This document discusses different classes of antiviral drugs used to treat various viral infections. It begins by outlining the challenges in designing antiviral treatments due to viruses parasitizing host cells and hijacking their metabolic pathways. The document then summarizes the general antiviral strategies of inhibiting viral enzymes, penetration/uncoating, reverse transcription, assembly/maturation, and release. It proceeds to classify specific antiviral drugs for herpes viruses, influenza, hepatitis viruses, and HIV/AIDS. The remainder provides more detailed descriptions of representative drugs in each class, including their mechanisms of action, antiviral spectra, pharmacokinetics, therapeutic uses, and adverse effects.
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.
synthetic antimicrobials having a quinolone structure that are active primarily against gram-negative bacteria, though newer fluorinated compounds also inhibit gram-positive ones.
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.
synthetic antimicrobials having a quinolone structure that are active primarily against gram-negative bacteria, though newer fluorinated compounds also inhibit gram-positive ones.
This presentation deals with important pathophysiological steps involved with HIV infection, the various classes of drugs used in treatment of this condition, along with WHO-guidelines for treatment regimen(depending on various ages & conditions).
Newer drugs have also been mentioned and emphasized upon.
MAINLY FOCUSING ON MONONCLONAL ANTIBODIES,TYPES OF IT, METHOD OF PRODUCTION, FDA APPROVED MABs, & HOSPITAL COMMONLY USED MONOCLONAL ANTIBODIES, DISSCUING THE ECONOMICS AS WELL.
A Power point presentation on Betalactam antibiotics suitable for undergraduate medical students. This Ppt is already presented in theory class lectures to the students of NEIGRIHMS, Shillong, Meghalaya
A Powerpoint presentation on drugs excretion and elimination suitable for UG medical students. This ppt is already presented to my students in one of the theory classes.
A PowerPoint presentation on "NSAIDS" suitable for reading by UG and PG Medical/Paramedical students of Pharmacology and Pharmacy sciences. This Ppt. is prepared for academic purpose only and already presented to my students in one of the theory classes of mine.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
1. ANTIVIRAL DRUGS
DR. D. K. BRAHMA
ASSOCIATE PROFESSOR
DEPARTMENT OF PHARMACOLOGY
NEIGRIHMS, SHILLONG
2. TREATMENT APPROACHES
• ULTIMATE EXPRESSION OF PARASITISM
• TAKES NUTRITION FROM HOST
• ALSO DIRECT HOST`S METABOLIC PATHWAYS TO SYNTHESIZE VIRUS PARTICLES
• CHALLENGES IN DESIGNING ANTI-VIRAL TREATMENTS:
– HOST CELL MUST BE IMMUNE TO TREATMENT! (TO LIMIT OFF-TARGET TOXICITY)
– VIRAL INFECTION DISEASE SYMPTOMS OFTEN ASSOCIATED WITH LATENCY PERIOD (REPLICATION AT PEAK WHEN
SYMPTOMS APPEAR) – INCUBATION PERIOD THERAPY
• GENERAL ANTI-VIRAL STRATEGIES ARE TO INHIBIT:
1. VIRAL ENZYMES:
• DNA/RNA POLYMERASES, ETC.
• REVERSE TRANSCRIPTASES, PROTEASES, ETC.
2. PENETRATION AND UNCOATING
3. REVERSE TRANSCRIPTION
4. ASSEMBLY AND MATURATION
5. RELEASE OF VIRUS
4. ANTI-HERPES VIRUS DRUGS
• EFFECTIVE AGAINST HERPES GROUP OF DNA VIRUSES
• HERPES SIMPLEXVIRUS – 1 (HSV-1 ), HERPES SIMPLEXVIRUS – 2 (HSV-2),
VARICELLAZO STER VIRUS (VZV), EPSTEIN-BARR VIRUS (EBV) AND
CYTO MEGALO VIRUS (CMV)
5. ANTI-HERPES VIRUS DRUGS
• IDOXURIDINE: 5-IODO 2-DEOXYURIDINE (IUDR) – FIRST PYRIMIDINE
ANTIMETABOLITE
• MOA: COMPETES WITH THYMIDINE AND GETS INCORPORATED IN DNA – FAULTY
DNA FORMS WHICH BREAKS DOWN EASILY
• USES: TOPICAL USES ONLY – HERPES SIMPLEX KERATITIS (SUPERFICIAL
DENDRITIC KERATITIS)
• WHEN RAPID ACTION REQUIRED – ACTS FASTER THAN ACYCLOVIR (MORE
USEFUL WHEN STROMAL INVOLVEMENT OF CORNEA)
• DRAWBACK: LOCAL TOXICITY, OCULAR IRRITATION, LOW VIRUS SELECTIVITY
AND QUICK RESISTANCE
• TRIFLURIDINE: FLUORINATED NUCLEOSIDE - HSV-1 , (HSV-2) AND CMV
AND RELATED VIRUSES – LOW VIRUS SELECTIVITY AND INTERFERES
HOST DNA SYNTHESIS – USED IN H. SIMPLEXKERATITIS
6. ACYCLOVIR
• SEEN AS A “NEW AGE” IN ANTIVIRAL THERAPY, GERTRUDE ELION, ITS CREATOR,
WAS GIVEN THE NOBEL PRIZE FOR MEDICINE IN 1988
• A WIDELY USED ANTIVIRAL WITH MAIN IMPLICATIONS IN THE TREATMENT OF
HERPES
• IT IS A NUCLEOSIDE ANALOGUE (DEOXYGUANOSINE) AND PREVENTS DNA
SYNTHESIS VIRAL REPLICATION IN INFECTED CELLS
• EXTREMELY SELECTIVE AND LOW IN TOXICITY
7. ACYCLOVIR – STRUCTURE
• Purine Mimic
• Similarity to 2`-deoxyguanosine (dGTP): lack of 3` hydroxyl
8. ACYCLOVIR - MOA
Step 1: Activation
Selectively taken up by
virus infected cells
No damage to host cells
9. ACYCLOVIR - MOA
Step 2: (i) Competitive Inhibition of herpes virus DNA polymerase
activity; (ii) Incorporation into growing DNA chain
Inhibits DNA-
polymerase
irreversibly
10. ACYCLOVIR – MOA (SUMMARY)
Acyclovir
Acyclovir Monophosphate
Acyclovir triphosphate
Herpes virus specific thymidine kinase
Cellular kinases
Inhibits herpes virus DNA
Polymerase competitively
Gets incorporated in viral DNA
and stops lengthening of DNA strands. The
terminated DNA
Inhibits DNA-polymerase
irreversibly
11. ACYCLOVIR – ANTIVIRAL SPECTRUM
• EFFECTIVE AGAINST THE FOLLOWING:
1.HERPES SIMPLEXVIRUS TYPE I (HSV-1)
2. HERPES SIMPLEXVIRUS TYPE II (HSV-2)
3. VARICELLA ZOSTERVIRUS (VZV)
4. EPSTEIN-BARRVIRUS (EBV)
5. CYTOMEGALOVIRUS (CMV) -- LEAST ACTIVITY
• RESISTANCE: HSV – MUTANTS DEFICIENT OF THYMIDINE
KINASE; VZS – CHANGE IN SPECIFICITY OF VIRUS DIRECTED
ENZYME- AFFINITY FORACYCLOVIRDECREASED
12. ACYCLOVIR - PHARMACOKINETICS
• POOR ORAL ABSORPTION AND IS ONLY 15 - 20%
(LIPOPHILIC) AND UNAFFECTED BY FOOD
• GOOD CSF PENETRATION (50% 0F PLASMA)
• AFTER TOPICAL APPLICATION – PENETRATES CORNEA
• EXCRETED UNCHANGED IN URINE – GLOMERULAR FILTRATION AND ACTIVE TUBULAR
SECRETION
• HALF-LIFE: 2-3 HRS ONLY
• RENAL IMPAIRMENT – DOSE REDUCTION
ADRS: LOCAL – STINGING AND BURNING SENSATION ON APPLICATION, ORAL – HEADACHE, NAUSEA
MALAISE, IV – RASH, SWEATING, EMESIS, HYPOTENSION. NEUROLOGIC TOXICITY (E.G.,
TREMORS, DELIRIUM, SEIZURES, DISORIENTATION, HALLUCINATIONS AND COMA)
DOSE DEPENDENT DECREASE IN GFR
13. ACYCLOVIR – THERAPEUTIC USES
1. GENITAL HERPES SIMPLEX: HSV – II (TOPICAL, ORAL AND IV))
– PRIMARY DISEASE: GENERALLY OINTMENT IN MILD – MORE SEVERE CASES - ORAL (1 GM/DAY IN 5 DIVIDED
DOSES)
– RECURRENT DISEASE: ORAL (NOT EFFECTIVE) – IV (5 MG/KG INFUSED OVER 1 HOUR Q 8 HRLY FOR 10 DAYS)
(SUPPRESSIVE ORAL THERAPY 400 MG BD – PREVENT RECURRENCES – CONTINUOUS ORAL THERAPY FOR CASES
WITH >8 RECURRENCES PER YEAR)
1. MUCOCUTANEOUS H. SIMPLEX: HSV - I
– ACYCLOVIR CREAM
– ORAL OR IV IN IMMUNOCOMPROMIZED PATIENTS (15 MG/KG/DAY FOR 7 DAYS)
1 . H. SIMPLEX ENCEPHALITIS: DOC TYPE – 1
– 10 TO 20 MG/KG/8HR X 10 DAYS
1 . H. SIMPLEX KERATITIS: SUPERFICIAL DENDRITIC CORNEAL ULCER BETTER THAN IDOXURIDINE
(BETTER PENETRATION) – PREVENTION OF BLINDNESS
2. H. ZO STER – LESS SUSCEPTIBLE – USED ONLY IN IMMUNODEFICIENT PATIENTS – ALSO ORAL AND
OINTMENT THERAPY
3. CHICKENPOX: WITH IMMUNODEFICIENCY – DOC - 15 MG/KG/DAY IV FOR 7 DAYS – ALSO
PROPHYLACTIC VALUE
14.
15. ACYCLOVIR SUBSTITUTES – PHARMACOKINETIC
CONSIDERATION
• BIOAVAILABILITY CAN BE IMPROVED BY DESIGN
OF SUITABLE PRODRUGS
• VALACYCLOVIR: ESTER PRODRUG OF
ACYCLOVIR - DOC IN HZV
• FAMCICLOVIR: ESTER PRODRUG OF GUNINE
NUCLEOSIDE ANALOGUE PENCICLOVIR
• CONVERTED TO TRIPHOSPHATE BY VIRAL
THYMIDINE KINASE
• DNA POLYMERASE INHIBITOR
• INHIBITS HSV AND HZV – NOT USEFUL IN
ACYCLOVIR RESISTANCE
• USES: ALTERNATIVE TO ACYCLOVIR IN
GENITAL AND OROLABIAL HERPES ALSO IN
HEPATITIS B (HBV)
16. OTHER ANTI HERPES DRUGS
• GANCICLOVIR: ACYCLOVIR ANALOGUE – EFFECTIVE AGAINST ALL HERPES – INTRACELLULAR
ACTIVATION TO TRIPHOSPHATE – MOST ACTIVE AGAINST CMV
• ATTAINS MUCH HIGHER CONCENTRATION IN CMV INFECTED CELLS – PLASMA HALF LIFE 2-3 HOURS
BUT INSIDE CMV CELLS >24 HOURS
• POOR ORAL ABSORPTION (<10%) – VALGANCICLOVIR (PRODRUG)
• ADRS: BONE MARROW TOXICITY
• USES: SEVERE IMMUNOCOMPROMIZED PATIENTS WITH PNEUMONIA, COLITIS, RETINITIS – IV USE
AND TOPICAL – PROPHYLACTIC VALUE – PREVENTS BLINDNESS IN AIDS PATIENTS
• CIDOFOVIR: DOES NOT REQUIRE VIRAL ENZYME - EFFECTIVE AGAINST HSV RESISTANT TO
ACYCLOVIR AND CMV RESISTANT TO GANCICLOVIR – MONO PO4 CONVERTS TO DI PO4
• HALF LIFE 2 – 3 HOURS BUT REMAINS INSIDE CELL FOR LONG – WEEKLY THERAPY
• GIVEN IV WITH PROBENECID (IMPROVES BIOAVAILABILITY)
• USES: AIDS PATIENTS WITH CMV RETINITIS – GANCICLOVIR FAILED CASES; AND ALSO IN ACYCLOVIR
RESISTANT MUCOCUTANEOUS HERPES SIMPLEX IN IMMUNOCOMPROMIZED PATIENTS; ADRS:
KIDNEY DAMAGE AND HYPERSENSITIVITY REACTIONS
17. OTHER ANTI HERPES DRUGS – CONTD.
• FOSCARNET: UNRELATED TO ANY NUCLEIC ACID
• MOA: INHIBITS VIRAL DNA POLYMERASE AND REVERSE
TRANSCRIPTASE
• ACTION: EFFECTIVE AGAINST HSV (RESISTANT TO ACYCLOVIR),
CMV (GANCICLOVIR RESISTANT), OTHER HERPES VIRUSES AND
HIV
• DRAWBACK: LOW VIRAL SELECTIVITY, TOXICITY HIGH, KIDNEY
DAMAGE – RENAL DIABETES, ANAEMIA, PHLEBITIS, TREMOR,
CONVULSION ETC.
• USES: CMV RETINITIS AND OTHER CMV IN AIDS AND ACYCLOVIR
19. AMANTADINE - TRICYCLIC AMINE
• TRICYCLIC AMINE UNRELATED TO ANY NUCLEIC ACID PRECURSOR. APPROVED BY
FDA IN 1976 TO TREAT INFLUENZA A (NOT INFLUENZA B), RESISTANT TO H5N1
(AVIAN) AND H1N1 (SWINE).
• MECHANISM:
• INHIBITS THE UNCOATING OF THE VIRAL GENOME AND ALSO VIRAL ASSEMBLY IN
LATE STEP
• SPECIFICALLY TARGETS A PROTEIN CALLED M2 (AN ION CHANNEL) - INACTIVE
AGAINST INFLUENZA B, WHICH LACKS M2
• PHARMACOKINETICS:
• WELL ABSORBED ORALLY; CROSSES BBB
• 90% EXCRETED UNCHANGED; NO REPORTS OF METABOLIC PRODUCTS
• T1/2 – 16 HRS
• SIDE EFFECTS:
• LOW TOXICITY AT THERAPEUTIC LEVELS; NAUSEA, ANOREXIA, INSOMNIA AND
SOME CNS SIDE EFFECTS (NIGHTMARES AND SCARY HALLUCINATIONS)
• USES: PROPHYLAXIS OF INFLUENZA A2 (EPIDEMIC OR SEASONAL); TREATMENT OF
INFLUENZA AND PARKINSONISM. DOSES: 100 MG BD OR 200 MG OD
• RIMANTADINE – METHYL DERIVATIVE OF AMANTADINE
20. OSETALMIVIR (TAMIFLU)
• BROAD SPECTRUM – INFLUENZA A AND B, H5N1 (BIRD FLU) AND NH1N1
(SWINE FLU)
• KINETICS: OSELTAMIVIR IS A PRODRUG THAT IS ACTIVATED IN THE
GUT AND LIVER (HYDROLYSED) TO O. CARBOXYLATE
• WELL ABSORBED ORALLY (B - 80%)
• O. CARBOXYLATE IS FURTHER METABOLIZED AND EXCRETED BY KIDNEY
• T1/2 --- 6-10 HRS
• MOA: NEURAMINIDASE INHIBITOR (IMPORTANT FOR VIRAL PROGENY
RELEASE)
• USES: BOTH PROPHYLAXIS AND TREATMENT OF INFLUENZA A AND B,
H5N1 AND H1N1. REDUCES THE SEVERITY, DURATION AND
COMPLICATIONS
• ADRS: GASTRIC IRRITATION (NAUSEA AND VOMITING) – WITH FOOD
TO TAKE. HEADACHE, WEAKNESS, SADNESS, COUGH AND INSOMNIA
ETC.
• DOSE: 75 MG BD FOR 5 DAYS
21. ANTI-HEPATITIS VIRUS DRUGS
• SOME ANTIVIRAL DRUGS ARE VIRUS-NONSELECTIVE –
INHIBIT VIRUSES BELONGING TO DIFFERENT CLASSES (DNA
– RNA)
• FOR HEPATITIS B: LAMIVUDINE, DIPIVOXIL, TENOFOVIR
• FOR HEPATITIS C: RIBAVIRIN, INTERFERON Α
• HEPATITIS B (HBV) IS A DNA VIRUS – INTEGRATE INTO HOST
CHROMOSOME AND PERMANENT INFECTION
• HEPATITIS C (HCV) IS RNA VIRUS – DOES NOT INTEGRATE
INTO HOST CHROMOSOME CAUSE CHRONIC HEPATITIS
22. ADEFOVIRDIPIXOVIL
• MONOPHOSPHATE - ANALOGUE OF AMP. EFFECTIVE AGAINST HBV AND OTHER DNA VIRUSES
• KINETICS: ESTERASES IN INTESTINE AND LIVER RELEASE ACTIVE DRUG - BIOAVAILABILITY 60
% - EXCRETED IN KIDNEY – 7 HOURS HALF LIFE
• MOA: AFTER ENTERING CELL - PHOSPHORYLATED TO DIPHOSPHATE – HIGH AFFINITY FOR
HBV DNA POLYMERASE – NOT TO HOST DNA. POLYMERASE INHIBITED AND ADEVOFIR GETS
INCORPORATED IN DNA AND TERMINATES DNA CHAIN
• USES: CHRONIC HBV, LAMIVUDINE RESISTANT CASES AND HBV WITH CONCURRENT HIV
INFECTION
• DOSES: 10 MG/DAY FOR 1 YEAR - CLINICAL, BIOCHEMICAL, SEROLOGICAL, VIROLOGICAL,
HISTOLOGICAL IMPROVEMENT (50%) – NEEDS CONTINUATION
• ADRS: HEADACHE, SORE THROAT, FLU SYNDROME, NEPHROTOXICITY
23. TENOFOVIR
• MONOPHOSPHATE NUCLEOTIDE RELATED TO AMP
• EFFECTIVE AGAINST HBV AND HIV
• LOW ORAL ABSORPTION - ADMINISTERED AS PRODRUG (TENOFOVIR DISOPROXIL)
• HYDROLYSIS OF PRODRUG – CONVERTS TO TENOFOVIR DIPHOSPHATE BY
CELLULAR KINASE
• MOA: INHIBITS HBV DNA POLYMERASE AND ALSO HIV-REVERSE TRANSCRIPTASE
(LOW AFFINITY FOR HOST DNA POLYMERASE)
• KINETICS – HALF LIFE 16 HOURS (LONGER INTRACELLULAR HALF LIFE)
• USES: 300 MG DAILY IN HBV INFECTION (INCLUDING LAMIVUDINE RESISTANT CASES)
– 90% CURE RATE – LESSER TOXICITY
24. RIBAVIRIN (PURINE NUCLEOSIDE
ANALOGUE)
• BROAD SPECTRUM ANTIVIRAL ACTIVITY – INFLUENZA A AND B, RESPIRATORY SYNCITIAL
VIRUSES AND MANY OTHER DNA AND RNA VIRUSES
• MOA: INTRACELLULARLY GENERATES MONO- AND TRIPHOSPHATE DERIVATIVE – INHIBIT GTP
AND VIRAL RNA SYNTHESIS
• KINETICS: BIOAVAILABILITY 50%, ACCUMULATES IN THE BODY – HALF LIFE 10 DAYS
• USES: 1) SEVERE INFLUENZA A/B AND MEASLES IN IMMUNOSUPPRESSED PATIENTS; 2)
HERPES, ACUTE HEPATITIS. MONOTHERAPY – INCOMPLETE RESPONSE; 3) 1ST
LINE OF DRUG IN
HCV WITH PEGINTERFERONE FOR 6-12 MONTHS. NEBULIZED FORM GIVEN IN RESPIRATORY
SYNCYTIAL BRONCHIOLITIS VIRUS IN INFANTS AND CHILDREN – CONGENITAL HEART DISEASE
AND PREMATURITY- ALSO RARE VIRAL INFECTIOS
• DOSE: 200MG QID
• ADRS: ANAEMIA, BM DEPRESSION, HAEMOLYSIS AND TERATOGENICITY
25. INTERFERONE Α (IFNΑ)
• LMW GLYCOPROTEIN CYTOKINES PRODUCED BY HOST CELLS IN RESPONSE TO
VIRAL INFECTIONS, ALSO TNFΑ AND IL-1 – NONSPECIFIC ANTIVIRAL AND OTHER
IMMUNITY AND CELL PROLIFERATION EFFECTS
• MOA: BINDS TO CELL SURFACE RECEPTORS - ACT ON MULTISTEPS – VIRAL
PENETRATION, VIRAL SYNTHESIS OF MRNA, ASSEMBLY, AND RELEASE
• DIRECT OR INDIRECT SUPPRESSION OF VIRAL PROTEIN SYNTHESIS - TRANSLATION
• JAK-STAT TYROSINE KINASE RECEPTORS – PHOSPHORYLATES CELLULAR PROTEINS –
MIGRATE TO NUCLEUS – INDUCE TRANSCRIPTION OF INTERFERONE INDUCED PROTEINS
– ANTIVIRAL EFFECTS
• ACTION: INHIBITS MANY DNA AND RNA VIRUSES, BUT SPECIES SPECIFIC – 3 HUMAN
TYPES – Α, Β, - ONLYȢ IFNΑ2A AND IFNΑ2B AVAILABLE FOR USE - IM AND SC -
PEGYLATED FORMS ARE AVAILABLE FOR S.C USE
• PEG IFNΑ2A LONGER DURATION THAN PEG IFNΑ2B
• PHARMACOKINETICS: WELL DISTRIBUTED, DEGRADED IN LIVER. PERSISTS IN
PLASMA FOR LONGER TIME 24 HRS. PEG PRODUCTS PERSISTS LONGER – THRICE
WEEKLY VS WEEKLY ADMINISTRATION
26. INTERFERON (IFNΑ) – USES AND ADRS
1. CHRONIC HEPATITIS B: IFNΑ2A 2.5 TO 5 MU/M2 3 TIMES PER WEEK FOR 4-6
MONTHS. PEG PREPARATIONS 180 MCG SC WEEKLY FOR 24 TO 48 WEEKS –
ALSO IFNΑ2B (5-10 MU)
2. CHRONIC HEPATITIS C: IFNΑ2B (3 MU) 3 TIMES WEEKLY FOR 6-12 MONTHS –
PEGIFNS 180 MCG/WEK (MORE EFFECTIVE) – COMBINE WITH RIBAVIRIN
3. AIDS RELATED KAPOSI`S SARCOMA: HUMAN HERPES VIRUS 8
4. CONDYLOMA ACUMINATA - PAPILLOMA VIRUS
5. H. SIMPLEX, H. ZOSTER AND CMV IN IMMUNOCOMPROMISED PATIENTS – 2ND
LINE OF AGENT
6. CML, MULTIPLE MYELOMA, FOLLICULAR LYMPHOMA ETC.
• ADRS: FLUE LIKE SYMPTOMS, NEUROTOXICITY (NUMBNESS, NEUROPATHY,
ALTERED BEHAVIOUR), MYELOSUPRESSION-DOSE DEPENDENT NUTROPENIA,
AND HYPOTENSION, ARRHYTHMIA, ALOPECIA AND LIVER DYSFUNCTION ETC.
28. ANTI RETROVIRUS DRUGS
• DRUGS USED AGAINST RETROVIRUS – HIV
• USEFUL IN PROLONGING AND IMPROVING QUALITY OF LIFE – POSTPONE
COMPLICATIONS OF AIDS AND ARC - DO NOT CURE THE INFECTION
• CLINICAL EFFICACY – PLASMA HIV-RNA ASSAYS AND CD4 LYMPHOCYTE COUNT
• SINGLE STRANDED RNA – CARRIES OUT REVERSE TRANSCRIPTION OF PROVIRAL
DNA FROM VIRAL RNA (OPPOSITE OF NORMAL) – RNA DEPENDENT DNA
POLYMERASE (REVERSE TRANSCRIPTASE)
• ATTACKS CD4+ HELPER T- LYMPHOCYTES – LATER MACROPHAGES – DECREASED
IN CD4 COUNT
• >200 CELLS/µL CMI LOST – OPPORTUNISTIC INFECTIONS
• DRUGS TARGET – REVERSE TRANSCRIPTASE, HIV PROTEASES (POLYPROTEINS),
FUSION, CHEMOKINE CORECEPTOR (CCR5) ON HOST CELLS AND HIV-INTEGRASE –
ALWAYS USED IN COMBINATION (3 OR MORE)
30. ZIDOVUDINE – CONTD.
• ANOTHER MOA - ZIDOVUDINE MAY ITSELF GETS INCORPORATED IN PROVIRAL DNA AND
PREVENTS CHAIN ELONGATION
• ZIDOVUDINE PREVENTS INFECTION OF NEW CELLS BY HIV, BUT NOT EFFECTIVE ON
ALREADY INFECTED HOST CHROMOSOMES
• PHARMACOKINETICS: BIOAVAILABILITY 60 %, T1/2 – 1 HR, CROSSES BBB AND PLACENTA
AND IN MILK, EXCRETED IN URINE – 50% IN CSF
• ADRS: ANAEMIA AND NUTROPENIA (INHIBITION OF CELLULAR MITOCHONDRIAL DNA
POLYMERASE), MYOPATHY, PIGMENTATION OF NAILS, LACTIC ACIDOSIS AND
ENCEPHALOPATHY
• RESISTANCE: BY POINT MUTATION (ALTERATION OF RT ENZYME)
• DRUGINTERACTION: PARACETAMOL INCREASES TOXICITY, STAVUDINE ANTAGONIZES
EACH OTHER
• USES: IN HIV INFECTED PERSONS IN COMBINATION – 1ST LINE THERAPY BY NACO –
IMPROVEMENT AND REDUCTION IN KAPOSI`S LESIONS
31. DIDANOSINE AND STAVUDINE
• DIDANOSINE (DDL): PURINE NUCLEOSIDE
• MOA: CONVERTS TO TRIPHOSPHATE – COMPETES WITH ATP FOR INCORPORATION TO
VIRAL DNA – INHIBITS RT AND TERMINATES PROVIRAL DNA
• ACTION: EQUIVALENT TO AZT
• TOXICITY: PERIPHERAL NEUROPATHY (STOCKING AND GLOVE), PANCREATITIS - RARELY
USED NOW
• STAVUDINE: THYMIDINE ANALOGUE
• MOA: SAME AS ZIDOVUDINE – THYMIDINE KINASE PATHWAY
• KINETICS: 1.5 HOURS HALF-LIFE
• USES: COMBINATION THERAPY (NACO)
• ADRS: PERIPHERAL NEUROPATHY, LIPODYSTROPHY, LACTIC ACIDOSIS, PANCREATITIS
ZIDOVUDINE – NOT TO BE COMBINEDWITHSTAVUDINE AND STAVUDINE NOT TOBE
COMBINEDWITHDIDANOSINE
32. LAMIVUDINE (3TC)
• MOA: PHOSPHORYLATES INTRACELLULARLY AND INHIBITS – HIV RT AND ALSO HBV
DNA POLYMERASE – ALSO INCORPORATION TO DNA POLYMERASE – CHAIN
TERMINATION - HUMAN DNA POLYMERASE NOT AFFECTED – LOW TOXICITY
• QUICKRESISTANCE: POINT MUTAION OF HIV RT AND HBV-DNA POLYMERASE
• RESISTANCE STRAIN – SLOW GROWING AND LOWER VIRULENCE
• KINETICS: HIGHER BIOAVAILABILITY & LONGER T1/2(6-8 HRS) – LONGER
INTRACELLULARLY
• USES: 1ST
LINE OF DRUG IN HIV (EQUIEFFECTIVE AS ZIDOVUDINE) – SYNERGISTIC
ACTION WITH OTHER NRTIS - ALSO - 1ST
LINE OF DRUG IN CHRONIC HBV
• LOWTOXICITY – NO HAEMATOLOGICAL TOXICITY OR NEUROPATHY
• USES: HIGH PRIORITY IN COMBINATION THERAPY (HBV VIRAEMIA RETURNS AFTER
1- 4 YEARS)
33. NNRTIS - NEVIRAPINE AND EFAVIRENZ
• NUCLEOSIDE UNRELATED COMPOUNDS
• MOA: DIRECT INHIBITOR OF HIV REVERSE TRANSCRIPTASE (NONCOMPETITIVE)
• MORE POTENT THAN AZT ON HIV-1 BUT NOT INDICATED IN HIV-2
• USED ALONE RAPID RESISTANCE AND CROSS RESISTANCE BETWEEN THE 2 –
BUT NOT WITH NRTIS AND PIS
• ONCE NNRTIS FAIL - SHOULD NOT BE TREATED WITH ANOTHER ONE
• USES: EITHERONE OF THEM1ST
LINE OF DRUG IN COMBINATION THERAPY
NVP EFV
Metabolism Mainly by CYP3A4 Mainly by CYP2B6
Microsomal enzyme Inducer Inducer (also inhibits CYP3A4)
2 weeks dose adjustment Doubled Not required
Rifampicin (TB) Induces metabolism No induction
Hepatotoxicity Yes No
34. PROTEASE INHIBITORS (PIS)
• DRUGS - ATAZANAVIR, INDINAVIR, NELFINAVIR, SAQUINAVIR, AMPRENAVIR,
LOPINAVIR AND RITONAVIR
• MOA: AS DESCRIBED EARLIER – INHIBITION OF PROTEASE ENZYME INVOLVED IN
FRACTIONATION OF POLYPROTEINS – PREVENTION OF MATURATION OF NEW VIRAL
PARTICLES - BY BINDING TO THE ACTIVE SITE IN PROTEASE MOLECULE
• KINETICS: VARIABLE BIOAVAILABILITY: 2- 8 HOURS, METABOLIZED BY CYP3A4,
EXCEPT NFV (CYP2C19) – ALL ARE POTENT INHIBITOR OF CYP3A4 (MAINLY
RITONAVIR AND LOPINAVIR) – OTHER CYP MAY BE INDUCED
• ADVANTAGES: MORE EFFECTIVE THAN ZIDOVUDINE - ACT IN LAST STEP – EFFECTIVE IN
NEWLY FORMED AND CHRONICALLY INFECTED CELLS - PRODUCE NON-INFECTIOUS
IMMATURE VIRAL PROGENY
• DRAWBACKS: UNPREDICTABLE MANY DRUG INTERACTIONS (ENZYME INDUCTION AND
INHIBITION), RIFAMPICIN INTERACTION, LARGE TABLET LOAD (6-18) – LOW DOSE RITONAVIR
STRATEGY
• USES: COMBINATION THERAPY – BUT RESERVED (2ND
LINE AGENT)
35. PROTEASE INHIBITORS – CONTD.
• ADRS: GIT INTOLERANCE, HEADACHE, DIZZINESS, LIMB AND FACIAL
TINGLING
• LIPODYSTROPHY (ABDOMINAL OBESITY, BUFFALO HUMP WITH WASTING OF LIMB
AND FACE
• RAISED TRIGLYCERIDES AND CHOLESTEROL
• INSULIN RESISTANCE
• INDINAVIR – URINARY CALCULI
36. HIV TREATMENT GUIDELINES
• COMPLEX, PROLONGED, NEEDS EXPERTISE AND STRONG
MOTIVATION AND COMMITMENT OF PATIENT AND EXPENSIVE
• NO MONOTHERAPY - HIGHLY ACTIVE ANTIRETROVIRAL THERAPY
(HAART) – COMBINATION OF 3 OR MORE DRUGS
• AIM OF HAART – NONE ARTS CAN ERADICATE, THEREFORE:
• MAXIMALLY AND DURABLY INHIBIT VIRAL REPLICATION SO THAT PATIENT CAN
MAINTAIN ADEQUATE IMMUNE RESPONSE
• GREATER THE SUPPRESSION LESSER IS THE CHANCE OF RESISTANCE
• EFFECTIVE ART REDUCES TRANSMISSION
• HAART - >99% KILLING, BUT RELAPSE
37. INITIATION OF THERAPY
1. ALL SYMPTOMATIC HIV PATIENTS
2. ASYMPTOMATICS WITH CD4 CELL COUNT BELOW 350/µL
3. HIV PATIENT COINFECTED WITH HBV/HBC
4. ALL PREGNANT HIV POSITIVE WOMEN
5. ALL PATIENT WITH HIV NEPHROPATHY
ADDITIONALLY NACO:
1. ALL HIV POSITIVE IN STAGE 3 AND 4
2. HIV POSITIVE FOR 6 – 8 YEARS AGO
3. HISTORY OF TB AND HERPES ZOSTER
4. HIV INFECTED PARTNER OF AIDS PATIENTS
5. ALL HIV POSITIVE BELOW 15 YEARS OF AGE
38. THERAPEUTIC REGIMEN - NACO
• 1ST
LINE REGIME FOR UNTREATED PATIENTS
• ALL REGIMENS SHOULD HAVE 2 NRTIS AND 1 NNRTI
• INCLUDE LAMIVUDINE IN ALL REGIMENS
• THE OTHER ONE CAN BE ZIDOVUDINE OR STAVUDINE
• CHOSE NNRTI FROM EFAVIRENZ OR NEVIRAPINE
• EFAVIRENZ IN HEPATIC DYSFUNCTION AND IN PATIENTS RECEIVING
RIFAMPICIN
• DO NOT USE EFAVIRENZ IN PREGNANT
• TREATMENT LIFELONG
39. FIRST LINE REGIMENS
• PREFERRED: LAMIVUDINE + ZIDOVUDINE + NEVIRAPINE
• ALTERNATIVE:
1. LAMIVUDINE + ZIDOVUDINE + EFAVIRENZ
2. LAMIVUDINE + STAVUDINE + EFAVIRENZ (ANEMIA)
3. LAMIVUDINE + STAVUDINE + NEVIRAPINE
• OTHEROPTIONS:
1. LAMIVUDINE + TENOFOVIR + NEVIRAPINE (TOXICITY AND CONTRAINDICATION)
2. LAMIVUDINE + TENOFOVIR + EFAVIRENZ (TOXICITY AND CONTRAINDICATION)
3. LAMIVUDINE + ZIDOVUDINE + TENOFOVIR (UNABLE TO TOLERATE E OR N)
FOR NAÏVE PATIENTS – 2 NRTIS + 1 NNRTI
PIS RESERVED FOR ADVANCED CASES – 2 NRTIS + PI OR NRTI + NNRTI + PI
IF RESISTANCE – ENTIRE REGIME REPLACEMENT – NO REDUCTION OF DOSE
NO DRUG HOLIDAY AND NO CONTRAINDICATION IN PREGNANCY
40. WHEN REGIME FAILED
• FAILURE OF A REGIME
• 6 MONTHS TREATMENT – HIV-RNA <50µL
• REPEATED DETECTION OF VIRUS IN PLASMA AFTER INITIAL REDUCTION
• CLINICAL DETERIORATION AND FALL IN CD4 COUNT
• POST EXPOSURE PROPHYLAXIS
• LOW RISK: LAMIVUDINE 150MG + ZIDOVUDINE 300 MG – TWICE DAILY FOR 4 WEEKS
• HIGH RISK: LAMIVUDINE 150MG + ZIDOVUDINE 300 --- TWICE DAILY + INDINAVIR (800 MG)
- THRICE DAILY – THRICE DAILY FOR 4 WEEKS
• PREGNANT WOMEN: ZIDOVUDINE + LAMIVUDINE + NEVIRAPINE