Fosinopril
(2S, 4S )-4- cyclohexyl-1 - { 2' -[( ( R, S) -2-methyl 1 propionyloxypropoxy ) - (4- phenylbutyl ) phosphinoyl ] acetyl} pyrrolidine-2 -carboxylic acid
- C30H46NO7P ( Fosinopril )
- C30H46NNaO7P ( fosinopril · sodium salt)
- 98048-97-6 ( Fosinopril )
- 88889-14-9 ( fosinopril · sodium salt)
C09AA09
Inhibition of angiotensin converting enzyme
- 563.66 g · mol -1 ( Fosinopril )
- 585.64 g.mol -1 ( Fosinopril · sodium salt)
Template: Infobox chemical / molecular formula search available
Fosinopril is a drug from the group of ACE inhibitor for the treatment of hypertension (high blood pressure) and heart failure is used. Fosinopril itself is an inactive prodrug. Its active principle is based upon activation of fosinoprilat through inhibition of the angiotensin converting enzyme (ACE).
Pharmacology
Areas of application
Fosinopril is preferably used as monotherapy and in combination with other blood pressure medicines diuretics for the treatment of hypertension and for the treatment of heart failure, and it is therefore of synergistic effects and to a reduction of blood pressure. In severe cases of heart failure, a combination with digitalis is possible and appropriate.
Mechanism of Action
Fosinopril performs as an inhibitor of angiotensin converting enzyme in a reduced formation of angiotensin II from angiotensin I. This reduced formation of angiotensin II causes a decrease in the tonus of the blood vessels and thus a decrease in blood pressure. Also the decrease in angiotensin II levels leads to a reduction of aldosterone release from the adrenal cortex and thus to influence the water budget (see also the renin -angiotensin -aldosterone system ).
Side effects
Most side effects of fosinopril be associated with a conditional by ACE inhibitors slow degradation and the accumulation of bradykinin. These include skin reactions such as rashes and hives, and also angioneurotic edema. Severe allergic skin Reaktione other hand, are rarely observed.
Among the side effects of the respiratory system include dry cough, hoarseness and sore throat. Asthma attacks and shortness of breath may also, though rarely, occur.
As a result, the main effect of fosinopril may result in an excessively strong Bludrucksenkung. As a result, can be observed occasionally dizziness, headache and dizziness. From serious cardiovascular events such as angina pectoris, myocardial infarction, and syncope have been reported only in individual cases.
By intervening in the water and Elektrolyhaushalt functional renal dysfunction can be observed occasionally. Proteinuria ( excretion of proteins in urine ), however, was only rarely observed.
Since fosinopril may cause during pregnancy, inter alia, growth and bone formation disorders associated with increased mortality in children, fosinopril should not be used at this time and should be replaced with other suitable therapeutic measures.
Interactions
Fosinopril potentiates the blood glucose lowering effect of insulin and oral hypoglycemic agents, and the blood- changing effects of immunosuppressants.
By intervening in the water and Elektrolyhaushalt the excretion of electrolytes can be slowed down, which in therapy should be considered especially with lithium and potassium-sparing diuretics.
In combination with other antihypertensive drugs increased blood pressure reduction should be considered.
Potencies
Fosinopril is available in dosage strengths of 5, 10 and 20 mg, and combined with the diuretic hydrochlorothiazide ( HCT) in 20/12, 5 mg are available.
Dose adjustment in hepatic or renal dysfunction is not necessary, since an elimination ( excretion ) are alike and so sufficient compensation options are available.
Chemistry
Fosinopril is an ACE inhibitor used the second generation, only the removed has similarity to other drugs of the otherwise largely mono- form group of ACE inhibitors. In the synthesis is one of the amino acid (2S, 4R) - from 4-hydroxyproline, which is implemented in a multi-step reaction sequence to fosinopril. Fosinopril is currently the only ACE inhibitor with a phosphate structure.
The substance is an inactive prodrug that is obtained by esterification and acetalization. The terminal acetyl group is cleaved by esterases in the body by the liver. The hemiacetal thus formed gradually breaks down and causes the active fosinoprilat.
Stereoisomerism
Fosinopril contains four stereocenters, three of carbon atoms and one at the phosphorus atom. Theoretically, there is thus 16 stereoisomers. The stereocenters on the pyrrolidine ring are clearly defined [( 2S, 4R) ]. However, the absolute configuration of the stereocenter at the carbon atom in the side chain and on the phosphorus atom is not uniform. The drug fosinopril is thus a mixture of diastereomers. Stereoisomers have different pharmacological effects in general.
Trade names
Dynacil (D), fosinopril (D), Fositen (CH), Fositens (A ), various generics (A)
Dynacil comp ( D), Fosicomp (A, CH), fosinopril comp ( D), Fosinopril HCT (A, CH)