This document discusses various classes of antifungal drugs including polyenes, echinocandins, azoles, and allylamines. It provides details on specific drugs in each class like amphotericin B, fluconazole, terbinafine, and caspofungin. It also covers the mechanisms of action, indications, dosing considerations, toxicities and interactions for many of these antifungal agents. Finally, it discusses several topical antifungal drugs and their uses in treating superficial fungal infections.
Tetracyclines slide contains full information about uses, adverse effect, marketed preparation, precaution, route of drug administration, antimicrobial spectrum, mechanism of action, pharmacokineticks and pharmacodynamics of tetracyclines. This slide is very helpful for pharmacy and pharmacology student for the study about tetracyclines.
Tetracyclines slide contains full information about uses, adverse effect, marketed preparation, precaution, route of drug administration, antimicrobial spectrum, mechanism of action, pharmacokineticks and pharmacodynamics of tetracyclines. This slide is very helpful for pharmacy and pharmacology student for the study about tetracyclines.
Fungal infections are more common in men and in women, especially in younger people due to their clothing style. they must be stopped at the budding stage, if not it might spread to multiple areas of body.
Psoriasis is an inflammatory skin disease that is associated with multiple comorbidities and substantially diminishes patients' quality of life. Topical therapies remain the cornerstone for treating mild psoriasis. Therapeutic advancements for moderate to severe plaque psoriasis include biologics that inhibit TNF-α, p40IL-12/23, IL-17, and p19IL-23, as well as an oral phosphodiesterase 4 inhibitor.
Hello friends. In this PPT I am talking about anti-fungal 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.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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
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.
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
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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
5. •Amphotericin B deoxycholate (C-AMB) nephrotoxicity
•Amphotericin B colloidal dispersion (ABCD) (not available in the U.S.)
Associated with acute reactions, including infusion-related fever and chills
•Liposomal amphotericin B (L-AMB)
•Amphotericin B lipid complex (ABLC)
7. ACUTE REACTION
•each infusion and chills, fever, aches and pain all over, nausea, vomiting and
dyspnoea lasting for 2–5 hour,
•When the reaction is severe—the dose should be increased gradually. Usually
the intensity of reaction decreases with continued medication.
•Injection of hydrocortisone 0.6 mg/ kg with the infusion may reduce the
intensity of reaction. Thrombophlebitis .
8. LONG-TERM TOXICITY
•Nephrotoxicity . dose-related. azotemia, reduced g.f.r., acidosis,
hypokalaemia and inability to concentrate urine.
• reverses slowly and often incompletely after stoppage of therapy. Anaemia:
develop progressing anaemia due to bone marrow depression. reversible.
•CNS toxicity: occurs only on intrathecal injection—headache, vomiting,
nerve palsies, etc.
9. FLUCYTOSINE
• Cryptococcosis (with amphotericin B)
Has broad activity but emergence of resistance limits usefulness as single-
agent therapy
• ↓ Dosage in patients with ↓ renal function
• Toxicity more frequent in patients with AIDS or azotemia
• depress bone marrow, leukopenia and thrombocytopenia
10.
11.
12. KETOCONAZOLE
•decreases androgen production from testes
•displaces testosterone from protein binding sites.
•Gynaecomastia, loss of hair and libido, and oligozoospermia
•Menstrual irregularities occur in some women due to suppression of estradiol
synthesis.
•dose-dependent decrease in serum hydrocortisone due to synthesis inhibition
has also been noted
13. •Orally administered KTZ is effective in dermatophytosis because it is
concentrated in the stratum corneum.
•It is an alternative to griseofulvin, but use is restricted due to potential adverse
effects. Used as a lotion or shampoo, KTZ is quite effective in seborrhoea of
scalp and dandruff.
•effective in monilial vaginitis, oral therapy (for 5–7 days) with KTZ is reserved
for recurrent cases or those not responding to topical agents.
•Administered orally, KTZ is effective in several types of systemic mycosis, but
triazoles, being more active with fewer side effects, have largely replaced it for
these indications.
•occasionally used in dermal leishmaniasis and in kala azar.
•High-dose used in Cushing’s syndrome to decrease corticosteroid production.
14. FLUCONAZOLE
• Invasive candidiasis
• Cryptococcosis
• Coccidioidomycosis
• Prophylaxis and empirical therapy in immunocompromised host
• Plasma concentrations are essentially the same whether the drug is given
orally or intravenously.
• Concentrations in CSF = 50%–90% of CP
• Inhibitor of CYP3A4 and CYP2C9
• Contraindicated during pregnancy
15. ITRACONAZOLE
• Invasive aspergillosis
• Blastomycosis
• Coccidioidomycosis
• Histoplasmosis
• Pseudallescheriasis
• Sporotrichosis
• Ringworm
• Onychomycosis
• Substrate for and potent inhibitor of CYP3A4
• Hepatotoxic
• Contraindicated in pregnancy and in women considering becoming pregnant
16. VORICONAZOLE
• Invasive aspergillosis
• Invasive candidiasis
• Pseudallescheriasis
• Oral bioavailability is 96%.
• Metabolized by CYPs 2C19/2C9 /3A4
• prolong the QTc interval
• Transient visual or auditory hallucinations are frequent after the first dose.
• Contraindicated in pregnancy
17. POSACONAZOLE
• Oropharyngeal candidiasis
• Prophylaxis in immunocompromised host against aspergillosis and
candidiasis
• Oral bioavailability enhanced by food
• Drugs that ↓ gastric acid ↓ posaconazole exposure
• Inhibits CYP3A4
• Can prolong the QTc interval
• headache and GI disorders
19. ECHINOCANDINS
Caspofungin
• ↓ Dose in moderate hepatic impairment
Micafungin
• Reduction of micafungin dose in moderate hepatic failure is not required.
Anidulafungin
• No dose adjustment is needed for hepatic or renal failure
22. ALLYLAMINES
Inhibit fungal squalene epoxidase and reduce ergosterol biosynthesis
Terbinafine
• Ringworm
• Onychomycosis
• Bioavailability is ∼ 40% due to first-pass metabolism in the liver.
• accumulates in skin, nails, and fat.
• initial t1/2 is ~ 12 h but extends to 200–400 h at steady state.
23. AGENTS ACTIVE AGAINST
MICROSPORIDIA AND PNEUMOCYSTIS
Albendazole
• Microsporidia infection
• Anthelmintic
• Inhibitor of α-tubulin polymerization
24. Fumagillin
• Microsporidia infection
• Used in immunocompromised individuals with intestinal microsporidiosis
due to Enterocytozoon bieneusi unresponsive to albendazole
• Not approved for human use in the U.S.
25. Pentamidine
• Pneumocystis jiroveci pneumonia
• Prophylaxis use to prevent PJP in at-risk individuals who cannot tolerate
trimethoprim-sulfamethoxazole
35. Topical Antifungal Agents-Tolnaftate
•tinea cruris and tinea corporis
•Because of poor penetrability, it is less effective in tinea pedis and other
hyperkeratinized lesions. ineffective in tinea capitis (involving scalp) and
tinea unguium (involving nails).
•Symptomatic relief occurs early, but if applications are discontinued before
the fungus bearing tissue is shed—relapses are common. Resistance does not
occur.
•Salicylic acid can aid tolnaftate by keratolytic action. Tolnaftate causes little
irritation, but is inferior in efficacy to imidazoles.not effective in candidiasis
or other types of superficial mycosis.
36. Topical Antifungal Agent-Ciclopirox
Olamine
•tinea infections, pityriasis versicolor and dermal candidiasis.
•High cure rates are reported. It penetrates superficial layers and reaches hair
roots but systemic absorption is negligible.
•Local tolerance without irritation is good. Sensitization occurs occasionally.
•Formulated as nail lacquer, it has been used in onychomycosis.
•Vaginal candidiasis can be treated by 1% ciclopirox vaginal cream
38. Topical Antifungal Agents-Benzoic Acid
•antifungal and antibacterial property in slightly acidic medium.
•Fungistatic action is weaker than tolnaftate; eradication of the fungus needs
prolonged application till infected keratin is totally shed.
• hyperkeratotic lesions, as Whitfield’s ointment: benzoic acid 5%, salicylic
acid 3%. its keratolytic action, helps to remove the infected tissue and
promotes the penetration of benzoic acid into the lesion.
•Irritation and burning sensation
Amphotericin B and other polyenes (e.g., nystatin) bind to ergosterol in fungal cell membranes and increase membrane permeability.
imidazoles and triazoles (itraconazole, etc.) inhibit 14-α-sterol demethylase, prevent ergosterol synthesis, and lead to accumulation of toxic 14-α-methylsterols.
allylamines (e.g., naftifine and terbinafine) inhibit squalene epoxidase and prevent ergosterol synthesis.
echinocandins (e.g., caspofungin) inhibit the formation of glucans in the fungal cell wall.
Metabolites of 5-fluorocytosine can disrupt fungal RNA and DNA synthesis.
Griseofulvin inhibits microtubule assembly, thereby blocking fungal mitosis.
The antifungal activity of amphotericin B depends on its capacity to bind ergosterol in the fungal cell membrane.
B. Ergosterol, here depicted as a green rod, decorates both bilayers of the fungal membrane. C. Amphotericin B appears to form aggregates that sequester and effectively extract ergosterol from lipid bilayers, much like a selective sponge, disrupting membrane structure and resulting in fungal cell death.
Associated with significant nephrotoxicity, including azotemia, renal tubular acidosis, and hypochromic, normocytic anemia
C-AMB is tolerated by premature neonates much better than older children and adults; as a result, it remains an important part of the antifungal formulary in the critical care nursery.
Infusion-related reactions typically decrease with subsequent infusions. While less toxic, the lipid formulations are much more costly than C-AMB, making them unavailable in many countries and dictating prudent use in the U.S. and other resource-rich areas.
Invasive candidiasis is an infection caused by a yeast (a type of fungus) called Candida. Unlike Candida infections in the mouth and throat (also called “thrush”) or vaginal “yeast infections,” invasive candidiasis is a serious infection that can affect the blood, heart, brain, eyes, bones, and other parts of the body.
Blastomyces dermatitidis
HISTOPLASMA CAPSULATUM
Coccidioides. immitis or Coccidioides posadasii fungi.
Cryptococcus neoformans and Cryptococcus gattii.
MUCORMYCESES / ZYGOMYCESES Mucor, Rhizopus, Absidia, and Cunninghamella genera
also termed rose gardener's or rose handler's disease) is an infection caused by the fungus Sporothrix schenckii
probably due to release of cytokines (IL, TNFα).
Azotemia is an elevation of blood urea nitrogen (BUN) and serum creatinine levels.
All susceptible fungi are capable of deaminating flucytosine to 5FU, a potent antimetabolite that is used in cancer chemotherapy. Fluorouracil is metabolized first to 5FUMP) by the enzyme UPRTase. uracil phosphoribosyltransferase .5FUMP is then either incorporated into RNA (via synthesis of 5-fluorouridine triphosphate) or metabolized to 5FdUMP, a potent inhibitor of thymidylate synthase, ultimately inhibiting DNA synthesis.
The selective action of flucytosine is due to the lack of cytosine deaminase in mammalian cells, which prevents metabolism to fluorouracil.
A. Fungal ergosterol synthesis proceeds via a series of enzymic steps that include Erg11, a 14-α-sterol demethylase. The completed ergosterol is then inserted into both leaflets of the membrane bilayer. B. Imidazole and triazole antifungals inhibit the activity of 14-α-sterol demethylase, thereby reducing the biosynthesis of ergosterol and leading to the accumulation of 14-α-methylsterols. These methylsterols are toxic, disrupting the close packing of acyl chains of phospholipids, impairing the functions of certain membrane-bound enzyme systems, and thus inhibiting growth of the fungi.
Pseudallescheriasis is a fungal infection caused by Pseudallescheria species, such as Pseudallescheria boydii
Ringworm, also known as dermatophytosis, dermatophyte infection, or tinea, is a fungal infection of the skin.
Onychomycosis, also known as tinea unguium, is a fungal infection of the nail. Symptoms may include white or yellow nail discoloration, thickening of the nail, and separation of the nail from the nail bed. Toenails or fingernails may be affected, but it is more common for toenails to be affected.
Itraconazole is a triazole that lacks the corticosteroid suppression associated with ketoconazole while retaining most of ketoconazole’s pharmacological properties and extending the antifungal spectrum. Importantly, itraconazole has activity against Aspergillus spp. While imidazoles do not.
• Invasive candidiasis
• Empirical therapy in the immunocompromised host
Prophylaxis in the immunocompromised host
The strength of the fungal cell wall is maintained by fibrillar polysaccharides, largely β-1,3-glucan and chitin, which bind covalently to each other and to proteins. A glucan synthase complex in the plasma membrane catalyzes the synthesis of β-1,3-glucan; the glucan is extruded into the periplasm and incorporated into the cell wall. Echinocandins inhibit the activity of the glucan synthase complex, resulting in loss of the structural integrity of the cell wall. The Fks1p subunit of glucan synthase appears to be the target of echinocandins, and mutations in Fks1p cause resistance to echinocandins.