Here are the answers to the questions:
1) It is difficult to treat fungal infections because fungi are eukaryotic organisms like humans, so antifungal drugs must target differences between fungal and human cells to avoid toxicity.
2) The target of many antifungal drugs is ergosterol synthesis.
3) The main families of antifungal agents are polyenes (amphotericin B), azoles (fluconazole), and echinocandins (caspofungin).
4) Amphotericin B is commonly used to treat invasive fungal infections. It binds ergosterol in the fungal cell membrane, causing leakage of ions. The major
Description on types of fungal organisms with differences between bacteria and fungi. A note on useful and harmful fungi. Brief insight on Antifungal classification, mechanism of actions and pharmacological profile with drug of choices for various fungal infections.
Medicinal Chemistry and Pharmacology of Antifungal Agents and how to take care from fungal infections. Useful Course study material for the undergraduate , postgraduate and aspirants of Pharmacy , Pharmacology and Medicinal Chemistry.
Description on types of fungal organisms with differences between bacteria and fungi. A note on useful and harmful fungi. Brief insight on Antifungal classification, mechanism of actions and pharmacological profile with drug of choices for various fungal infections.
Medicinal Chemistry and Pharmacology of Antifungal Agents and how to take care from fungal infections. Useful Course study material for the undergraduate , postgraduate and aspirants of Pharmacy , Pharmacology and Medicinal Chemistry.
An antifungal medication is a pharmaceutical fungicide used to treat and prevent mycoses such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available OTC (over-the-counter).
Antifungals work by exploiting differences between mammalian and fungal cells to kill the fungal organism with fewer adverse effects to the host. Unlike bacteria, both fungi and humans are eukaryotes. Thus, fungal and human cells are similar at the biological level. This makes it more difficult to discover drugs that target fungi without affecting human cells. As a consequence, many antifungal drugs cause side-effects. Some of these side-effects can be life-threatening if the drugs are not used properly.
Tetanus is a acute disease manifested by skeletal muscle spasm and autonomic nervous system disturbance.
It is caused by Clostridium tetani.
Morphology
It is a gram positive rod shaped bacterium.
They are obligatory anaerobic.
They produces terminal spore with “drum stick appearance”.
They commonly found in soils, hospital environment, intestine of man and animals
Tetanus is a acute disease manifested by skeletal muscle spasm and autonomic nervous system disturbance.
It is caused by Clostridium tetani.
Morphology
It is a gram positive rod shaped bacterium.
They are obligatory anaerobic.
They produces terminal spore with “drum stick appearance”.
They commonly found in soils, hospital environment, intestine of man and animals
Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbesto...EPL, Inc.
“Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 18 Months Post Exposure.” Willson GA (presenter), Dodd DA, Roberts KC, Wall HG, Jarabek AM, Gavett SH. The 33rd Society of Toxicologic Pathology Annual Meeting. Washington, DC. June 22-26, 2014.
“Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 18 Months Post Exposure.” Dodd DA (presenter), Willson GA, Roberts KC, Wall HG, Jarabek AM, Gavett SH. The 53rd Annual Society of Toxicology Meeting. Phoenix, AZ. March 23-27, 2014.
For full-resolution viewing, please open or save as a PDF.
Basic definition and types of toxicology (general, mechanistic, regulatory and descriptive), Regulatory guidelines for conducting toxicity studies OECD, ICH, EPA and Schedule Y OECD principles of Good laboratory practice (GLP)
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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
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.
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
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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
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.
2. Early Beginnings – Difficulties Treating
Common Fungal Infections
Antifungal Drugs
Newer Therapies
Assigned Reading/References/Homework
3. About 1408 Million Years
Ago, fungi and animals
phyla split
We are more closely related
to fungi then plants!
This will prove difficult for
one to treat mycotic
infections due to the
similarities between the
eukaryotic fungus and the
eukaryotic host (us! )
5. Symptoms: scaling,
flaking, and itching of the
feet.
Caused by: Microsporum
and Trichophyton
Treated with: various
allylamines and azoles,
miconazole nitrate, and
tolnaftate
6. Symptoms: Scaling of the
skin, characteristic
circular rash
Caused by: Microsporum
and Trichophyton
Treated with: Miconazole,
Clotrimazole,
Ketoconazole
9. Symptoms: Delirium,
failure of organs, death!
Caused by: Inhalation
of fungal spores from
genus Aspergillus
Treated with: nystatin,
ketoconazole,
fluconazole,
capsofungin
10. Many of the common fungal infections described
affect the general population. There is a vaster
majority of fungi that cause serious harm to
people that are immunocompromised!!
11. Amphotericin B
Fluconazole
Capsofungin
Terbinafine
Keep in mind: We need to target differences between our cell and
the fungal cell. Antibiotics will not work because of both cells
are eukaryotic and the medication could kill off the good gut
flora that competes with the fungus for nutrients. Treatments
usually include many combinations of different antifungals.
12. Known as a polyene macrolide
38 – Membered Ring
Isolated 1955, market 1958
Amphiphilic!
Anyone want to guess the Mech Of Action?!?!
13. Mech of Action!
Associates with the membrane and
causes leakage of Na, K, and Ca
across membrane. But how does it
differentiate between fungal cells
and human cells??
14. Instead of cholesterol in the cell membrane, fungal
cells have ergosterol. The heptaene portion of the
ring interacts strongly with ergosterol instead of
cholesterol.
Cholesterol Ergosterol
vs
15. Bistriazole
Azole => Conjugated five-membered ring with at least 1 N and other
non carbon atoms (could be N)
Belongs to a larger class of well known antifungals – imidazoles
(Clotrimazole, Miconazole)
Fluconazole is newer though!
Imidazoles synthesized to treat both superficial AND systematic infections.
Fluconazole Clotrimazole Miconazole
16. Mech of Action:
Specifically inhibits the cytochrome P450 fungal enzyme C-
14(alpha) demethylase. This enzyme is require in the 20 step
pathway [thank goodness we didn’t have to memorize this]
from lanosterol (intermediate in cholesterol synthesis) to
ergosterol. Fluconazole binds to the Fe center of the enzyme
(one of the nitrogens coordinates to the Fe).
17. Semisynthetic cyclic lipid-bearing polypeptide
Belongs to class of antifungals: echinocandins –
derived from the cyclic polypeptide.
Large MW, low oral bioavailability =>
administered intravenously.
Market 2001
18. Mech of Action:
Potent inhibitor of the fungal enzyme 1,3-(beta)-D glucan
synthase. This enzyme catalyzes glucan polymerization (glucan
is just a polymeric sugar molecule), which is essential in the
synthesis of a fungi’s cell wall. Human cells do not possess a
cell wall, so the drug is effective.
19. Belongs to class of antifungals – the allylamines.
Treats mainly superficial infections.
Discovered by accident in 1974 - antifungal potential related
directly to the tertiary allylamine and the 1-substituted
naphthalene ring. Eventually developed terbinafine.
Terbinafine
Butenafine
(Lotrimin)
20. Mech of Action: All allylamines work similarly. They inhibit
ergosterol synthesis by inhibiting squalene epoxidase (oh
snap!), the enzyme that catalyzes the epoxide formation
between the 2 and 3 carbon of squalene. From this 2,3-
oxidosqualene intermediate, we produce lanosterol and
eventually ergosterol. *****
Terbinafine
21. Molecules and Medicine. EJ Corey. John Wiley and
Sons: 2007
Recent Advances in the Chemistry of Anti-Infective
Agents. Editors PH Bentley and R. Ponsford. Royal
Society of Chemistry: 1993.
http://www.doctorfungus.org. DoctorFungus
Corporation
http://faculty.swosu.edu/scott.long/phcl/antifung.htm
. Long, Scott, Southwestern Oklahoma State
University
22. Mathew, Bijoy P.; Nath, Mahendra. Recent
approaches to antifungal therapy for invasive
mycoses. ChemMedChem (2009), 4(3),
310-323.
23. 1) Why is it so difficult to treat fungal infections?
2) The target of which biomolecule’s synthesis is the subject of many antifungal
drugs?
3) What are the main families of antifungal agents? Name a member of each
family.
4) What is the most commonly employed antifungal agent to treat invasive fungal
infections? Describe its mechanism of action. What is the major side effect of this
agent?
5) What enzyme is the biological target of the azole antifungal agents? What is
the most common mechanism of fungal resistance to these agents?
6) The echinocandin caspofungin was approved by the FDA in 2001 for salvage
therapy in cases of resistant invasive aspergillosis. What is the most likely target of
these drugs?
7) Another class of antifungal agents is the allylamines, including terbinafine.
Draw the structure of terbinafine and define the allylamine moiety. What is the
biological target of allylamines?