Ph T4 - Antifungal

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flucytosine

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Also known as 5-fluorocytosine (antimetabolite)
Taken up by fungal cells & interferes with DNA synthesis
Result: fungal cell death
Older drug; newer drugs are more commonly used

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griseofulvin

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Disrupts cell division
Result: inhibited fungal mitosis (reproduction)
Older drug; newer drugs are more commonly used

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Polyenes: amphotericin B & nystatin

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Bind to sterols in cell membrane lining
Result: fungal cell death
Do not bind to human cell membranes or kill human cells
Amphotericin B is the drug of choice for treatment of severe systemic mycoses

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Imidazoles & triazoles: ketoconazole, fluconazole

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Inhibit fungal cell cytochrome P-450 enzymes, resulting in cell membrane leaking
Lead to altered cell membrane
Result: altered cellular metabolism & fungal cell death

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Echinocandins: capsofungin, micafungin

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Prevent the synthesis of glucans, which are essential components of fungal cell walls
Causes fungal cell death

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Antifungal Drugs: Contraindications

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Liver failure
Renal failure
Porphyria (griseofulvin): a group of rare disorders passed down through families, in which an important part of hemoglobin, called heme, is not made properly.
Drug allergy

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amphotericin B :
Nursing Implications

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To reduce the severity of the infusion-related reactions, pretreatment with an antipyretic (acetaminophen), antihistamines, antiemetics, & corticosteroids may be given
Use IV infusion pumps & the most distal veins possible (point furthest from the point of attachment to the body)
should be administered primarily to patients with progressive, potentially life-threatening fungal infections
Amphotericin B overdoses can result in potentially fatal cardiac or cardiopulmonary arrest

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Protozoal Infections

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Parasitic protozoa: live in or on humans
Malaria
Leishmaniasis
Amebiasis
Giardiasis
Trichomoniasis

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Antimalarial Drugs

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Attack the parasite during the asexual phase, when it is vulnerable
Erythrocytic phase drugs: chloroquine, hydroxychloroquine, quinine, mefloquine, pyrimethamine
Primaquine: kills parasite in both phases
May be used together or with a sulfonamide for synergistic or additive killing power

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Antimalarial Drugs: Mechanism of Action

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4-Aminoquinoline derivatives: chloroquine & hydroxychloroquine

Bind to parasite nucleoproteins & interfere with protein synthesis; also alter pH within the parasite
Interfere with parasite’s ability to metabolize & use erythrocyte hemoglobin
Effective only during the erythrocytic phase
Alter pH within the parasite

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Diaminopyrimidines (pyrimethamine &
trimethoprim)

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Inhibit protein synthesis essential for growth & survival
Only effective during the erythrocytic phase
These drugs may be used with sulfadoxine or dapsone for synergistic effects

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Primaquine

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Only exoerythrocytic drug (works in both phases)
Binds & alters parasitic DNA

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Sulfonamides, tetracyclines, clindamycin

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Used in combination with antimalarials to increase protozoacidal effects

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Antimalarial Drugs: Indications

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Used to kill Plasmodium organisms, the parasites that cause malaria
The drugs have varying effectiveness on the different malaria organisms
Some drugs are used for prophylaxis against malaria
Hydrochloroquine has anti-inflammatory effects & is also used for rheumatoid arthritis & systemic lupus erythematosus

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Antiprotozoal Drugs

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atovaquone (Mepron)
metronidazole (Flagyl)
pentamidine (Pentam-300)
paromomycin (Humatin)

Several drugs used to treat malaria are also used to treat nonmalarial protozoal infections

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Amebiasis

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infection of intestines caused by parasite Entamoeba histolytica, amebic dysentery.

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Giardiasis

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infection of small intestine caused by a microscopic organism (protozoa), Giardia lamblia

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Pneumocystosis

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infection of lungs caused by microorganism Pneumocystis carinii.

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Toxoplasmosis

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infection due to parasite Toxoplasma gondii.

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Trichomoniasis

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sexually transmitted infection caused by the parasite Trichomonas vaginalis.

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Leishmaniasis

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parasitic disease spread by the bite of the sandfly

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Protozoal Infections

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Patients with compromised immune systems are at risk for acquiring these infections
-aids, leukemia, immunosupprive drugs

Protozoal infections are often fatal in these cases

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atovaquone (Mepron)

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Protozoal energy comes from the mitochondria
Atovaquone: selective inhibition of mitochondrial electron transport
Result: no energy, leading to cellular death
Used to treat mild to moderate Pneumocystis jiroveci

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metronidazole (Flagyl)

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Disruption of DNA synthesis as well as nucleic acid synthesis
Bactericidal, amebicidal, trichomonacidal
Used for treatment of trichomoniasis, amebiasis, giardiasis, & antibiotic-associated pseudomembranous colitis
Also has anthelmintic activity

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pentamidine

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Inhibits DNA & RNA
Binds to & aggregates ribosomes
Directly lethal to Pneumocystis jirovecii
Mainly used to prevent & treat P. jirovecii pneumonia
Used for other protozoal infections

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Anthelmintic Drugs

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Drugs used to treat parasitic worm infections: helminthic infections
Unlike protozoa, helminths are large & have complex cellular structures
Drug treatment is very specific to the organism

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Anthelmintic Drugs (cont’d)

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It is VERY IMPORTANT to identify the causative worm
Done by finding the parasite ova or larvae in feces, urine, blood, sputum, or tissue
Cestodes (tapeworms)
Nematodes (roundworms)
Trematodes (flukes)
Platyhelminthes (flatworms)

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pyrantel (Antiminth)

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Blocks acetylcholine at the neuromuscular junction, resulting in paralysis of the worms, which are then expelled through the GI tract
Used for intestinal roundworm infections, ascariasis, enterobiasis, nematodes, other helmintic infections

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mebendazole (Vermox)

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Inhibits uptake of glucose & other nutrients, leading to autolysis & death of the parasitic worm
Used to treat roundworms, hookworms, & some tapeworms

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praziquantel (Biltricide)

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Paralyzes worms’ musculature & immobilizes
their suckers
Causes worms to dislodge from mesenteric veins
to the liver; then killed by host tissue reactions
Used to treat fluke infections, some tapeworms

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NSAIDs

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Large & chemically diverse group of drugs with the following properties:
Analgesic
Antiinflammatory
Antipyretic
Antirheumatic

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NSAIDs are also used to treat:

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Mild to moderate headache
Myalgia
Neuralgia
Arthralgia
Alleviation of post-op pain
Arthritis-type pain
Gout
Hyperuricemia

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Analgesia

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Block the chemical activity of either or both COX enzymes (prostaglandin [PG] pathway) & lipoxygenase (LT pathway)
Result in limiting the undesirable inflammatory effect of PGs

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Antipyretic

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Inhibits prostaglandin E2 within the area of the brain that controls temperature

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Salicylates

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Aspirin is the most common & is OTC
Others require a prescription
diflunisal (Dolobid)
Magnesium trisalcylate (Trilisate)
Salsalate (Salsitab)

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Reye’s Syndrome

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Potentially life threatening illness associated with aspirin administration to children & teenagers typically with a viral illness

Symptoms of Reye syndrome include:
persistent or recurrent vomiting,
listlessness,
personality changes including irritability or combativeness,
disorientation or confusion,
delirium,
convulsions,
loss of consciousness

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celecoxib (Celebrex

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First & only remaining COX-2 inhibitor
Indicated for osteoarthritis, rheumatoid arthritis, acute pain symptoms, ankylosing spondylitis, & primary dysmenorrhea

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Salicylic acid (aspirin)

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More potent effect on platelet aggregation & thermal regulatory center in the brain
Analgesic
Antipyretic
Antiinflammatory
Antithrombotic effect: used in the treatment of MI & other thromboembolic disorders

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Antigout Drugs: Indications

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NSAIDs are considered 1st line therapy
After NSAIDs: Specific Antigout Drugs
allopurinol (Zyloprim)
Used to reduce production of uric acid
Colchicine (2nd line therapy)
Reduces inflammatory response to the deposits of urate crystals in joint tissue-MOA unclear
probenecid (Benemid) & sulfinpyrazone (Anturane)
Increase excretion of uric acid in the urine

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NSAIDs: Interactions

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Anticoagulants
Aspirin
Corticosteroids & other ulcerogenic drugs
Protein bound drugs
Diuretics & ACE Inhibitors
Others

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Herbal Products: Glucosamine & Chondroitin

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Used to treat the pain of osteoarthritis
Adverse effects
GI discomfort
Drowsiness, headache, skin reactions (glucosamine)
Drug interactions
Enhance effects of warfarin
May increase insulin resistance (glucosamine)