FOSINOPRIL-ACE inhitbitor

                                      

DESCRIPTION-

Fosinopril is an angiotensin converting enzyme (ACE) inhibitor[1] used for the treatment of hypertension and some types of chronic heart failure. Fosinopril is the only phosphinate-containing ACE inhibitor marketed, by Bristol-Myers Squibb under the trade name Monopril.

MECHANISM OF ACTION-

There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Fosinoprilat, the active metabolite of fosinopril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Fosinoprilat also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors.

ROUTE OF ADMINISTRATION – Oral

HALF LIFE – 12

BIOAVAILABILITY- ~36%

METABOLISM – Hepatic G.I.T mucosa

BIOLOGICAL HALF LIFE – 12 HOURS

PROTEIN BINDING – 87%

USES –

        In the treatment of - heart failure

        Kidney problem

        High blood pressure

ADVERSE EFFECT  - 

                    * Weakness

                    * Fainting

                    * Dry cough

                    *Dizziness

DRUG INTERACTION-

FOSINOPRIL + LEVODPA – Fosinopril may increase the orthostatic hypertensive activity of levodopa.

FOSINOPRIL + ALFUZOSIN – Alfuzosin may increase the hypertensive activity of fosinopril.

FOSINOPRIL + HEPARIN – Heparin may increase the hyperkalemic activity of fosinopril.

FOOD INTERACTION-

* Do not take calcium, aluminum, magnesium or iron supplements, or antacids within 2 hours of taking this medication.

* Fosinopril may decrease the excretion of potassium. Salt substitutes containing potassium may increase the risk of hyperkalemia.

* Herbs that may attenuate the antihypertensive effect of fosinopril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.

* High salt intake may attenuate the antihypertensive effect of fosinopril.

* Take without regard to meals.

REFERENCE-

Tripathi K.D,"Essentials of medical pharmacology",7th edition,page no- 501, 503