Antimalarial, Antiprotozoal, and Anthelmintic Drugs



Antimalarial, Antiprotozoal, and Anthelmintic Drugs


Objectives


When you reach the end of this chapter, you will be able to do the following:



Drug Profiles



Key Terms


Anthelmintic A drug that destroys or prevents the development of parasitic worm (helminthic) infections. Also called antihelmintic or vermicide; notice that the terms for the drug categories are spelled with only one h, which appears in the second syllable of the term, whereas the term for worm infection (helminthic) is spelled with two h’s, appearing in both the first and third syllables of the term. (p. 700)


Antimalarial drugs Drugs that destroy or prevent the development of the malaria parasite (Plasmodium sp.) in humans. Antimalarial drugs are a subset of the broader category of antiprotozoal drugs. (p. 694)


Antiprotozoal A drug that destroys or prevents the development of protozoans in humans. (p. 698)


Helminthic infections Parasitic worm infections. (p. 700)


Malaria A widespread protozoal infectious disease caused by four species of the genus Plasmodium. (p. 693)


Parasite Any organism that feeds on another living organism (known as a host) in a way that results in varying degrees of harm to the host organism. (p. 693)


Parasitic protozoans Harmful protozoans that live on or in humans or animals and cause disease in the process. (p. 693)


Protozoans Single-celled organisms that are the smallest and simplest members of the animal kingdom. (p. 693)


image


http://evolve.elsevier.com/Lilley



Anatomy, Physiology, and Pathophysiology Overview


There are more than 28,000 known types of protozoans, which are single-celled organisms. Those that live on or in humans are called parasitic protozoans. Billions of people worldwide are infected with these organisms, and, as a result, these infections are considered a serious public health problem. Some of the more common protozoal infections are malaria, leishmaniasis, trypanosomiasis, amebiasis, giardiasis, and trichomoniasis. They are relatively uncommon in the United States but are becoming increasingly prevalent in immunocompromised individuals, including those with acquired immunodeficiency syndrome (AIDS). Protozoal diseases are especially prevalent among people living in tropical climates because it is easier for protozoans to survive and be transmitted in environments that are warm and humid year round. Although the population of the United States is relatively free of many of these protozoal infections, international travel and the immigration of people from other countries where such infections are endemic are providing opportunities for increased exposure.


Pathophysiology of Malaria


The most significant protozoal disease in terms of morbidity and mortality is malaria. Worldwide, it is estimated that 350 to 500 million people are infected, with an annual death rate of 1 million to 2 million people. In Africa alone, malaria accounts for more than 1 million infant deaths per year. The geographic areas with the highest prevalence are sub-Saharan Africa, Southeast Asia, and Latin America. Approximately 1200 cases of malaria are reported in the United States annually, seen mostly in people who traveled to malaria-infested countries. Malaria is caused by a particular genus of protozoans called Plasmodium, and there are four species of organisms in this genus, each with its own characteristics and its own ability to resist being killed by antimalarial drugs. These four species are Plasmodium vivax, Plasmodium falciparum, Plasmodium malariae, and Plasmodium ovale. Although P. vivax is the most widespread of the four, P. falciparum is nearly as widespread and causes greater problems with drug resistance. The two remaining species are much less common and more geographically limited in their occurrence, but they can still cause serious malarial infections.


Most commonly, malaria is transmitted by the bite of an infected female anopheline mosquito. This type of mosquito is endemic to many tropical regions of the earth. Malaria can also be transmitted by blood transfusions, congenitally from mother to infant via an infected placenta, or through the use of contaminated needles. Despite the combined efforts of many countries to eradicate malaria, it remains one of the most devastating infectious diseases in the world. As is also the case with tuberculosis (see Chapter 41) and AIDS (see Chapter 40), many lives are lost to malaria, and the cost of treating and preventing the disease imposes a tremendous economic burden on the often poor countries where the disease is prevalent.


The Plasmodium life cycle is quite complex and involves many stages. The organism has two interdependent life cycles: the sexual cycle, which takes place inside the mosquito, and the asexual cycle, which occurs in the human host (Figure 43-1). In addition, the asexual cycle of the parasite consists of a phase outside the erythrocyte (primarily in liver tissues) called the exoerythrocytic phase (or the tissue phase) and a phase inside the erythrocyte called the erythrocytic phase (or the blood phase). The malarial parasite undergoes many changes during these two phases (Figure 43-2).




Malaria signs and symptoms are often described in terms of the classic malaria paroxysm. A paroxysm is a sudden recurrence or intensification of symptoms. Symptoms include chills and rigors, followed by fever of up to 104° F (40° C) and diaphoresis, frequently leading to extreme fatigue and prolonged sleep. This syndrome often repeats itself periodically in 48- to 72-hour cycles. Other common symptoms include headache, nausea, and joint pain.


Pharmacology Overview


Antimalarial Drugs


Treatment for malaria is not initiated until the diagnosis has been confirmed by laboratory tests. Once confirmed, appropriate antimalarial treatment must be initiated immediately. Treatment is guided by three main factors: the infecting Plasmodium species, the clinical status of the patient, and the drug susceptibility of the infecting parasites as determined by the geographic area where the infection was acquired. Because the resistance patterns are constantly changing, depending on geographic location, the reader is referred to the website of the Centers for Disease Control and Prevention (CDC) at www.cdc.gov/malaria/ for the most up-to-date information. People traveling to different parts of the world may require antimalarial prophylaxis and need to check with their prescribers and/or the CDC website mentioned above for specific drug therapy.


Antimalarial drugs administered to humans cannot affect the parasite during its sexual cycle when it resides in the mosquito. Instead, these drugs work against the parasite during its asexual cycle, which takes place within the human body. Often these drugs are given in various combinations to achieve an additive or synergistic antimalarial effect. One example is the combination of the two antiprotozoal drugs atovaquone and proguanil (Malarone). The antibiotic combination of pyrimethamine and sulfadoxine (Fansidar) is also commonly used, especially in cases caused by drug-resistant organisms.


Mechanism of Action and Drug Effects


The mechanisms of action of the various antimalarial drugs differ depending on the chemical family to which they belong. The 4-aminoquinoline derivatives (chloroquine and hydroxychloroquine) work by inhibiting deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) polymerase, enzymes essential to DNA and RNA synthesis by the parasite cells. Parasite protein synthesis is also disrupted, because protein synthesis is dependent on proper nucleic acid (DNA and RNA) function. These drugs also raise the pH within the parasite, which interferes with the parasite’s ability to metabolize and use erythrocyte hemoglobin; this is one reason these drugs are ineffective during the exoerythrocytic (tissue) phase of infection. All of these actions contribute to the destruction of the parasite. Quinine, quinidine, and mefloquine are thought to be similar to the 4-aminoquinoline derivatives in their actions in that all are also believed to raise the pH within the parasite.


The diaminopyrimidines (pyrimethamine and trimethoprim [see Chapter 38]) work by inhibiting dihydrofolate reductase, an enzyme that is needed for the production of certain vital substances in malarial parasites. Specifically, inhibiting this enzyme blocks the synthesis of tetrahydrofolate, which is a precursor of purines and pyrimidines (nucleic acid components) and certain amino acids (protein components) that are essential for the growth and survival of plasmodia parasites. These two drugs are effective only during the erythrocytic phase. Pyrimethamine and trimethoprim are often used with a sulfonamide (sulfadoxine or dapsone) because of the resulting synergistic effects exerted by such drug combinations. Tetracyclines such as doxycycline (see Chapter 38) and lincomycins such as clindamycin (see Chapter 39) may also be used in combination with some of the other antimalarial drugs because of the synergistic effects resulting from these drug combinations.


Primaquine, an 8-aminoquinoline that is structurally similar to the 4-aminoquinolines, has the ability to bind to and alter parasitic DNA. It is one of the few drugs that is effective in the exoerythrocytic phase. Atovaquone/proguanil also works by interference with nucleic acid synthesis.


The drug effects of the antimalarial drugs are mostly limited to their ability to kill parasitic organisms, most of which are Plasmodium species (spp.). However, some of these drugs have other effects and therapeutic uses. Hydroxychloroquine also has antiinflammatory effects and is sometimes used in the treatment of rheumatoid arthritis and systemic lupus erythematosus. Quinine and quinidine can also decrease the excitability of both cardiac and skeletal muscles. Quinidine is still currently used to treat certain types of cardiac dysrhythmias (see Chapter 25).


Indications


Antimalarial drugs are used to kill Plasmodium organisms, the parasites that cause malaria. The various antimalarial drugs work during different phases of the parasite’s growth inside the human. The antimalarials that exert the greatest effect on all four Plasmodium organisms during the erythrocytic or blood phase are chloroquine, hydroxychloroquine, and pyrimethamine. Other drugs that are known to work during the blood phase are quinine, quinidine, and mefloquine. Because these drugs are ineffective during the exoerythrocytic phase, however, they cannot prevent infection. The most effective antimalarial drug for eradicating the parasite during the exoerythrocytic phase is primaquine, which actually works during both phases. Primaquine is indicated specifically for infection with P. vivax. Chloroquine and hydroxychloroquine (4-aminoquinolines) are the drugs of choice for the treatment of susceptible strains of malarial parasites. They are highly toxic to all Plasmodium spp., except resistant strains of P. falciparum.


Quinine is indicated for infection with chloroquine-resistant P. falciparum, which can cause a type of malaria that affects the brain. Quinine can be used alone but is more commonly given in combination with pyrimethamine, a sulfonamide, or a tetracycline (such as doxycycline). Pyrimethamine is another antimalarial antibiotic that is commonly used in combination with the sulfonamide antibiotic sulfadoxine (Fansidar) for prophylaxis against chloroquine-resistant P. falciparum and P. vivax. However, drug resistance in most locations has reduced its use for this purpose. Other antimalarial drugs are generally preferred for the treatment of active disease. Mefloquine is an antimalarial drug that may also be used for both prophylaxis and treatment of malaria caused by P. falciparum or P. vivax. The drug combination atovaquone and proguanil (Malarone) is also used for prevention and treatment of P. falciparum infection.


Contraindications


Contraindications to various antimalarial drugs include drug allergy, tinnitus (ear ringing), and pregnancy (quinine). Severe renal, hepatic, or hematologic dysfunction may also be a contraindication to the use of antimalarial drugs. Other drug-specific contraindications are noted in the drug profiles that follow.


Adverse Effects


Antimalarial drugs cause diverse adverse effects, and these are listed for each drug in Table 43-1.



Interactions


Some common drug interactions associated with antimalarial drugs are listed in Table 43-2.



Dosages


For dosage information on selected antimalarial drugs, see the table on this page.


Drug Profiles


The dosing instructions for several of the antimalarial drugs can be confusing, because tablet strengths listed on the medication packaging often indicate the strength of the tablet in terms of the entire salt form of the drug, not just the active ingredient itself, which is referred to as the base ingredient. However, dosing guidelines often list recommended dosages in terms of the base ingredient and not the entire salt. For example, as described later in the drug profile for chloroquine, the tablets come in 250-mg and 500-mg strengths of the salt form of the drug, but these tablets actually only have 150 mg and 300 mg, respectively, of the active ingredient or base. Be mindful of these distinctions.


♦ chloroquine and hydroxychloroquine


Chloroquine (Aralen) is a synthetic antimalarial drug that is chemically classified as a 4-aminoquinoline derivative. In addition to malaria, it is also indicated for treatment of other parasitic infections, such as amebiasis. Hydroxychloroquine is another synthetic 4-aminoquinoline derivative that differs from chloroquine by only one hydroxyl group (–OH). Its efficacy in treating malaria is comparable to that of quinine. Both medications also possess antiinflammatory actions and have been used to treat rheumatoid arthritis and systemic lupus erythematosus since the 1950s. However, only hydroxychloroquine (Plaquenil) is now used for these indications.


Contraindications include visual field changes, optic neuritis, and psoriasis, but its use may still be warranted in urgent clinical situations, based on sound clinical judgment.



Dosages
Selected Antimalarial Drugs




























































DRUG (PREGNANCY CATEGORY) PHARMACOLOGIC CLASS USUAL DOSAGE RANGE INDICATIONS/USES
♦ chloroquine (Aralen) (C) Synthetic antimalarial and antiamebic Adult∗
PO: 300 mg base weekly, beginning 2 wk before and continuing for 8 wk after visiting endemic area
Malaria prophylaxis
    PO: 600 mg base on day 1, followed by 300 mg 6 hr later and on days 2 and 3 Malaria treatment
♦ hydroxychloroquine (Plaquenil) (C) Synthetic antimalarial Adult∗
PO: 310 mg base weekly, beginning 1-2 wk before and continuing through 4 wk after visiting endemic area
Malaria prophylaxis
    PO: 620 mg base on day 1, followed by 310 mg 6 hr later and once daily on days 2 and 3 Malaria treatment
mefloquine (Lariam) (C) Synthetic antimalarial Adult and children weighing over 45 kg
PO: 250 mg weekly beginning 1-2 wk before travel and continuing until 4 wk after visiting endemic area
Pediatric
PO: Dosing varies based on weight.		 Malaria prophylaxis
    Adult
PO: 1250 mg (5 tabs) in a single dose
Pediatric
PO: 15-25 mg/kg in a single dose, not to exceed 1250 mg		 Malaria treatment
♦ primaquine (generic only) (C) Synthetic antimalarial Adult
30 mg PO daily × 14 days after leaving endemic area. Doses vary if dealing with drug-resistant malaria.		 Malaria prophylaxis
    Adult
PO: 15 mg base daily × 14 days
Pediatric
PO: 0.5 mg base/kg/day × 14 days		 Malaria treatment
pyrimethamine (Daraprim) (C) Folic acid antagonist, antimalarial, antitoxoplasmotic Adult and pediatric older than 10 yr
PO: 25 mg weekly
Pediatric 4-10 yr
PO: 12.5 mg weekly
Pediatric infant to 3 yr
PO: 6.25 mg weekly		 Malaria prophylaxis
    Adult and pediatric older than 10 yr
PO: 50 mg daily × 2 days
Pediatric 4-10 yr
PO: 25 mg daily × 2 days		 Malaria treatment


Image


PO, oral.


∗Only adult dosages are given. Pediatric dosages range from 5 to 10 mg/kg but not to exceed adult dosages.


Chloroquine and hydroxychloroquine are available only for oral use. Both drugs are classified as pregnancy category C drugs, but it is recommended that they be used in pregnant women only in truly urgent clinical situations. These drugs are also distributed into breast milk.



Tags:
May 9, 2017 | Posted by in NURSING | Comments Off on Antimalarial, Antiprotozoal, and Anthelmintic Drugs

Full access? Get Clinical Tree
Get Clinical Tree app for offline access