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.
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.
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.
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.
I am Dr. Anil. this is my Lecture delivered to 3rd year MBBS for the subject of Pharmacology. These slides cover basics of Antifungal drugs mainly its pharmacology.
Antiviral drugs are a class of medication used specifically for treating viral infections.Like antibiotics for bacteria, specific antivirals are used for specific viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit their development.
Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic (also termed antibacterial), antifungal and antiparasitic drugs,or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from viricides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Antivirals also can be found in essential oils of some herbs, such as eucalyptus oil and its constituents.
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.
I am Dr. Anil. this is my Lecture delivered to 3rd year MBBS for the subject of Pharmacology. These slides cover basics of Antifungal drugs mainly its pharmacology.
Antiviral drugs are a class of medication used specifically for treating viral infections.Like antibiotics for bacteria, specific antivirals are used for specific viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit their development.
Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic (also termed antibacterial), antifungal and antiparasitic drugs,or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from viricides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Antivirals also can be found in essential oils of some herbs, such as eucalyptus oil and its constituents.
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.
This is a lecture by Joe Lex, MD from the Ghana Emergency Medicine Collaborative. To download the editable version (in PPT), to access additional learning modules, or to learn more about the project, see http://openmi.ch/em-gemc. Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution Share Alike-3.0 License: http://creativecommons.org/licenses/by-sa/3.0/.
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The presentation gives an in-depth review of the Anti-fungal drugs used to treat various acute and chronic fungal infections along with their uses and MOA.
Anti-fungal medication is used to treat to fungal infections. They most commonly affect our skin, hair and nails .Nowadays skin problems are found very often.
Subspecialty of dermatology and pathology focused on performing and interpreting tests on human tissue samples to provide scientific data and consultative opinions to referring clinicians
Vitiligo is an acquired pigmentary disorder of the skin and mucous membranes characterized by circumscribed depigmented macules and patches that result from a progressive loss of functional melanocytes that are selectively destroyed.
Androgenetic alopecia (AGA), also referred to as male-pattern hair loss or common baldness in men and as female-pattern hair loss in women is the most common hair loss disorder
Acne vulgaris is a common chronic skin disease involving blockage and/or inflammation of pilosebaceous units
Acne can present as noninflammatory lesions, inflammatory lesions, or a mixture of both,
affecting mostly the FACE but also the back and chest.
There are several dermatoses that occur during pregnancy or immediately postpartum, in particular polymorphic eruption of pregnancy, pemphigoid gestationis, and atopic eruption of pregnancy. Pruritus due to intrahepatic cholestasis of pregnancy leads to nonspecific skin lesions, including excoriations due to scratching.
Impetigo herpetiformis simply represents pustular psoriasis occurring during pregnancy, and this may be related to the relative hypocalcemia of pregnancy. Lastly, there are physiologic changes that occur during pregnancy.
ABNORMAL REDNESS of the skin resulting from dilation of blood vessels that is Blanch on pressure or Diascopy
Erythema Multiforme, Stevens Johnson Syndrome, and Toxic Epidermal Necrolysis
Figurate Erythemas
Urticaria is characterized by WEALS (hives) or ANGIOEDEMA (swellings, in 10%) or both (in 40%). There are several types of urticaria
Spontaneous urticaria
Acute spontaneous urticaria Spontaneous wheals and/or angioedema <6 />6 wk
Urticarias induced by physical agents
dermographic urticaria Eliciting factor: mechanical shearing forces (wheals arising after 1–5 min)
Cold contact urticaria Eliciting factor: cold objects/air/fluids/wind
Solar urticaria Eliciting factor: UV and/or visible light
Delayed pressure urticaria Eliciting factor: vertical pressure (wheals arising with a 3–12 h latency)
Heat contact urticaria Eliciting factor: localized heat Hot water bottle Hot drink
Vibratory urticaria/angioedema Eliciting factor: vibratory forces, e.g. pneumatic hammer/Jack hammer
Other inducible urticarias
Contact urticaria Elicitation by contact with urticariogenic substance
Aquagenic urticaria Eliciting factor: water
Cholinergic urticaria Elicitation by increase of body core temperature due to physical exercises, spicy food, stress
Exercise-induced anaphylaxis/urticaria Eliciting factor: physical exercise
The major forms of dermatitis include
Atopic,
Contact
Seborrheic,
Asteatotic (xerotic),
Stasis,
Disseminated Eczema (Autosensitization)
Nummular. (Discoid)
Pompholyx
The major forms of dermatitis include
Atopic,
Contact
Seborrheic,
Asteatotic (xerotic),
Stasis,
Disseminated Eczema (Autosensitization)
Nummular. (Discoid)
Pompholyx
Insects Bites & Stings: can be divided into 2 groups venomous insect such as a bee or wasp, which uses this as a defense mechanism by injecting toxic and painful venom through its stinger.
Non-venomous insect bites pierce the skin to feed on blood. This usually results in intense itching.
Papular Urticaria:
common disorder manifested by chronic or recurrent papules caused by a HYPERSENSITIVITY REACTION to the bites of mosquitoes, fleas, bedbugs, and other insects
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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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
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
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.
3. • Fungi are eukaryotic, heterotrophic organisms that live as
saprobes or parasites.
• Complex organisms in comparison to bacteria.
• Have nucleus and well defined nuclear membrane, and
chromosomes.
• Have rigid cell wall composed of chitin (bacterial cell wall is
composed of peptidoglycan).
• Fungal cell membrane contains ergosterol (human cell
membrane is composed of cholesterol).
• Antibacterial agents are not effective against fungi.
4. • Superficial dermatophytoses usually respond to
topical antifungal agents which rarely have serious
side effects.
• Fungal infections of the hair and nails as well as
systemic mycoses, immunocompromised or who
have extensive skin involvement generally
necessitate treatment with systemic antifungal
medications.
5.
6.
7.
8.
9.
10. I. Antifungals inhibiting synthesis of THE CELL WALL
II. Antifungals altering PERMEABILITY OF THE CELL
MEMBRANE
III.Antifungals disrupt MICROTUBULE FUNCTION
Inhibit mitosis
IV.Antifungals inhibiting synthesis of THE NUCLEIC
ACIDS
25. 1. DERMATOPHYTE infections such as tinea corporis, tinea
cruris, tinea faciei, tinea manuum, tinea pedis.
2. As an ADJUNCT to oral therapy for tinea capitis, tinea
barbae and onychomycosis.
3. YEAST infections; mucocutaneous candidiasis, pityriasis
versicolor.
4. SEBORRHEIC DERMATITIS; Ketoconazole, selenium sulfide &
ciclopirox olamine.
5. MOULD skin infections such as tinea nigra.
26. I. Skin: cream, gel, ointment, lotion, solution, powder,
aerosol solution, aerosol powder, aerosol foam.
II. Hair: shampoo, gel, lotion, solution.
III. Nail: nail lacquer, nail solution.
IV. Oral mucosa: oral drops, oral gel, troches, lozenges.
V. Vaginal mucosa: cream, vaginal suppositories,
vaginal tablets.
27.
28.
29.
30. DRUG CLASS MECHANISMS OF ACTION
IMIDAZOLES
• Inhibition of fungal cytochrome P450-dependent 14-α-demethylase
prevents synthesis of ergosterol Interfere with CM synthesis.
• Most azoles are fungistatic, some are fungicidal at high concentration.
• Also inhibit neutrophil chemotaxis, calmodulin activity, synthesis of
leukotrienes & prostaglandins, and histamine release from mast cells.
ALLYLAMINES
BENZYLAMINE
THIOCARBAMATES
• Inhibition of squalene epoxidase accumulation of intracellular squalene
(fungicidal) Interfere with CM synthesis.
• Have both fungistatic and fungicidal effects.
POLYENES
• Bind irreversibly to ergosterol pore in CM CM permeability.
• Fungistatic at low concentrations & fungicidal at high concentration.
HYDROXY-
PYRIDONE
• Chelates polyvalent cations (e.g. Fe3+) that have important functions in
fungal cytochromes, catalases and peroxidases; it thereby inhibits
respiration, blocks transport of amino acids & alters CM permeability.
• Active against dermatophytes, Malassezia spp., Candida, actinomycetes,
molds, and Gram-positive & Gram-negative bacteria.
SELENIUM
SULFIDE
• Antimitotic properties; reduces cellular adhesion in the stratum corneum,
facilitating shedding of fungi.
31. • The creams are applied to the affected area twice daily for
two to four weeks, including a margin of several
centimetres of normal skin.
• Continue for one or two weeks after the last visible rash has
cleared. Repeated treatment is often necessary.
• Shampoos are used every 3 to 4 days and are left in place
for 5 minutes before rinsing.
• Nystatin oral suspension is held in the mouth for as long as
possible before swallowing or expectorating repeated 4
times/d.
32. • The most common is LOCAL SKIN IRRITATION, which may be
more severe with occlusion.
• Clinical manifestations include burning, stinging, pruritus,
erythema, edema, peeling, blistering and allergic contact
dermatitis.
• Clioquinol can cause discoloration of clothes, skin, hair and
nails.
33.
34. I. Antifungals inhibiting synthesis of THE CELL WALL
– Caspofungin
II. Antifungals altering PERMEABILITY OF THE CELL MEMBRANE
1. Polyenes
2. Azoles
3. Allylamines
III. Antifungals disrupt MICROTUBULE FUNCTION Inhibit mitosis
– Griseofulvin
IV.Antifungals inhibiting synthesis of THE NUCLEIC ACIDS
– Flucytosine
35. MAY BE REQUIRED FOR A FUNGAL INFECTION IF:
1. It is extensive or severe.
2. It resists topical antifungal therapy.
3. It affects hair-bearing areas (tinea capitis and tinea
barbae) or nails.
36.
37. • Amphotericin B and Nystatin interacts with ergosterols, forms
pores that increase membrane permeability and allow leakage
of intracellular ions & macromolecules from fungal cell cell
death.
• Amphotericin has a lesser affinity for the mammalian cell
membrane component cholesterol, but this interaction does
account for most adverse toxic effects.
• Too toxic for systemic use, nystatin is limited to the topical
treatment of superficial infections caused by C. albicans.
38.
39. • Antifungal agent with the broadest spectrum of activity
• Drug of choice for the vast majority of life-threatening
systemic fungal infections.
• Intrathecal infusion of amphotericin B is useful in patients
with meningitis caused by Coccidioides.
40.
41. • Griseofulvin is an oral fungistatic agent available since 1958
used in the long-term treatment of dermatophyte infections
caused by Epidermophyton, Microsporum, and Trichophyton
spp.
• Produced by the mould, Penicillium griseofulvum.
• It is not effective against yeasts such as candida or malassezia.
• Griseofulvin may still be preferable for tinea capitis, especially
when due to Microsporum canis infection, and is generally well
tolerated in children.
• It has been withdrawn from the market in many countries, as it
has been superceded by more effective and safer antifungal
drugs.
42.
43. MOA:
• It inhibits fungal growth by binding to the
microtubules responsible for mitotic spindle
formation.
• Interacting with microtubules disrupts
mitotic spindle inhibiting mitosis.
• The drug binds to keratin precursor cells and
newly synthesized keratin in the stratum
corneum of the skin, hair, and nails, stopping
the progression of dermatophyte infection.
44. ADME:
• They should be taken after a fatty meal or drink of milk as fat
increases the absorption. Drug particle size reduction through
micronization and ultra-micronization has also significantly
enhanced oral absorption.
• It is carried into the skin by sweat and within a couple of weeks is
concentrated in the outer skin layers.
• Eliminated in urine and faeces.
• It is quickly cleared from skin and hair when it is stopped so
treatment should be continued until clinical cure.
45. USES & DOSAGES:
• Dermatophytosis only.
• Can be taken once daily.
• Adults: 500 mg to 1 g /day.
• Children: 10-25 mg/kg/day.
• Duration of treatment;
– 2–4 weeks for tinea corporis
– 4–8 weeks for tinea pedis
– 6–12 weeks for tinea capitis
– 4 months for tinea unguium of fingernail
– 6 months for tinea unguium of toenail or until all signs of nail
infection have gone.
46. SIDE EFFECTS:
1. Gastrointestinal disturbances: nausea, vomiting, heartburn, cramps, flatulence, taste
disturbance.
2. Central nervous system disturbances: Headaches (most common as well as
gastrointestinal upsets), visual disturbance, dizziness, depression, nightmares, insomnia.
fever.
3. Liver affection: Hepatotoxicity.
4. Allergic reactions: including urticaria, fixed drug eruption, exfoliative dermatitis, lupus
erythematosus and photosensitivity.
5. Urinary disturbance: frequency, enuresis.
6. Sore throat.
7. Menstrual disturbance.
8. Can precipitate or exacerbate porphyria.
47. Griseofulvin Side Effects Mnemonic
Do Dizziness | Depression
U Urinary disturbances
Have Headaches | Hepatotoxicity
G Gastrointestinal disturbances
R Reactions
I Insomnia
S Sore throat
E Exfoliative dermatitis
O ------
F Fever | Fixed drug eruption
U Urticaria
L Lupus erythematosus
V Visual disturbance
I ------
N Nervous system disturbances | Nightmares
Pills Photosensitivity | Porphyria
Mammy? Menstrual disturbance
49. DRUG INTERACTIONS:
1. Griseofulvin interacts with alcohol and can induce a disulfiram-like
reaction and can cause severe nausea and vomiting.
2. Griseofulvin can cause an increase in a liver enzyme reducing the
concentration of:
i. Warfarin
ii. Oral contraceptive (increasing the chance of pregnancy)
iii. Salicylates
50.
51. • They are synthetic drugs with broad-
spectrum fungistatic activity. Azoles
can be divided into two groups:
A. IMIDAZOLES (azole nucleus
contains 2 nitrogen atoms): older
agents Ketoconazole, Miconazole,
Econazole, Clotrimazole…….
B. TRIAZOLES (azole nucleus contains
3 nitrogen atoms): newer agents
Itraconazole, Fluconazol, Vorionazole
→ systemic treatment
52. MOA:
• Inhibition of fungal cytochrome P450-dependent 14-α-
demethylase prevents synthesis of ergosterol Reduced
fungal membrane ergosterol concentrations result in
damaged, leaky cell membranes.
• The toxicity of these drugs depends on their relative affinities
for mammalian and fungal cytochrome P450 enzymes.
53.
54. • Contain 2 Nitrogen atoms attached to the ring.
• Reduce the formation of ergosterol in the cell membrane. which
become permeable to cellular constituents.
• They lack selectivity, and also inhibits human gonadal and steroid
synthesis leading to decreased testosterone and cortisol production.
• Agents:
– Ketoconazole
– Miconazole
– Clotrimazole
– Isoconazole
– Tioconazole……….
55.
56.
57. • It is imidazole antifungal agent taken orally.
• Epigastric distress can be reduced by taking ketoconazole with
food.
• It remains useful in the treatment of cutaneous and mucous
membrane dermatophyte and yeast infections, but it has been
replaced by the newer triazoles in the treatment of most
serious Candida infections and disseminated mycoses.
• Ketoconazole is usually effective in the treatment of thrush, but
fluconazole is superior to ketoconazole for refractory thrush.
• Not used in pregnancy, lactation, hepatic dysfunction.
58. ADME:
• Well absorbed orally as acidic environment favors its dissolution.
• Ketoconazole and itraconazole may not be absorbed in patients with
achlorhydria. Cola drinks improve its absorption in patients with
achlorhydria.
• Bioavailability is impaired with food.
• 84% is bound to plasma proteins.
• Metabolized extensively in liver and inactive products appear in the
feces.
• Moderate hepatic dysfunction has no effect on drug concentration.
• It does not enter CSF.
60. USES & DOSAGES:
• Effective against most dermatophytes, Candida spp.
• Used via oral route only to treat;
1. Superficial fungal infections: widespread, severe or resistant to topical antifungals
– Oral & vaginal candidiasis: 200 mg once-daily for 5 days
– Pityriasis versicolor: 200 mg once-daily for 5 days
– Dermatophytosis;
• In adults is 200 to 400 mg daily, taken for two to eight weeks. Nail infections are treated for up to
twelve months.
• The dose in children is usually 50 mg per day for those weighing less than 20 kg and 100 mg daily for
those 20-40 kg.
2. Systemic fungal infections:
– Histoplasmosis, non-meningeal cryptococcosis, Blastomycosis.
61. SIDE EFFECTS:
1. Gastrointestinal disturbances: Nausea, vomiting, anorexia, abdominal pain (dose
dependent).
2. Central nervous system disturbances.
3. Liver affection: Idiosyncratic hepatotoxicity (rare) - but may prove fatal. Liver enzyme
elevations during therapy are usually reversible.
4. Allergic reactions: Anaphylaxis, urticaria, pruritus.
5. Alopecia.
6. At higher doses, suppresses synthesis of adrenal gonadal steroids testosterone and cortisol
which leads to menstrual irregularities in women, loss of libido, impotence, reduced sperm
count and gynaecomastia in males. These hormonal effects have led to the use of
ketoconazole as a potential adjunctive treatment for prostatic carcinoma.
62. • Decrease in the
ergosterol in the
fungal membrane
by ketoconazole
reduces the
fungicidal action
of amphotericin
63. • In August 2013, the FDA announced that clinicians should no
longer prescribe ketoconazole (Nizoral) tablets as a first-line
therapy for any fungal infection, including Candida and
dermatophyte infections, because of the risk for severe liver
injury, adrenal insufficiency, and adverse drug interactions.
• Ketoconazole tablets were also withdrawn from the market in
the European Union in July 2013.
64. • They are more selective i.e. higher affinity to fungal enzyme.
• Penetrate to CNS.
• Resistant to degradation.
• Cause less endocrine disturbance.
• They tend to have fewer side effects, better absorption, better drug
distribution in body tissues, and fewer drug interactions.
• Main Agents:
1. Itraconazole
2. Fluconazole
3. Voriconazole
65.
66. • It is a synthetic broad spectrum triazole.
• Administered orally as well as IV.
• Food increases its absorption.
• Requires a gastric pH for absorption may not be absorbed in patients
with achlorhydria.
• Highly lipid soluble, and water insoluble.
• Oral bioavailability is variable (20 to 60%).
• Lacks endocrine side effects of ketoconazole.
67. FORMULATIONS:
1. Capsules 100 mg should be taken with a full
meal to enhance absorption.
2. Oral solution 10 mg/ml should be taken on
an empty stomach as oral solution is 60%
more bioavailable than the capsules.
Pediatric dosing is 5 mg/kg daily.
3. Intravenous infusion, given 200 mg
intravenously twice a day for four doses and
then 200 mg every day.
68. ADME:
• Food increases its absorption.
• Absorption is improved by acid may be taken with orange juice or cola.
• It is highly protein bound (99%) and is metabolized in the liver and excreted into
the bile.
• It is highly lipid soluble and well distributed to skin, sebum, bone, sputum and
adipose tissue & to less extent sweat.
• Half life is 1-1.5 d.
• Does not penetrate into CSF adequately.
• The capsule is better absorbed with food, but the oral solution is better absorbed in
the fasting state.
• Therapeutic levels in the skin persist for 2-4 w after last dose.
69. USES & DOSAGES :
• Effective against dermatophytes, yeasts some molds.
I. Superficial fungal infections: widespread, severe or resistant to topical antifungals. 200 to 400
mg/day. Doses exceeding 200 mg/day are given in 2 divided doses
– Pityriasis versicolor: 200 mg daily for 5-7 days.
– Tinea corporis, tinea cruris: 100 mg daily for 2 w or 200 mg daily for 1 w.
– Tinea pedis, tinea manuum: 100 mg daily for 2-4 weeks OR 200 mg twice daily for one week.
– Tinea capitis: 5 mg/kg/d for 2 to 4 weeks or as 1- to 3-week-long pulses.
– Onychomycosis: 200 mg/day for 1.5-2 months (fingernails) or 3-4 months (toenails), OR 200 mg twice daily for 7 days,
repeated monthly for 2 months (fingernails) or 3-4 months (toenails).
– Vulvo-vaginal candidiasis: 200 mg twice for one day.
– Oropharyngeal and esophageal candidiasis (solution): Taken fasting in a dose of 100-200 mg once daily and swished
vigorously for few seconds in the mouth before swallowing to optimize topical effect for 1–3 weeks should be
continued for at least 2 weeks after symptoms resolve.
II. Systemic fungal infections: Blastomycosis, sporotrichosis, histoplasmosis and aspergillosis
– It can safely be administered prophylactically in patients receiving bone marrow transplants.
70. SIDE EFFECTS:
1. Gastrointestinal disturbances: anorexia,
nausea, vomiting, abdominal pain Relative to
capsules, the oral solution of itraconazole
more frequently causes diarrhea, abdominal
cramps, anorexia, and nausea.
2. Central nervous system disturbances:
fatigue, headaches, dizziness.
3. Liver affection: Hepatic dysfunction and
death. Elevated serum aminotransferases
hypertriglyceridemia if symptoms of
hepatotoxicity occur, the drug should be
discontinued and liver function assessed.
4. Allergic reactions: Morbilliform eruption,
pruritus, urticaria, Stevens–Johnson
syndrome (rarely), infusion site reactions in
parenteral administration.
5. Alopecia.
6. Fever.
7. Lower limb edema.
8. Hypokalemia.
71.
72. • It is a synthetic broad spectrum triazole.
• It is relatively hydrophilic compared to other systemic azole
antifungal drugs.
• It is not affected gastric acidity.
• C. krusei is fluconazole-resistant.
73. ADME
• Bioavailability not altered by food or gastric acidity. Does not require an acidic
environment, as does ketoconazole and itraconazole for GI absorption.
• Excellent bioavailability by oral route (about 80 to 90% of an orally administered dose
is absorbed, yielding high serum drug levels).
• The t ½ of the drug is 1-1.5 d, permitting once-daily dosing in patients with normal
renal function. Only 10% of the circulating drug is bound to plasma proteins.
• The drug penetrates widely into most body tissues. Readily diffuses into body fluids,
including breast milk, sputum, saliva, and CSF.
• About 80% of the drug is excreted unchanged in the urine. Dosage reductions are
required in the presence of renal insufficiency.
74. FORMULATIONS:
• Capsules for oral administration 50 or 150 mg.
• Powder for oral suspension 50 mg/5ml
• Intravenous solutions containing 2 mg/ml.
75. USES & DOSAGES:
1. Superficial fungal infections:
– Pityriasis versicolor: 300 mg once weekly for 2 weeks.
– Candidiasis: very effective in the treatment of infections with most Candida spp.
• Single dose of 150 mg is effective in uncomplicated vaginal candidiasis.
• Oropharyngeal candidiasis: 200 mg on the first day and then 100 mg daily for at least 2 weeks.
• Thrush or esophageal candidiasis in the AIDS patient, which may be refractory to nystatin, clotrimazole, and ketoconazole.
– Dermatophytosis:
• 150 mg/w 2-6w.
• Tinea capitis: 6 mg/kg/d 2–3 weeks.
• Onychomycosis: 150 mg /w 6-9-m.
2. Systemic fungal infections:
– Especially for cryptococcal meningitis 400-800 mg q24h.
– > 800 mg q24h in unstable patient.
– Maintenance: 400 mg/day, for the initial 8 weeks in the treatment in AIDS after the patient has been
stabilized with IV amphotericin B.
– Prophylactically: for end-stage AIDS or bone marrow transplant recipients 200 mg po qd.
76. SIDE EFFECTS:
1. Gastrointestinal disturbances: Nausea, abdominal pain, diarrhea and vomiting at
doses >200 mg/day.
2. Central nervous system disturbances: Headache.
3. Liver affection: Asymptomatic liver enzyme elevation has been described, and
several cases of drug associated hepatic necrosis have been reported. Rare
deaths due to hepatic failure.
4. Allergic reactions: skin rash, morbilliform eruption, exfoliative dermatitis (rarely),
Stevens-Johnson syndrome.
5. Reversible alopecia may occur with prolonged high-dose therapy.
6. Highly teratogenic: Associated with skeletal and cardiac deformities in infants
born to women taking high doses during pregnancy and should be avoided
during pregnancy.
77.
78.
79. • Reversible noncompetitive inhibition of squalene epoxidase accumulation of
intracellular squalene (fungicidal) decrease in lanosterol production decrease
in ergosterol Interfere with CM synthesis.
• These agents exhibit fungicidal activity against dermatophytes and fungistatic
activity against yeasts.
• Agents:
1. Naftifine is available for topical use only in the treatment of cutaneous dermatophyte and Candida
infections.
2. Terbinafine is available for topical and systemic use in the treatment of dermatophyte skin and nail
infections.
80.
81.
82. • Terbinafine is a synthetic allylamine antifungal agent. It is
especially effective against dermatophytes.
• Antifungal spectra Epidermophyton spp., Trichophyton spp.
• More selective to fungal enzyme so it appears to be a relatively
safe drug. Side effects, usually minor, arise occasionally. Serious
side effects occur rarely.
83. ADME:
• It is absorbed well when taken orally, with or without food.
• It is bound to proteins such as albumin in the circulating blood and
becomes concentrated in fat cells (lipophilic) and within skin (epidermal
& sebum), hair and nails.
• Skin concentrations may be up to 75-fold higher than those in the blood.
• It may persist in the skin for up to 8 weeks after the drug has been
discontinued and in the nails for up to a year.
• Metabolized in the liver into inactive compounds then slowly eliminated
in faeces and urine. Doses may need to be reduced in the presence of
kidney disease.
84. USES & DOSAGES:
• Only in dermatophytosis.
• The oral dose of terbinafine for adults is 250 mg daily.
1. Tinea corporis, tinea cruris, tinea pedis, tinea manuum: 1 to 4 weeks.
2. Tinea unguium: for 6 weeks (fingernails) or 12 weeks (toenails).
3. Tinea capitis for children over 2 years old, the tablets can be hidden in
food – the tablets taste unpleasant taken for 4 weeks:
– Weight <20 kg 62.5 mg/day
– Weight 20-40 kg 125 mg/day
– Weight >40 kg 250 mg/day
– Sometimes, if the fungal infection does not clear, the dose in children may
need to be increased.
• Treatment can be repeated if necessary.
85. SIDE EFFECTS:
1. Gastrointestinal disturbances: nausea, feeling of fullness, diarrhea, abdominal pain.
2. Central nervous system disturbances: Headache, dizziness, taste disturbance, loss of
appetite (uncommon, <1%), visual disturbance.
3. Liver affection: Elevated liver enzymes so tests for liver function should be performed
before and during treatment. But sever liver disease is rare (<0.01%).
4. Allergic reactions: including urticaria (common, <10%), morbilliform eruption and
Stevens-Johnson and toxic epidermal necrolysis (very rare, but potentially dangerous,
<0.01%), pustular psoriasis, subacute cutaneous lupus erythematosus.
5. Painful muscles and joints.
6. Reduced neutrophil white blood cell count (very rare, <0.01%).
86. DRUG INTERACTIONS:
• Terbinafine does not generally alter the concentration of
other medications.
1. Rifampicin results in a decrease in the concentration of
terbinafine by doubling its rate of clearance.
2. Cimetidine may increase the concentration of terbinafine.
3. Cyclosporine terbinafine increases its clearance.
4. Antidepressants: SSRIs, MAO i, TCA terbinafine may increase
their serum levels and toxic effects.
87.
88. • Is an antimetabolite analogue of cytosine that was
originally synthesized for possible use as an
antineoplastic agent. 5-FC is converted to 5-fluorouracil
inside the cell by the fungal enzyme cytosine deaminase.
• The active metabolite 5-fluorouracil interferes with
fungal DNA synthesis by inhibiting thymidylate
synthetase. Incorporation of these metabolites into
fungal RNA inhibits protein synthesis.
• Flucytosine has a significant antifungal activity against
Candida spp. and the fungal organisms responsible for
chromomycosis.
89.
90. • Caspofungin is a semisynthetic lipopeptide. It
inhibits the synthesis of β-glucan, a cell wall
component of filamentous fungi.
• Echinocandins are available only for IV
administration.
• Caspofungin is approved for the treatment of
invasive aspergillosis in patients not responding to
amphotericin B, and itraconazole.
• Adverse effects are mediated through histamine
release: facial flushing, rash, fever, and pruritus.
91. • Bolognia 3rd ed.
• http://dermnetnz.org
• Google images
• Dr. Mrs Borkar (Presentation)
• Mechanisms in Medicine