE PRODUCES A LOT OF PROGENY DNA VIRUSES SEEM TO HAVE ACCESS TO PROOF READING,
More informationChapter 49. Antiviral Agents
Chapter 49 Antiviral Agents Antiviral Drugs 1. Characters of Virus Viruses are obligate intracellular parasites their replication depends primarily on synthetic processes of the host cell. 2.Classification
More informationAntiviral Chemotherapy
12 Antiviral Chemotherapy Why antiviral drugs? Vaccines have provided considerable success in preventing viral diseases; However, they have modest or often no therapeutic effect for individuals who are
More information*viruses have no cell wall and made up of nucleic acid components.
Anti-viral drugs {Please read these notes together with the slides since I only wrote what the doctor added} Apologies in advance for any mistakes In this sheet we are going to talk about anti-viral drugs,
More informationnumber Done by Corrected by Doctor Ashraf
number 6 Done by حسام أبو عوض Corrected by Doctor Ashraf 1 Antiviral Drugs When dealing with drugs, it is always important to keep an eye on what you want to target (viruses here), so here is a reminder
More informationThe head of a pin can hold five hundred million rhinoviruses (cause of the
The head of a pin can hold five hundred million rhinoviruses (cause of the common cold). One sneeze can generate an aerosol of enough cold viruses to infect thousands of people! DNA-containing Viruses:
More informationAntiviral Agents I. Tutorial 6
Antiviral Agents I Tutorial 6 Viruses, the smallest of pathogens, are unable to conduct metabolic processes on their own, they use the metabolic system of the infected cell to replicate ( intracellular
More informationMID 40. Diagnosis of Viral Infections. Antiviral Therapy. Herpes Zoster. Challenges to the Development of Effective Antiviral Agents
Diagnosis of Viral Infections Antiviral Therapy Scott M. Hammer, M.D. Clinical suspicion Is syndrome diagnostic of a specific entity? Is viral disease in the differential diagnosis of a presenting syndrome?
More informationTreatment of respiratory virus infection Influenza A & B Respiratory Syncytial Virus (RSV) modified by Diala Abul Haija
Treatment of respiratory virus infection Influenza A & B Respiratory Syncytial Virus (RSV) modified by Diala Abul Haija Amantadine and Rimantadine very limited capabilities reduces symptoms Use is limited
More informationAntiviral Agents. Scott M. Hammer, M.D. Challenges to the Development of Effective Antiviral Agents
Antiviral Agents Scott M. Hammer, M.D. Challenges to the Development of Effective Antiviral Agents Myriad number of agents Need knowledge of replication at molecular level to define targets Viruses as
More informationDiagnosis of Viral Infections. Antiviral Agents. Herpes Zoster. Challenges to the Development of Effective Antiviral Agents
Diagnosis of Viral Infections Antiviral Agents Scott M. Hammer, M.D. Clinical suspicion Is syndrome diagnostic of a specific entity? Is viral disease in the differential diagnosis of a presenting syndrome?
More informationAntiviral Drugs. Munir Gharaibeh MD, PhD, MHPE School of Medicine, The University of Jordan November 2018
Antiviral Drugs Munir Gharaibeh MD, PhD, MHPE School of Medicine, The University of Jordan November 2018 Viruses Viruses are the smallest infective agents, consisting of nucleic acid (DNA or RNA) enclosed
More informationAntiviral Drugs. Munir Gharaibeh MD, PhD, MHPE School of Medicine, The University of Jordan November 2018
Antiviral Drugs Munir Gharaibeh MD, PhD, MHPE School of Medicine, The University of Jordan November 2018 Viruses Viruses are the smallest infective agents, consisting of nucleic acid (DNA or RNA) enclosed
More informationNon HIV Anti Virals Prof. Mary Klotman
Mary Klotman, M.D. Professor of Medicine and Microbiology Mount Sinai School of Medicine New York, NY 1 Nucleoside analogues: first line herpes antivirals Parent Oral prodrug Valganciclovir 2 Phosphorylation
More informationHIV - Life cycle. HIV Life Cyle
Human Immunodeficiency Virus Retrovirus - integrated into host genome ne single-strand RA 7,000 bases HIV1 > HIV2 > HIV0 Pathology Destruction of CD4+ T lymphocytes Loss of immune function pportunistic
More informationChapters 21-26: Selected Viral Pathogens
Chapters 21-26: Selected Viral Pathogens 1. DNA Viral Pathogens 2. RNA Viral Pathogens 1. DNA Viral Pathogens Smallpox (pp. 623-4) Caused by variola virus (dsdna, enveloped): portal of entry is the respiratory
More informationAntivirals. Lecture 20 Biology 3310/4310 Virology Spring 2017
Antivirals Lecture 20 Biology 3310/4310 Virology Spring 2017 You can t go back and you can t stand still. If the thunder don t get you, then the lightning will. JERRY GARCIA The Wheel (lyrics by Robert
More informationHuman Herpes Viruses (HHV) Mazin Barry, MD, FRCPC, FACP, DTM&H Assistant Professor and Consultant Infectious Diseases KSU
Human Herpes Viruses (HHV) Mazin Barry, MD, FRCPC, FACP, DTM&H Assistant Professor and Consultant Infectious Diseases KSU HERPES VIRUS INFECTIONS objectives: ØTo know the clinically important HHVs. ØTo
More informationMedChem 401~ Retroviridae. Retroviridae
MedChem 401~ Retroviridae Retroviruses plus-sense RNA genome (!8-10 kb) protein capsid lipid envelop envelope glycoproteins reverse transcriptase enzyme integrase enzyme protease enzyme Retroviridae The
More informationYear 2002 Paper two: Questions supplied by Jo 1
Year 2002 Paper two: Questions supplied by Jo 1 Question 9 A 37 year old man with known human immunodeficiency virus (HIV) infection for 10 years presents with severe renal colic for which he has no prior
More informationHIV and AIDS. Shan Nanji
HIV and AIDS Shan Nanji HIV 2 Description: Enveloped Positive Sense HIV 3 Structural Genes: Cleavage of gp160 leads to formation of ENV: Gp120: attachment to host CD4 T Cell Gp41: GAG (p24) Capsid protein
More informationMedChem401 Herpesviridae. Herpesviridae
MedChem401 Herpesviridae Members of the herpesvirus family have been identified in more than 80 different animal species Eight have been identified as human pathogens Herpes viruses are a leading cause
More informationMultiple Choice Questions - Paper 1
Multiple Choice Questions - Paper 1 Instructions for candidates The examination consists of 30 multiple choice questions, each divided into 5 different parts. Each part contains a statement which could
More informationHIV medications HIV medication and schedule plan
Living with HIV (human immunodeficiency virus) It may be scary to find out that you re HIV-positive or have AIDS. Coping with this news may be difficult. Although HIV is a serious infection, people with
More informationContinuing Education for Pharmacy Technicians
Continuing Education for Pharmacy Technicians HIV/AIDS TREATMENT Michael Denaburg, Pharm.D. Birmingham, AL Objectives: 1. Identify drugs and drug classes currently used in the management of HIV infected
More informationVirology Introduction. Definitions. Introduction. Structure of virus. Virus transmission. Classification of virus. DNA Virus. RNA Virus. Treatment.
DEVH Virology Introduction Definitions. Introduction. Structure of virus. Virus transmission. Classification of virus. DNA Virus. RNA Virus. Treatment. Definitions Virology: The science which study the
More informationTHE HIV LIFE CYCLE. Understanding How Antiretroviral Medications Work
THE HIV LIFE CYCLE Understanding How Antiretroviral Medications Work DEFINITIONS Host: The animal or cell that another organism lives in. In HIV human CD4 T-cells are the host for HIV. Nucleus: The core
More informationRepetitorium of selected human viruses HIV
Repetitorium of selected human viruses HIV Chair and Department of Medical Microbiology Poznan University of Medical Sciences Chairman: prof. dr hab. Andrzej Szkaradkiewicz Wieniawskiego Street 3, 61-712
More informationAntiviral Agents, chapter 43
Antiviral Agents, chapter 43 Different living organisms Eucaryotes Mono or polycellular Cell nucleus; DA May have cell wall sexual and / or asexual replication Animals Plants Fungi Protocista: - Protozoea
More informationViruses. CLS 212: Medical Microbiology Miss Zeina Alkudmani
Viruses CLS 212: Medical Microbiology Miss Zeina Alkudmani History Through the 1800s, many scientists discovered that something smaller than bacteria could cause disease and they called it virion (Latin
More informationHIV Update Objectives. Epidemiology. Epidemiology, Transmission and Natural History. Transmission Risk by Exposure. Transmission 9/29/2014
Objectives HIV Update 2014 Jay Sizemore, MD, MPH Medical Director Chattanooga CARES Assistant Professor UTCOM Chattanooga 2October 2014 Review HIV epidemiology and screening/testing guidelines Discuss
More informationProkaryotic Biology. VIRAL STDs, HIV-1 AND AIDS
Prokaryotic Biology VIRAL STDs, HIV-1 AND AIDS Prokaryotic Biology FROM THE CDC VIRAL STDs, HIV-1 AND AIDS VIRAL STDs & CONTACT VIRAL DISEASES A. GENITAL HERPES & COLD SORES 1. HERPES SIMPLEX VIRUS-2 (HHV-2)
More informationMONTGOMERY COUNTY COMMUNITY COLLEGE CHAPTER 13: VIRUSES. 1. Obligate intracellular parasites that multiply in living host cells
MONTGOMERY COUNTY COMMUNITY COLLEGE CHAPTER 13: VIRUSES I. CHARACTERISTICS OF VIRUSES A. General Characteristics 1. Obligate intracellular parasites that multiply in living host cells 2. Contain a single
More informationMedical Virology. Herpesviruses, Orthomyxoviruses, and Retro virus. - Herpesviruses Structure & Composition: Herpesviruses
Medical Virology Lecture 2 Asst. Prof. Dr. Dalya Basil Herpesviruses, Orthomyxoviruses, and Retro virus - Herpesviruses Structure & Composition: Herpesviruses Enveloped DNA viruses. All herpesviruses have
More informationARV Mode of Action. Mode of Action. Mode of Action NRTI. Immunopaedia.org.za
ARV Mode of Action Mode of Action Mode of Action - NRTI Mode of Action - NNRTI Mode of Action - Protease Inhibitors Mode of Action - Integrase inhibitor Mode of Action - Entry Inhibitors Mode of Action
More information104 MMWR December 17, 2004
104 MMWR December 17, 2004 TABLE 8. Substantial pharmacokinetic drug-drug interactions for drugs used in the treatment of opportunistic Drugs Interacting with Mechanism/effects Recommendations Acyclovir
More informationB. Incorrect! Peginterferon α-2a is used for the treatment of chronic hepatitis B and may be preferable to interferon- α.
Pharmacology - Problem Drill 24: Antibiotics, Antifungal and Antiviral Drugs Question No. 1 of 10 1. reduces the replication of influenza A and B viruses by inhibiting viral neuraminidase. Question #01
More informationHIV epidemiology since HIV in the United States. HIV Transmission
HIV epidemiology since 1999 8% increase in HIV diagnoses Men who have sex with men (MSM) increased 14% Heterosexual increased 10% IVDU decrease about 30% Young Black MSM 15% incidence HIV in the United
More informationAntifungals, antivirals, antiprotozoals, and anthelmintics
Antifungals, antivirals, antiprotozoals, and anthelmintics Joseph K. Ritter, PhD Asst. Prof Department of Pharmacology and Toxicology MSB Room 530 jritter@hsc.vcu.edu Difficulties associated with treatment
More informationAntiviral Therapies in Children: Has Their Time Arrived?
Pediatr Clin N Am 52 (2005) 837 867 Antiviral Therapies in Children: Has Their Time Arrived? David W. Kimberlin, MD Department of Pediatrics, Division of Pediatric Infectious Diseases, The University of
More informationInfluenza viruses. Virion. Genome. Genes and proteins. Viruses and hosts. Diseases. Distinctive characteristics
Influenza viruses Virion Genome Genes and proteins Viruses and hosts Diseases Distinctive characteristics Virion Enveloped particles, quasi-spherical or filamentous Diameter 80-120 nm Envelope is derived
More informationnumber Done by Corrected by Doctor
number 34 Done by حسام ابو عوض Corrected by Waseem Alhaj Doctor مالك الزحلف Antiviral Chemotherapy (chemotherapy is another way of saying drugs بنحب نتفلسف وهيك.(بس When dealing with viruses we are entering
More information0.14 ( 0.053%) UNAIDS 10% (94) ( ) (73-94/6 ) 8,920
0.14 UNAIDS 0.053% 2 250 60 10% 94 73 20 73-94/6 8,920 12 43 Public Health Service Task Force Recommendations 5-10% for Use of Antiretroviral Drugs in 10-20% Pregnant HIV-1-Infected Women for Maternal
More informationHistory electron microscopes
Viruses History Through the 1800s, many scientists discovered that something smaller than bacteria could cause disease and they called it virion (Latin word- poison) In the 1930s, after the invention of
More informationACQUIRED IMMUNODEFICIENCY SYNDROME AND ITS OCULAR COMPLICATIONS
ACQUIRED IMMUNODEFICIENCY SYNDROME AND ITS OCULAR COMPLICATIONS Acquired immunodeficiency syndrome (AIDS ) is an infectious disease caused by a retrovirus, the human immunodeficiency virus(hiv). AIDS is
More informationChapter III ANTIVIRAL AND ANTIFUNGAL DRUGS
Chapter III ANTIVIRAL AND ANTIFUNGAL DRUGS AN OUNCE OF PREVENTION WORTH POUND OF CURE Year III Pharm.D Dr. V. Chitra ANTIVIRAL DRUGS Viruses are small(20-30 nm) infective agents that are incapable of reproduction
More informationImmunodeficiencies HIV/AIDS
Immunodeficiencies HIV/AIDS Immunodeficiencies Due to impaired function of one or more components of the immune or inflammatory responses. Problem may be with: B cells T cells phagocytes or complement
More informationvirology MCQs 2- A virus commonly transmitted by use of contaminated surgical tools & needles produces a disease called serum hepatitis.
virology MCQs 1- A virus which causes AIDS is: a- Small pox virus. b- Coxsackie B virus. c- Mumps virus. d- Rubella virus. e- HIV-III virus. 2- A virus commonly transmitted by use of contaminated surgical
More informationIntroduction to Viruses That Infect Humans: The DNA Viruses
Chapter 24 Introduction to Viruses That Infect Humans: The DNA Viruses Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 24.1 Viruses in Human Infections and Diseases
More informationPrinciples of Antiretroviral Therapy
Principles of Antiretroviral Therapy Ten Principles of Antiretroviral Therapy Skills Building Workshop: Clinical Management of HIV Infection and Antiretroviral Therapy, 11 th ICAAP, November 21st, 2011,
More informationImage of Ebola viruses exiting host cells HUMAN VIRUSES & THE LIMITATION OF ANTIVIRAL DRUG AGENTS
Image of Ebola viruses exiting host cells HUMAN VIRUSES & THE LIMITATION OF ANTIVIRAL DRUG AGENTS APRIL 2017 Infectious viruses are a global health threat Since the approval of the first antiviral drug
More informationImage of Ebola viruses exiting host cells HUMAN VIRUSES & THE LIMITATION OF ANTIVIRAL DRUG AGENTS
Image of Ebola viruses exiting host cells HUMAN VIRUSES & THE LIMITATION OF ANTIVIRAL DRUG AGENTS MAY 2017 1 Infectious viral pathogens are a significant global health threat to mankind 2 Since the approval
More informationBritish HIV Association Guidelines for the Management of Hepatitis Viruses in Adults Infected with HIV 2013 Appendix 2
British HIV Association Guidelines for the Management of Hepatitis Viruses in Adults Infected with HIV 2013 Appendix 2 Systematic literature search 2.1 Questions and PICO criteria Data bases: Medline,
More informationThe chemical name of acyclovir, USP is 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6Hpurin-6-one; it has the following structural formula:
Acyclovir Ointment, USP 5% DESCRIPTION Acyclovir, USP, is a synthetic nucleoside analogue active against herpes viruses. Acyclovir ointment, USP 5% is a formulation for topical administration. Each gram
More informationPart I. Content: History of Viruses. General properties of viruses. Viral structure. Viral classifications. Virus-like agents.
Viruses Part I Content: History of Viruses. General properties of viruses. Viral structure. Viral classifications. Virus-like agents. History Through the 1800s, many scientists discovered that something
More informationHuman Immunodeficiency Virus. Acquired Immune Deficiency Syndrome AIDS
Human Immunodeficiency Virus Acquired Immune Deficiency Syndrome AIDS Sudden outbreak in USA of opportunistic infections and cancers in young men in 1981 Pneumocystis carinii pneumonia (PCP), Kaposi s
More informationChapter 13 Viruses, Viroids, and Prions. Biology 1009 Microbiology Johnson-Summer 2003
Chapter 13 Viruses, Viroids, and Prions Biology 1009 Microbiology Johnson-Summer 2003 Viruses Virology-study of viruses Characteristics: acellular obligate intracellular parasites no ribosomes or means
More informationHerpes Simplex Viruses. HSV-1 HSV-2 Herpesvirus hominis Infection mucocutaneous surfaces, CNS
Viral disorders Herpes Simplex Viruses HSV-1 HSV-2 Herpesvirus hominis Infection mucocutaneous surfaces, CNS Etiologic agent Double-stranded DNA HSV-1, -2 Latency: viral genomes present in neuronl cells
More informationConcomitant antiretroviral therapy : Avifanz must be given in combination with other antiretroviral medications.
Avifanz Tablet Description Avifanz is the brand name for Efavirenz. Efavirenz, a synthetic antiretroviral agent, is a non-nucleoside reverse transcriptase inhibitor. While Efavirenz is pharmacologically
More informationgram neg.(semisynthetic) Bacteria Drugs that inhibit cell wall synthesis Drug Action Organisms Comments Spectrum of Action Mycobacterium
Mickey Dufilho s Drugs and Bugs Revised 10/10/15 Bacteria Drugs that Inhibit Cell Wall Synthesis Drug Action Spectrum of Action Comments Spectrum of Action Bacitracin Beta-Lactam antibiotics Penicillin
More informationViral Genetics. BIT 220 Chapter 16
Viral Genetics BIT 220 Chapter 16 Details of the Virus Classified According to a. DNA or RNA b. Enveloped or Non-Enveloped c. Single-stranded or double-stranded Viruses contain only a few genes Reverse
More informationالحترمونا من خري الدعاء
الحترمونا من خري الدعاء Instructions for candidates The examination consists of 30 multiple choice questions, each divided into 5 different parts. Each part contains a statement which could be true or
More informationOrthomyxoviridae and Paramyxoviridae. Lecture in Microbiology for medical and dental medical students
Orthomyxoviridae and Paramyxoviridae Lecture in Microbiology for medical and dental medical students Orthomyxoviridae and Paramyxoviridae are ss RNA containng viruses Insert Table 25.1 RNA viruses 2 SIZE
More informationQ: If antibody to the NA and HA are protective, why do we continually get epidemics & pandemics of flu?
Influenza virus Influenza virus Orthomyxoviridae family of viruses RNA enveloped viruses that make up three genera Influenzavirus A Influenzavirus B Influenzavirus C The type A viruses are the most virulent
More informationPOST-EXPOSURE PROPHYLAXIS, PRE-EXPOSURE PROPHYLAXIS, & TREATMENT OF HIV
POST-EXPOSURE PROPHYLAXIS, PRE-EXPOSURE PROPHYLAXIS, & TREATMENT OF HIV DISCLOSURE Relevant relationships with commercial entities none Potential for conflicts of interest within this presentation none
More informationChapter 25. 바이러스 (The Viruses)
Chapter 25 바이러스 (The Viruses) Generalized Structure of Viruses 2 2 Virus Classification Classification based on numerous characteristics Nucleic acid type Presence or absence of envelope Capsid symmetry
More informationViruses. Poxviridae. DNA viruses: 6 families. Herpesviridae Adenoviridae. Hepadnaviridae Papovaviridae Parvoviridae
Viruses DNA viruses: 6 families Poxviridae Herpesviridae Adenoviridae Hepadnaviridae Papovaviridae Parvoviridae Human herpesviruses Three subfamilies (genome structure, tissue tropism, cytopathologic effect,
More informationProperties of Herpesviruses
Herpesviruses Properties of Herpesviruses Structure and Composition Spherical icosahedron, 150-200 nm Double-stranded DNA, linear More than 35 proteins Enveloped Replication from nucleus (budding) Features
More information0% 0% 0% Parasite. 2. RNA-virus. RNA-virus
HIV/AIDS and Treatment Manado, Indonesia 16 november HIV [e] EDUCATION HIV is a 1. DNA-virus 2. RNA-virus 3. Parasite 0% 0% 0% DNA-virus RNA-virus Parasite HIV HIV is a RNA-virus. HIV is an RNA virus which
More informationClinical Aspect and Application of Laboratory Test in Herpes Virus Infection. Masoud Mardani M.D,FIDSA
Clinical Aspect and Application of Laboratory Test in Herpes Virus Infection Masoud Mardani M.D,FIDSA Shahidhid Bh BeheshtiMdi Medical lui Universityit Cytomegalovirus (CMV), Epstein Barr Virus(EBV), Herpes
More informationTreatment Op+ons for Chronic Hepa++s B. Judith Feinberg, MD Project ECHO Jan. 19, 2017
Treatment Op+ons for Chronic Hepa++s B Judith Feinberg, MD Project ECHO Jan. 19, 2017 Treatment of Chronic Hepatitis B can be prevented by vaccinacon (part of infant series since 1992-3) goal of drug therapy
More informationViruses. Properties. Some viruses contain other ingredients (e.g., lipids, carbohydrates), but these are derived from their host cells.
Viruses Properties They are obligate intracellular parasites. Probably there are no cells in nature that escape infection by one or more kinds of viruses. (Viruses that infect bacteria are called bacteriophages.)
More information19 Viruses BIOLOGY. Outline. Structural Features and Characteristics. The Good the Bad and the Ugly. Structural Features and Characteristics
9 Viruses CAMPBELL BIOLOGY TENTH EDITION Reece Urry Cain Wasserman Minorsky Jackson Outline I. Viruses A. Structure of viruses B. Common Characteristics of Viruses C. Viral replication D. HIV Lecture Presentation
More informationViral Hepatitis Diagnosis and Management
Viral Hepatitis Diagnosis and Management CLINICAL BACKGROUND Viral hepatitis is a relatively common disease (25 per 100,000 individuals in the United States) caused by a diverse group of hepatotropic agents
More informationPHARMACOKINETICS OF ANTIRETROVIRAL AND ANTI-HCV AGENTS
8. PHARMACOKINETICS OF ANTIRETROVIRAL AND ANTI-HCV AGENTS David Burger José Moltó Table 8.1a: INFLUENCE OF FOOD ON ABSORPTION (AREA UNDER THE CURVE) OF ANTIRETROVIRAL AGENTS NUCLEOSIDE ANALOGUES NtRTI
More informationRama Nada. - Malik
- 2 - Rama Nada - - Malik 1 P a g e We talked about HAV in the previous lecture, now we ll continue the remaining types.. Hepatitis E It s similar to virus that infect swine, so its most likely infect
More informationTenofovir disoproxil STADA 245 mg film-coated tablets , Version 1.2 PUBLIC SUMMARY OF THE RISK MANAGEMENT PLAN
Tenofovir disoproxil STADA 245 mg film-coated tablets 9.3.2016, Version 1.2 PUBLIC SUMMARY OF THE RISK MANAGEMENT PLAN VI.2 Elements for a public summary VI.2.1 Overview of disease epidemiology HIV-1 infection
More informationStructured Treatment Interruption in HIV Positive Patients. Leah Jackson, BScPhm Pharmacy Resident HIV Rotation January 23, 2007
Structured Treatment Interruption in HIV Positive Patients Leah Jackson, BScPhm Pharmacy Resident HIV Rotation January 23, 2007 Objectives To become re-acquainted with the basics of HAART for HIV infection
More informationVirion Genome Genes and proteins Viruses and hosts Diseases Distinctive characteristics
Hepadnaviruses Virion Genome Genes and proteins Viruses and hosts Diseases Distinctive characteristics Hepatitis viruses A group of unrelated pathogens termed hepatitis viruses cause the vast majority
More informationChapter 08 Lecture Outline
Chapter 08 Lecture Outline See separate PowerPoint slides for all figures and tables preinserted into PowerPoint without notes. Copyright 2016 McGraw-Hill Education. Permission required for reproduction
More informationHBV : Structure. HBx protein Transcription activator
Hepatitis B Virus 1 Hepatitis B Virus 2 Properties of HBV a member of the hepadnavirus group Enveloped, partially double-stranded DNA viruses, smallest DNA virus Replication involves a reverse transcriptase
More informationOdefsey. (emtricitabine, rilpivirine, tenofovir alafenamide) New Product Slideshow
Odefsey (emtricitabine, rilpivirine, tenofovir alafenamide) New Product Slideshow Introduction Brand name: Odefsey Generic name: Emtricitabine, rilpivirine, tenofovir alafenamide (TAF) Pharmacological
More informationClinical Presentation of Viral Hepatitis 1-The symptoms of acute viral hepatitis caused by HAV, HBV, HCV, HDV, and HEV are similar (3).
5 th Year Therapeutics 2015 Viral Hepatitis Introduction 1-There are five types of viral hepatitis: hepatitis A (HAV), B (HBV), C (HCV), D (HDV), and E (HEV). These types may present as either acute or
More informationAP Biology. Viral diseases Polio. Chapter 18. Smallpox. Influenza: 1918 epidemic. Emerging viruses. A sense of size
Hepatitis Viral diseases Polio Chapter 18. Measles Viral Genetics Influenza: 1918 epidemic 30-40 million deaths world-wide Chicken pox Smallpox Eradicated in 1976 vaccinations ceased in 1980 at risk population?
More informationViral Hepatitis. Dr. Abdulwahhab S. Abdullah CABM, FICMS-G&H PROF. DR. SABEHA ALBAYATI CABM,FRCP
Viral Hepatitis Dr. Abdulwahhab S. Abdullah CABM, FICMS-G&H PROF. DR. SABEHA ALBAYATI CABM,FRCP Viral hepatitis Viral hepatitis must be considered in any patient presenting with hepatitis on LFTs (high
More informationViral reproductive cycle
Lecture 29: Viruses Lecture outline 11/11/05 Types of viruses Bacteriophage Lytic and lysogenic life cycles viruses viruses Influenza Prions Mad cow disease 0.5 µm Figure 18.4 Viral structure of capsid
More informationHepatitis B and C. And the rest of the alphabet
Hepatitis B and C And the rest of the alphabet Adapté des exposés de la Chaire Franqui 2003 "Antiviral drugs and Discoveries in Medicine" Prof. E. De Clercq, KU-Leuven http://www.md.ucl.ac.be/chaire-francqui/
More informationHerpesviruses. Virion. Genome. Genes and proteins. Viruses and hosts. Diseases. Distinctive characteristics
Herpesviruses Virion Genome Genes and proteins Viruses and hosts Diseases Distinctive characteristics Virion Enveloped icosahedral capsid (T=16), diameter 125 nm Diameter of enveloped virion 200 nm Capsid
More informationLECTURE OUTLINE. B. AGENT: Varicella-zoster virus. Human herpes virus 3. DNA virus.
Viral Vaccines II LECTURE OUTLINE 5/24/04 I. CASE HISTORY A 5-year old comes home from school with a red skin rash on his chest that spreads to over 300 itchy blisters that spread further to his face,
More information