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Pentamidine
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Pentamidine isethionate is an antimicrobial medication primarily given for prevention and treatment of Pneumocystis jiroveci pneumonia... formerly known as Pneumocystis carinii pneumonia (PCP), a severe interstitial type of pneumonia often seen in patients with HIV infection. PCP is considered an 'opportunistic infection', endagering only immunodeficient patients such as those with HIV/AIDS. The mortality of untreated PCP is very high. Additionally, pentamidine has good clinical activity in treating Leishmaniasis, sleeping sickness caused by different strains of Trypanosoma, and yeast infections caused by the organism candida albicans. Pentamidine is also used as a prophylactic antibiotic for children undergoing treatment for leukaemia. The exact mechanism of its anti-protozoal action is unknown, despite the fact that its a basic therapeutic modality (in concurrence with multiple antifungal medications) when treating Acanthamoeba infections in the immunocompromised patients.
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Pentamidine is an antiparasitic agent used to treat the opportunistic infection Pneumocystis carinii pneumonia [1-6]. Unfortunately, hyperkalemia is an important complication of therapy, observed in as many as 100% of patients with the acquired immunodeficiency syndrome (AIDS) receiving pentamidine for more than 6 days [1-4]. This elevation in the serum potassium level can be seen in the absence of adrenal insufficiency, hyporeninemic hypoaldosteronism, interstitial nephritis, or hyperglycemia (pentamidine-induced pancreatic islet cell dysfunction). Investigators have ... reported azotemia in 25% to 95% of patients infected with the human immunodeficiency virus (HIV) who receive pentamidine [6-8]. However, hyperkalemia is usually out of proportion to the degree of coexisting renal insufficiency and is frequently associated with hyperchloremic metabolic acidosis [6, 7, 9]. These findings have led several groups to postulate that pentamidine might directly effect renal tubular K+ secretion [1, 4, 6].
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Pentamidine isethionate and sulfamethoxazole-trimethoprim are effective in the treatment of Pneumocystis carinii pneumonia in the immunosuppressed pediatric patient. To compare their efficacy and toxicity, 25 pediatric cancer patients with biopsy-proved P carinii pneumonia were randomly assigned to receive either pentamidine intramuscularly or sulfamethoxazole-trimethoprim orally for 14 days. No differences in response or frequency of side effects were noted between the two drug regimens, with recovery occurring in 24 (96%) of 25 children. Skin eruptions and hematologic abnormalities were the most common side effects of sulfamethoxazole-trimethoprim therapy, while local reactions at injection sites, abnormal renal function, and hypoglycemia were the most frequent complications of pentamidine treatment. The ease of administration and less serious side effects of sulfamethoxazole-trimethoprim make it the drug of first choice for treating P carinii pneumonia. Pentamidine remains an important drug for patients who fail to respond to this initial therapy.
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Pentamidine ... may cause low blood sugar (hypoglycemia). Symptoms include cold sweats, clammy feeling, dizziness, weakness, nervousness, unusual hunger, abnormal heartbeat, blurred vision, confusion, slurred speech, and unconsciousness. These effects may be severe and can occur even after pentamidine is discontinued. Pentamidine also may cause high blood sugar (hyperglycemia). Symptoms include frequent urination, increased thirst, weakness, dizziness, and headache. Your health care provider will advise you what to do if you develop low or high blood sugar; write down these directions so that you can refer to them later.
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Pentamidine, 1,5-bis(4-amidinophenoxy)pentane, is used clinically to treat the severe infections caused by Pneumocystis carinii in AIDS and other immunodeficient states; it is ... used to treat African trypanosomiasis and leishmaniasis (1,2). The mechanism of pentamidine action is not understood, although several mechanisms have been suggested for its action against different microorganisms (3–6). Pentamidine has long been known to bind to DNA, RNA and nucleotides (7). Pentamidine has been shown to be selectively bound in the minor groove of AT-rich DNA duplexes, with the amidinium groups hydrogen bonded to N3 atoms of adenine and the drug molecule occupying a groove site spanning 4–5 bp (8–10). However, the antimicrobial effects of pentamidine have not been proven to be due to DNA binding (11).
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Pentamidine-treated hERG-HEK cells were ... examined for the expression of the hERG polypeptide by using the Western blot analysis. Whole-cell lysates were prepared and electrophoresed on a 4–12% bis-acrylamide gel, and subsequently transferred to nitrocellulose. The membrane was probed with a hERG antibody, stripped and reprobed with an antibody against GAPDH. The hERG band (155kb) densities were measured and normalized against the corresponding GAPDH levels (Figure 5b). The results indicated 44% (P<0.05) and 81% (P<0.001) reductions of the hERG polypeptide in cells treated with 3 and 10
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Pentamidine