Download Free Medical Quinolones Oxiquinolones Nitrofurans and Antiviral agents PowerPoint Presentation

Quinolones Oxiquinolones Nitrofurans and Antiviral agents PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical presentation on Pharmacology, which is titled "Quinolones, Oxiquinolones, Nitrofurans, and Antiviral agents", to know about auinolones, oxiquinolones, nitrofurans, and antiviral agents.

Tags : Pharmacology, Quinolones, Oxiquinolones, Nitrofurans, Antiviral agents

Published on : Jul 18, 2021 | Views : 1121 | Downloads : 0

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Medical University of Sofia, Faculty of Medicine Department of Pharmacology and Toxicology Quinolones Oxiquinolones Nitrofurans Antiviral agents (Summary) Assoc. Prof. Ivan Lambev (www.medpharm-sofia.eu)
Slide 2-

(inhibitors of DNA gyrase, resp. inhibitors of topomerases) Nalidixic acid and its derivatives QUINOLONES Fluoroquinolones
Slide 3-

Nalidixic acid has been available for over 60 years but low activity poor tissue distribution, and adverse effects limited its use to being a second- and third- line oral treatment for Gram (-) urinary tract infections.
Slide 4-

Nalidixic acid (Nelidix®) Gramurin®  E. coli  Salmonella  Shigella  P. aeruginosa Gr (—):
Slide 5-

Changes to the basic quinolone structure such as the addition of fluorine and piperazine ring have dramatically increased antibacterial potency, particularly against P. aeruginosa. The new compounds are called 4-fluoro- quinolones (or fluoroquinolones)
Slide 6-

Ciprofloxacin Bactericidal effect Gr (+): topoisomerase IV Gr (–): topoisomerase II (DNA gyrase)
Slide 7-

Bacterial DNA topoisomerase II and IV) (-) Fluoroquinolones
Slide 8-

Bactericidal effect; very broad antibacterial spectrum High activity against P. aeruginosa, Salmonella, Shigella, Neisseria, Campylobacter, and Chlamydia Beta-lactamase stability Limited activity against streptococci
Slide 9-

ppt slide no 9 content not found
Slide 10-

>70% F (p.o.) DD/2 applications 50–80%/24 h urinary excretion Good intracellular distribution
Slide 11-

INDICATIONS (infections): urinary respiratory GIT genital (incl. gonorrhoea) septicemia ophthalmic (topically)
Slide 12-

ppt slide no 12 content not found
Slide 13-

CIPROFLOXACIN Ciprobay® tabl. 500 mg 500 mg/12 h (5–10 days)
Slide 14-

Co-administration of ciproflo- xacin and theophylline causes eleveted plasma theophylline concentrations due to inhibi- tion of cytochrome P450. Both drugs are epileptogenic
Slide 15-

Moxifloxacin Tabl. 400 mg NB: 400 mg once daily
Slide 16-

Gatifloxacin Levofloxacin (Tavanic®) – S-isomer of ofloxacin 500 mg/24 h p.o. 10 days Norfloxacin Lomefloxacin Ofloxacin Pefloxacin Trovafloxacin, etc.
Slide 17-

Fluoroquinolones Adapted from Bennett and Brown (2003)
Slide 18-

convulsions (in patients with epilepsy or commotion) arthritis (in growing animals) dizziness hepatic and renal damage ruptura tendinorum in old people crystallization (in excessively alkaline urine and dehydration) cartilage damage. The mechanism of cartilage damage may be related to chelation of magnesium in joints. ADVERSE EFFECTS
Slide 19-

The mechanism of cartilage damage may be related to chelation of magnesium in joints. Lesions have been documented in dogs given ﬁve times the recom- mended dose and occur within 1–2 days of beginning administration. It is recommended that ﬂuoroquino- lones be avoided in large breed dogs up to 18 months of age (12 months for medium breeds, 9 months for small breeds). If a ﬂuoroquinolone must be used because there is no suitable alternative, strict exercise restriction (especially for large breed dogs) and use of chondroprotectives are advised.
Slide 20-

Contraindications pregnancy old people epilepsy meningitis children
Slide 21-

TILBROQUINOL – enteroantiseptic with antiamoebic activity NITROXOLIN – broad spectrum uroantiseptic (p.o.) They block RNA polymerase. OXIQUINOLONES
Slide 22-

FURAZOLIDONE, NIFUROXAZIDE – enteroantiseptics (Salmonella etc.) NITROFURANTOIN (p.o.) – uroantiseptic: E. coli, Proteus mirabilis, Staph. aureus, Klebsiella, Serratia, Pseudomonas. It blocks carbohydrate metabolism by inhibiting its acetyl CoA synthesis. NITROFURANS – broad spectrum antibacterial agents
Slide 23-

ppt slide no 23 content not found
Slide 24-

Furazolidone
Slide 25-

Nitrofurantoin (Furadantin®):
Slide 26-

ANTIVIRAL AGENTS Viruses are composed of a core genome consisting of either double-stranded or single-stranded DNA or RNA surrounded by a protein shell known as a capsid. Some viruses are further surrounded by a lipoprotein membrane or envelope. Both the capsid and lipoprotein membrane may be antigenic. Viruses cannot replicate independently and must usurp the host’s metabolic machinery to replicate. Therefore viruses are obligate intracellular parasites. The host’s pathways of energy generation, protein synthesis, and DNA or RNA replication provide the virus with the means of viral replication. For some viruses, replication is initiated by viral enzymes.
Slide 27-

ppt slide no 27 content not found
Slide 28-

Cells respond to viral infection in three ways: infection may have no impact on the cell or its function, cellular death may occur (which may preclude subsequent infection), or the cell may be transformed such that host control of cell growth is lost to viral activities. Viral replication occurs in five or six sequential steps: cell entry, including host cell attachment, generally through specific receptors, followed by host cell penetration; disassembly or uncoating resulting in release of viral genome; transcription of viral genome (or viral messenger RNA), which is dependent on virus-specified enzyme; translation of regulatory (early) or structural (late) viral proteins; post-translation modifications (incl. proteolytic cleavage); assembly of virion components; and release of the virus, generally by budding or cell lysis.
Slide 29-

TARGETS OF ANTIVIRAL THERAPY Potential targets in the viral life cycle that might be pharmacologically inhibited are expressed during extracellular stages of viral infection (i.e., penetration), intracellular stages (i.e., replication, assembly, and viral release), and dissemination. Antivirals that diminish penetration of host cells by the virus are more viral specific and less toxic from those that prevent viral replication. Because cell penetration is enhanced by viral-induced immunosuppression, pharmacologic immunomodulation (resp. immunostimulation) may also help prevent viral penetration especially during the early stages of infection, which are often missed because of the lack of clinical signs.
Slide 30-

(Ag) (Ag)
Slide 31-

Cyclic amines inhibit influenza-A DNA replication. Rimantadine is from two to 8-fold times more active than Amantadine.
Slide 32-

Rimantadine (Flumadine): p.o. Vitamin C Esberitox N (immunostimulant) Indications: prophylaxis and treatment of influenza A viral infection: А (H5N1)
Slide 33-

Rimantadine - adverse effects: orthostatic hypotension dizziness, confusion headache, insomnia vomiting, xerostomia urinary retention
Slide 34-

inhibits neuraminidase and prevents replication of influenza-A and B-virus application: per inhalationem b) Neuraminidase inhibitors (active against virus A and B Zanamivir:
Slide 35-

Oseltamivir – Tamiflu® against virus А, B A (H5N1): bird or avian flu (influenza) – (2 s/78 °C) A (H1N1): swine or pig flu (influenza) Treatment: 75 mg/12 h 5 days Prophylaxis: 75 mg/24 h about 30 days
Slide 36-

Pig flu: Bird flu:
Slide 37-

ppt slide no 37 content not found
Slide 38-

ppt slide no 38 content not found
Slide 39-

ppt slide no 39 content not found
Slide 40-

ppt slide no 40 content not found
Slide 41-

ppt slide no 41 content not found
Slide 42-

ppt slide no 42 content not found
Slide 43-

Symptomatic therapy
Slide 44-

Paracetamol Metamizole
Slide 45-

Please, give me something against influenza.
Slide 46-

Influenza Virus Vaccines (PRC C) Against virus А (H5N1) Fluarix Fluogen Inflexal V Influvac Invivac Vaxigrip Vacciflu Against virus – A (H1N1) : Celvapan® Focetria® Pandemrix® Prepandrix® 0,5 ml i.m./deep s.c.
Slide 47-

ppt slide no 47 content not found
Slide 48-

It is time to get vaccinated against influenza virus A (H1N1)
Slide 49-

William Osler (1849-1919) ,,Good humor helps enormously both in the study and practice of medicine.”
Slide 50-

2. INTERFERONS (IFNs) They are cytokines (mediators of cell growth and function). They are glycoproteins secreted by cells infected with viruses or foreign DNA.
Slide 51-

Interferons are active against a wide range of viruses. Main types of IFNs: α – produced by leukocytes β – produced by fibroblasts γ – produced by lymphocytes
Slide 52-

IFN gamma has significant immunoregulatory function. Interferon alfa-2b (Intron) is used in chronic hepatitis, Kaposi’s sarcoma in AIDS, multiple myeloma, etc. Interferon beta-1b (Betaferon) used s.c. in multiple sclerosis (MS).
Slide 53-

Adverse effects of IFNs fever (influenza-like syndrome) lympho- and thrombocytopenia anorexia and weight loss alopecia confusion, tremor, and fits transient hypotension cardiac arrhythmias hypothyroidism
Slide 54-

3. Antiherpetic Drugs They are prodrugs – nucleoside analogues. H. simplex
Slide 55-

After phosphorylation nucleoside analogs convert into active metabolites, which inhibit viral DNA polymerase (reverse transcriptase) and block viral replication.
Slide 56-

Indications: H. simplex and varicella-zoster infections aciclovir ganciclovir valaciclovir brivudine
Slide 57-

Herpes zoster infection Treatment of postherpetic neuralgia: ●Anticonvulsants Gabapentin, Pregabalin ●Antidepressants Nortriptyline, Duloxetine ●Opioid painkillers Tramadol
Slide 58-

Acyclovir and Valacyclovir Acyclovir is is structurally similar to guanosine (purine nucleoside). Valacyclovir is an L-valyl ester prodrug of acyclovir. Efficacy of acyclovir depends on activation of the drug to its monophosphate derivative by viral thymidine kinase. Subsequent phosphorylation to the diphosphate and then triphosphate form is mediated selectively by cells infected with herpesvirus. The formation of acyclovir-GTP results in the inhibition of viral DNA polymerase and incorporation of acyclovir-GTP into viral DNA, which terminates viral DNA synthesis. The drug has a greater affinity for viral (versus host) thymidine synthetase. Antiviral activity of acyclovir is limited essentially to herpesviruses. The in vitro activity of acyclovir is 100 times than of vidarabine.
Slide 59-

Ointment or cream ophthalmicum 5% 5 g Aciclovir (INN)
Slide 60-

Aciclovir Vials (fl.) 250 mg i.v. In herpes simplex encefalitis: 10–12.5 mg/kg/8 h i.v. inf. 10 days
Slide 61-

Ganciclovir Ganciclovir is structurally similar to acyclovir. Its spectrum includes herpesvirus, with particular efficacy against cytomegalovirus. Resistance most commonly reflects point mutations or deletions in viral DNA, resulting in reduced formation of viral phosphotransferase. The primary ARs is myelosuppression, with neutropenia occurring in up to 40% and thrombocytopenia in 5–20% of patients. Myelosuppression more commonly occurs with i.v. administration and is generally reversible by 1 week after discontinuation of therapy. Therapeutic use of ganciclovir includes cytomegalovirus retinitis, particularly in humans with AIDS. Ganciclovir is also used for treatment of any infection or prevention of infection (particularly in transplant recipients) associated with cytomegalovirus.
Slide 62-

ppt slide no 62 content not found
Slide 63-

4. Antiretroviral Drugs Indications: AIDS a) Nucleoside analogues (prodrugs – DNA polymerase inhibitors) Abacavir, Didanozine, Inosine (?) Lamivudine, Stavudine, Zalcitabine Zidovudine (AZT)
Slide 64-

Blood Blood products Sexual secretions HIV infections
Slide 65-

The HIV lifecycle
Slide 66-

ppt slide no 66 content not found
Slide 67-

ppt slide no 67 content not found
Slide 68-

ppt slide no 68 content not found
Slide 69-

ppt slide no 69 content not found
Slide 70-

Retrovir® caps. 100 mg Zidovudine analogue of thymidine AZT (azidothymidine - USA)
Slide 71-

AZT AZT-MP AZT-TP (-) Viral DNA polymerase MP - monophosphate TP - 3-phosphate ...
Slide 72-

Bone marrow suppression (anaemia in 15%) vomiting, fatigue, headache, insomnia Unwanted reactions
Slide 73-

Zalcitabine Oral bioavailabilty 86% Urinary excretion 70%
Slide 74-

Unwanted reactions peripheral neuropathies in 23% of patients stomatitis aftosa skin rash myopathy
Slide 75-

CombivirТМ – Lamivudine – Zidovudine Trizivir™ – Abacavir – Lamivudine – Zidovudine
Slide 76-

Inosine Inosine (Isoprinosine) is a nucleoside analog which can inhibit cytopathic effects of several viruses in culture. The mechanism of antiviral activity appears to involve specific suppression of viral mRNA. Inosine does not appear to be as efficacious as several antimetabolite antiviral compounds. Inosine can also induce T-cell differentiation similar to that induced by thymic hormones, apparently by augmenting RNA synthesis. Thus Inosine may be more useful as an immunostimulant in immunodeficient patients.
Slide 77-

b) Non-nucleoside analogues used in AIDS: Еfavirenz Nevirapine
Slide 78-

c) HIV-protease inhibitors Amprenavir, Indinavir, Nelfinavir, Ritonavir They prevent cleavage of protein precursors essential for HIV infection of new cells and viral replication.
Slide 79-

Indinavir Ritonavir
Slide 80-

ENFUVIRITIDE (Fuzeon®) – s.c. e) Integrase inhibitors – act on the gene level RALTEGRAVIR d) Drugs, inhibiting HIV with target membrane of human cells
Slide 81-

g) Infective complications of HIV-infections Pneumocystis carinii pneumonia high dose co-trimoxazole (21 days i.v./p.o. is first-line standard therapy Oropharyngeal candidiasis fluconazole (14 days p.o.) Tbc: M. avium complex (with Rifabutin)
Slide 82-

Feline Immunodeficiency Virus (FIV)
Slide 83-

FIV can attack the immune system of cats, much like the HIV can attack the immune system of human beings. FIV infects many cell types in its host, including CD4+ and CD8+ T lymphocytes, B lymphocytes, and macrophages. FIV can be tolerated well by cats, but can eventually lead to debilitation of the immune system in its feline hosts by the infection and exhaustion of T-helper (CD4+) cells. FIV and HIV are both lentiviruses; however, neither can infect the other's usual host: humans cannot be infected by FIV nor can cats be infected by HIV. FIV is transmitted primarily by way of saliva and blood throwgh bite wounds during territorial battles between males. Cats housed exclusively indoors are much less likely to be infected.
Slide 84-

5. HPV vaccines: SILGARD®: 0, 2, and 6 month i.m. (from 9 to 26 years old) CERVARIX® Cervarix® HPV
Slide 85-

HPV vaccines: SILGARD®: 0, 2, and 6 month i.m. (from 9 to 26 years old) CERVARIX® Cervarix® HPV may causes cancer…
Slide 86-

Prof. G. Gorchev, MD, DSc, oncogynecologist, Medical University – Pleven