1. Lecture 10: Antifungal therapy
Dr. Mahmoud H. Taleb

2. 4- Fungal infections and antifungal Agents
Fungal infections are usually more difficult to treat than bacterial infections, because fungal organisms grow slowly and because fungal infections often occur in tissues that are poorly penetrated by antimicrobial agents (e.g., devitalized or avascular tissues).
-Therapy of fungal infections usually requires prolonged treatment.
-Advances in medical technology, including organ and bone marrow transplantation, cytotoxic chemotherapy, the widespread use of indwelling intravenous (IV) catheters, and the increased use of potent broad-spectrum antimicrobial agents all have contributed to the
dramatic increase in the incidence of fungal infections worldwide.
- Superficial mycoses are among the most common infections in the World .
Dr. Mahmoud H. Taleb

3. - Systemic fungal infection
-Mucocutaneous candidiasis may occur in three forms, oropharyngeal, esophageal, and vulvovaginal disease. - Superficial mycotic infections of the skin are referred to as dermatophytoses.( Tinae capities- Tinae pedis, Tinae, corporis, Tinae cruris, Tinae ungum).
- A general approach to treatment of superficial mycotic infections includes keeping the infected area dry and clean and limiting exposure to the infected reservoir.
* *Topical agents generally are considered to be first-line therapy for infections of the skin.
* * Oral therapy is preferred when the infection is extensive or severe.
Dr. Mahmoud H. Taleb

4. Antifngal drugs 1- Amphotericin B
- Amphotericin B is one of a family of some 200 polyene macrolide antibiotics.
Mechanism of action :
- The antifungal activity of amphotericin B depends principally on its binding to a sterol moiety, primarily ergosterol that is present in the membrane of sensitive fungi. By virtue of their interaction with these sterols, polyenes appear to form pores or channels that increase the permeability of the membrane, allowing leakage of a variety of small molecules.
Amphotericin has a lesser affinity for the mammalian cell membrane component cholesterol, but this interaction does account for most adverse toxic effects associated with this drug.
Pharmacokinetics :
- Gastrointestinal absorption of all amphotericin B formulations is negligible.
- It is administered as repeated daily intravenous infusions.
- Amphotericin B is highly bounded to protein and its major route of elimination is by metabolism, with little intact drug detected in urine or bile.
Dr. Mahmoud H. Taleb

5. 2- Flucytosine Clinical use :
- Amphotericin B is most commonly used to treat serious disseminated yeast and dimorphic fungal infections in immunocompromised hospitalized patients.
Adverse effects :
- The major acute reaction to intravenous amphotericin B formulations is fever and chills.
- Nephrotoxicity is the most common and the most serious long-term toxicity of amphotericin B administration.
- Nausea, vomiting, and anorexia are a persistent problem for some patients.
Hypochromic, normocytic anemia may occur. Decreased production of erythropoietin is the probable mechanism.
2- Flucytosine
Flucytosine is a fluorinated pyrimidine related to fluorouracil and floxuridine.
Mechanism of action :
- Flucytosine is converted to 5-fluorouracil inside the cell by the fungal enzyme cytosine deaminase. Subsequently, 5-fluorouracil metabolites interfere with fungal DNA synthesis by inhibiting thymidylate synthetase. Incorporation of these metabolites into fungal RNA may inhibit protein synthesis.
- The selective action of flucytosine is due to the lack or low levels of cytosine deaminase in mammalian cells.
Dr. Mahmoud H. Taleb

6. Figure ( 34 ) Mode of action of flucytosine
Figure ( ) Mode of action of flucytosine. 5-FdUMP = 5-fluorodeoxyuridine 5'-monophosphate; dTMP = deoxythymidine 5'-monophosphate.
Dr. Mahmoud H. Taleb

7. Pharmacokinetics:
- Flucytosine is absorbed rapidly and well from the gastrointestinal tract.
- It is widely distributed in the body, with a volume of distribution that approximates total body water, and is minimally bound to plasma proteins.
- Approximately 80% of a given dose is excreted unchanged in the urine.
- Flucytosine concentration in CSF is about 65% to 90% of that found simultaneously in the plasma. The drug also appears to penetrate into the aqueous humor.
Clinical uses :
- Flucytosine is used predominantly in combination with amphotericin B, flucytosine caused no added toxicity. When it is used as monotherapy, resistance and clinical failure are common.
Adverse effects :
- Flucytosine may depress the bone marrow and lead to leukopenia and thrombocytopenia - Rash, nausea, vomiting, diarrhea, and severe enterocolitis have been noted.
Dr. Mahmoud H. Taleb

8. 3 - Griseofulvin
- This agent inhibits fungal growth by binding to the microtubules responsible for mitotic spindle formation, as the drug inhibits fungal mitosis. Ineffective topically, griseofulvin is administered orally but has poor gastrointestinal absorption; absorption can be improved by microcrystalline processing of the drug and by taking the drug with fatty meals.
- Griseofulvin is metabolized in the liver. 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.
- Griseofulvin is usually well tolerated. Headache is common with initiation of therapy. Hepatotoxicity, dermatitis, and gastrointestinal distress also occur.
Dr. Mahmoud H. Taleb

9. 4- Imidazoles and Triazoles
The azole antifungals include two broad classes, imidazoles and triazoles, which share the same antifungal spectrum and mechanism of action. The systemic triazoles are metabolized more slowly and have less effect on human sterol synthesis than do the imidazoles.
Mechanism of action :
The major effect of imidazoles and triazoles on fungi is inhibition of 14- α -sterol demethylase, thus impair the biosynthesis of ergosterol for the cytoplasmic membrane and lead to the accumulation of 14-α-methylsterols. These methylsterols may disrupt the close packing of acyl chains of phospholipids, impairing the functions of certain membrane-bound enzyme systems.
Dr. Mahmoud H. Taleb

10. Specific agents * Ketoconazole
- Ketoconazole , administered orally, has been replaced by itraconazole for the treatment of all mycoses except when the lower cost of ketoconazole outweighs the advantage of itraconazole. Ketoconazole was the first oral azole introduced into clinical use. It is distinguished from triazoles by its greater propensity to inhibit mammalian cytochrome P450 enzymes, it is less selective for fungal P450 than are the newer azoles.
- Ketoconazole sometimes is used to inhibit excessive production of glucocorticoids in patients with Cushing's syndrome.
- Nausea, vomiting, and anorexia occur commonly with ketoconazole, especially when high doses are prescribed. Epigastric distress can be reduced by taking ketoconazole with food.
- At high doses, ketoconazole causes a clinically significant reduction in testosterone synthesis, This hormonal effect have led to the use of ketoconazole as a potential adjunctive treatment for prostatic carcinoma.
Dr. Mahmoud H. Taleb

11. Figure ( 35 ) Mode of action of ketoconazole.
Dr. Mahmoud H. Taleb

12. Antifungal spectrum :
Ketoconazole is active against many fungi, including Histoplasma, Blastomyces, Candida,and Coccidioides, but not aspergillus species. Although itraconazole has largely replaced ketoconazole in the treatment of most mycoses because of its broader spectrum, greater potency, and fewer adverse effects, ketoconazole, as a second-line drug, is a less expensive alternative for the treatment of mucocutaneous candidiasis. Strains of several fungal species that are resistant to ketoconazole have been identified.
Dr. Mahmoud H. Taleb

13. Pharmacokinetics:
Ketoconazole is only administered orally . It requires gastric acid for dissolutioand is absorbed through the gastric mucosa. Drugs that raise gastric pH, such as antacids, or that interfere with gastric acid secretion, such as H2-histamine receptor blockers and proton-pump inhibitors, impair absorption. Administering acidifying agents, such as cola drinks, before taking the drug can improve absorption in patients with achlorhydria. Ketoconazole is extensively bound to plasma proteins. Although penetration into tissues is limited, it is effective in the treatment of histoplasmosis in lung, bone, skin, and soft tissues. The drug does not enter the CSF. Extensive metabolism occurs in the liver, and excretion is primarily through the bile. Levels of parent drug in the urine are too low to be effective against mycotic infections of the urinary tract.
Dr. Mahmoud H. Taleb

14. Drug interactions and contraindications:
Adverse effects:
1- In addition to allergies, dose-dependent gastrointestinal disturbances, including nausea, anorexia, and vomiting, are the most common adverse effects of ketoconazole treatment.
2- Endocrine effects, such as gynecomastia, decreased libido, impotence, and menstrual irregularities, result from the blocking of androgen and adrenal steroid synthesis by ketoconazole. Transient increases in serum transaminases are found
in from 2 to 10 percent of patients.
Frank hepatitis occurs rarely but requires immediate cessation of treatment.
Drug interactions and contraindications:
By inhibiting cytochrome P450, ketoconazole can potentiate the toxicities of drugs such as cyclosporine, phenytoin, tolbutamide, and warfarin, among others . Rifampin, an inducer of the cytochrome P450 system, can shorten the duration of action of ketoconazole and the other azoles. Drugs that decrease gastric acidity, such as H2-receptor blockers, antacids, proton-pump inhibitors, and sucralfate, can decrease absorption of ketoconazole. Ketoconazole and amphotericin B should not be used together, because the decrease in ergosterol in the fungal membrane reduces the fungicidal action of amphotericin B . Finally, ketoconazole is teratogenic in animals, and it should not be given during pregnancy.
Dr. Mahmoud H. Taleb

15. * Itraconazole
- Itraconazole lacks ketoconazole's corticosteroid suppression, while retaining most of ketoconazole's pharmacological properties and expanding the antifungal spectrum.
- Itraconazole is lipophilic and water insoluble and requires a low gastric pH for absorption.
- Oral bioavailability is variable, only 50 to 60% when taken with food and 20% or less when the drug is taken on an empty stomach.
- Itraconazole is metabolized in the liver. It is both a substrate for and a potent inhibitor of CYP3A4.
- The native drug and metabolite are >99% bound to plasma proteins. Neither appears in urine or CSF. - Itraconazole is usually well tolerated but can be associated with nausea and epigastric distress. - High doses may cause hypokalemia, hypertension, and edema. - Hepatotoxicity occurs in fewer than 5% of cases and is usually manifested by reversible liver enzyme elevations.
Dr. Mahmoud H. Taleb

16. * Fluconazole
- Fluconazole is almost completely absorbed from the gastrointestinal tract and its bioavailability is unaltered by food or gastric acidity.
- About 80% of the drug is excreted unchanged in the urine, and 10% is excreted unchanged in the feces.
- A single dose of 150 mg is effective in uncomplicated vaginal candidiasis.
- Fluconazole is very effective in the treatment of infections with most Candida spp.
Fluconazole is well tolerated. Nausea, vomiting, abdominal pain, diarrhea, and skin rash have been reported in fewer than 3% of patients. - Alopecia has been reported as a common adverse event in patients receiving prolonged high-dose therapy.
*Voriconazole
*Posaconazole
Dr. Mahmoud H. Taleb

17. * Miconazole * Clotrimazole
- Miconazole is a broad-spectrum imidazole antifungal agent used in the topical treatment of cutaneous dermatophyte infections and mucous membrane Candida infections, such as vaginitis.
- Minimal absorption occurs from skin or mucous membrane surfaces.
- Local irritation to skin and mucous membranes can occur with topical use; headaches, urticaria, and abdominal cramping have been reported with treatment for vaginitis.
* Clotrimazole
- Clotrimazole is a broad-spectrum fungistatic imidazole drug used in the topical treatment of oral, skin, and vaginal infections with C. albicans. It is also employed in the treatment of infections with cutaneous dermatophytes.
- Topical use results in therapeutic drug concentrations in the epidermis and mucous membranes; less than 10% of the drug is systemically absorbed.
Although clotrimazole is generally well tolerated, local abdominal cramping, increased urination, and transient liver enzyme elevations have been reported.
Dr. Mahmoud H. Taleb

18. 5- Allylamines * Terbinafine
Terbinafine is the drug of choice for treating dermatophytoses and, especially, onychomycoses (fungal infections of nails). It is better tolerated, requires shorter duration of therapy, and is more effective than either itraconazole or griseofulvin.
Mechanism of action :
Terbinafine inhibits fungal squalene epoxidase, thereby decreasing the synthesis of ergosterol. This plus the accumulation of toxic amounts of squalene result in the death of the fungal cell. [Note: Significantly higher concentrations of terbinafine are needed to inhibit human squalene epoxidase, an enzyme required for the cholesterol synthetic pathway.]
Dr. Mahmoud H. Taleb

19. Figure (36) Mode of action of terbinafine.
Antifungal spectrum :
The drug is primarily fungicidal. Antifungal activity is limited to dermatophytes and Candida albicans. Therapy is prolonged usually about 3 months but considerably shorter than that with griseofulvin.
Dr. Mahmoud H. Taleb

20. Pharmacokinetics : Adverse effects :
Terbinafine is orally active, although its bioavailability is only 40 % due to first-pass metabolism. Absorption is not significantly enhanced by food. Terbinafine is greater than % bound to plasma proteins. It is deposited in the skin, nails, and fat.
Terbinafine accumulates in breast milk and therefore, should not be given to nursing mothers. A prolonged terminal half-life of 200 to 400 hours may reflect the slow release from these tissues. Terbinafine is extensively metabolized prior to urinary excretion. Patients with either moderate renal impairment or hepatic cirrhosis have reduced clearance.
Adverse effects :
The most common adverse effects due to terbinafine are gastrointestinal disturbances (diarrhea, dyspepsia, and nausea), headache, and rash. Taste and visual disturbances have been reported as well as transient elevations in serum liver enzyme levels. All adverse effects resolve upon drug discontinuation. Rarely, terbinafine may cause hepatotoxicity and neutropenia.
6- Echinocandins: Caspofungin, micafungin, and anidulafungin
7- Tolnaftate -
Dr. Mahmoud H. Taleb

21. 8-Polyene Antifungal Antibiotics (Nystatin)
- Nystatin is structurally similar to amphotericin B and has the same mechanism of action. - Nystatin is not absorbed from the gastrointestinal tract, skin, or vagina.
- Nystatin is useful only for candidiasis and is supplied in preparations intended for cutaneous, vaginal, or oral administration for this purpose.
- Infections of the nails and hyperkeratinized or crusted skin lesions do not respond.
- Topical preparations include ointments, creams, and powders, all of which contain ,000 units/g.
- An oral suspension that contains 100,000 units/ml of nystatin is given four times a day. - Too toxic for systemic use, nystatin is limited to the topical treatment of superficial infections caused by C. albicans.
Dr. Mahmoud H. Taleb

22. 9-Benzoic Acid and Salicylic Acid 10- Ciclopirox Olamin.
10- Ciclopirox Olamin
11- Undecylenic Acid -
Dr. Mahmoud H. Taleb

23. Chemotherapy of protozoal infections
Protozoal infections are common among people in underdeveloped tropical and subtropical countries, where sanitary conditions, hygienic practices, and control of the vectors of transmission are inadequate. However, with increased world travel, protozoal diseases such as amebiasis, giardiasis, trichomoniasis, leishmaniasis, Toxoplasmosis, trypanosomiasis, and malaria are no longer confined to specific geographic locales. Protozoal diseases are thus less easily treated than bacterial infections, and many of the antiprotozoal drugs cause serious toxic effects in the host, particularly on cells showing high metabolic activity, such as neuronal, renal tubular, intestinal, and bone marrow stem cells. Most antiprotozoal agents have not proved to be safe for pregnant patients. Drugs used to treat protozoal infections are summarized in Figure
Dr. Mahmoud H. Taleb

24. Figure ( 37) Summary of antiprotozoal agents.
Dr. Mahmoud H. Taleb

25. 1-Metronidazole
- Metronidazole is clinically effective in trichomoniasis, amebiasis, and giardiasis, as well as in a variety of infections caused by obligate anaerobic bacteria, including Bacteroides, Clostridium, and microaerophilic bacteria such as Helicobacter and Campylobacter species.
- Metronidazole is a prodrug that requires reduction before it becomes active. The enzyme, pyruvate-ferredoxin oxidoreductase, found only in anaerobic organisms, reduces metronidazole and thereby activates the drug. Reduced metronidazole disrupts replication and transcription and inhibits DNA repair.
- Preparations of metronidazole are available for oral, intravenous, intravaginal, and topical administration. The drug has complete and rapid absorption after oral intake. - The half-life of metronidazole in plasma is about 8 hours, and its volume of distribution is approximately that of total-body water.
The most frequently observed adverse reactions to metronidazole include nausea, vomiting, cramps, diarrhea, and a metallic taste. - The urine is often dark or red brown.
- While metronidazole has been taken during all stages of pregnancy with no apparent adverse effects, its use during the first trimester generally is not advised.
Other clinically effective 5-nitroimidazoles closely related in structure and activity to metronidazole are tinidazole and ornidazole.
- Although tinidazole and metronidazole are equally effective, tinidazole is given in a shorter course and is better tolerated.
Dr. Mahmoud H. Taleb

26. Tinidazole:
Tinidazole is a second-generation nitroimidazole that is similar to metronidazole in spectrum of activity, absorption, adverse effects and drug interactions Tinidazole is as effective as metronidazole, with a shorter course of treatment, yet is more expensive than generic metronidazole.
2-Diloxanide furoate
It is an effective luminal amebicide but is not active against tissue trophozoites. In the gut, diloxanide furoate is split into diloxanide and furoic acid; about 90% of the diloxanide is rapidly absorbed and then conjugated to form the glucuronide, which is promptly excreted in the urine. The unabsorbed diloxanide is the active antiamebic substance. The mechanism of action of diloxanide furoate is unknown.
Diloxanide furoate is considered the drug of choice for asymptomatic luminal infections It is used with a tissue amebicide, usually metronidazole, to treat serious intestinal and extra intestinal infections. Diloxanide furoate does not produce serious adverse effects. Flatulence is common, but nausea and abdominal cramps are infrequent and rashes are rare. The drug is not recommended in pregnancy.
Dr. Mahmoud H. Taleb

27. 6- Emetine and dehydroemetine: 7- Iodoquinol:
3-Paromomycin
4- Furazolidone
5- Chloroquine:
6- Emetine and dehydroemetine:
7- Iodoquinol:
8- Other protozoal agents
Pentamidine, Eflornithine, Nifurtimox, Melarsoprol, Sodium stibogluconate, Amphotericin, , Tetracyclines, Spiramicin, suramin and Fumagillin.
Dr. Mahmoud H. Taleb

28. Chemptherapy of Helminthic Diseases
- Most intestinal helminthic infections may not be associated with clearly defined manifestation of disease, but they can cause significant pathology. One factor that determines the pathogenicity of helminths is their population density. Light infections may be fairly well tolerated, whereas high populations of intestinal helminths can result in predictable disease presentations. Helminthic infections include nematode,cestode and trematode infections as shown in table (8).
- Anthelmintics are drugs that act either locally to expel worms from the gastrointestinal tract or systemically to eradicate adult helminths or developmental forms that invade organs and tissues.
Dr. Mahmoud H. Taleb

29. 1- Benzimidazoles (BZAs)
- The BZAs, exemplified by mebendazole, flubendazole and albendazole. BZAs produce many biochemical changes in susceptible nematodes including inhibition of mitochondrial fumarate reductase, reduced glucose transport, and uncoupling of oxidative phosphorylation, but their primary action likely is to inhibit microtubule polymerization by binding to β-tubulin.
- The selective toxicity of these agents results because the BZAs bind parasite β-tubulin with much higher affinity than they do the mammalian protein.
- Appropriate doses of mebendazole, flubendazole and albendazole are highly effective in treating ascariasis, enterobiasis, trichuriasis, and hookworm as well as less common human nematode infections.
- These drugs are active against both larval and adult stages of nematodes that cause these infections. Immobilization and death of susceptible gastrointestinal parasites occur slowly, and their clearance from the GI tract may not be complete until several days after treatment.
- Albendazole is superior to mebendazole in curing hookworm and trichuriasis infections in children, especially when used as a single dose.
Dr. Mahmoud H. Taleb

30. - Overall, the BZAs have excellent safety profiles.
Pharmacokinetics
- Tablet formulations of mebendazole are poorly and erratically absorbed, the tablets should be chewed before swallowing and concentrations of the drug in plasma are low and do not reflect the dosage taken.
- Albendazole is variably and erratically absorbed after oral administration; absorption is enhanced by the presence of fatty foods and possibly by bile salts.
Clinical Uses
Mebendazole always is taken orally, and the same dosage schedule applies to adults and children more than 2 years of age. For treatment of enterobiasis, a single 100-mg tablet is taken; a second should be given after 2 weeks. For control of ascariasis, trichuriasis, or hookworm infections, the recommended regimen is 100 mg of mebendazole taken in the morning and evening for 3 consecutive days (or a single 500-mg tablet administered once). If the patient is not cured 3 weeks after treatment, a second course should be given.
- Like mebendazole, albendazole provides safe and highly effective therapy against infections with gastrointestinal nematodes, including mixed infections of Ascaris, Trichuris, and hookworms. For treatment of enterobiasis, ascariasis, trichuriasis, and hookworm infections, albendazole is taken as a single oral 400-mg dose by adults and children more than 2 years of age. In children between the ages of 12 and 24 months, the WHO recommends a reduced dose of 200 mg.
- Overall, the BZAs have excellent safety profiles.
Dr. Mahmoud H. Taleb

31. Adverse Reactions, Contraindications, & Cautions
Short-term mebendazole therapy for intestinal nematodes is nearly free of adverse effects. Mild nausea, vomiting, diarrhea, and abdominal pain have been reported infrequently. Rare side effects, usually with high-dose therapy, are hypersensitivity reactions (rash, urticaria), agranulocytosis, alopecia, and elevation of liver enzymes.
Mebendazole is teratogenic in animals and therefore contraindicated in pregnancy. It should be used with caution in children under 2 years of age because of limited experience and rare reports of convulsions in this age group.
Dr. Mahmoud H. Taleb

32. 2- Pyrantel pamoate
- Pyrantel pamoate is a agonist at the nicotinic acetylcholine receptor, and its actions result in depolarization and spastic paralysis of the helminth muscle.
- Its selective toxicity occurs primarily because the neuromuscular junction of helminth muscle is more sensitive to the drug than is mammalian muscle.
Anthelmintic Actions
Pyrantel is effective against mature and immature forms of susceptible helminths within the intestinal tract but not against migratory stages in the tissues or against ova.
Pyrantel pamoate along with mebendazole, is effective in the treatment of infectionscaused by roundworms, pinworms, and hookworms. Clinical Uses
The standard dose is 11 mg (base)/kg (maximum, 1 g), given orally once with or without food. For pinworm the dose is repeated in 2 weeks, and cure rates are greater than 95%.
. Pyrantel should be used with caution in patients with liver dysfunction, since low, transient aminotransferaseelevations have been noted in a small number of patients. Experience with the drug in pregnant women and children under age 2 years is limited.
Dr. Mahmoud H. Taleb

33. 3- Niclosamide
Niclosamide is a second-line drug for the treatment of most tapeworm infections.
Uses
The adult dose of niclosamide is 2 g once, given in the morning on an empty stomach. The tablets must be chewed thoroughly and are then swallowed with water.
T Saginata (Beef Tapeworm), T Solium (Pork Tapeworm), and Diphyllobothrium Latum (Fish Tapeworm) . Infrequent, mild, and transitory adverse events include nausea, vomiting, diarrhea, and abdominal discomfort. The consumption of alcohol should be avoided on the day of treatment and for 1 day afterward. The safety of the drug has not been established in pregnancy or for children under 2 years of age.
Dr. Mahmoud H. Taleb

34. 4- Praziquantel
- The neuromuscular effects of praziquantel appear to increase parasite motility leading to spastic paralysis. The drug increases calcium permeability through parasite-specific ion channels-. It is the most effective of the drugs used in the treatment of schistosomiasis,
5- Oxamniquine
Oxamniquine is an alternative to praziquantel for the treatment of S mansoni infections. It has also been used extensively for mass treatment. It is not effective against S haematobium.
Dr. Mahmoud H. Taleb

35. 7- Diethylcarbamazine Citrate
6- Thiabendazole
Thiabendazole is an alternative to ivermectin for the treatment of strongyloidiasis and cutaneous larva migrans.
7- Diethylcarbamazine Citrate
Diethylcarbamazine is a drug of choice in the treatment of filariasis.
8- Other anthelmintics
-- Emetine and hydroemetine.
- Bithionol.
--Suramin.
Dr. Mahmoud H. Taleb

36. Figure () Characteristics of and therapy for commonly encountered nematode infections
Dr. Mahmoud H. Taleb

37. Figure () Characteristics of and therapy for commonly encountered trematode infections.
Dr. Mahmoud H. Taleb

38. Figure (41) Characteristics of and therapy for commonly encountered cestode infections.
Dr. Mahmoud H. Taleb

39. Antiscabietic and antipediculosis drugs
1- Sulfur
2-Crotamiton
3-Lindane (Hexachlorocyclohexane)
4- Permethrin( Ectomethrin, Tick tack, lice nock, zehuze)
5- Malathion
6- Other alternatives scabicedes
*Benzyl benzoate ( Benzanil, Scabicide).
* Ivermectin
Dr. Mahmoud H. Taleb

40. Table(8) Summary of anthelmintic agents.
Dr. Mahmoud H. Taleb

41. Dr. Mahmoud H. Taleb

42. Antiviral drugs Viruses
Viruses are autonomous infectious particles that differ widely from other microorganisms in a number of characteristics: they have no cellular structure, consisting only of proteins and nucleic acid (DNA or RNA). They have metabolic systems of their own, but rather depend on the synthetic mechanism of a living host cell, whereby the viruses uset normal cellular metabolism by delivering their own genetic information, i.e., nucleic acid, into the host cell.
The host cell accepts the nucleic acid and proceeds to produce the components of new viruses in accordance with the genetic information it contains.
Viruses infect bacteria (so-called bacteriophages), plants, animals, and humans.
Dr. Mahmoud H. Taleb

43. Figure ( )Essential Characteristics of Viruses
Dr. Mahmoud H. Taleb

44. Dr. Mahmoud H. Taleb

45. Figure () The major sites of antiviral drug action.
Dr. Mahmoud H. Taleb

46. Dr. Mahmoud H. Taleb

47. Viruses are obligate intracellular parasites; their replication depends primarily on synthetic processes of the host cell. Consequently, to be effective, antiviral agents must either block viral entry into or exit from the cell or be active inside the host cell. Nonselective inhibitors of virus replication may interfere with host cell function and produce toxicity. The search for chemicals that inhibit virus-specific functions is currently one of the most active areas of pharmacologic investigation. Research in antiviral chemotherapy began in the early 1950s, when the search for anticancer drugs generated several new compounds capable of inhibiting viral DNA synthesis.
Dr. Mahmoud H. Taleb

48. Recent research has focused on the identification of agents with greater selectivity, in vivo stability, and lack of toxicity. Selective antiretroviral agents that inhibit a critical HIV-1 enzyme such as reverse transcriptase or the protease required for final packaging of the virus particle have become available. In many viral infections, replication of the virus peaks at or before the manifestation of clinical symptoms. Optimal clinical efficacy in many viral illnesses therefore depends either on early initiation of therapy (eg, acyclovir for treatment of varicella or zoster infection) or on prevention of infection (eg, chemoprophylaxis against influenza A using a neuraminidase inhibitor or amantadine. Alternatively, potent inhibition of viral replication may be of clinical benefit in chronic illnesses such as HIV infection or viral hepatitis.
Dr. Mahmoud H. Taleb

49. Pharmacokinetics: Administration of acyclovir can be by an intravenous, oral, or topical route. The drug distributes well throughout the body, including the cerebrospinal fluid (CSF). Acyclovir is partially metabolized to an inactive product.
Excretion into the urine occurs both by glomerular filtration and by tubular secretion. Acyclovir accumulates in patients with renal failure.
Adverse effects: Side effects of acyclovir treatment depend on the route of administration. For example, local irritation may occur from topical application; headache, diarrhea, nausea, and vomiting may result after oral administration. Transient renal dysfunction may occur at high doses or in a dehydrated patient receiving the drug intravenously.
Dr. Mahmoud H. Taleb

50. II. Treatment of Respiratory Virus Infections Neuraminidase inhibitors
Inhibitors of viral uncoating
Ribavirin
Dr. Mahmoud H. Taleb

51. III. Treatment of Hepatic Viral Infections Interferon Lamivudine
IV. Treatment of Herpes virus Infections
Acyclovir
. Ganciclovir C. Penciclovir and
D. famciclovi E. Vidarabine
F. Foscarent
Dr. Mahmoud H. Taleb

52. IV. Treatment of Herpes virus Infections
A. Acyclovir
Herpes simplex virus (HSV) Types 1 and 2, varicella-zoster virus (VZV)and some Epstein-Barr virus mediated infections are sensitive to acyclovir. It is the treatment of choice in HSV encephalitis.The most common use of acyclovir is in therapy for genital herpes infections. It is also given prophylactically to seropositive patients before bone marrow and after heart transplants to protect such individuals during posttransplant immunosuppressive treatments.
Mode of action: Acyclovir, is monophosphorylated in the cell by the herpes virus encoded enzyme, thymidine kinase . Therefore, virus-infected cells are most susceptible. The monophosphate analog is converted to the di- and triphosphate forms by the host cells. Acyclovir triphosphate competes with deoxyguanosine triphosphate as a substrate for viral DNA polymerase and is itself incorporated into the viral DNA, causing premature DNA-chain termination .
Resistance:
Altered or deficient thymidine kinase and DNA polymerases have been found in some resistant viral strains and are most commonly isolated from immunocompromised patients. Cross-resistance to the other cyclovirs occurs.
Dr. Mahmoud H. Taleb

53. V. Treatment of HIV Infection
Dr. Mahmoud H. Taleb