پنتاميدين

{{drugbox | IUPAC_name = 4-{[5-(4-carbamimidoylphenoxy)pentyl]oxy benzene-1-carboximidamide | image = Pentamidine-2D-skeletal.png | CAS_number = 100-33-4 | ATC_prefix = P01 | ATC_suffix = CX01 | ATC_supplemental = | PubChem = 4735 | DrugBank = APRD00303 | C=19 | H=24 | N=4 | O=2 | molecular_weight = 340.42 g/mol | bioavailability = | protein_bound = 69% | metabolism = | elimination_half-life = 6.4-9.4 hours | pregnancy_US = C | legal_status = | routes_of_administration = IV, IM, inhalation پنتاميدين إيزيثيونات Pentamidine isethionate هومضاد بكتيرى دواء يعطى ميدئيا لعلاج and treatment of Pneumocystis إلتهاب رئوي (PCP)الذى , يعهد سابقا Pneumocystis carinii pneumonia (PCP), شديد فراغى نوع من [[ إلتهاب رئوي]] يرى غالبا في عدوى سقمى إيدز . PCPقد يكون أويعد 'العدوى الانتهازية', تهدد سقمي نقص المناعة مثل HIV/إيدز.

الإستعمال

ويستعمل پنتاميدين للوقاية في السقمى الذين يتلقون العلاج الكيميائى ولديهم جهاز مناعة متدنى الفعالية كأثر جانيى مباشر للأدوية المستخدمة . نسبة الوفيات للنمط الذى لم يتلقى علاجا من PCP عالية جدا. بالإضافة الى أن, بنتاميدين يمتلك فعالية سريرية جيدة في علاج ليشمانيا, سقم النوم الذى تسببه فصائل عديدة من عدوى تريبانوسوما, الخميرة التى تسببها عضويات Candida albicans.بنتاميدين يستخدم أيضا, في الوقاية للأطفال الذين يتلقون علاجا مضادا بكتيريا, مع العلاج الخاص ب اللوكيميا .

The exact mechanism of its anti-protozoal action is unknown (though it may involve reactions with ubiquitin), despite the fact that it's a basic therapeutic modality (in concurrence with multiple antifungal medications) when treating Acanthamoeba infections in the immunocompromised patients. The drug has also activity against (missing microbe) in clinically relevant concentrations. In the الولايات المتحدة, pentamidine is currently designated an orphan drug by the U.S. Food and Drug Administration.

علاج الحالات الحادة PCP

In the acute treatment of PCP, pentamidine is considered equally or slightly less active than co-trimoxazole (brand names Bactrim, Septrin, or Septra). Clinical evidence suggests that pentamidine is often better tolerated than co-trimoxazole because a high dose of co-trimoxazole is needed, which is associated with a high incidence and severity of side effects such as hepatitis, bone-marrow-damage, renal-damage, and life threatening skin disease (Lyell-syndrome). Moreover, many patients are or become allergic to co-trimoxazole. For treatment of PCP, أربعة milligrams of pentamidine per kilogram of body weight is given intravenously once daily for 14 to 21 days. Treatment exceeding 21 days may be necessary, but is associated with increased toxicity. Intramuscular injection is not recommended. The effect of pentamidine often becomes evident within the first 2 days of treatment, with reduction in fever and improvement of respiratory function. In any case, improvements of chest x-ray studies occur withinستة toثمانية days, provided therapy is successful. Pentamidine therapy cures 50 to 70% of all patients treated.

الوقاية الأولية والثانوية PCP

Primary prophylaxis of severely immunocompromised patients can be indicated where PCP has not yet been diagnosed. Secondary prophylaxis aims to prevent recurrent infections by PCP. For both forms of prophylaxis, an aerosolized formulation of pentamidine given by nebulizer once monthly in a dose of 300mg is used. In primary prophylaxis, this reduces the long term likelihood of PCP by 70% when compared to no prophylaxis.

أخريات

For other indications, such as leishmaniasis or sleeping sickness, special treatment schedules developed by the WHO or CDC exist.

Use as an antitumor drug has also been proposed.

مضادات الإستعمال

الحساسية الحادة؛ no others in PCP patients in whom a proper diagnosis has been made

نظرية العمل

The mechanism is not well characterized, but there is some evidence that it may involve mitochondrial function.

الآثار الجانبية

Pentamidine can cause allergic and toxic side effects, which in part depend on the daily and/or cumulative dose:

Kidney : 25 percent develop signs of nephrotoxicity ranging from mild, asymptomatic azotemia (increased serum كرياتينين وurea) to irreversible فشل كلوي. Ample fluids or intravenous hydration may prevent some nephrotoxicity.
Cardiovascular : انخفاض ضغط الدم, which may be severe, severe or fatal arrhythmias and فشل القلب are quite frequent.
Gastrointestinal : الغثيان، قيء، gastrointestinal discomfort, الاسهال, unpleasant taste
Pancreas : Hypoglycemia that requires symptomatic treatment is frequently seen. On the other hand, pentamidine may cause or worsen diabetes mellitus.
Liver : Elevated liver enzymes are associated with intravenous use of pentamidine. Hepatomegaly and hepatitis have been encountered with long term prophylactic use of pentamidine inhalation.
Skin : Severe local reactions after extravasculation of intravenous solutions or following intramuscular injection treatment have been seen. Pentamidine itself may cause rash, or rarely Stevens-Johnson syndrome or Lyell syndrome.
Blood : Pentamidine frequently causes leukopenia and less often thrombopenia, which may cause symptomatic bleeding. Some cases of anemia, possibly related to folic acid deficiency, have been described.
Neurological : Dizziness, drowsiness, neuralgia, confusion, hallucinations, seizures and other central side effects are reported.
Respiratory : Cough and bronchospasm, most frequently seen with inhalation.
Others : Eye discomfort, conjunctivitis, throat irritation, splenomegaly, Herxheimer reaction, electrolyte imbalances (e.g. hypocalcemia).

تفاعلات الأدوية

The additional or sequential use of other nephrotoxic drugs like aminoglycosides, amphotericin B, capreomycin, colistin, polymyxin B, vancomycin, foscarnet, or cisplatin should be closely monitored, or whenever possible completely avoided.

الأسماء التجاريةوالأشكال

للاستنشاق الفموي: NebuPent 300mg Nebulizer
For parenteral treatment : Pentacrinat, Pentam 300, and Pentamidine isethionate for injection (Abbot); all containing 300mg of Pentamidine

المراجع

^ Nguewa PA, Fuertes MA, Cepeda V; et al. (2005). "Pentamidine is an antiparasitic and apoptotic drug that selectively modifies ubiquitin". Chem. Biodivers. 2 (10): 1387–400. doi:10.1002/cbdv.200590111. PMID 17191940. Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
^ Lee MS, Johansen L, Zhang Y; et al. (2007). "The novel combination of chlorpromazine and pentamidine exerts synergistic antiproliferative effects through dual mitotic action". Cancer Res. 67 (23): 11359–67. doi:10.1158/0008-5472.CAN-07-2235. PMID 18056463. Unknown parameter |month= ignored (help); Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
^ Sun T, Zhang Y (2008). "Pentamidine binds to tRNA through non-specific hydrophobic interactions and inhibits aminoacylation and translation". Nucleic Acids Res. 36 (5): 1654–64. doi:10.1093/nar/gkm1180. PMC 2275129. PMID 18263620. Unknown parameter |month= ignored (help)