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
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watch video:https://www.youtube.com/watch?v=v3rI1lf2TZ8&t=403s
This slide describes the Important Synthesis of Antiviral Drugs
antiviral drugs medicinal chemistry by padala varaprasadVaraprasad Padala
medicinal chemistry of antiviral drugs by padala varaprasad
mainly includes structures, SAR , mechanism of action, uses and toxicity of antiviral drugs
Antiviral Agents,Medicinal Chemistry
•Introduction to Viruses
•Structure of Virus
•Types of Viruses.
•The viral Life cycle.
•Classification of Antiviral Agents
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
subscribe the channel :Work&Life Hobbies
watch video:https://www.youtube.com/watch?v=v3rI1lf2TZ8&t=403s
This slide describes the Important Synthesis of Antiviral Drugs
antiviral drugs medicinal chemistry by padala varaprasadVaraprasad Padala
medicinal chemistry of antiviral drugs by padala varaprasad
mainly includes structures, SAR , mechanism of action, uses and toxicity of antiviral drugs
Antiviral Agents,Medicinal Chemistry
•Introduction to Viruses
•Structure of Virus
•Types of Viruses.
•The viral Life cycle.
•Classification of Antiviral Agents
classification of antiviral agents,replication of HIV virus and replication of virus.targets of virus,classification of antiviral agents with structure and mechanism action of antiviral agents
MICROBIAL BIOTRANSFORMATION & ITS APPLICATIONS.pptxAnupkumar Sharma
The presentation focuses on the method of microbial biotransformation and various reactions involved in the process. It also describes the various applications of microbial biotransformation.
Hello friends. In this PPT I am talking about Anti-viral drugs drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
Adult HIV was developed by doctors and nurses with wide experience in the care of adults with HIV, under the auspices of the Desmond Tutu HIV Foundation at the University of Cape Town. It covers: introduction to HIV infection, management of HIV-infected adults at primary-care clinics, preparing patients for antiretroviral (ARV) treatment, ARV drugs, starting and maintaining patients on ARV treatment, opportunistic infection. The aim of the book is to enable healthcare workers at primary-care clinics to manage all aspects of HIV-related patient care.
classification of antiviral agents,replication of HIV virus and replication of virus.targets of virus,classification of antiviral agents with structure and mechanism action of antiviral agents
MICROBIAL BIOTRANSFORMATION & ITS APPLICATIONS.pptxAnupkumar Sharma
The presentation focuses on the method of microbial biotransformation and various reactions involved in the process. It also describes the various applications of microbial biotransformation.
Hello friends. In this PPT I am talking about Anti-viral drugs drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
Adult HIV was developed by doctors and nurses with wide experience in the care of adults with HIV, under the auspices of the Desmond Tutu HIV Foundation at the University of Cape Town. It covers: introduction to HIV infection, management of HIV-infected adults at primary-care clinics, preparing patients for antiretroviral (ARV) treatment, ARV drugs, starting and maintaining patients on ARV treatment, opportunistic infection. The aim of the book is to enable healthcare workers at primary-care clinics to manage all aspects of HIV-related patient care.
Several virus-coded enzyme activities are generally required for the replication of viral DNA. These are helicase (with ATPase activity) to unwind the double helix, helix-destabilizing protein to keep the two separated strands apart, DNA polymerase to copy each strand from the origin of replication, RNAse to degrade the RNA primer after it has served its purpose, DNA ligase to join the Okazaki fragments together
Ques-7Viruses contain DNA (deoxyribonucleic acid) or RNA (ribonuc.pdfaquacare2008
Ques-7:
Viruses contain DNA (deoxyribonucleic acid) or RNA (ribonucleic acid) as their genetic
material, and they reproduce in the host cells. Bacteriophage is a type of virus that can infect
bacteria and inject its genome into the host, the bacteria then produces dozens of viral lineages.
Retrovirus such as HIV (human immune deficiency virus) reproduces in a different way, as they
contain reverse transcriptase enzyme. In this, a complementary DNA is transcribed from the
RNA genome, and it is called as DNA provirus.
The rate of evolution in RNA-based viruses (microcosm), like HIV-1 has million times higher
mutation rate when compared to that of DNA-based organisms (bacteria humans etc). It can
rapidly changes its genome components under biological conditions to acquire adaptations for
survival (resistance against drugs, immune components) in the biological host cell medium
compared to the DNA based organisms in which lower rate of evolutionary adaptations were
observed. This property of high genomic mutation rate in HIV-1 retrovirus is due to the
following mechanisms.
Viral genome transcribe via reverse transcription finally proved HIV-1 mRNA (after splicing)
with Rev 350 nucleotide sequences. These Rev produced once the viral mRNA transferred to the
cytoplasm from the nucleus for translation. Virulence is the factor of causing extensive damage
to the host cell and infecting new host cell in which pathogen is going to undergo extensive rate
of reproduction & phase variation along with genome modification to defend host immune
system. This is the main basis of evolution and an example ahs described below.
Several mutated viral lineages are produced due to the nucleotide integration into the host cells
& change their genome finally code for the enzymatic proteins such as reverse transcriptase,
ribonuclease, and integrase in order to promote severe multiplication of integrated host genome
with viral protein predominanlty result in several lineages (multiple capies of virions).
For example: Viral evolution mechanism with new genome & producetion of several viral
lineages
1. After viral particle entry, viral genome integrates into the host cell genome and replicate
followed by expression. Later the novel synthesized viral proteins are going to be transported to
specific sites for assembly into progeny virus thereby-----> more assembly/progeny
2. Even though viral assembly is going to takes place in the host cell plasma membrane, but a
variety of viral genomes initiate assembly in intracellular organelles or nucleus predominantly.
Thereby further particle/plaque forming units associate with exocytosis of the viral and host cell
integrated genome after lysis. Finally again mature viral lineages are going to target new cells.
Reverse transcriptase induced complementary DNA synthesis followed by mRNA synthesis for
viral protein -coding repoitre. This enzyme enables to produce more viral genome particle by
integrating into the host cell followed by vir.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
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micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
1. ANTI RETRO VIRAL DRUGS
G Vijay Narasimha Kumar
Asst. Professor,
Dept. of. Pharmacology,
Sri Padmavathi School of Pharmacy
2. RETRO VIRUS
A retrovirus is a virus that has RNA as its genetic
material instead of DNA. When a retrovirus infects a
cell, it makes a DNA copy of its genome that is
inserted into the DNA of the host cell by using an
enzyme reverse transcriptase.
Example: Human immunodeficiency virus (HIV).
4. STRUCTURE OF HIV
HIV is an Icosahedral (20 sided), enveloped virus.
Family : Retroviruses.
Subfamily : Lentivirus
Retroviruses transcribe RNA to DNA.
Viral strands of RNA is found in core surrounded by
protein outer coat.
Outer envelope contains a lipid matrix within which
specific viral glycoproteins are imbedded.
These knob-like structures are responsible for
binding to target cell.
5.
6.
7. Envelope:
It is an outer lipid surface of the virus which
is embedded with glycoproteins. These glycoproteins
includes gp120 and gp41 which are formed from
gp160.
Functions:
Gp120- helps in recognition of target cells(CD4+
cells) by binding to target cell receptors.
CD4+ cells – Macrophages
Monocytes
T-helper cells
Microglial cells
Langerhan cells
Dendritic cells.
8. Gp41 – helps in fusion of virus with host cell
membrane.
After binding to CD4 cells, Gp120 undergoes
confirmational changes and produce CCR5 and
CXCR4 domains .These domains bind with the CCR5
and CXCR4 chemokine recptors found on
macrophages and Th lymphocytes respectively, which
helps in fusion.
9.
10. Supporting the glycoproteins, matrix is present
which is made up of P17 proteins.
Core capsid that contains HIV RNA is made up of
P24 and P7 proteins among which P24 is
abundantly distributed.
[Host macrophages produces antibodies against P24 which are useful
in diagnosis by ELISA and Western blot test]
11. RNA:
HIV consists of two single stranded RNA.These two strands
are identical but not complementary to each other.
HIV RNA ressembles eukaryotic m-rna with poly-A tail a
guanosine 5 prime capping. But it was unable to enter in
host ribosomes directly unless, it undergoes rever
transcription.
HIV RNA consists of three main structural genes:
• Group Specific Antigen - Gag gene
• Envelope- Env gene
• Polymerase- Pol gene
12. Gag gene codes for P24,P7,P17 proteins of capsid
and matrix.
Env gene codes for envelope proteins gp160 which is
cleaved into gp120 and gp41.
These proteins involved with fusion and attachment of
HIV to host cells.
Pol gene codes for p66 and p51 which are subunits of
reverse transcriptase and p31 an endonuclease
[integrase and protease].
13.
14.
15. VIRAL REPLICATION
The virus goes through multiple steps to reproduce itself
and create many more virus particles.
The seven stages of the HIV life cycle are:
1) Binding 2) Fusion
3) Reverse transcription
4) Integration
5)Transcription and translation
6) Assembly
7) Budding
16. BINDING/ ATTACHMENT:
• In early phase HIV infection, initial viruses are M-
tropic. Their envelope glycoprotein gp120 is able to
bind to CD4 molecules and chemokine receptors
called CCR5 found on macrophages .
• In late phase HIV infection, most of the viruses are T-
tropic, having gp120 capable of binding to CD4 and
CXCR4 found on Th-lymphocytes.
17. FUSION :
HIV envelope and the CD4 cell membrane fuse with
the help of gp41 which allows HIV to enter the CD4
cells and uncoating occurs to release the viral RNA.
18. REVERSE TRANSCRIPTION:
A special enzyme called reverse
transcriptase changes the genetic material of the
virus, i.e., from RNA to DNA, so it can be integrated
into the host DNA.
RT has two domains namely, RNA dependent DNA
polymerase domain and RNAase domain.
19. RNA dependent DNA
polymerase
Forms complementary
DNA to viral RNA
By using host DNA
polymerase the single
stranded DNA is
converted into double
stranded [pro-viral DNA]
RNAase cleaves the
RNA after DNA
formation
Two identical single
stranded DNAs are
formed
20. INTEGRATION: The virus DNA enters
the nucleus of the CD4 cell and uses an
enzyme called integrase to integrate itself into
host DNA, where it may “hide” and stay
inactive for several years.
21. TRANSCRIPTION : Viral DNA ends are sticky in
nature and contains GAG gene ,POL gene, ENV
gene. It also contains long terminal repeats [LTRs] at
its ends . These LTRs contains promoter box which
promotes the transcription.
Viruses use host transcriptional machinery for its
transcription process and it also use some virus
transcriptional factors like TAT and forms m-RNA.
22.
23. TRANSLATION:
The formed m-RNA translates into inactive long chain
polyproteins.
ASSEMBLY: By using the enzyme called as protease
the poly proteins are cleaved into active viral proteins.
GAG gene P24, P7, P17 proteins.
POL gene Reverse transcriptase ,
integrase ,protease.
ENV gene gp160 [gp41 and gp120]
If all the three genes continously transcribed at a time,
the genomic RNA was formed.
All the proteins and RNA assembles to form a new
virus .
24. BUDDING:
This is the final stage of the virus life cycle. In
this stage, the virus pushes itself out of the host
cell [buds] by exocytosis and contains all of the
structures necessary to bind to a new CD4 cell
receptors and begin the process again and infect
the other cells.
25. (1) Viral genome
and reverse
transcriptase
enter cell.
(2) DNA copy synthesized by
reverse transcriptase.
(3) RNA degraded;
second DNA strand
synthesized.
(8) Final viral assembly
and budding
take place.
(5) With host cell
activation, viral
DNA is transcribed,
yielding messenger RNAs
and viral genome RNA.
(6) Viral RNAs are
translated, yielding
viral enzymes
(including protease)
and structural
proteins.
Host cell
nucleus
Host cell
genome
Site of action of AZT
and other reverse
Transcriptase
inhibitors
Site of action
of protease
inhibitors
RNA
DNA
DNA
DNA
(7) Viral membrane proteins are
transported to host cell membrane.
(4) DNA circularizes (unintegrated
provirus) or integrase functions
to incorporate DNA into host cell
genome (integrated provirus).
Site of action
of antiretroviral
drugs
under
development
27. (1) Viral genome
and reverse
transcriptase
enter cell.
(2) DNA copy synthesized by
reverse transcriptase.
RNA
DNA
28. (1) Viral genome
and reverse
transcriptase
enter cell.
(2) DNA copy synthesized by
reverse transcriptase.
Site of action of AZT
and other reverse
Transcriptase
inhibitors
RNA
DNA
(3) RNA degraded;
second DNA strand
synthesized.
DNA
DNA
29. (1) Viral genome
and reverse
transcriptase
enter cell.
(2) DNA copy synthesized by
reverse transcriptase.
(3) RNA degraded;
second DNA strand
synthesized.
Host cell
nucleus
Host cell
genome
Site of action of AZT
and other reverse
Transcriptase
inhibitors
RNA
DNA
DNA
DNA
(4) DNA circularizes (unintegrated
provirus) or integrase functions
to incorporate DNA into host cell
genome (integrated provirus).
Site of action
of antiretroviral drugs
under development
30. (1) Viral genome
and reverse
transcriptase
enter cell.
(2) DNA copy synthesized by
reverse transcriptase.
(3) RNA degraded;
second DNA strand
synthesized.
(5) With host cell
activation, viral
DNA is transcribed,
yielding messenger RNAs
and viral genome RNA.
Host cell
nucleus
Host cell
genome
Site of action of AZT
and other reverse
Transcriptase
inhibitors
RNA
DNA
DNA
DNA
(4) DNA circularizes (unintegrated
provirus) or integrase functions
to incorporate DNA into host cell
genome (integrated provirus).
Site of action
of antiretroviral drugs
under development
31. (1) Viral genome
and reverse
transcriptase
enter cell.
(2) DNA copy synthesized by
reverse transcriptase.
(3) RNA degraded;
second DNA strand
synthesized.
(5) With host cell
activation, viral
DNA is transcribed,
yielding messenger RNAs
and viral genome RNA.
(6) Viral RNAs are
translated, yielding
viral enzymes
(including protease)
and structural
proteins.
Host cell
nucleus
Host cell
genome
Site of action of AZT
and other reverse
Transcriptase
inhibitors
Site of action
of protease
inhibitors
RNA
DNA
DNA
DNA
(4) DNA circularizes (unintegrated
provirus) or integrase functions
to incorporate DNA into host cell
genome (integrated provirus).
Site of action
of antiretroviral drugs
under development
32. (1) Viral genome
and reverse
transcriptase
enter cell.
(2) DNA copy synthesized by
reverse transcriptase.
(3) RNA degraded;
second DNA strand
synthesized.
(5) With host cell
activation, viral
DNA is transcribed,
yielding messenger RNAs
and viral genome RNA.
(6) Viral RNAs are
translated, yielding
viral enzymes
(including protease)
and structural
proteins.
Host cell
nucleus
Host cell
genome
Site of action of AZT
and other reverse
Transcriptase
inhibitors
Site of action
of protease
inhibitors
RNA
DNA
DNA
DNA
(7) Viral membrane proteins are
transported to host cell membrane.
(4) DNA circularizes (unintegrated
provirus) or integrase functions
to incorporate DNA into host cell
genome (integrated provirus).
Site of action
of antiretroviral drugs
under development
33. (1) Viral genome
and reverse
transcriptase
enter cell.
(2) DNA copy synthesized by
reverse transcriptase.
(3) RNA degraded;
second DNA strand
synthesized.
(8) Final viral assembly
and budding
take place.
(5) With host cell
activation, viral
DNA is transcribed,
yielding messenger RNAs
and viral genome RNA.
(6) Viral RNAs are
translated, yielding
viral enzymes
(including protease)
and structural
proteins.
Host cell
nucleus
Host cell
genome
Site of action of AZT
and other reverse
Transcriptase
inhibitors
Site of action
of protease
inhibitors
RNA
DNA
DNA
DNA
(7) Viral membrane proteins are
transported to host cell membrane.
(4) DNA circularizes (unintegrated
provirus) or integrase functions
to incorporate DNA into host cell
genome (integrated provirus).
Site of action
of antiretroviral drugs
under development
34. REGULATORY PROTEINS :
Some regulatory proteins are produced by the viral
DNA by frame shift process.
TAT protein : Enhances transcription.
REV protein : Enhances translation by enhancing the
movement of m-rna into ribosomes.
VIF protein : Inhibits APOBEC3G, there by enhances
the viral infectivity
VPR protein : Enhances viral replication
VPU protein : Enhances viral release by inhibiting the
tethrin [an IFN protein ]
NEF protein : Inhibits cell mediated immunity.
35. STAGES OF HIV INFECTION
Normal CD4 count-500 to 1200cells/cumm
36. • The persons of all three stages are able to transmit
HIV infection to others.
DIAGNOSIS :
• Antibody test – ELISA ,western blot test.
• Viral antigen test – P24 antigen test.
• Nucleic acid amplification testing.
• Window periods for this tests are 24 , 16 , 12 days
respectively.
60. Mechanism of action:
These drugs acts as false nucleotides/sides.
Due to similar structure as that of
nucleotides,these are incorporated into growing
DNA strand instead of nucleotides and
terminate the synthesis of DNA due to lack of
OH group.
61. PHARMACOKINETICS:
o Orally well absorbed.
o All are metabolised in liver by CYP450 enzymes
except ABACAVIR.
o ABACAVIR is metabolised by Alcohol
dehydrogenase .
o All drugs are renally excreted.
62. Adverse effects :
o These drugs do have some affinity to human
mitochondrial DNA polymerase ( except Abacavir)
which leads to the following adverse effects.
• Bonemarrow toxicity [anaemia,leucopaenia].
• Hepatotoxicity [fatty liver, hepatic steatosis,
hepatomegaly , hepatic lactic acidosis].
• Lipodystrophy.
• Peripheral neuritis.
64. TENOFOVIR
o It is an acyclic phosphonate of adenosine mono
phosphate and converts to triphosphate in liver. It has
long half life.
o It directly inhibits reverse transcriptase (DNA polymerase)
. But, as it is an nucleoside analogue it is categorised as
NRTI.
ADRs:
o Only GI disturbances.
o Enzyme inducer that may increase the metabolism of
Atazanavir.
65. ABACAVIR
o Not used due to potent ADR’s.
ADR’s:
Hypersensitivity, nausea, vomiting, diarrhea.
LAMIVUDINE
2-Deoxy-thiacytidine
converts
tri phosphate
act as
analogues that competes with dCTP
inhibits
reverse transcriptase.
66. ADRs:
o No bone marrow toxicity due to less affinity to
mitochondrial DNA polymerase.
o But in kidney disease creatinine clearance have to be
monitored.
USE: Besides HIV It also inhibits replication of
hepatitis-B virus.Hence used in Hepatitis also.
67. EMTRICITABINE
o It is flouro derivative of lamivudine.
o High bioavailability.
o Extracelluar:10hrs.
o Intracellular:39hrs.
o Due to it’s low t1/2 it is preffered with TENOFOVIR.
o It Causes hyperpigmentation of palms and soles.
68. ZIDOVUDINE (AZT)
o Zidovudine is an Azido deoxy thymidine
monophosphate which is converted into triphosphate.
o More CNS penetration and crosses placental barrier
and breast milk.
o Causes severe ADR’s except peripheral neuritis.
o Due to its potency it was used in prevention of
perinatal transmission as prophylaxis (Zidovudine IV
was given during labour).
69. STAVUDINE
oNot used widely due to its potency to cause
peripheral neuritis and other potent adverse effects.
70. NNRTIs (lipophillic)
o These are non competitive inhibitors of DNA
polymerase of reverse transcriptase . These drugs
binds with the allosteric site of an enzyme.
NEVIRAPINE:
o Metabolised by liver hence it may cause
hepatotoxicity.
o It cross CNS and cause headache,dizziness, vivid
dreams.
o It causes Type-1 and Type-2 Hypersensitivity
reactions, mostly rashes, stevens johnsons syndrome
, toxic epidermal necrolysis. So not used widely.
71. DELAVIRIDINE
o Poor antiviral activityand hence not used.
EFAVERINZ
o Less toxicities, only skin rashes may occur.
o It is teratogenic hence in pregnancy it is not used.
ETRAVIRINE,RILPIVIRINE
o Second generation and less resistant NNRTIs.
o Use only when in patients who are on HAART therapy
and even though viral load increases.
o NRTI’S have less chance of resistance(these are
analogues),where as NNRTI’S have more chances
for cross resistance(many drugs on same site
directly).
72. PROTEASE INHIBITORS
MOA :
Inhibits HIV aspartyl protease
leads to synthesis of
Non functional long polypeptide chains.
PHARMACOKINETICS:
• Orally well absorbed.
• Have protein binding nature.
• Metabolised in liver.
• Renal excretion .
73. ADRs:
• Protease inhibitors are CYP450 inhibitors there by
inhibits metabolism of other drugs.
Eg: WARFARIN which leads toBleeding.
ATORVASTATIN- Rhabdomyolysis.
ANTIARRHYTHMICS- CVS abnormalities.
ANTIEPILETICS-Sedation.
SEDATIVES-Sedation.
74. o They should not be taken with RIFAMPICIN because
it is an enzyme inducer. Hence it decrease levels of
protease inhibitors.
o GI disturbances like nausea, vomiting, diarrhea.
o Parasthesias.
o They cause various metabolic disturbances like
hyperglycaemia, hyper cholesteraemia which leads to
Buffalo hump and accumulation of fats in abdomen in
males and breast enlargement along with buffalo
hump in females.
75. RITONAVIR
o Not used due to ADR’s but given as pharmacokinetic
booster at subtherapeutic levels 100mg.
o In subtherapeutic levels it inhibits CYP450 enzyme.
Hence it increases bioavailability of other
concomitantly taken protease inhibitors such as
ATAZANAVIR and DARUNAVIR except NELFINAVIR.
76. INTEGRASE STRAND TRANSFER
INHIBITORS
The enzyme integrase contains active site which
contains metal ions.
Integrase inhibitors
forms complexes with metal ions
Inhibits cleavage of DNA and there by integration.
ADR’s:
GI disturbances
77. Fusion inhibitors
ENFUVIRITIDE: Gp41 blocker
Inhibits fusion of virus with host cell membrane.
• It is a polypeptide,so given subcutaneously but not orally.
• It is given in patients who are on HAART therapy and
even though viral load increases.
MARAVIROC: CCR5 antagonist
• Not used due to potential adverse effects.
78. HighlyActiveAnti Retroviral Therapy
[HAART]
GOALS :
To decrease viral replication.
To restore/preserve immunological function.
To prolong the life span of patient.
To improve the quality of life of the patient.
HAART regimen:
2NRTIs + 1protease inhibitor/ 1 NNRTI / 1 Integrase
inhibitor
79. Criteria forselection of drugs
No NRTIs
having same
structure
analogues
are selected.
Patient factors like
comorbidities,
oppurtunistic
infections,patient
adherence should
be considered.
Drugs having
drug –drug
interactions
should not be
selected.
Two drugs
having same
toxicities
should not be
selected.
80. Mostly used regimens
Tenofovir + Emtricitabine + Nevirapine.
Tenofovir + Emtricitabine + Ritonavir.
Tenofovir + Emtricitabine + Atazanavir + Ritonavir
booster.
Tenofovir + Emtricitabine + Darunavir.
Tenofovir + Emtricitabine + Raltegravir.
NOTE:
Ritonavir booster was given in sub therapeutic dose
which maintains the Atazanavir concentration as
Tenofovir increase the metabolism of Atazanavir.
Tenofovir , Emtricitabine was mostly prefered due to
less adverse effects and good bioavailability.
81. HIV in pregnancy
Viral load should be maintained at <1000 virus/ml.
Rx- ZIDOVUDINE
EMTRICITABINE
LAMIVUDINE
TENOFOVIR
NRTI’S: NEVIRAPINE was used only when CD4+
count is <200 cells because it cause hepatotoxicity.
82. Zidovudine IV was given during labour to prevent perinatal
transmission.
After 6 hours of delivery ,the child was given with HAART
irrespective of infection.
This therapy was continued upto 6 weeks then Bactrim
was given to prevent pneumonia.
HIV test was done three times for child i.e., at 16-20 days
, at 4 weeks and at 4-6 months.
Breast feeding was contraindicated.
Caesarian delivery at 38 weeks (2 weeks before expected
date of delivery) is prefered rather than normal vaginal
delivery.