The presentation defines brief introduction of anti HIV agents as well as anti mycobacterial agent including Structures, SAR, mode of action, adverse effects.
Antibiotics acting on cell wall 3 Carbapenems and Monobactums 03-05-2018Ravi Kant Agrawal
Carbapenems and monobactams are new classes of β-lactam antibiotics that act on cell wall synthesis. Carbapenems like imipenem and meropenem have a broad spectrum of activity against gram-positive and gram-negative bacteria. They are often used as last resort drugs for serious infections but resistance is emerging. Meropenem has advantages over imipenem like not requiring an inhibitor and being more soluble. Ertapenem also has activity against anaerobes but not pseudomonas. Monobactams have a monocyclic structure and are isolated from bacteria.
This document discusses anti-HIV drugs, their mechanisms of action, and treatment regimens. It describes established drug targets for anti-HIV drugs like CCR5 coreceptors and reverse transcriptase. It provides details on first line treatment regimens including two NRTIs with an NNRTI or PI/r. It also discusses treatment failure, adverse effects, special populations, and co-infections.
Antiviral drugs work by targeting specific parts of the viral replication cycle using mechanisms like inhibiting viral enzymes or incorporating into viral DNA to stop replication. They are classified based on the virus or viral enzyme they target, such as anti-herpes drugs like acyclovir that inhibit viral DNA polymerase, or anti-HIV drugs that include reverse transcriptase inhibitors, protease inhibitors, and integrase inhibitors. Developing effective antiviral drugs is challenging because viruses replicate inside cells and mutate rapidly, so they must target virus-specific processes without harming host cells.
The document discusses antiviral drugs, including their classification, mechanisms of action, and examples. It describes how viruses lack cellular structures and can only replicate inside host cells. Antiviral drugs target specific stages of the viral lifecycle, such as viral entry, DNA/RNA synthesis and replication, and viral release. Common classes include purine and pyrimidine nucleotides, adamantane derivatives, and phosphorus derivatives. Examples like acyclovir, amantadine, and idoxuridine are summarized in terms of their structures, mechanisms of action inhibiting viral enzymes or DNA replication, and clinical uses for treating viruses like influenza, herpes, and cytomegalovirus.
This document discusses antiviral drugs used to treat various DNA and RNA viruses. It provides classifications of viruses based on their genome and structure. It then covers the viral replication cycles and mechanisms of different classes of antiviral drugs, including DNA polymerase inhibitors, mRNA synthesis inhibitors, immunomodulators, viral penetration/uncoating inhibitors, and release inhibitors. Specific antiviral drugs are discussed for treating infections caused by DNA viruses like herpes, hepatitis B, and cytomegalovirus as well as RNA viruses including influenza, hepatitis C, and respiratory syncytial virus. Adverse effects and mechanisms of action are provided for many of the antiviral drugs.
Sulfonamides and cotrimoxazole are classes of antibiotics that work by inhibiting the enzyme dihydropteroate synthase, interrupting the biosynthesis of nucleic acids. Cotrimoxazole is a combination of trimethoprim and sulfamethoxazole that have synergistic antibacterial effects through sequential blockade in bacterial folate metabolism. It has broad spectrum activity against both gram-positive and gram-negative bacteria. Common adverse effects include hypersensitivity reactions. The drugs are well absorbed orally and have a volume of distribution that allows penetration into tissues and body fluids.
Viruses are obligate intracellular parasites that use host cell machinery to replicate. They consist of DNA or RNA enclosed in a protein capsid. Current antiviral drugs target viruses like HIV, hepatitis B/C, herpes, influenza and RSV. These include nucleoside/non-nucleoside reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, and integrase inhibitors used in HAART for HIV. Specific drugs like acyclovir inhibit viral DNA polymerase. Zidovudine is a nucleoside reverse transcriptase inhibitor used to treat HIV that competitively inhibits viral DNA chain elongation.
Antibiotics acting on cell wall 3 Carbapenems and Monobactums 03-05-2018Ravi Kant Agrawal
Carbapenems and monobactams are new classes of β-lactam antibiotics that act on cell wall synthesis. Carbapenems like imipenem and meropenem have a broad spectrum of activity against gram-positive and gram-negative bacteria. They are often used as last resort drugs for serious infections but resistance is emerging. Meropenem has advantages over imipenem like not requiring an inhibitor and being more soluble. Ertapenem also has activity against anaerobes but not pseudomonas. Monobactams have a monocyclic structure and are isolated from bacteria.
This document discusses anti-HIV drugs, their mechanisms of action, and treatment regimens. It describes established drug targets for anti-HIV drugs like CCR5 coreceptors and reverse transcriptase. It provides details on first line treatment regimens including two NRTIs with an NNRTI or PI/r. It also discusses treatment failure, adverse effects, special populations, and co-infections.
Antiviral drugs work by targeting specific parts of the viral replication cycle using mechanisms like inhibiting viral enzymes or incorporating into viral DNA to stop replication. They are classified based on the virus or viral enzyme they target, such as anti-herpes drugs like acyclovir that inhibit viral DNA polymerase, or anti-HIV drugs that include reverse transcriptase inhibitors, protease inhibitors, and integrase inhibitors. Developing effective antiviral drugs is challenging because viruses replicate inside cells and mutate rapidly, so they must target virus-specific processes without harming host cells.
The document discusses antiviral drugs, including their classification, mechanisms of action, and examples. It describes how viruses lack cellular structures and can only replicate inside host cells. Antiviral drugs target specific stages of the viral lifecycle, such as viral entry, DNA/RNA synthesis and replication, and viral release. Common classes include purine and pyrimidine nucleotides, adamantane derivatives, and phosphorus derivatives. Examples like acyclovir, amantadine, and idoxuridine are summarized in terms of their structures, mechanisms of action inhibiting viral enzymes or DNA replication, and clinical uses for treating viruses like influenza, herpes, and cytomegalovirus.
This document discusses antiviral drugs used to treat various DNA and RNA viruses. It provides classifications of viruses based on their genome and structure. It then covers the viral replication cycles and mechanisms of different classes of antiviral drugs, including DNA polymerase inhibitors, mRNA synthesis inhibitors, immunomodulators, viral penetration/uncoating inhibitors, and release inhibitors. Specific antiviral drugs are discussed for treating infections caused by DNA viruses like herpes, hepatitis B, and cytomegalovirus as well as RNA viruses including influenza, hepatitis C, and respiratory syncytial virus. Adverse effects and mechanisms of action are provided for many of the antiviral drugs.
Sulfonamides and cotrimoxazole are classes of antibiotics that work by inhibiting the enzyme dihydropteroate synthase, interrupting the biosynthesis of nucleic acids. Cotrimoxazole is a combination of trimethoprim and sulfamethoxazole that have synergistic antibacterial effects through sequential blockade in bacterial folate metabolism. It has broad spectrum activity against both gram-positive and gram-negative bacteria. Common adverse effects include hypersensitivity reactions. The drugs are well absorbed orally and have a volume of distribution that allows penetration into tissues and body fluids.
Viruses are obligate intracellular parasites that use host cell machinery to replicate. They consist of DNA or RNA enclosed in a protein capsid. Current antiviral drugs target viruses like HIV, hepatitis B/C, herpes, influenza and RSV. These include nucleoside/non-nucleoside reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, and integrase inhibitors used in HAART for HIV. Specific drugs like acyclovir inhibit viral DNA polymerase. Zidovudine is a nucleoside reverse transcriptase inhibitor used to treat HIV that competitively inhibits viral DNA chain elongation.
In 1935, Gerhard Domagk discovered the first sulphonamide--prontosil rubrum. Four years later he received the Noble Prize.
Developed mouse model of sepsis with Streptococcus hemolyticus infection
Lethal model with most mice dead in 24 hours
Tested azo-dyes directly in this model.
Others had shown some azo dyes to be active in vitro against a number of bacteria but not to have any in vivo activity
Tuberculosis is caused by infection with Mycobacterium tuberculosis. It infects over a billion people worldwide and kills millions each year. A combination of drugs, including isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin, are used to treat tuberculosis. Isoniazid and rifampin are the most effective drugs but multi-drug therapy is required to prevent resistance. Both drugs have bactericidal effects and penetrate tissues well but can cause adverse reactions like hepatitis which requires monitoring during treatment.
This document discusses various antimycobacterial drugs used to treat tuberculosis and leprosy. It describes the mechanisms of action, development of resistance, and importance of drug combinations for isoniazid, rifampin, ethambutol, pyrazinamide, streptomycin, fluoroquinolones, linezolid, bedaquiline, and dapsone. Resistance develops rapidly if these drugs are used alone rather than in combination regimens.
This document summarizes several antifungal agents classified based on their mechanism of action. It describes the echinocandins caspofungin, micafungin, and anidulafungin which inhibit cell wall synthesis. It also details the polyene amphotericin B which disrupts cell membranes. Finally, it outlines the azole antifungals including imidazoles and triazoles such as fluconazole, itraconazole, and voriconazole which inhibit ergosterol synthesis. For each class of antifungals, the document discusses mechanisms of action, formulations, pharmacokinetics, therapeutic uses, and adverse effects.
This document discusses various antifungal drugs, including their mechanisms of action, classifications, and clinical uses. It covers major drug classes like azoles, polyenes, and echinocandins. Key drugs discussed include amphotericin B, which disrupts fungal cell membranes; azoles like fluconazole and itraconazole, which inhibit ergosterol synthesis; and echinocandins like caspofungin that target fungal cell wall synthesis. The document provides details on pharmacokinetics, mechanisms, resistance, administration routes and adverse effects of these important antifungal medications.
Tuberculosis is caused by Mycobacterium tuberculosis and is one of the world's most deadly infectious diseases. It primarily affects the lungs but can spread throughout the body. First line drugs used to treat tuberculosis include isoniazid, rifampin, pyrazinamide, and ethambutol. Isoniazid and rifampin are the most effective. Treatment requires combination drug therapy for an extended period of time to address both actively growing and dormant bacilli. Short course multidrug regimens introduced by the WHO have improved treatment completion rates. Problems in tuberculosis chemotherapy include the slow growth of mycobacteria and risk of resistance development with single drug therapy.
This document discusses antimycobacterial drugs used to treat tuberculosis. It begins by describing tuberculosis and how it is caused by Mycobacterium tuberculosis. It then discusses the various drugs used to treat tuberculosis, including their mechanisms of action, pharmacokinetics, adverse drug reactions, and classifications as first-line versus second-line treatments. Rifampin, isoniazid, pyrazinamide, and ethambutol are described as first-line treatments, while second-line treatments include drugs like capreomycin, fluoroquinolones, and cycloserine. The document concludes by discussing the different types of tubercular infections treated by these drugs.
This document discusses various antiviral drugs used to treat different viral infections. It begins by classifying antiviral drugs into categories based on the virus they target, such as anti-herpes viruses like acyclovir and valacyclovir, anti-influenza viruses like amantadine and oseltamivir, anti-hepatitis viruses/nonselective drugs like lamivudine and ribavirin, and anti-retroviruses used to treat HIV. It then provides more details on the mechanism of action, pharmacokinetics, uses, and side effects of representative drugs from each category.
This document summarizes anti-tubercular drugs used to treat tuberculosis and other mycobacterial diseases. It discusses first-line drugs like isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin which are effective, less toxic options routinely used to treat tuberculosis. Second-line drugs discussed include fluoroquinolones, macrolides, rifapentine, and rifabutin which are used for multidrug-resistant tuberculosis or atypical mycobacterial infections. World Health Organization recommended treatment regimens including the directly observed treatment short course protocol are mentioned. Mechanisms of action, pharmacokinetics, uses, and side effects of various anti
This document summarizes different types of antiviral agents. It discusses how viruses infect cells and the routes of viral transmission. It then covers the immune response in hosts and examples of DNA and RNA containing viruses. The document classifies antiviral agents into those that inhibit initial viral replication, interfere with viral nucleic acid replication, and affect ribosomal translation. Specific antiviral drugs are then described, including their uses and modes of action. Amantadine, zidovudine, acyclovir, idoxuridine, and methisazone are all discussed as antiviral agents.
The document provides information on antiretroviral drugs used to treat HIV/AIDS. It discusses how HIV works, how it is transmitted, the stages of HIV infection, and how antiretroviral drugs target different stages of the viral lifecycle. It also summarizes several commonly used antiretroviral drugs, including their mechanisms of action, contraindications, warnings, and adverse effects.
Introduction to HIV/AIDS
Epidemiology
Structural information of HIV
Life cycle of HIV
Symptoms & causes of AIDS due to HIV
Pathophysiology
Pharmacological Classification along with mechanism of action
Novel targets for Anti-retroviral Drugs
Summary
References
Vote of thanks
This document provides information about anti-viral drugs. It begins by defining viruses and their structure. It then discusses different classes of anti-viral drugs, including those that block viral attachment and entry, inhibit penetration, act as uncoating inhibitors, and are nucleic acid inhibitors that target polymerases or reverse transcriptase. Specific drugs are discussed for each class, along with their mechanisms of action, structures, and importance for treating various viral diseases like HIV, hepatitis, herpes, and influenza.
Sulfonamides are antimicrobial agents containing a sulfonamide group. Domagk discovered their efficacy in 1938 by inhibiting the growth of streptococci with prontosil. Sulfonamides work by competing with para-aminobenzoic acid to inhibit dihydrofolic acid synthesis. They are classified based on duration of action and are used to treat various bacterial, protozoal, and chlamydial infections. Common adverse effects include gastrointestinal issues, hematological toxicity, hypersensitivity, and renal toxicity. Trimethoprim is a diaminopyrimidine that also inhibits dihydrofolic acid synthesis and has synergistic effects when combined with sulfonamides in co-tri
This document provides an overview of antiviral agents for medical students. It discusses the targets of antiviral drugs, including viral enzymes and virus-specific steps. Several classes of antiviral agents are described, including drugs for influenza, hepatitis, HIV, and herpes viruses. Specific drugs like acyclovir, ganciclovir, and famciclovir are examined in depth, outlining their mechanisms of action, pharmacokinetics, uses, and side effects in treating herpes virus infections. The conclusion emphasizes that antiviral drugs achieve selective toxicity by targeting viral processes and that classification is based on activity against different virus families.
Carbapenems are a class of beta-lactam antibiotics with a fused beta-lactam ring. They include imipenem, meropenem, ertapenem, and aztreonam (a monobactam). Carbapenems have broad spectra of activity against both gram-positive and gram-negative bacteria. Imipenem is inactivated by renal dipeptidases but combined with cilastatin. Meropenem and ertapenem are more stable. Aztreonam only covers gram-negatives but is useful in penicillin allergic patients. Carbapenems are used to treat various infections including respiratory, abdominal, skin and bone infections.
medicinal chemistry of Antiviral drugsFatenAlsadek
medicinal chemistry of antiviral drugs with its chemical structures and how they chemically work
Done by: Faten Al-Sadek , Pharmacy student at Mohammed Al-Mana college for Health Sciences -MACHS
This document discusses various antibiotics that act on the bacterial cell wall. It begins by describing the structure and function of the bacterial cell wall and how antibiotics can disrupt it. It then lists several common antibiotics that target the cell wall, including penicillin, cephalosporins, cycloserine, bacitracin, and vancomycin. It provides details on the source and therapeutic uses of each. The remainder of the document goes into further depth about the mechanisms of action and effects of beta-lactam antibiotics like penicillin, focusing on how they inhibit cell wall synthesis and cross-linking. It describes the structures, spectra, uses and side effects of various penicillin derivatives in detail.
This document provides an overview of antiretroviral therapies (ART) used to treat HIV and issues with patient adherence to these treatment regimens. It discusses the history of HIV/AIDS and the development of early treatments like AZT. The major classes of ART are described, including how they work to inhibit different stages of the HIV replication cycle. Challenges to effective adherence are reviewed, such as medication side effects, complex dosing schedules, and social/personal barriers patients may face. High adherence to combination ART is emphasized as critical for suppressing the virus and preventing drug resistance.
In 1935, Gerhard Domagk discovered the first sulphonamide--prontosil rubrum. Four years later he received the Noble Prize.
Developed mouse model of sepsis with Streptococcus hemolyticus infection
Lethal model with most mice dead in 24 hours
Tested azo-dyes directly in this model.
Others had shown some azo dyes to be active in vitro against a number of bacteria but not to have any in vivo activity
Tuberculosis is caused by infection with Mycobacterium tuberculosis. It infects over a billion people worldwide and kills millions each year. A combination of drugs, including isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin, are used to treat tuberculosis. Isoniazid and rifampin are the most effective drugs but multi-drug therapy is required to prevent resistance. Both drugs have bactericidal effects and penetrate tissues well but can cause adverse reactions like hepatitis which requires monitoring during treatment.
This document discusses various antimycobacterial drugs used to treat tuberculosis and leprosy. It describes the mechanisms of action, development of resistance, and importance of drug combinations for isoniazid, rifampin, ethambutol, pyrazinamide, streptomycin, fluoroquinolones, linezolid, bedaquiline, and dapsone. Resistance develops rapidly if these drugs are used alone rather than in combination regimens.
This document summarizes several antifungal agents classified based on their mechanism of action. It describes the echinocandins caspofungin, micafungin, and anidulafungin which inhibit cell wall synthesis. It also details the polyene amphotericin B which disrupts cell membranes. Finally, it outlines the azole antifungals including imidazoles and triazoles such as fluconazole, itraconazole, and voriconazole which inhibit ergosterol synthesis. For each class of antifungals, the document discusses mechanisms of action, formulations, pharmacokinetics, therapeutic uses, and adverse effects.
This document discusses various antifungal drugs, including their mechanisms of action, classifications, and clinical uses. It covers major drug classes like azoles, polyenes, and echinocandins. Key drugs discussed include amphotericin B, which disrupts fungal cell membranes; azoles like fluconazole and itraconazole, which inhibit ergosterol synthesis; and echinocandins like caspofungin that target fungal cell wall synthesis. The document provides details on pharmacokinetics, mechanisms, resistance, administration routes and adverse effects of these important antifungal medications.
Tuberculosis is caused by Mycobacterium tuberculosis and is one of the world's most deadly infectious diseases. It primarily affects the lungs but can spread throughout the body. First line drugs used to treat tuberculosis include isoniazid, rifampin, pyrazinamide, and ethambutol. Isoniazid and rifampin are the most effective. Treatment requires combination drug therapy for an extended period of time to address both actively growing and dormant bacilli. Short course multidrug regimens introduced by the WHO have improved treatment completion rates. Problems in tuberculosis chemotherapy include the slow growth of mycobacteria and risk of resistance development with single drug therapy.
This document discusses antimycobacterial drugs used to treat tuberculosis. It begins by describing tuberculosis and how it is caused by Mycobacterium tuberculosis. It then discusses the various drugs used to treat tuberculosis, including their mechanisms of action, pharmacokinetics, adverse drug reactions, and classifications as first-line versus second-line treatments. Rifampin, isoniazid, pyrazinamide, and ethambutol are described as first-line treatments, while second-line treatments include drugs like capreomycin, fluoroquinolones, and cycloserine. The document concludes by discussing the different types of tubercular infections treated by these drugs.
This document discusses various antiviral drugs used to treat different viral infections. It begins by classifying antiviral drugs into categories based on the virus they target, such as anti-herpes viruses like acyclovir and valacyclovir, anti-influenza viruses like amantadine and oseltamivir, anti-hepatitis viruses/nonselective drugs like lamivudine and ribavirin, and anti-retroviruses used to treat HIV. It then provides more details on the mechanism of action, pharmacokinetics, uses, and side effects of representative drugs from each category.
This document summarizes anti-tubercular drugs used to treat tuberculosis and other mycobacterial diseases. It discusses first-line drugs like isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin which are effective, less toxic options routinely used to treat tuberculosis. Second-line drugs discussed include fluoroquinolones, macrolides, rifapentine, and rifabutin which are used for multidrug-resistant tuberculosis or atypical mycobacterial infections. World Health Organization recommended treatment regimens including the directly observed treatment short course protocol are mentioned. Mechanisms of action, pharmacokinetics, uses, and side effects of various anti
This document summarizes different types of antiviral agents. It discusses how viruses infect cells and the routes of viral transmission. It then covers the immune response in hosts and examples of DNA and RNA containing viruses. The document classifies antiviral agents into those that inhibit initial viral replication, interfere with viral nucleic acid replication, and affect ribosomal translation. Specific antiviral drugs are then described, including their uses and modes of action. Amantadine, zidovudine, acyclovir, idoxuridine, and methisazone are all discussed as antiviral agents.
The document provides information on antiretroviral drugs used to treat HIV/AIDS. It discusses how HIV works, how it is transmitted, the stages of HIV infection, and how antiretroviral drugs target different stages of the viral lifecycle. It also summarizes several commonly used antiretroviral drugs, including their mechanisms of action, contraindications, warnings, and adverse effects.
Introduction to HIV/AIDS
Epidemiology
Structural information of HIV
Life cycle of HIV
Symptoms & causes of AIDS due to HIV
Pathophysiology
Pharmacological Classification along with mechanism of action
Novel targets for Anti-retroviral Drugs
Summary
References
Vote of thanks
This document provides information about anti-viral drugs. It begins by defining viruses and their structure. It then discusses different classes of anti-viral drugs, including those that block viral attachment and entry, inhibit penetration, act as uncoating inhibitors, and are nucleic acid inhibitors that target polymerases or reverse transcriptase. Specific drugs are discussed for each class, along with their mechanisms of action, structures, and importance for treating various viral diseases like HIV, hepatitis, herpes, and influenza.
Sulfonamides are antimicrobial agents containing a sulfonamide group. Domagk discovered their efficacy in 1938 by inhibiting the growth of streptococci with prontosil. Sulfonamides work by competing with para-aminobenzoic acid to inhibit dihydrofolic acid synthesis. They are classified based on duration of action and are used to treat various bacterial, protozoal, and chlamydial infections. Common adverse effects include gastrointestinal issues, hematological toxicity, hypersensitivity, and renal toxicity. Trimethoprim is a diaminopyrimidine that also inhibits dihydrofolic acid synthesis and has synergistic effects when combined with sulfonamides in co-tri
This document provides an overview of antiviral agents for medical students. It discusses the targets of antiviral drugs, including viral enzymes and virus-specific steps. Several classes of antiviral agents are described, including drugs for influenza, hepatitis, HIV, and herpes viruses. Specific drugs like acyclovir, ganciclovir, and famciclovir are examined in depth, outlining their mechanisms of action, pharmacokinetics, uses, and side effects in treating herpes virus infections. The conclusion emphasizes that antiviral drugs achieve selective toxicity by targeting viral processes and that classification is based on activity against different virus families.
Carbapenems are a class of beta-lactam antibiotics with a fused beta-lactam ring. They include imipenem, meropenem, ertapenem, and aztreonam (a monobactam). Carbapenems have broad spectra of activity against both gram-positive and gram-negative bacteria. Imipenem is inactivated by renal dipeptidases but combined with cilastatin. Meropenem and ertapenem are more stable. Aztreonam only covers gram-negatives but is useful in penicillin allergic patients. Carbapenems are used to treat various infections including respiratory, abdominal, skin and bone infections.
medicinal chemistry of Antiviral drugsFatenAlsadek
medicinal chemistry of antiviral drugs with its chemical structures and how they chemically work
Done by: Faten Al-Sadek , Pharmacy student at Mohammed Al-Mana college for Health Sciences -MACHS
This document discusses various antibiotics that act on the bacterial cell wall. It begins by describing the structure and function of the bacterial cell wall and how antibiotics can disrupt it. It then lists several common antibiotics that target the cell wall, including penicillin, cephalosporins, cycloserine, bacitracin, and vancomycin. It provides details on the source and therapeutic uses of each. The remainder of the document goes into further depth about the mechanisms of action and effects of beta-lactam antibiotics like penicillin, focusing on how they inhibit cell wall synthesis and cross-linking. It describes the structures, spectra, uses and side effects of various penicillin derivatives in detail.
This document provides an overview of antiretroviral therapies (ART) used to treat HIV and issues with patient adherence to these treatment regimens. It discusses the history of HIV/AIDS and the development of early treatments like AZT. The major classes of ART are described, including how they work to inhibit different stages of the HIV replication cycle. Challenges to effective adherence are reviewed, such as medication side effects, complex dosing schedules, and social/personal barriers patients may face. High adherence to combination ART is emphasized as critical for suppressing the virus and preventing drug resistance.
MANAGEMENT OF HIV FALLS UNDER THREE MAJOR CATEGORIES
1.POST EXPOSURE PROPHYLAXIS(P.E.P)
2.TREATMENT/MANAGEMENT OF HIV-AIDS
3.TREATMENT OF ADJOINING CONDITIONS
eg-
-Fungal Infections
-Bacterial infections
-Viral infections
-NEOPLASIAS
-misc.( recurrent apthos ulcers, xerostomia,salivary G. enlargement)
The document discusses the characteristics, transmission, stages, and treatment of HIV/AIDS. It provides details on the structure and life cycle of the HIV virus. It describes the various classes of antiretroviral drugs used to treat HIV/AIDS, including reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and entry inhibitors. The treatment section discusses the goals of antiretroviral therapy and examples of specific drugs from different classes like zidovudine, efavirenz, raltegravir, and maraviroc.
Human Immunodeficiency Virus (HIV) is an enveloped RNA virus that infects and destroys CD4+ T cells of the immune system. HIV belongs to the retrovirus family and has two types, HIV-1 and HIV-2. HIV replication involves binding to CD4 receptors on cells, integration into the host genome, and production of new virus particles. Infection progresses to AIDS as CD4 cells are depleted. There is currently no cure for HIV/AIDS, but treatment with antiretroviral drugs can suppress the virus and prolong life.
This document discusses antiviral agents for nonretrovirals. It begins by outlining the key learning objectives which are to describe viral infections, classification of antiviral agents, their mechanisms of action and resistance. It then classifies antiviral agents into non-retroviral and antiretroviral categories. Under non-retroviral agents, it describes treatments for influenza, herpes and hepatitis viruses. It provides details on specific drugs for each virus type, including their mechanisms of action, resistance and pharmacokinetics.
The document provides information about HIV/AIDS, including:
1) It describes what HIV and AIDS are, how HIV causes AIDS by compromising the immune system over time.
2) It provides statistics on HIV infections in the US since 1981, including that 1 in 5 people living with HIV are unaware of their status.
3) It summarizes research showing that HIV likely originated from transmission from chimpanzees to humans in the early 20th century.
4) It lists symptoms that can emerge when HIV progresses to AIDS and compromises the immune system.
The document discusses anti-HIV drugs and their mechanisms of action. It introduces that HIV causes AIDS and replicates using the reverse transcriptase enzyme. There are several classes of anti-HIV drugs that target different stages of the viral lifecycle including reverse transcriptase inhibitors like nucleoside analogs and non-nucleoside inhibitors, as well as protease inhibitors. Each drug class is described along with examples of drugs, their mechanisms of action, therapeutic uses, and common adverse effects. Modifications to drug structures are also discussed to improve potency and reduce toxicity.
This document summarizes key information about HIV/AIDS, including its history, virology, diagnosis, treatment, and prevention. It describes how HIV was first identified in 1981 as the cause of AIDS, belongs to the retrovirus family, and has two types, HIV-1 and HIV-2. Over 30 million people have died of AIDS since 1981, and approximately 2.5 million people are newly infected with HIV each year.
Antiviral drugs treat specific viral infections by targeting different parts of the viral lifecycle. They include reverse transcriptase inhibitors, protease inhibitors, and nucleosides for HIV; amantadine, oseltamivir, and zanamivir for influenza; and acyclovir, ganciclovir, and valacyclovir for herpes and cytomegalovirus. Most antivirals have limited safety data during pregnancy and breastfeeding due to a lack of studies, so their use should be restricted to situations where benefits outweigh risks. Common side effects include nausea, headache, and renal or liver dysfunction.
HIV causes AIDS by infecting immune cells and weakening the immune system. It is transmitted through bodily fluids and can be prevented by safe sex practices and not sharing needles. The virus attaches to CD4 receptors and integrates its DNA into host cells. This leads to reduced CD4 counts and opportunistic infections defining AIDS. Treatment involves antiretrovirals that target different stages of the viral lifecycle to suppress the virus and ART to control the disease.
This document provides an overview of HIV/AIDS, including its history, epidemiology in India, transmission, diagnosis, treatment with antiretroviral therapy, classification of antiretroviral drugs, and prevention. It discusses how HIV infects CD4+ cells and replicates. Current first-line and second-line regimens recommended by WHO and NACO are mentioned. Recent drug approvals by the FDA for treatment of HIV are also summarized. References are provided at the end.
Human Immunodeficiency Virus (HIV) is an enveloped RNA virus that causes acquired immunodeficiency syndrome (AIDS). It belongs to the retrovirus family and there are two types, HIV-1 and HIV-2. HIV infects and destroys CD4+ T cells of the immune system, ultimately weakening the body's ability to fight infections and disease. Common routes of transmission include sexual contact, contaminated blood transfusions, and from mother to child during pregnancy, childbirth or breastfeeding. While antiretroviral treatment can slow the progression of the disease, there is currently no cure for HIV/AIDS.
Viruses are obligate intracellular parasites that rely on host cell machinery to replicate. Antiviral drugs work by blocking different stages of the viral replication cycle, either inside or outside infected cells. Common antiviral classes include nucleoside analogs, which interfere with viral DNA/RNA synthesis, and protease/reverse transcriptase inhibitors for HIV. Side effects depend on the specific agent but can include bone marrow suppression, renal toxicity, and gastrointestinal issues.
This document provides an overview of antiviral drugs, including their mechanisms of action, classifications, and examples. It discusses how antiviral drugs work by inhibiting viral replication and preventing the virus from multiplying, rather than destroying the pathogen. The main classes covered are nucleoside analogs, including purine and pyrimidine analogs like acyclovir and idoxuridine; non-nucleoside reverse transcriptase inhibitors like nevirapine; protease inhibitors used to treat HIV; and miscellaneous agents like foscarnet sodium. For each drug class, examples are given along with descriptions of their structures, mechanisms of action, therapeutic uses, and dosages.
Etiology, pathophysiology, Pharmacotherapy of AIDS .pptxdrsriram2001
Definition of AIDS:
Acquired Immunodeficiency Syndrome (AIDS) is a late stage of HIV (Human Immunodeficiency Virus) infection. It is characterized by a severe depletion of the immune system, making the individual susceptible to opportunistic infections and certain cancers.
2. Etiology (HIV):
HIV Structure:
HIV is a retrovirus that primarily targets CD4+ T cells, a crucial component of the immune system.
The virus has two main types: HIV-1 and HIV-2, with HIV-1 being the most common and virulent worldwide.
3. Transmission:
Modes of Transmission:
HIV is primarily transmitted through unprotected sexual intercourse with an infected person.
It can also be transmitted through sharing of contaminated needles, from an infected mother to her child during childbirth or breastfeeding, and through blood transfusions with infected blood (though this is rare now due to blood screening).
4. Clinical Stages:
Acute HIV Infection:
Occurs within the first few weeks after exposure.
Presents with flu-like symptoms such as fever, fatigue, and swollen lymph nodes.
Chronic HIV Infection (Asymptomatic Stage):
Can last for several years with few or no symptoms.
The virus is actively replicating, and the immune system is gradually compromised.
Symptomatic HIV Infection (Symptomatic Stage):
As the immune system weakens, symptoms such as persistent fever, weight loss, and diarrhea may occur.
AIDS:
Diagnosed when the immune system is severely compromised, typically when the CD4+ T cell count falls below a critical threshold.
Opportunistic infections (e.g., Pneumocystis jirovecii pneumonia) and certain cancers (e.g., Kaposi's sarcoma) become more common.
5. Preventive Measures:
Condom Use:
Consistent and correct use of condoms during sexual intercourse helps prevent the sexual transmission of HIV.
Pre-Exposure Prophylaxis (PrEP):
Antiretroviral medications, when taken consistently by HIV-negative individuals at high risk, can prevent HIV infection.
Post-Exposure Prophylaxis (PEP):
Emergency treatment with antiretroviral drugs within 72 hours of potential exposure to HIV to prevent infection.
Needle Exchange Programs:
Reducing the sharing of needles among injecting drug users helps prevent the transmission of HIV.
Highly active antiretroviral therapy incidence of adverse drug reactionspharmaindexing
This document summarizes research on adverse drug reactions (ADRs) experienced by patients taking highly active antiretroviral therapy (HAART) to treat HIV/AIDS. Several studies cited found that the most common ADRs were anemia, hepatotoxicity, gastrointestinal issues, hematological issues, neurological issues, and skin problems. Risk factors for ADRs included CD4 count below 200 cells/μl, female gender, tuberculosis co-infection, and hepatitis C co-infection. While ADR rates were high, some studies found they did not often lead to HAART interruptions. Overall the document examines the incidence and types of ADRs experienced on HAART as well as risk factors. Close patient monitoring
Highly active antiretroviral therapy: Incidence of adverse drug reactionspharmaindexing
The Acquired Immunodeficiency Syndrome (AIDS) was first recognized in 1981, in theUnitedStates of America in young homosexual men who had Kaposi sarcoma and serious infections. HIV is transmitted through unprotected sexual intercourse, transfusion ofcontaminated blood, sharing of contaminated needles and between a mother and her infant during pregnancy, childbirth and breastfeeding. In India, an estimated 0.1 percent of adults aged 15-49 are living with HIV, which seems low when compared to HIV prevalence in some parts of sub- Saharan Africa.The HIV prevalence at antenatal clinics was 1% in 2007. This number is smaller than the reported 1.26% in 2006, but remains the highest out of all states. HIV prevalence at STD clinics was very high at 17% in 2007.Although adverse reactions are common and often predictable, their management must be individualized.In addition, the patient's report of severity can be inconsistent with the clinical interpretation and this must be considered when determining the management of adverse reactions.Antiretroviral therapy is effective for HIV treatment but also increasingly complex. The many adverse effects of therapy may cause symptoms affecting a variety of organ systems. Patient nonadherence is the reason for the treatment failure to antiretroviral therapy. To optimize adherence treating physicians must focus on early detection and prevention of ADRs, when possible and distinguishing those that are self-limited from those that are potentially serious. Pharmacist should be able to detect ADRs and the culture of reporting ADRs should be instructed. All ART centers should have pharmacovigilance cell. All ADRs reported should be analyzed as per WHO guidelines of causal assessment.Our study concluded that there is a need of active Pharmacovigilance centre with intensive monitoring for ADRs by the Pharmacist in Indian HIV positive patients
Highly Active Antiretroviral Therapy (HAART) involves using a combination of at least three antiretroviral drugs to suppress the HIV virus and stop the progression of HIV disease. HAART decreases the viral load, improves immune function, and prevents opportunistic infections. The goals of HAART are to prolong life, improve quality of life, achieve maximal viral suppression, restore immune function, reduce HIV transmission, and rationally sequence drugs to limit toxicity while maintaining treatment options. Current guidelines recommend starting ART for all individuals regardless of CD4 count. Second line regimens are recommended when clinical or immunological failure occurs on first line therapy. Managing adverse events and comorbidities like hepatitis co-infection is also
This document provides information about Highly Active Antiretroviral Therapy (HAART) for treating HIV. It discusses the history and development of HAART, which involves using multiple antiretroviral drugs together to suppress the virus. Early combinations included two nucleoside reverse transcriptase inhibitors with a protease inhibitor. The goals of ART are to prolong life, improve quality of life, and reduce viral load and transmission risk while maintaining treatment options. Guidelines recommend starting ART for all individuals to reduce disease progression.
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1. 1
All India Shri Shivaji Memorial society college of pharmacy,
Pune
2. 2Outline
Anti HIV agent -What is HIV?
-What is AIDS?
-Lifecycle of HIV
-Antiretroviral therapy
Antimycobacterial -Introduction of mycobacteria
Anti tubercular agent -Introduction to Tuberculosis
-Anti-tubercular agent
Anti leprotic agent
-What is leprosy?
-Classification of leprosy
-Antileprotic agent
Key references
4. HIV(1)
H - Human. This virus infects human beings.
I - Immunodeficiency. This virus attacks a person's immune system. The
immune system is the body's defense against infections, such as bacteria
and viruses. Once attacked by HIV, the immune system becomes deficient
and doesn't work properly.
V - Virus. A virus is a type of germ too small to be seen even with a
microscope.
4
Ref: https://www.hiv.va.gov/patient/basics/what-is-HIV.asp
5. HIV takes over certain immune system cells that are supposed to defend the
body. These cells are called CD4 cells, or T cells
When HIV takes over a CD4 cell, it turns the cell into a virus factory. It
forces the cell to produce thousands of copies of the virus.
These copies then infect other CD4 cells. Infected cells don't work well and
they die early.
Over time, the loss of CD4 cells weakens the immune system, making it
harder for the body to stay healthy.
HIV is retrovirus.
A retrovirus is a single-stranded positive-sense RNA virus with a DNA
intermediate and, as an obligate parasite, targets a host cell.
5
Ref: https://www.hiv.va.gov/patient/basics/what-is-HIV.asp
6. Structure of HIV(6)
HIV Capsid : HIV cores that
contain HIV RNA
HIV envelope : Outer surface of
HIV
HIV enzymes : Protein that
carry out steps in HIV life cycle
HIV glycoprotein's : Protein
spikes embedded in HIV enevelope
HIV RNA : Genetic material
6
Ref: https://www.google.co.in/search?q=HIV+image
7. What is AIDS(1)
A - Acquired. This condition is acquired, meaning that a person becomes infected
with it.
I - Immuno. HIV affects a person's immune system, the part of the body that fights
off germs such as bacteria or viruses.
D - Deficiency. The immune system becomes deficient and does not work properly.
S - Syndrome. A person with AIDS may experience other diseases and infections
because of a weakened immune system.
7
Ref: https://www.hiv.va.gov/patient/basics/what-is-HIV.asp(Date of acess: 7/3/18)
8. AIDS is the most advanced stage of infection caused by HIV.
But most people who are HIV positive do not have AIDS.
An HIV-positive person is said to have AIDS when his or her immune system
becomes so weak it can't fight off certain kinds of infections and cancers, such as
kaposi sarcoma, and memory impairment.
Even without one of these infections, an HIV-positive person is diagnosed with
AIDS if his or her immune system weakens, as indicated by the number of CD4 cells
in his or her blood.
A CD4 cell count less than 200 in an HIV-infected person gives someone a diagnosis
of AIDS.
It can take between 2 to 10 years, or longer, for an HIV-positive person to develop
AIDS if he or she is not treated.
8
Ref: https://www.hiv.va.gov/patient/basics/what-is-HIV.asp(Date of acess : 7/3/18)
9. Life cycle of HIV(3)
9
Retroviruses are unable to replicate outside of living host cells and do
not contain deoxyribonucleic acid (DNA).
The pathogenesis of HIV infection is a function of the virus life cycle,
host cellular environment, and quantity of viruses in the infected
individual.
After entering the body, the viral particle is attracted to a cell with the
appropriate CD4 receptor molecules where it attaches by fusion to a
susceptible cell membrane or by endocytosis and then enters the cell.
Ref: Edward C Klatt et al, “Pathology of HIV/AIDS”, Version 27, Mercer University, April 2016, page no. 1-118.
10. 10
Steps in life cycle (4)
1. Binding
2. Fusion
3. Reverse transcriptase
4. Integration
5. Replication
6. Assembly
7. Budding
Ref: http://aidsinfo.nih.gov.(Date of acess: 7/3/18)
11. Antiretroviral therapy/treatment(5) :
11
• There are 6 classes of FDA-approved antiretroviral agents and 22 individual drugs
• Antiretroviral agents must be used in combination for effective treatment of HIV
infection
• Highly Active Antiretroviral Therapy [HAART] has led to life expectancies approaching
the general population.
Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
12. Why antiretroviral ? (8)
12
Availability of potent ART associated with dramatic reductions in HIV-associated
morbidity and mortality
ART can prevent HIV transmission
Life expectancy among many HIV populations increasing
Currently recommended ART is effective and well tolerated
Treatment of chronic HIV infection(5)
Prevention of mother-to-child transmission [PMTCT] (5)
Occupational and non-occupational post-exposure prophylaxis [PEP] (5)
Ref: Benjamin Young et al, “HIV Medication and side effect”,International Association of Physicians in AIDS Care, page no. 1-30
13. FDA-approved Antiretroviral Classes (5)
13
1. Nucleoside reverse transcriptase inhibitors (NsRTIs)
a. Purine analogue:
1. Adenosine analogue: Tenofovir, Didanosine
2. Guanine analogue: Abacavir
b. Pyrimidine analogue:
1. Thymidine analogue: Zidovudine
2. Cytosine analogue: Lamivudine
1. Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
2. Protease Inhibitors (PIs)
3. Fusion inhibitor
4. CCR5 antagonist
5. Integrase inhibitor Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
14. 14
Targets in antiretroviral therapy
Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
15. 1. Nucleoside Reverse Transcriptase Inhibitors (5,7)
(NsRTI)
15
First class of antiretrovirals developed.
•Must undergo intracellular triphosphorylation to become active against HIV
•NsRTI are the anlogue of the nucleotide
• Mechanism of action
- NRTI’s compete with host nucleotides to serve as the substrate for reverse
transcriptase chain elongation
- Absence of 3’-OH group on sugar moiety prevents the addition of another
nucleotide resulting in chain termination
- Viral DNA chain elongation is aborted and viral replication ceases
Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
16. 16
Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
17. 17
Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
18. 18
Example:
Tenofovir disoproxil fumarate (TDF)(8)
- Tenofovir Disoproxil Fumarate is a pro-drug,
- fumaric acid salt form of tenofovir,
- a nucleoside reverse Transcriptase inhibitor
- analog of adenosine.
• NtRTI is similar in its mechanism of action that it acts as
a DNA chain terminator
•Tenofovir contains a phosphate group and therefore only
requires diphosphorylation to become active
• Adverse effects:
nephrotoxicity, Fanconi’s syndrome, bone mineralization
disorders
Tinofovir disoproxyl fumarate
Ref: Benjamin Young et al, “HIV Medication and side effect”,International Association of Physicians in AIDS Care, page no. 1-30
19. 19
Zidovudine (8)
It is a dideoxynucleoside compound in which the 3'-
hydroxy group on the sugar moiety has been replaced by an
azido group.
This modification prevents the formation of phosphodiester
linkages which are needed for the completion of nucleic acid
chains.
The compound is a potent inhibitor of HIV replication,
acting as a chain-terminator of viral DNA during reverse
transcription.
It improves immunologic function, partially reverses the
HIV-induced neurological dysfunction, and improves certain
other clinical abnormalities associated with AIDS.
Adverse effect:
Its principal toxic effect is dose-dependent suppression of
bone marrow, resulting in anemia and leukopenia.
Zidovudine
Ref: Benjamin Young et al, “HIV Medication and side effect”,International Association of Physicians in AIDS Care, page no. 1-30
20. 202. Non Nucleodide reverse transcriptase inhibitor
(NNRTIs)(5)
Second class of antiretroviral agents developed
• Mechanism of action:
- NNRTI’s inhibit the HIV reverse transcriptase by binding a hydrophobic pocket close to the active site
-Lock the enzyme’s active site in an inactive conformation
-NNRTIs work in a completely different fashion, by directly binding the reverse transcriptase enzyme.
-They are NOT nucleoside analogs and are NOT incorporated into the DNA strand. NNRTIs work by non-
competitive inhibition.
• Potent but subject to rapid emergence of resistance
• Active against HIV-1 but NOT active against HIV-2
Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
21. 21
Mechanism of action Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
22. 22
Delaviridine Mesylate
Delaviridine Mesylate (8)
- Delavirdine Mesylate is a mesylate salt form
of delavirdine, a synthetic, non-nucleoside reverse
transcriptase inhibitor. In combination with other anti-
retroviral drugs.
-This agent has been shown to reduce HIV viral load and
increase CD4 leukocyte counts in patients.
-As an inhibitor of the cytochrome P450
system, delavirdine may result in increased serum levels
of co-administered protease inhibitors metabolized by the
cytochrome P450 system.
- Delavirdine is associated with a low rate of transient
serum aminotransferase elevations during therapy and is a
rare cause of clinically apparent acute liver injury.
Ref: Benjamin Young et al, “HIV Medication and side effect”,International Association of Physicians in AIDS Care, page no. 1-30
23. 23
Nevirapine
Nevirapine (8)
Nevirapine is a benzodiazepine non-nucleoside reverse transcriptase
inhibitor.
In combination with other antiretroviral drugs, nevirapine reduces
HIV viral loads and increases CD4 counts, thereby retarding or
preventing the damage to the immune system and reducing the risk of
developing AIDS.
The mechanism of action of nevirapine is as a Non-Nucleoside
Reverse Transcriptase Inhibitor, and Cytochrome P450 3A Inducer,
and Cytochrome P450 2B6 Inducer.
Ref: Benjamin Young et al, “HIV Medication and side effect”,International Association of Physicians in AIDS Care, page no. 1-30
24. NNRTI’s: Drug Interactions and Adverse Effects (5) 24
• Metabolized by CYP3A4 isoenzyme of the hepatic cytochrome p450 system
• Are either potent inducers or inhibitors of CYP3A4
• Potential for major drug interactions with HIV and non-HIV agents, including
antimycobacterials
• Adverse effects:
Rash, hepatotoxicity, neurocognitive impairment (efavirenz), teratogenicity (efavirenz)
Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
25. Protease Inhibitors (PIs)(5) 25
Third class of antiretroviral agents developed
• Mechanism of action:
- Inhibit HIV protease by binding to its active site, preventing the cleavage of gag and
gag-pol precursor proteins
-Virions are produced but they are incomplete and non-infectious
• Side effects:
Abdominal upset, diarrhea, dyslipidemia, lipodystrophy, atherosclerosis
Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
26. 26
Mode of action
Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
27. 27
• HIV protease is an enzyme required for the proteolytic cleavage of viral
polyprotein precursors into individual functional proteins found in infectious
HIV. (9)
•Example,
Saquinavir Mesylate (8)
•Saquinavir is a peptide-like substrate analogue that binds to the protease active
site and inhibits the activity of the enzyme.
Saquinavir mesylate
• Saquinavir mesylate is an HIV protease inhibitor
which acts as an analog of an HIV protease cleavage
site.
• It is a highly specific inhibitor of HIV-1 and HIV-2
proteases, and also inhibits CYTOCHROME P-450
CYP3A.
Ref: Benjamin Young et al, “HIV Medication and side effect”,International Association of Physicians in AIDS Care, page no. 1-30
28. 28
Ritonavir (8)
Ritonavir is a Cytochrome P450 3A Inhibitor and Protease
Inhibitor.
The mechanism of action of ritonavir is as a HIV Protease
Inhibitor and Cytochrome P450 3A Inhibitor and
Cytochrome P450 2D6 Inhibitor and Cytochrome P450
2C19 Inducer and Cytochrome P450 3A Inducer and P-
Glycoprotein Inhibitor and Breast Cancer Resistance Protein
Inhibitor and Cytochrome P450 3A4 Inhibitor and
Cytochrome P450 1A2 Inducer and Cytochrome P450 2C9
Inducer and Cytochrome P450 2B6 Inducer and UDP
Glucuronosyltransferases Inducer.
Ritonavir
Ref: Benjamin Young et al, “HIV Medication and side effect”,International Association of Physicians in AIDS Care, page no. 1-30
29. Protease Inhibitors: Drug Interactions (5) 29
• Metabolized by the CYP3A4 isoenzyme of the hepatic p450 system
• Are inhibitors of CYP3A4 to varying degrees
• Ritonavir is one of the most potent CYP3A4 inhibitors known and is used to
“boost” levels of other PI’s
• Potential for major drug interactions with numerous HIV and non-HIV drugs
Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
30. Fusion inhibitors(5)
30
Fusion inhibitor prevents entry by binding to glycoprotein on the viral envelope
- Enfuvirtide T20
- Binds to the gp41 envelope glycoprotein
- Injectable only
- CCR5 antagonist prevents entry by binding to the chemokine coreceptor on the host CD4+
cell.
- Enfuvirtide is used in combination with other antiretroviral agents for the treatment of HIV-1
infection in treatment-experienced patients with evidence of HIV-1 replication despite
ongoing antiretroviral therapy.
- Enfuvirtide must be paired with at least one other antiretroviral agent that is active in vitro
according to HIV resistance tests and drug history.
Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
31. 31
This indication is based on analyses of plasma HIV-1 RNA levels and CD4 cell
counts in controlled studies of enfuvirtide of 24 weeks duration.
Maraviroc
- Binds to CCR5 coreceptor
- Active against CCR5 tropic virus only
Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
32. 32
Mode of actionRef 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
33. Integrase inhibitor (5)
33
Integrase is a viral enzyme that integrates retroviral DNA into the host cell genome.
Integrase inhibitors are a new class of drugs used in the treatment of HIV.
The first integrase inhibitor, raltegravir, was approved in 2007 and other drugs were
in clinical trials in 2011.
Mechanism of action
- Inhibits DNA strand transfer into host-cell genome and thus prevents viral integration
- Very potent in-vitro and in-vivo
Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
34. 34Mode of action
Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
35. 35•Raltegravir is a pyrrolidinone derivative and HIV INTEGRASE INHIBITOR
that is used in combination with other ANTI-HIV AGENTS for the treatment
of HIV INFECTION.
Raltegravir
Ref 5: Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”, page no. 1-40.
37. Mycobacteria (10)
Mycobacteria are immobile, slow-growing rod-shaped, gram-positive bacteria
with high genomic G+C content (61-71%).
Due to their special staining characteristics under the microscope, which is
mediated by mycolic acid in the cell wall, they are called acid-fast.
This is also the reason for the hardiness of mycobacteria.
Mycobacteria can be divided into three groups:
Mycobacterium tuberculosis complex – causative pathogen of tuberculosis
Nontuberculous mycobacteria (NTM)
Mycobacterium leprae – causative pathogen of leprosy
37
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
38. Antimycobacterial agent (11)
38
An antimycobacterial is a type of drug used to treat mycobacteria infections.
• Types include:
1. Tuberculosis treatments
2. Leprostatic agents
Ref: Simon Tiberi et al, “Classifying new antitubercular drugs : rationale and future perspectives”, Oct 2016, page no. 181-184.
39. Tuberculosis (11)
It is an infectious bacterial disease characterized by the growth of nodules
(tubercles) in the tissues, especially the lungs.
TB is spread from person to person through the air. When people with lung TB
cough, sneeze or spit, they propel the TB germs into the air. A person needs to
inhale only a few of these germs to become infected.
About one-third of the world's population has latent TB, which means people
have been infected by TB bacteria but are not (yet) ill with disease and cannot
transmit the disease.
39
Ref: Simon Tiberi et al, “Classifying new antitubercular drugs : rationale and future perspectives”, Oct 2016, page no. 181-184.
40. Symptoms (11)
chest pain, coughing up
blood, and a
productive, prolonged cough for more than three weeks.
Systemic symptoms include fever, chills, nigh
sweats, appetite loss, weight
loss, pallor, and fatigue.
40
Ref: Simon Tiberi et al, “Classifying new antitubercular drugs : rationale and future perspectives”, Oct 2016, page no. 181-184.
42. Antitubercular drugs (11)
The World Health Organization (WHO) has recently updated the classification of new anti-
tuberculosis (TB) drugs based on a meta-analysis and expert panel recommendations.
42
In the previous WHO guidelines (2011), the choice of drugs was based on efficacy and
toxicity in a step-down manner, from group 1 to group 5.
Group 1 included first-line drugs and groups 2–5 included second-line drugs.
Group 5 included the drugs with (at the time) potentially limited efficacy or limited
clinical evidence.
Ref: Simon Tiberi et al, “Classifying new antitubercular drugs : rationale and future perspectives”, Oct 2016, page no. 181-184.
43. 43
WHO 2011 drug
classification
WHO 2016 drug
classification
Possible Future evolution
Group 1
First-line oral
anti-TB drugs
• Isoniazid
• Rifampicin
• Ethambutol
• Pyrazinamide
Group A
Fluoroquinolones
• Levofloxacin
• Moxifloxacin
• Gatifloxacin
Group A
Fluoroquinolones
Levofloxacin
Moxifloxacin
Gatifloxacin
Group 2
Injectable anti-
TB drugs
(injectable or
parenteral
agents)
• Streptomycin
• Kanamycin
• Amikacin
• Capreomycin
Group B
Second-line
injectable
Agents
• Amikacin
• Capreomycin
• Kanamycin
• (Streptomycin
)
Group B
Other core
second-line
agents
Bedaquiline
Delamanid
Ethionamide/[1T
D$DIF]
prothionamide
Cycloserine/[1T
D$DIF]
terizidone
Linezolid
Clofazimine
44. 44
Group 3
Fluoroquinolo
nes
• Levofloxacin
• Moxifloxacin
• Gatifloxacin
• Ofloxacin
Group C
Other core
second-line
agents
-Ethionamide/
prothionamide
-Cycloserine/
terizidone
-Linezolid
-Clofazimine
Group C
Second-line
injectable
agents
-Amikacin
-Capreomycin
-Kanamycin
-Meropenem/
Clavulanate
Group 4
Oral
bacteriostatic
second-line
anti-TB drugs
• Ethionamide/p
rothionamide
• Cycloserine/
terizidone
• P-
Aminosalicyli
c acid
Group D
Add-on
agents
(not core
MDR-TB
regimen)
D1
• Pyrazinami
de
• Ethambutol
• High-dose
isoniazid
Group D
Add-on agents
(not core
MDR-TB
regimen
components)
• Pyrazinami
de
• Ethambutol
• High-dose
Isoniazid
Ref: Simon Tiberi et al, “Classifying new antitubercular drugs : rationale and future perspectives”, Oct 2016, page no. 181-184.
45. 45
Group 5
Anti-TB drugs
with limited
data
on efficacy
and long-term
safety in the
treatment of
drug-resistant
TB
Linezolid
Clofazimine
Amoxicillin/cla
vulanate
Imipenem/
Cilastatin
Meropenem
High-dose
isoniazid
Thioacetazone,
Clarithromycin
D2
-Bedaquiline
-Delamanid
D3
- p-Aminosalicylic
acid
-Imipenem
-cilastatin
-Meropenem
-Amoxicillin
-clavulanate
(Thioacetazone)
-p-
Aminosalicylic
acid
-Amoxicillin
-clavulanate
-Rifabutin
Ref: Simon Tiberi et al, “Classifying new antitubercular drugs : rationale and future perspectives”, Oct 2016, page no. 181-184.
46. Isoniazide(10)
46
-Inhibit synthesis of mycolic acid.
-It’s a pro drug activated by by KatG.
-INH enters the bacilli by passive diffusion.
-It must be activated to become toxic to bacilli.
Essential component of all anti TB regimen (except intolerance to H or resistance)
-It is tuberculocidal , kills fast multiplying organism & inhibit slow acting organism
-Acts both on intracellular ( present in macrophages ) & extracellular bacilli
Mechanism of action
Isoniazide
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
47. 47
-It became toxic by Kat G (multifunctional Catalase - peroxidase , a bacterial enzyme )
which catalyzes the product from INH an Isonicotinoyl radical that subsequently inter-
acts with mycobacterial NAD & NADP to produce dozen of adducts , one of these a
nicotinoyl NAD isomer which ↓ the activity of enoyl acyl carrier protein reductase (Inh
A) & β- ketoacyl carrier protein synthase ( Kas A) , inhibition of these enzymes↓ the
synthesis of mycolic acid an essential component of the mycobacterial cell wall &
causes cell death.
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
48. MOA of isoniazide (10)
Mycolic Acid
Arabinogalactan
Peptidoglycan
Cell membrane
R
I
B
O
S
O
M
e
Protein
Isoniazid
-
Pyrazinamide
- Mitochondria
(ATP)
- Rifampin
-
Ethambutol
-
Streptomycin
-
Cytoplasm
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
49. 49
SAR(10):
1. Substitution of hydrazine portion of INH
with alkyl and aryl substitution resulted in
a series of active and inactive derivatives.
2. Substitution on the N2 position (R
1,R2=alkyl,R3=H)---- active compounds.
3. Any Substitution at N1-
hydrogen(R3=alkyl)-- ----------destroy the
activity.
4. Any Substitution--- not superior than
INH.
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
Isoniazide
50. 50
Pharmacokinetics:
-Well absorbed from GIT
-Fatty food & aluminum-containing antacids may reduce absorption
-CSF penetration: 20% of plasma concentration with non-inflamed meninges
-Penetrate well into caseous material
-Excretion - urine
Metabolism
By acetylation – genetically determined
Slow acetylation – better response
t ½ - 3h
Fast acetylation – t ½ - 1h
Adverse effect : -Hepatotoxicity
-Elderly, slow acetylators more prone
-Polyneuropathy
-Prevented by concurrent pyridoxine
-Rashes, acne
-Heamatological – haemolytic anaemia in G6PD deficiency
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
51. Rifampin(10)
Inhibits bacterial DNA-dependent RNA polymerase
bactericidal
Gram positive and negative
kill intracellular organism
-Semisynthetic derivative of Rifamycin B from Streptomyces mediterranei
-Bactericidal to M. Tuberculosis & others –S. aureus
51
Mechanism:
-Inhibit DNA dependant RNA Synthesis (by ↓ bact RNA polymerase , selective because does not↓ mammalian
RNA polymerase )
-TB patient usually do not get primary Rifampicin resistance – If occurs is due to mutation in the repo -B gene (β
subunit of RNA polymerase ).
- No cross resistance Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
52. 52Pharmacokinetics
-Well absorbed from GIT
-CSF penetration: 10-40% of plasma concentration with non-inflamed meninges
-Elimination hepatic, renal
Adverse effects
-Rashes, hepatotoxicity, thrombocytopenia
-Mild elevation of liver enzymes - common
-Orange discoloration of urine, sweat, tears
Potent CYP-P450 inducer- reduce the serum level of drugs
warfarin, oestrogen
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
53. Ethambutol(10)
53
Mechanism:
Inhibits arabinosyl transferases involved in cell wall biosynthesis & also interfere with mycolic acid
incorporation in mycobacterial cell wall
Bacteriostatic to M.tuberculosis
Resistance develops rapidly if used alone
Tuberculostatic , clinically active as Streptomycin
-Fast multiplying bact.s are more sensitive
-Also act against atypical mycobacteria
-If added in triple regimen (RHZ) it is found to hasten the rate of sputum conversion & to prevent
development of resist.
Ethambutol
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
54. 54SAR(10):
– Ethylene diamine chain --↑this chain length --
↓or destroy.
– Replacement of either N--↓or destroy.
– Increasing the size of Nitrogen substituents--
↓or destroy.
– Moving the location of alcohol groups--↓or
destroy. Ethambutol
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
55. 55Pharmacokinetics
-Well absorbed from GIT
-Bioavailability 80%
-CSF penetration poor
-Elimination renal
Adverse effects
-Optic retro-bulbar neuritis
-Red-green colour blindness → reduced visual acuity
-Dose-related
-Reversible
-May be unilateral
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
56. Pyrazinamide ( Z) (10) 56
Chemically≡ INH
-Weak tuberculocidal more active in acidic medium
-More lethal to intracellular bacilli & to those at sites showing an inflammatory response
( Therefore effective in first two months of therapy where inflammatory changes are present )
-Good sterilizing activity
-It’s use enabled total duration of therapy to be shortened & risk of relapse to be reduced.
Mechanism ≡ INH - ↓ fatty acid synthesis but by interacting with a different fatty acid synthesis
encoding gene .
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
57. 57
PZA is thought to enter M. tub. by passive diffusion and converted to
pyrazinoic acid(its active metabolite) by bact. Pyrazinamidase enz. .
This metabolite inhibits mycobact. Fatty acid synthase -I enz. and disrupts
mycolic acid synthesis needed for cell wall synthesis
Mutation in the gene (pcn A) that encodes pyrazinamidase enzyme is
responsible for drug resistance ( minimized by using drug combination therapy)
Pharmacokinetics :
-Absorbed orally, widely distributed ,Good penetration in CSF.
-Metabolized in liver & excreted in urine.
-t½ -6-10 hrs
ADRs :
-Hepatotoxic -dose related
-Arthralgia , hyperuricaemia, flushing , rashes , fever & anaemia
-Loss of diabetic control
Dose – 20-30 mg /kg daily , 1500 mg if > 50 kg
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
58. Second line drugs (10):
1. Streptomycin (S):
58
It was 1st clinically useful antibiotic drug
It is protein synthesis inhibitor by combining with 30S ribosome
It is tuberculocidal , but less effective than INH / Rifampicin
Acts on extracellular bacilli only ( poor penetration in the cells )
It penetrates tubercular cavities but does not cross BBB
- Resistance when used alone (in average popul.1 in 10 to the power 8 bacilli are resistant to streptomycin –
they multiply & cause relapse therefore stopped at the earliest .)
- Atypical mycobact.s are ineffective
-Popularity ↓ due to need of IM inj. & lower margin of safety ( because of ototox. & nephrotox.).
-Dose- 15 ( 12-18 ) mg/kg, >50 mg- 1000mg
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
59. Cycloserine (Cycs) (10): 59
- Obtained from S. archidacces & is a chemical analogue of D- alanine
-↓ Bacterial cell wall synthesis
-Tuberculostatic & ↓ other G -ve organisms ( E. coli , Chlamydia)
-Resistance develop slowly , no cross resist.
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
60. 60Fluoroquinolones (10)
SAR:
– Non fluorinated quinolones are inactive against mycobacteria.
– Different substitution in quinolones improve activity
toward Mycobacterium avium intracellular complex(MAC –
MAI) known as biophores.
• A cyclopropyl ring at N1position.
• F atom at position C-6 and C-8
• A C-7 heterocyclic substituents
– Excessive lipophillicity atN1 can↓activity.
– The N-7 substituents with greatest activity against
mycobacteria include substituted piperazines and
pyrrolidines
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
62. Leprosy (12)
Leprosy is caused by acid fast bacilli called Mycobacterium leprae (M. leprae),
It is an obligate intracellular bacterium.
It mainly affects nerves and skin. (only bacilli that can enter the nerve schwann
cell)
Bacilli have affinity for the cooler tissues.
Bacterium invades either dermal (cutaneous) nerves or main peripheral nerve
trunks situated superficially, in regions that are relatively cooler (face & limbs).
62
Ref: Dr. Janardhan M et al, “Pharmacotherapy of Leprosy”, Page no. 1-27
64. Classification of leprosy (12)
64
For operational purposes WHO divided leprosy into:
1. Paucibacillary leprosy (PBL) : Patient has few bacilli and is noninfectious. It
included the TT and BT types.
2. Multibacillary leprosy (MBL): Patient has large bacillary load and is infectious.
It included the LL, BL and BB types.
Ref: Dr. Janardhan M et al, “Pharmacotherapy of Leprosy”, Page no. 1-27
65. Anti-leprotic agent (12)
65
1. Sulfone:
Dapsone (DDS)
2. Phenazine derivative:
Clofazimine
3. Antitubercular drugs:
Rifampin,
Ethionamide
4. Other antibiotics :
Ofloxacin,
Moxifloxacin,
Minocycline,
Clarithromycin Ref: Dr. Janardhan M et al, “Pharmacotherapy of Leprosy”, Page no. 1-27
66. Dapsone (DDS) (12) 66
It is diamino diphenyl sulfone (DDS), the simplest, oldest,
cheapest, most active and most commonly used member of
its class.
Activity and mechanism :
Dapsone is chemically related to sulfonamides and has the same mechanism of action, i.e.
inhibition of PABA incorporation into folic acid by folate synthase.
The antibacterial action of dapsone is antagonized by PABA.
It is leprostatic at very low concentrations, while growth of many other bacteria sensitive to
sulfonamides is arrested at relatively higher concentrations.
Ref: Dr. Janardhan M et al, “Pharmacotherapy of Leprosy”, Page no. 1-27
67. 67
SAR (10):
– Relpcemnet of 1 benzene ring results in thiazosulfones— less active than DDS
– Substitution on benzene ring results in acetosulphone--↓ activity, ↓g.i.t
irritation(bz increase solubility)
– Substitution by methanesulfinate (CH2SO2)-gives sulfoxone Na, which is
water Soluble, ↓g.i.t irritation(bz increase solubility) –this drug is preferred who
can’t
tolerate DDS-but given 3times of DDS bz of its hydrolysis.
Dapsone
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
68. 68
Dapsone-resistance among M. leprae, first noted in 1964, has spread and has
necessitated the use of multidrug therapy (MDT).
Pharmacokinetics:
Dapsone is completely absorbed after oral administration and is widely
distributed in the body, though penetration in CSF is poor.
It is 70% plasma protein bound, but more importantly it is concentrated in skin
(especially lepromatous skin), muscle, liver and kidney.
Metabolites are excreted in bile and reabsorbed from intestine, so that ultimate
excretion occurs mostly in urine.
The plasma t½ of dapsone is variable, though often > 24 hrs
Contraindications:
Dapsone should not be used in patients with severe anaemia (Hb < 7 g/dl),
G-6-PD deficiency and in those showing hypersensitivity reactions.
Ref: Dr. Janardhan M et al, “Pharmacotherapy of Leprosy”, Page no. 1-27
69. Clofazimine (Clo) (12) 69
It is a dye with leprostatic and antiinflammatory properties.
The putative mechanisms of antileprotic action of clofazimine are:
Interference with template function of DNA in M.leprae
Alteration of membrane stucture and its transport function.
Disruption of mitochondrial electron transport chain.
When used alone, the clinical response to clofazimine is slower than that to dapsone, and
resistance develops in 1–3 years.
Dapsone resistant M. leprae respond to clofazimine, but apparently after a lag period of
about 2 months.
Clofazimine is used as a component of multidrug therapy (MDT) of leprosy. Because of its
antiinflammatory property,
Clofazimine
Ref: Dr. Janardhan M et al, “Pharmacotherapy of Leprosy”, Page no. 1-27
70. 70SAR (10):
– Basic nucleus –phenazine
– Halogen substitution at Pposition of two phenyls at BC-3, and C-10-enhance
activity but are not essential for activity.
– Br > Cl > CH3 >C2H5OH > H >F
Clofazimine
Ref: Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
71. Rifampin (12) 71
o This important tuberculocidal drug is also the most potent cidal drug for M.leprae; rapidly
renders leprosy patients noncontagious.
o Upto 99.99% M.leprae are killed in 3–7 days by 600 mg/day dose.
o Clinical effects of rifampin are very rapid; nasal symptoms in lepromatous leprosy
subside within 2–3 weeks and skin lesions start regressing by 2 months.
o Rifampin has been included in the MDT of leprosy whereby it shortens the duration
of treatment, and no resistance develops.
Rifampin
Ref: Dr. Janardhan M et al, “Pharmacotherapy of Leprosy”, Page no. 1-27
72. Ofloxacin (12) 72
Many fluoroquinolones like ofloxacin, pefloxacin, moxifloxacin, sparfloxacin are highly
active against M.leprae, but ciprofloxacin has poor activity.
It is cidal to M.leprae, and in one study, over 99.9% bacilli were found to be killed by 22
daily doses of ofloxacin monotherapy.
However, it is not yet included in the standard treatment protocols, but can be used in
alternative regimens in case rifampin cannot be used.
Ofloxacin
Ref: Dr. Janardhan M et al, “Pharmacotherapy of Leprosy”, Page no. 1-27
73. Minocycline (12)
73
Because of high lipophilicity, this tetracycline penetrates into M.leprae and is active against
them.
A dose of 100 mg/day produces peak blood levels that exceed MIC against M. leprae by
10–20 times.
Its antileprotic activity is less marked than that of rifampin, but greater than that of
clarithromycin.
Minocycline
Ref: Dr. Janardhan M et al, “Pharmacotherapy of Leprosy”, Page no. 1-27
74. Multidrug therapy (MDT) of leprosy (12) 74
To deal with dapsone resistant strains of M. leprae and to shorten the duration of treatment
(as well as to eliminate microbial persisters, i.e. dormant forms, if possible), multidrug
therapy with rifampin, dapsone and clofazimine was introduced by the WHO in 1981.
This was implemented under the NLEP in 1982.
The MDT is the regimen of choice for all cases of leprosy.
Its advantages are:
• Effective in cases with primary dapsone resistance.
• Prevents emergence of dapsone resistance.
• Affords quick symptom relief and renders MBL cases noncontagious within few days.
• Reduces total duration of therapy Initially under standard MDT, the PBL cases
Ref: Dr. Janardhan M et al, “Pharmacotherapy of Leprosy”, Page no. 1-27
75. 75
Multi drug therapy
Multibacillary Paucibacillary
Rifampicin 600 mg once a month
supervised
600 mg once a month
supervised
Dapsone 100 mg daily self
administered
100 mg daily self
administered
Clofamzimine 300 mg once a month
supervised and
50 mg daily self
administered
-
Duration 12 month 6 month
Doses to be reduced suitably for children
Multidrug therapy for leprosy
Ref: Dr. Janardhan M et al, “Pharmacotherapy of Leprosy”, Page no. 1-27
76. 76Regimen PBL MBL
Intermittent ROM R(600mg)+
Ofl(400mg)+Min(100
mg) once in monthupto
6 months
R(600mg)+Ofl(400mg
)+Min(100mg) once
in month- upto 24
months
Intermittent RMMx Mox(400mg)+Min(20
0mg)+R(600mg) once
in month-upto 6
months
Mox(400mg)+Min(20
0mg)+R(600mg) once
in month-upto 12
months
Four drug Regimen R(600mg)+Spar(200m
g)+Clar(500mg)+Min(
100mg)- 3 months
Alternative Regimen:
Ref: Dr. Janardhan M et al, “Pharmacotherapy of Leprosy”, Page no. 1-27
77. Conclusion (12) 77
1. Drug therapy of Leprosy started with chalmoogra oil .
2. Currently MDT therapy is advised.
3. Alternative regimens are ROM, RMMx and Four drug regimen.
4. Drug of choice in lepra reaction is corticosteroids.
Ref: Dr. Janardhan M et al, “Pharmacotherapy of Leprosy”, Page no. 1-27
78. 78
NRTIs inhibit this process because, as the name implies, they are analogues of the natural ATGC
nucleotides that are normally used by the reverse transcriptase to build DNA. However, NRTIs lack the 3' -
OH group necessary for the next DNA base to attach. Thus, NRTIs work by competitively inhibiting
reverse-transcriptase.
NNRTIs work in a completely different fashion, by directly binding the reverse transcriptase enzyme. They
are NOT nucleoside analogs and are NOT incorporated into the DNA strand. NNRTIs work by non-
competitive inhibition.
79. Key References
1. https://www.hiv.va.gov/patient/basics/what-is-HIV.asp
2. Neal Nathanson, et al, “ PATHOGENESIS OF AIDS-how does HIV cause AIDS?”,University of
Pennsylvania School of Medicine, page no. 1-25.
3. Edward C Klatt et al, “Pathology of HIV/AIDS”, Version 27, Mercer University, April 2016,
page no. 1-118.
4. http://aidsinfo.nih.gov.
5. Noga Shalev et al, “Antiretroviral Drugs in the Treatment and Prevention of HIV Infection”,
page no. 1-40.
6. https://www.google.co.in/search?q=HIV+image
7. McMichael et al. (2010) “The immune responses during acute HIV-1 infection: Clues for vaccine
development”, page no.11-23.
79
80. Key References
80
8. Benjamin Young et al, “HIV Medication and side effect”,International Association of
Physicians in AIDS Care, page no. 1-30
9. https://pubchem.ncbi.nlm.nih.gov(Date of acess: 8/3/2018)
10.Ahmed Aljifri et al, “Antimycobacterial”, page no.1-30
11.Simon Tiberi et al, “Classifying new antitubercular drugs : rationale and future perspectives”,
Oct 2016, page no. 181-184.
12.Dr. Janardhan M et al, “Pharmacotherapy of Leprosy”, Page no. 1-27.