Antifungal Agents Fungi are plantlike microorganisms that exist ubiquitously
throughout the soil and air and in plants and animals. A disease caused by fungal infection is also referred to as a
mycosis Some fungal infections are relatively local or superficial,
affecting cutaneous and mucocutaneous tissue Often, fungal infections are relatively innocuous because
they can be destroyed by the body’s normal immune defense mechanisms
Fungal infections that are relatively easy to treat in the immunocompetent person may become invasive and life threatening in those who lack adequate immune function
Systemic Antifungal Agents
Amphotericin BClinical Use. is one of the primary drugs used to treat severe systemic fungal
infections This drug is often chosen to treat systemic infections and meningitis caused
by Candida, Cryptococcus,
Mechanism of Action. Amphotericin B appears to work by binding to specific steroidlike lipids
(sterols) located in the cell membrane of susceptible fungi.
Adverse Effects. Most patients experience problems such as headache, fever, muscle and joint
pain, muscle weakness, and gastrointestinal distress (nausea, vomiting, stomach pain or cramping).
FluconazoleClinical Use. This drug is often the primary treatment for urinary tract infections,
pneumonia, and infections of the mouth and esophagus caused by the Candida species of fungus.
Mechanism of Action. Fluconazole and similar agents (itraconazole, ketoconazole) inhibit certain enzymes in
fungal cells that are responsible for the synthesis of important sterols. also directly damages the fungal membrane by destroying certain membrane
components such as triglycerides and phospholipids
Adverse Effects. Hepatotoxicity is the most serious adverse effect of fluconazole Other common side effects include headache and gastrointestinal disturbances
(abdominal pain, nausea, vomiting)
FlucytosineClinical Use. This drug is used systemically to treat endocarditis, urinary tract infections, and the
presence of fungi in the bloodstream (fungemia) during candidiasis. is also used to treat meningitis and severe pulmonary infections caused by
cryptococcosis
Mechanism of Action. is incorporated into susceptible fungi, where it undergoes enzymatic conversion to
fluorouracil,7 which acts as an antimetabolite during RNA synthesis in the fungus
Adverse Effects. may cause hepatotoxicity and may also impair bone marrow function, resulting in anemia,
leukopenia, and several other blood dyscrasias.
GriseofulvinClinical Use. is used primarily in the treatment of common fungal infections of the skin
known as tinea, or ringworm.
Mechanism of Action. enters susceptible fungal cells and binds to the mitotic spindle during cell
division
Adverse Effects. Common side effects of griseofulvin administration include headaches—
which may be severe—and gastrointestinal disturbances (nausea, vomiting, diarrhea).
Skin photosensitivity (increased reaction to ultraviolet light) may also occur
ItraconazoleClinical Use. is an azole antifungal agent that is effective against many systemic fungal
infections may also be used as the primary or alternative treatment for other fungal
infections, such as aspergillosis, chromomycosis, coccidioidomycosis, and various infections caused by the Candida species
Mechanism of Action. These drugs disrupt membrane function of the fungal cell by inhibiting the
synthesis of key membrane components such as sterols, and by directly damaging other membrane components such as phospholipids.
Adverse Effects. Side effects associated with itraconazole include headache, gastrointestinal
disturbances (nausea, vomiting), and skin rash.
KetoconazoleClinical Use. is used to treat a variety of superficial and deep fungal infections.
Mechanism of Action. Ketoconazole selectively inhibits certain enzymes that are responsible for the
synthesis of important sterols in fungal cells.
Adverse Effects. Gastrointestinal disturbances (nausea, vomiting, stomach pain) are the most
common adverse effects when ketoconazole is administered systemically. Some degree of hepatotoxicity may occur, and severe or even fatal hepatitis
has been reported on rare occasions
EchinocandinsClinical Use. These drugs are administered intravenously to treat severe esophageal
infections caused by Candida. is also used to treat systemic aspergillosis infections in patients who cannot
tolerate other drugs such as amphotericin B or fluconazole
Mechanism of Action. These drugs inhibit the glucan synthase enzyme that is responsible for the
biosynthesis of beta-D-glucan—a component of the fungal cell membrane
Adverse Effects. Primary side effects of caspofungin and micafungin include gastrointestinal
disturbances (nausea, vomiting) and headache.
TerbinafineClinical Use. is effective against a broad spectrum of fungi and can be administered
systemically to treat infections in the toenails and fingernails (onychomycosis) that are caused by various fungi.
Mechanism of Action. Terbinafine inhibits a specific enzyme (squalene epoxidase) that is
responsible for sterol synthesis in the fungal cell membrane.
Adverse Effects. Systemic administration of terbinafine may cause a hypersensitivity
reaction (skin rashes, itching) and gastrointestinal problems such as nausea, vomiting, and diarrhea.
VoriconazoleClinical Use. Voriconazole has a broad antifungal spectrum, and is administered
systemically to treat aspergillosis and other serious fungal infections caused by Scedosporium apiospermum and Fusarium
Mechanism of Action. Inhibits sterol biosynthesis in fungal cell membranes
Adverse Effects. Skin rashes and vision disturbances (blurred vision, seeing bright spots) are
common during voriconazole administration, but these side effects are usually transient and fairly uneventful.
Topical Antifungal Agents
Topical Azole AntifungalsClinical Use. these drugs are valuable in controlling fungal infections in the skin
andmucocutaneous tissues
Mechanism of Action. antifungal azoles work by inhibiting the synthesis of key components of the fungal cell
membrane; that is, these drugs impair production of membrane sterols, triglycerides, and phospholipids
Adverse Effects. Gastrointestinal distress (cramps, diarrhea, vomiting) can occur if azole lozenges are
swallowed. Other problems associated with topical use include local burning or irritation of the
skin or mucous membranes.
Antiprotozoal Agents
Protozoa are single-celled organisms that represent the lowest division of the animal kingdom.
One relatively common disease caused by protozoal infection is malaria. Malaria is caused by several species of a protozoan parasite known as plasmodia
Antimalarial Agents
ChloroquineClinical Use. chloroquine (Aralen) has been one of the primary antimalarial drugs This drug provides a safe, effective, and relatively inexpensive method for treating
malaria, and is also administered routinely to individuals who are traveling to areas of the world where they may be exposed to malaria infection
Mechanism of Action. chloroquine may impair metabolic and digestive function in the protozoa by becoming
concentrated within subcellular vacuoles and raising the pH of these vacuoles
Adverse Effects. The most serious problem associated with chloroquine is the possibility of toxicity to
the retina and subsequent visual disturbances
Hydroxychloroquine Hydroxychloroquine (Plaquenil) is derived chemically from chloroquine and is similar
to it in clinical use, mechanism of action, and adverse effects.
MefloquineClinical Use. Mefloquine (Lariam) has emerged as one of the most important antimalarial agents. This drug is especially important in the prevention and treatment of malaria that is resistant
to traditional antimalarial drugs such as chloroquine and quinine
Mechanism of Action. mefloquine may exert antimalarial effects similar to chloroquine; that is, these drugs inhibit
hemoglobin digestion in malarial parasites, thus causing heme by-products to accumulate within the protozoa and cause toxicity and death of this parasite.
Adverse Effects. At higher doses, such as those used to treat infection, mefloquine may cause dizziness,
headache, fever, joint and muscle pain, and gastrointestinal problems (abdominal pain, nausea, vomiting, diarrhea).
PrimaquineClinical Use. Primaquine is typically used to treat the relapses of specific forms of malaria, and is generally
administered in acute or severe exacerbations
Mechanism of Action. appears to impair DNA function in susceptible parasites
Adverse Effects. Gastrointestinal disturbances (nausea, vomiting, abdominal pain), headache, and visual
disturbances
PyrimethamineClinical Use. is only of minor use in treating and preventing malaria. the antimalarial effectiveness of pyrimethamine is increased dramatically by
combining it with the antibacterial drug sulfadoxine
Mechanism of Action. Pyrimethamine blocks the production of folic acid in susceptible protozoa by
inhibiting the function of the dihydrofolate reductase enzyme.
Adverse Effects. Toxicity is fairly common when these drugs are given in high dosages for prolonged
periods, and adverse effects include gastrointestinal disturbances (vomiting, stomach cramps, loss of appetite), blood dyscrasias (agranulocytosis, leukopenia, thrombocytopenia), CNS abnormalities (tremors, ataxia, seizures), and hypersensitivity reactions (skin rashes, anaphylaxis, liver dysfunction).
QuinineClinical Use. Quinine is one of the oldest forms of antimalarial chemotherapy remains one of the most effective antimalarial drugs and is currently used to treat
severe malaria that is resistant to other drugs
Mechanism of Action. This drug probably exerts antimalarial effects similar to those of chloroquine—that is,
inhibition of hemoglobin digestion and subsequent accumulation of toxic heme by-products that lead to death in susceptible protozoa
Adverse Effects. This drug may produce disturbances in the CNS (headache, visual disturbances, ringing in
the ears), gastrointestinal system (nausea, vomiting, abdominal pain), and cardiovascular system (cardiac arrhythmias). Problems with hypersensitivity, blood disorders, liver dysfunction, and hypoglycemia may also occur in some individuals.
Other Antimalarials: Use of Artemisinin DerivativesClinical Use. These agents act rapidly and appear to be effective against all malarial parasites that
infect humans
Mechanism of Action. appear to work by a two-step process occurring within the malarial parasite first step, the drug is activated when it is cleaved by the heme-iron component within the
protozoa. second step, reacts with and destroys essential protozoal proteins.
Adverse Effects. Because these drugs are fairly new, the potential for side effects remains to be
determined fully.
Drugs Used to Treat Protozoal Infections in the Intestines and Other Tissues
AtovaquoneClinical Use. is used primarily to treat the protozoon that causes toxoplasmosis and the fungus that
causes pneumocystis pneumonia in immunocompromised patients
Mechanism of Action. appears to selectively inhibit electron transport in susceptible microorganisms
Adverse Effects. may cause side effects such as fever, skin rash, cough, headache, and gastrointestinal
problems (nausea, vomiting, diarrhea).
Emetine and DehydroemetineClinical Use. are used primarily to treat protozoal infections in the intestinal tract and extraintestinal
sites such as the lungs and liver.
Mechanism of Action. These drugs exert a direct effect on susceptible protozoa by causing degeneration of
subcellular components
Adverse Effects. problems with cardiotoxicity may occur, as reflected by arrhythmias, palpitations, and
other changes in cardiac conduction and excitability.
IodoquinolClinical Use. is used primarily to treat protozoal infections within the intestinal tract,51 and it is
often combined with a second tissue amebicide, which kills protozoa at extraintestinal sites.
Mechanism of Action. The mechanism of action of iodoquinol as an amebicide is unknown.
Adverse Effects. Iodoquinol is neurotoxic and may produce optic and peripheral neuropathies when
administered in large dosages for prolonged periods.
MetronidazoleClinical Use. is effective against a broad spectrum of protozoa and is often the primary agent used
against protozoal infections in intestinal and extraintestinal tissues
Mechanism of Action. The exact mechanism of action of metronidazole is not known.
Adverse Effects. Gastrointestinal disturbances including nausea, vomiting, diarrhea, stomach pain, and
an unpleasant taste in the mouth are relatively common with metronidazole.
NitazoxanideClinical Use. is a relatively new agent that is used primarily to treat diarrhea caused by intestinal
cryptosporidia and giardia infections
Mechanism of Action. appears to inhibit electron transport in susceptible protozoa, thus inhibiting energy
metabolism in these parasites.
Adverse Effects. Gastrointestinal disturbances (vomiting, diarrhea) and headache
ParomomycinClinical Use. is an aminoglycoside antibacterial that is used primarily to treat mild to moderate
intestinal infections (amebiasis)
Mechanism of Action. Paromomycin acts selectively on protozoa within the intestinal lumen and destroys
these parasites by a direct toxic effect
Adverse Effects. problems with gastrointestinal distress (nausea, vomiting, abdominal pain) may
occur
PentamidineClinical Use. is effective against several types of extraintestinal protozoal infections, including
certain forms of trypanosomiasis (African sleeping sickness) and visceral infections caused by Leishmania protozoa
Mechanism of Action. Some possible antiprotozoal actions of this drug include the inhibition of protein and
nucleic acid synthesis, cellular metabolism, and oxidative phosphorylation in susceptible parasites.
Adverse Effects. The primary adverse effect of systemic pentamidine administration is renal toxicity.
Anthelmintics Infection from helminths, or parasitic worms, is the most common form of disease in
the world Worms can enter the body by various routes but often are ingested as eggs in
contaminated food and water Once in the body, the eggs hatch, and adult worms ultimately lodge in various
tissues, especially the digestive tract. The adult worms begin to steal nutrients from their human host and may begin to
obstruct the intestinal lumen or other ducts if they reproduce in sufficient numbers.
Albendazole is primarily used to treat infections caused by the larval form of certain cestodes
(tapeworms). albendazole is used as an adjunct to the surgical removal of these cysts or as the
primary treatment if these cysts are inoperable This drug is also effective against many gastrointestinal roundworms and hookwo Albendazole exerts its anthelmintic effects by acting on the intestinal cells of
parasitic worms and by inhibiting glucose uptake and glycogen storage by these parasites.
Long-term treatment for conditions such as hydatid disease may result in abnormal liver function tests (e.g., increased serum aminotransferase activity), and liver function
Diethylcarbamazine is used to treat certain roundworm infections of the lymphatics and connective
tissues, including loiasis, onchocerciasis, and Bancroft filariasis. This agent immobilizes immature roundworms (microfilariae) and facilitates the
destruction of these microfilariae by the body’s immune system. Side effects associated with diethylcarbamazine include headache, malaise,
weakness, and loss of appetite.
Ivermectin is the primary treatment for filarial nematode infections (onchocerciasis) that invade
ocular tissues and cause loss ofvision (river blindness). Ivermectin binds to chloride ion channels in parasitic nerve and muscle cells, thereby
increasing membrane permeability to chloride. may cause swollen or tender lymph glands, fever, skin rash, itching, and joint and
muscle pain
Mebendazole is effective against many types of roundworms and a few tapeworms that parasitize
humans. this drug selectively damages intestinal cells in these worms, thus inhibiting the
uptake and intracellular transport of glucose and other nutrients into these parasites. Mebendazole is a relatively safe drug, although some mild, transient gastrointestinal
problems may occur.
Niclosamide This drug inhibits certain mitochondrial enzymes in these parasites, which ultimately
results in the breakdown of the protective integument of the worm, thus allowing the digestive enzymes in the host (human) intestine to attack the parasite.
There are relatively few adverse effects of niclosamide treatment, probably because the drug is not absorbed to any great extent from the human intestine.
Oxamniquine is effective against a genus of parasitic worms known as blood flukes
(schistosomes). Oxamniquine inhibits muscular contraction of the sucker that holds the fluke to the
vessel wall, thus allowing the worm to dislodge and travel to the liver. Common side effects associated with this drug include headache, dizziness, and
drowsiness.
Piperazine Citrate is typically used as a secondary agent in ascariasis (roundworm) and enterobiasis
(pinworm) infections This drug appears to paralyze the worm by blocking the effect of acetylcholine at the
parasite’s neuromuscular junction Side effects such as headache, dizziness, and gastrointestinal disturbance
Praziquantel is one of the most versatile and important anthelmintic agents, and is the drug of
choice in treating all major trematode (fluke) infections and several common types of tapeworm infections
may stimulate muscular contraction of the parasite, resulting in a type of spastic paralysis, which causes the worm to lose its hold on intestinal or vascular tissue.
frequent side effects, including gastrointestinal problems (abdominal pain, nausea, vomiting), CNS effects (headache, dizziness), and mild hepatotoxicity
Pyrantel Pamoate is one of the primary agents used in several types of roundworm and pinworm
infections This drug stimulates acetylcholine release and inhibits acetylcholine breakdown at
the neuromuscular junction, thus producing a prolonged state of excitation and muscular contraction that causes spastic paralysis of the worm
Thiabendazole The anthelmintic mechanism of this drug is not fully understood, but selective
inhibition of certain key metabolic enzymes in susceptible parasites is probable. The most common side effects associated with this drug involve gastrointestinal
distress (nausea, vomiting, loss of appetite).
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