PHARMACOLOGY LECTURE I 1ST SEMESTER I 2ND TERM 4. ANTIFUNGAL & ANTIPROTOZOAL AGENTS ANTIFUNGAL WHAT IS A FUNGUS? - Composed of a rigid cell wall and made up of chitin and various polysaccharides - A cell membrane containing ergosterol (acts to maintain membrane integrity) - Protective layers of the fungal cell make the organism resistant to antibiotics PATIENTS SUSCEPTIBLE TO FUNGAL INFECTIONS - Patients with aids and aids – related complex (arc) Patient taking immunosuppressant drugs Patients who have undergone transplantation surgery or cancer treatment Members of growing elderly population no longer protected from environmental fungi CULTURE - Culture is needed prior to prescribing antifungal agents Patients on antifungal agents are immuno-compromised (immune defenses are low, affecting its ability to fight off infections and diseases) at onset THERAPY/MEDICATIONS ANTIFUNGALS (ANTIMYCOTIC DRUGS) - Are used to treat mycosis or infections of fungi - Fungi are different from bacteria in the sense that their cell walls are made up of chitin and various polysaccharides rendering these organisms resistant to antibiotics. COMMON FUNGAL INFECTIONS - ATHLETE'S FOOT JOCK ITCH RINGWORM OF THE SCALP (TINEA CAPITIS) TINEA VERSICOLOR CUTANEOUS CANDIDIASIS ONYCHOMYCOSIS (TINEA UNGUIUM) TRANSCRIBED BY: REGINE MAE RICAFRENTE ATHLETE'S FOOT (TINEA PEDIS) - Is a fungal infection that affects the skin on feet - Often between your toes Symptoms: - Itching or a burning sensation bet. your toes or on the soles of your feet - Skin that appears red, scaly, dry, or flaky; cracked or blistered skin JOCK ITCH (TINEA CRURIS) - Fungal skin infection – area of your groin and thighs Symptoms: - Itchy rash that typically starts in the groin area or around the upper thighs. the rash may get worse after exercise or other physical activity and can spread to the buttocks and abdomen - Affected skin may appear scaly, flaky, or cracked - The outer border of the rash can be slightly raised and darker RINGWORM OF THE SCALP (TINEA CAPITIS) - Affects the skin of the scalp and associated hair shafts - Most common in young children and needs treated with prescription oral medication as well an antifungal shampoo Symptoms: - Localized bald patches that may appear scaly or red - Associated scaling and itching - Associated tenderness or pain in the patches TINEA VERSICOLOR - Sometimes called pityriasis versicolor - Fungal/yeast skin infection that causes small oval discolored patches to develop on the skin - Caused by fungus (malassezia) which is present on the skin of about 90% of adults - Most often seen on the back, chest, and upper arms. may be lighter or darker than the rest of your skin, and can be red, pink, tan, or brown. these patches can be itchy, flaky, or scaly - Tinea versicolor is more likely during summer or in areas with a warm, wet climate 1 CUTANEOUS CANDIDIASIS - Skin infection that is caused by candida fungi. fungi present on and inside our bodies. when it overgrows, an infection can happen - Candida skin infection occurs in areas that are warm, moist, and poorly ventilated. (example: under the breast and in the folds of the buttocks (such as diaper rash) Symptoms of skin rash - a red rash - itching - small red pustules ONYCHOMYCOSIS (TINEA UNGUIUM) - Fungal infection of your nails - Can affect the fingernails or the toenails - Although infections of the toenails are more common - You may have onychomycosis if you have nails that are: - Discolored - Typically yellow - Brown - White - Brittle or break easily - Thickened TYPES OF ANTIFUNGAL THERAPY SYSTEMIC ANTIFUNGALS - Used to treat systemic mycoses - Can be toxic to the host and not to be used indiscriminately - Important to get culture of the fungus causing the infection to ensure that the right drug is being used so that the patient is not put at additional risk from the toxic adverse effects associated with these drugs TOPICAL ANTIFUNGALS - Used to treat a variety of mycoses of skin and mucous membranes - Some systemic have topical forms TRANSCRIBED BY: REGINE MAE RICAFRENTE CLASSIFICATION OF ANTIFUNGAL AGENTS CUTANEOUS/TOPICAL INFECTIONS - NYSTATIN - GRISEOFULVIN - CLOTRIMAZOLE - ECONAZOLE - OXICONAZOLE - MICONAZOLE - BENZOIC ACID - UNDECYLENIC ACID - SODIUM METABISULFITE SYSTEMIC / SUBCUTANEOUS INFECTION - AMPHOTERICIN B - KETOCONAZOLE - VORICONAZOLE - ITRACONAZOLE - POSACONAZOLE - MICAFUNGIN - CASPOFUNGIN - FLUCONAZOLE CLASSIFICATION OF ANTIFUNGAL DRUGS - POLYENES ECHINOCANDINS ANTIMETABOLITES ALLYLAMINES AZOLES (IMIDAZOLES & TRIAZOLES) POLYENES - Mechanism of actions: - Act by binding to ergosterol in the fungal cell membrane - Binding results depolarization of the membrane - Formation of pores that increase permeability to proteins and monovalent and divalent actions, eventually to cell death - Most common medication: - AMPHOTERICIN ECHINOCANDINS - Mechanism of actions - Noncompetitively inhibit beta – 1, 3-d-glucan synthesis enzyme complex in susceptible fungi - Beta – glucan destruction prevents resistance against osmotic forces – leads to cell death - They have fungistatic activity against: aspergillus species - Most common medications: - CASPOFUNGIN (CANCIDAS) - Given via iv (intravenous) - Approved for the TX of invasive aspergillosis in patients who are refractory (resistant) to other TX 2 ANTIMETABOLITES - Mechanism of actions - Inhibits fungal protein synthesis by replacing uracil with 5 fluorouracil in fungal rna - Inhibit thymidylate synthetase via 5-flour deoxy-uridine monophosphate and thus interferes with fungal dna synthesis - Most common medication: - FLUCYTOSINE (ANCOBON) - Less toxic drug used for the TX of systemic infections caused by candida or cryptococcus ALLYLAMINES - Mechanism of actions - Inhibits ergosterol synthesis by inhibiting the enzyme squalene epoxidase - Most common medication: - TERBINAFINE (LAMISIL) - Blocks the formulation of ergosterol - Inhibits a cyp2d6 enzyme system - Oral drugs for the TX of onychomycosis of the toenail or fingernail AZOLES - Mechanism of actions - Inhibition of cytochrome p450 14a-demethylase - This enzyme is in the sterol biosynthesis pathway that leads from lanosterol to ergosterol - Most common medications: - KETOCONAZOLE (NIZORAL) - FLUCONAZOLE (DIFLUCAN) - ITRACONAZOLE (SPORANOX) - VORICONAZOLE (VFEND) MOST COMMON MEDICATIONS OF AZOLES KETOCONAZOLE (NIZORAL) - Used orally to treat many of the same mycoses as amphotericin b - Works by blocking activity of a steroid in the fungal wall - Has side effects of blocking the activity of human steroids, including testosterone and cortisol Pharmacokinetics: - Absorbed from gi tract - Metabolized in the liver - Excreted in the feces Contraindications: - Not drug of choice for patients with endocrine or fertility problems Drug-to-drug interactions: - Many FLUCONAZOLE (DIFLUCAN) - Not associated with endocrine problems seen with ketoconazole - Used to treat candidiasis, cryptococcal meningitis, and other systemic fungal infections - Prophylactic (prevent) agent for reducing the incidence of candidiasis in bone marrow transplant recipients Pharmacokinetics: - Available in oral and iv preparations, excreted unchanged in the urine Contraindications: - Renal dysfunction ITRACONAZOLE (SPORANOX) - An oral agent used for TX of associated systemic mycoses - Associated with hepatic failure - Slowly absorbed from GI tract - Metabolized in the liver by the cyp450 system - Excreted in the urine and feces VORICONAZOLE (VFEND) - Available in oral and iv forms - TX invasive aspergillosis and serious infections caused by scedosporium apiospermum (lung infection) and fusarium (onychomycosis, skin infection, and keratitis) species TRANSCRIBED BY: REGINE MAE RICAFRENTE 3 OVERALL CONTRAINDICATION TO SYSTEMIC ANTIFUNGAL - - Anyone with known allergy Pregnant or lactating women Patients with renal or liver disease: drug metabolism or excretion may be altered, or condition may worsen as a result of the actions of the drug CNS effects: headache, dizziness, fever, shaking, and chills GI effects: nausea, vomiting, dyspepsia (indigestion), anorexia Hepatic dysfunction Dermatologic effect: rash and pruritus (itchy skin) associated with local irritation Renal dysfunction PROTOZOAN PARASITES IDENTIFIED AS CAUSES OF MALARIA PLASMODIUM FALCIPARUM - Considered the most protozoan dangerous type of PLASMODIUM VIVAX - Milder form of the disease; seldom results in death PLASMODIUM MALARIA - Endemic (occurring within an area) in tropical countries; mild symptoms PLASMODIUM OVALE - Rarely seen; in the process of being eradicated ANTIPROZOAL AGENTS PROTOZOAL DISEASE - Antiprotozoals are agents to treat protozoan infections Common in tropical areas Protozoans are single – celled organisms that pass through several stages in their life cycles Including at least one phase as a human parasite Protozoans thrive in tropical climate They may also survive and reproduce in any areas where people live in very crowded and unsanitary conditions CAUSES OF PROTOZOAL INFECTIONS INSECT BITES: - Malaria - Trypanosomiasis - Leishmaniasis INGESTION OR CONTACT ORGANISM: - Amebiasis - Giardiasis - Trichomoniasis - MALARIA AMEBIASIS LEISHMANIASIS TRYPANOSOMIASIS TRICHOMONIASIS GIARDIASIS DRUG THERAPY FOR ANTIPROTOZOAL AGENTS Commonly used oral antiprotozoal drugs can be generally classified into two main groups: 1. ANTIMALARIAL DRUGS 2. MISCELLANEOUS ANTIPROTOZOALS ANTIMALARIALS - WITH CAUSAL - TRANSCRIBED BY: REGINE MAE RICAFRENTE Are agents used to attack plasmodium at various stages of its life cycle These agents can be: SCHIZONTICIDAL (acting against the rbc phase of the life cycle) GAMETOCYTOCIDAL (acting against the gametocytes) SPORONTOCIDAL (acting against the parasites that are developing in the mosquito) SCHIZONTS as prophylactic or antirelapse agent work against tissue 4 DRUG THERAPY QUININE (QUALAQUININE) - Was the first drug found to be effective in the TX of malaria - TX of chloroquine – resistant plasmodium infections CHLOROQUINE (ARALEN) - Prevention and TX of plasmodium malaria - TX of extraintestinal amebiasis HALOFANTRINE (HALFAN) - TX of plasmodium malaria combination with other drugs ANTIMYCOBACTERIALS - in HYDROXYCHLOROQUINE (PLAQUENIL) MEFLOQUINE (LARIAM) PRIMAQUINE (GENERIC) PREVENTION OF P. VIVAX AND P. MALARIAE RADICAL CURE OF P. VIVAX MALARIA PYRIMETHAMINE (DARAPRIM) THERAPEUTIC ACTION - Entering human rbc and changing the metabolic pathways necessary for reproduction - Chloroquine, the mainstay of TX, directly toxic to parasites and decreases the ability of the parasite to synthesize dna - Interrupt plasmodium reproduction od protein synthesis - Agents that do not appear to affect the sporozoles are used to prophylaxi CONTRAINDICATIONS - Known allergy, liver disease, alcoholism, lactation - Cautions: retinal disease or damage, psoriasis ADVERSE EFFECT - Headache, dizziness, fever, chills, malaise, nausea, vomiting, hepatic dysfunction DRUG-TO-DRUG INTERACTIONS - Quinine derivatives and quinine create risk for cardiac toxicity - Antifolate drugs with pyrimethamine can increase risk for bone marrow suppression TRANSCRIBED BY: REGINE MAE RICAFRENTE OTHER ANTIPROTOZOAL DRUGS - Actions: inhibiting dna synthesis in susceptible protozoa, interfering with cell’s ability to reproduce, subsequently leading to cell death - Contraindications: known allergy, pregnancy, CNS disease, & hepatic disease - Adverse reactions: headache, dizziness, ataxia (without coordination), vomiting, & diarrhea Contain pathogens causing tuberculosis and leprosy INDICATIONS: - TX of acid-fast tuberculosis) bacteria (mycobacterium ACTIONS: - Act on the dna of the bacteria, leading to lack of growth and eventual bacterial death PHARMACOKINETICS: - Adequately absorbed from the GI tract - Metabolized in the liver & excreted in the urine CONTRAINDICATIONS: - Allergy & renal or hepatic failure ADVERSE EFFECTS: - CNS effect & GI irritation DRUG-TO-DRUG INTERACTIONS: - Rifampin and inh(isoniazid) can cause liver toxicity COMMON THERAPY FOR AMEBICIDES MNEMONICS I’M A TINY CD PLAYER - IODOQUINOL - METRONIDAZOLE - TINIDAZOLE - CHLOROQUINE - DEHYDROEMETINE - PAROMOMYCIN Please note: All content used in this work is properly credited to the respective authors/creators, and their intellectual property rights are fully acknowledged and respected. 5
