أمفوتريسين ب


أمفوتريسين ب {{{English
الاسم النظامي (أيوپاك)
الاسم النظامي (أيوپاك)
(3S, 5R, 6R, 9R, 11R, 15S, 16R, 17R, 18S, 19E, 21E, 23E, 25E, 27E, 29E, 31E, 33R, 35S, 36R, 37S)-33-((2S, 3R, 4R, 5R, 6S)-4-amino-3, 5-dihydroxy-6-methyltetrahydro-2H-pyran-2-yloxy)-1, 3, 5, 6, 9, 11, 17, 37-octahydroxy-15, 16, 18-trimethyl-13-oxo-14, 39-dioxabicyclo[33.3.1]nonatriaconta-19, 21, 23, 25, 27, 29, 31-heptaene-36-carboxylic acid
المعينات Identifiers
رقم CAS	1397-89-3
كود ATC	A01AB04 A07AA07, G01AA03, J02AA01
PubChem	14956
بنك العقاقير	APRD00797
بيانات كيميائية
الصيغة	₄₇₇₃₁₇
كتلة جزيئية	924.084
بيانات الحركية الدوائية Pharmacokinetic
التوافر الحيوي	100% (IV)
الأيض	renal
عمر النصف	initial phase : 24 hours, second phase : approx. 15 days
اخراج	40% found in urine after single cumulated over several days biliar excretion also important
اعتبارات علاجية
فئة السلامة أثناء الحمل	B(الولايات المتحدة)
الوضع القانوني	Rx-only, hospitalization recommended.
المسارات	slow i.v.-infusion only

أمفوتيريسين ب أمفوتيريسين ب , (Fungilin, Fungizone, Abelcet, AmBisome, Fungisome, Amphocil, Amphotec),هودواء مضاد للفطريات polyene, يستعمل حقنا في الوريد للعدوى الفطرية المركزية. ويستخلص من Streptomyces nodosus, a filamentous bacterium, في عام 1955 بواسطة شركة Squibb للأبحاث الدوائية من مغرسة streptomycete مستخلصة من تربة جمعت من Orinoco River region of Venezuela. إثنان من صور الدواء Amphotericin A وAmphotericin B قيد الإستعمال ولكن فقط B يستعمل ,لكونه أكثر فعالية in vivo. وفى الواقع الدواء متوافر ك plain Amphotericin B وك cholesteryl sulfate complex , lipid complex, and as liposomal formulation. والهجريب الأخير قد طور لتحسين إحتمال الدواء بالنسبة للمريض , ولكن يمكن حتى تظهر حراكا دوائيا مختلفا, مقارنة با أمفوتيريسين ب العادى.

الإستعمالات

خاصية المضادة للفطريات

صيغ أمفوتيريسين ب التى تستعمل عن طريق الفم تستعمل لعلاج thrush; وهى يفترض حتى تكون غير سامة بالمقارنة بالصور المستخدمة للحقن الوريدى.واحدة من أبرز الإستخدامات للصورة المستخدمة للحقن الوريدى هى لعلاج الكثير من الأمراض المركزية(غير الجلدية السطحية),مثل السقمى السيئ الحال comorbidly immunocompromised patients. أمفوتيريسين ب يستعمل أيضا في tissue culture لمنع الفطريات من تلويث مزارع الخلايا البشرية. ويباع أمفوتيريسين ب في عبوات بهجريزات عالية, سواء بمفرده أومع المضادات الحيوية مثل penicillin وstreptomycin.

المفعول المضاد للأوليات

إستعمال وريدى آخر للأوليات مثل leishmaniasis and primary amoebic meningoencephalitis.

كمضاد حيوي

يستعمل أيضا في الأصل heroic measure فىfebrile immunocompromised patients الذين لايستجيبون للمضادات الحيوية ^{[بحاجة لمصدر]}

نظرية العمل

كما مثل جميع ال polyene antifungals, أمفوتيريسين ب يرتبط مع ergosterol, وهوغشاء كيميائى للفطر, مكونا ثقبا يؤدى الى تسريب مؤديا الى موت خلية الفطر . ويعتقد حتى أمفوتيريسين ب يتفاعل مع الغشاء الأستيرولى (ergosterol) لينتج aggregateقد يكون transmembrane channel Intermolecular hydrogen bonding interactions among hydroxyl, carboxyl and amino groups stabilize the channel in its open form, destroying activity and allowing the cytoplasmic contents to leak out

الآثار الجانبية

Amphotericin B is well-known for its severe and potentially lethal side effects. It is colloquially known among medical professionals as "amphoterrible" due to these side effects. Very often a serious acute reaction after the infusion (1 to ثلاثة hours later) is noted consisting of high fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, dyspnea, and tachypnea. This reaction sometimes subsides with later applications of the drug and may in part be due to histamine liberation. An increase in prostaglandin-synthesis may also play a role. This nearly universal febrile response necessitates a critical (and diagnostically difficult) professional determination as to whether the onset of high fever is a novel symptom of a fast-progressing disease, or merely the induced effect of the drug. In order to decrease the likelihood and severity of the symptoms, initial doses should be low and increased slowly. Acetaminophen, pethidine, diphenhydramine and/or hydrocortisone have all been used to treat or prevent the syndrome, but the prophylactic use of these drugs is often limited by the patient's condition.

Intravenously administered Amphotericin B has also been associated with multiple organ damage in therapeutic doses. Nephrotoxicity (kidney damage) is a frequently reported side-effect, and can be severe and/or irreversible. It is much milder when delivered via liposomes (AmBisome) if possible. Electrolyte imbalances (e.g. hypokalemia and hypocalcemia) may also result. In the liver, increased liver enzymes and hepatotoxicity (up to and including fulminant liver failure) are common. In the circulatory system, several forms of anemia and other blood dyscrasias (leukopenia, thrombopenia), serious cardiac arrhythmias (including ventricular fibrillation), and even frank cardiac failure have been reported. Skin reactions, including serious forms, are also possible.

التفاعلات الدوائية

Flucytosine : Toxicity of Flucytosine increased and vice versa
Diuretics or Cisplatin : Increased renal toxicity and incrised risk of hypokalemia
Corticosteroids : Increased risk of hypokalemia
Cytostatic drugs : Increased risk of kidney damage, hypotension and bronchospasms.
Other nephrotoxic drugs : Increased risk of serious renal damage. Monitor patients closely.
Foscarnet, Ganciclovir, Tenofovir, Adefovir : Risk of hematological and renal side-effects of Amphotericin B increased.
Transfusion of Leukocytes : Risk of pulmonal (lung) damage. Space intervals between the application of Amphotericin B and the transfusion and monitor pulmonary function.

Liposomal and lipid complex preparations

From studies it appears that liposomal amphotericin B preparations exhibit fewer side-effects while having similar efficacy. Various preparations have recently been introduced. All of these are more expensive than plain Amphotericin B.

AmBisome is a liposomal formulation of amphotericin B for injection, developed by NeXstar Pharmaceuticals (acquired by Gilead Sciences in 1999). It is marketed by Gilead in Europe and licensed to Astellas Pharma (formerly Fujisawa Pharmaceuticals) for marketing in the USA, and Sumitomo Pharmaceuticals in Japan.

Fungisome is a liposomal complex of Amphotericin B and being the latest and cheapest addition to the lipid formulations of Amphotericin B has many advantages. It is marketed by Lifecare Innovations of India. Other formulations include Amphotec (Intermune) and Abelcet (Enzon Pharmaceuticals).

Abelcet is not a liposomal preparation but rather a lipid complex preparation.

المراجع

^ Kafetzis DA, Velissariou IM, Stabouli S, Mavrikou M, Delis D, Liapi G (2005). "Treatment of paediatric visceral leishmaniasis: amphotericin B or pentavalent antimony compounds?". Int. J. Antimicrob. Agents. 25 (1): 26–30. doi:10.1016/j.ijantimicag.2004.09.011. PMID 15620822. Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^ Veerareddy PR, Vobalaboina V, Ali N (2008). "Antileishmanial activity, pharmacokinetics and tissue distribution studies of mannose-grafted amphotericin B lipid nanospheres". J Drug Target: 1. doi:10.1080/10611860802528833. PMID 19089691. Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)